Neural changes underlying the development of episodic memory during middle childhood

Highlights ▸ In this review, neural substrates of episodic memory development are discussed. ▸ We argue that hippocampus-mediated binding continues to develop during middle childhood along with other cortical regions in the prefrontal and parietal cortex. ▸ We underscore the role of development of hippocampal projections to and from cortical regions.

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title: The Nature of Recollection and Familiarity: A Review of 30 Years of Research
abstract: To account for dissociations observed in recognition memory tests, several dual-process models have been proposed that assume that recognition judgments can be based on the recollection of details about previous events or on the assessment of stimulus familiarity. In the current article, these models are examined, along with the methods that have been developed to measure recollection and familiarity. The relevant empirical literature from behavioral, neuropsychological, and neuroimaging studies is then reviewed in order to assess model predictions. Results from a variety of measurement methods, including task-dissociation and process-estimation methods, are found to lead to remarkably consistent conclusions about the nature of recollection and familiarity, particularly when ceiling effects are avoided. For example, recollection is found to be more sensitive than familiarity to response speeding, division of attention, generation, semantic encoding, the effects of aging, and the amnestic effects of benzodiazepines, but it is less sensitive than familiarity to shifts in response criterion, fluency manipulations, forgetting over short retention intervals, and some perceptual manipulations. Moreover, neuropsychological and neuroimaging results indicate that the two processes rely on partially distinct neural substrates and provide support for models that assume that recollection relies on the hippocampus and prefrontal cortex, whereas familiarity relies on regions surrounding the hippocampus. Double dissociations produced by experimental manipulations at time of test indicate that the two processes are independent at retrieval, and single dissociations produced by study manipulations indicate that they are partially independent during encoding. Recollection is similar but not identical to free recall, whereas familiarity is similar to conceptual implicit memory, but is dissociable from perceptual implicit memory. Finally, the results indicate that recollection reflects a thresholdlike retrieval process that supports novel learning, whereas familiarity reflects a signal-detection process that can support novel learning only under certain conditions. The results verify a number of model predictions and prove useful in resolving several theoretical disagreements.

title: The medial temporal lobe and recognition memory.
abstract: The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there is considerable debate about how these kinds of memory are supported by regions in the medial temporal lobes (MTL). Here, we review evidence for the distinction between recollection and familiarity and then consider the evidence regarding the neural mechanisms of these processes. Evidence from neuropsychological, neuroimaging, and neurophysiological studies of humans, monkeys, and rats indicates that different subregions of the MTL make distinct contributions to recollection and familiarity. The data suggest that the hippocampus is critical for recollection but not familiarity. The parahippocampal cortex also contributes to recollection, possibly via the representation and retrieval of contextual (especially spatial) information, whereas perirhinal cortex contributes to and is necessary for familiarity-based recognition. The findings are consistent with an anatomically guided hypothesis about the functional organization of the MTL and suggest mechanisms by which the anatomical components of the MTL interact to support the phenomenology of recollection and familiarity.

title: The emergence of autobiographical memory: a social cultural developmental theory.
abstract: The authors present a multicomponent dynamic developmental theory of human autobiographical memory that emerges gradually across the preschool years. The components that contribute to the process of emergence include basic memory abilities, language and narrative, adult memory talk, temporal understanding, and understanding of self and others. The authors review the empirical developmental evidence within each of these components to show how each contributes to the timing, quantity, and quality of personal memories from the early years of life. The authors then consider the relevance of the theory to explanations of childhood amnesia and how the theory accounts for and predicts the complex findings on adults' earliest memories, including individual, gender, and cultural differences.

title: Self-projection and the brain
abstract: When thinking about the future or the upcoming actions of another person, we mentally project ourselves into that alternative situation. Accumulating data suggest that envisioning the future (prospection), remembering the past, conceiving the viewpoint of others (theory of mind) and possibly some forms of navigation reflect the workings of the same core brain network. These abilities emerge at a similar age and share a common functional anatomy that includes frontal and medial temporal systems that are traditionally associated with planning, episodic memory and default (passive) cognitive states. We speculate that these abilities, most often studied as distinct, rely on a common set of processes by which past experiences are used adaptively to imagine perspectives and events beyond those that emerge from the immediate environment.

title: Childhood Head Injury and Metacognitive Processes in Language and Memory
abstract: We studied the metacognitive functioning of children with severe and mild traumatic brain injury (TBI) and typically developing children. To test metacognition for memory, children were tested on a modified Judgment of Learning task. We found that children with severe TBI were impaired in their ability to predict recall of specific items prior to study-recall trials, but were unimpaired in predicting recall on a delayed test when the judgment was made after study-recall trials. Metacognitive knowledge impairment for memorial abilities was also demonstrated in children with severe TBI by poor estimation of memory span and exaggerated overconfidence in performance. To test metacognition within the language domain, we gave children a sentence anomaly detection and repair task in which spoken sentences were monitored for semantic anomalies. Children with severe TBI were impaired on the detection of semantic anomalies, especially under conditions of high memory load. However, metalinguistic knowledge in the form of adequate repairs of anomalous sentences, was preserved. Results are discussed in terms of effects of age at test and injury severity.

title: Incidental retrieval of emotional contexts in post-traumatic stress disorder and depression: An fMRI study
abstract: In the present study, we used fMRI to assess patients suffering from post-traumatic stress disorder (PTSD) or depression, and trauma-exposed controls, during an episodic memory retrieval task that included non-trauma-related emotional information. In the study phase of the task neutral pictures were presented in emotional or neutral contexts. Participants were scanned during the test phase, when they were presented with old and new neutral images in a yes/no recognition memory task. fMRI results for the contrast between old and new items revealed activation in a predominantly left-sided network of cortical regions including the left middle temporal, bilateral posterior cingulate, and left prefrontal cortices. Activity common to all three groups when correctly judging pictures encoded in emotional contexts was much more limited. Relative to the control and depressed groups the PTSD group exhibited greater sensitivity to correctly recognised stimuli in the left amygdala/ventral striatum and right occipital cortex, and more specific sensitivity to items encoded in emotional contexts in the right precuneus, left superior frontal gyrus, and bilateral insula. These results are consistent with a substantially intact neural system supporting episodic retrieval in patients suffering from PTSD. Moreover, there was little indication that PTSD is associated with a marked change in the way negatively valenced information, not of personal significance, is processed.

title: Specificity of episodic and semantic aspects of autobiographical memory in relation to symptoms of posttraumatic stress disorder (PTSD).
abstract: Two studies examined the relationship between the ability to access specific autobiographical material in memory and presence/symptoms of posttraumatic stress. In Study 1, a sample of refugees with a diagnosis of posttraumatic stress disorder (PTSD) completed the Autobiographical Memory Test (AMT) in which they had to generate specific episodic autobiographical memories in response to emotion-related cue words. Results showed that reduced specificity of memories on the AMT was associated with an increased frequency of trauma-related flashbacks but with reduced use of effortful avoidance to deal with trauma-related intrusions in the day-to-day. Study 2 examined retrieval of semantic autobiographical information from previous lifetime periods in groups of cancer survivors with posttraumatic stress and healthy controls. The cancer survivors were able to generate fewer specific semantic details about the personal past compared to the controls. The more symptomatic survivors showed the greatest memory impairment. The data from both studies are discussed in terms of compromised access to specific autobiographical material in distressed trauma survivors reflecting a process of affect regulation.

title: Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: perspectives from cognitive neuroscience.
abstract: A significant proportion of military personnel deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been exposed to war-zone events potentially associated with traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). There has been significant controversy regarding healthcare policy for those service members and military veterans who returned from OEF/OIF deployments with both mild TBI and PTSD. There is currently little empirical evidence available to address these controversies. This review uses a cognitive neuroscience framework to address the potential impact of mild TBI on the development, course, and clinical management of PTSD. The field would benefit from research efforts that take into consideration the potential differential impact of mild TBI with versus without persistent cognitive deficits, longitudinal work examining the trajectory of PTSD symptoms when index trauma events involve TBI, randomized clinical trials designed to examine the impact of mild TBI on response to existing PTSD treatment interventions, and development and examination of potential treatment augmentation strategies.

title: Neuropsychological functions in anxiety disorders in population-based samples: evidence of episodic memory dysfunction.
abstract: Most of the available evidence on neuropsychological functioning in anxiety disorders is based on clinical samples, investigating persons affected by obsessive-compulsive disorder. Knowledge is sparse regarding cognitive functions in other types of anxiety disorders. The aim of this study was to examine whether persons diagnosed with an anxiety disorder show neuropsychological impairments relative to healthy controls in tasks tapping episodic memory, verbal fluency, psychomotor speed, and executive functioning. Population-based samples comprising individuals affected by panic disorder with and without agoraphobia or agoraphobia (n=33), social phobia (n=32), generalised anxiety disorder (n=7), obsessive-compulsive disorder (n=16), and specific phobia (n=24) were compared with healthy controls (n=175) in test performance. Overall, the total anxiety disorder group exhibited significant impairments in episodic memory and executive functioning. Separate analyses on the respective anxiety subgroup indicated that panic disorder with and without agoraphobia, and obsessive-compulsive disorder were related to impairments in both episodic memory and executive functioning. In addition, social phobia was associated with episodic memory dysfunction. Verbal fluency and psychomotor speed were not affected by anxiety. Specific phobia and generalised anxiety disorder did not affect neuropsychological functioning.

title: Neurocognitive deficit in schizophrenia: a quantitative review of the evidence.
abstract: The neurocognitive literature on test performance in schizophrenia is reviewed quantitatively. The authors report 22 mean effect sizes from 204 studies to index schizophrenia versus control differences in global and selective verbal memory, nonverbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language, and interhemispheric tactile-transfer test performance. Moderate to large raw effect sizes (d > .60) were obtained for all 22 neurocognitive test variables, and none of the associated confidence intervals included zero. The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.

title: Levels-of-processing effect on word recognition in schizophrenia
abstract: Individuals with schizophrenia have difficulty organizing words semantically to facilitate encoding. This is commonly attributed to organizational rather than semantic processing limitations. By requiring participants to classify and encode words on either a shallow (e.g., uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of-processing paradigm eliminates the need to generate organizational strategies.



This paradigm was administered to 30 patients with schizophrenia and 30 healthy comparison subjects to test whether providing a strategy would improve patient performance.



Word classification during shallow and deep encoding was slower and less accurate in patients. Patients also responded slowly during recognition testing and maintained a more conservative response bias following deep encoding; however, both groups showed a robust levels-of-processing effect on recognition accuracy, with unimpaired patient performance following both shallow and deep encoding.



This normal levels-of-processing effect in the patient sample suggests that semantic processing is sufficiently intact for patients to benefit from organizational cues. Memory remediation efforts may therefore be most successful if they focus on teaching patients to form organizational strategies during initial encoding.

title: Memory skills of boys with fragile X syndrome.
abstract: Multiple aspects of memory were examined in 42 boys with fragile X syndrome and a comparison group of 42 typically developing boys matched on MA. Working memory, incidental memory, and deliberate memory were assessed with a battery that included both free-recall and recognition tasks. Findings indicated that boys with fragile X syndrome performed more poorly than their matches on most measures. The exception was free recall, in which their accuracy was equal to that of the control participants. Results from analyses of a subset of boys with fragile X syndrome who exhibit characteristics of autism and their MA matches, though preliminary, support the conclusion that memory deficits are especially marked in boys who have fragile X syndrome and evidence autistic behaviors.

title: Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project.
abstract: Childhood neurobehavioral deficits in offspring of schizophrenic, affectively ill, and psychiatrically normal parents were evaluated as predictors of schizophrenia-related psychoses in adulthood.



The offspring were tested with neurobehavioral measures at 7-12 years of age and assessed in mid-adulthood for axis I diagnoses. The relationships of childhood deficits in attention, verbal memory, and gross motor skills to adulthood schizophrenia-related psychoses were examined in separate path analyses by using logistic regression equations. Sensitivity and specificity were determined for each of the childhood dysfunctions.



For the offspring of schizophrenic parents, childhood deficits in verbal memory, gross motor skills, and attention identified 83%, 75%, and 58%, respectively, of the subjects with schizophrenia-related psychoses; 50% were identified by all three variables combined. False positive rates in subjects who did not develop schizophrenia-related psychoses ranged from 18% for those with deficits in attention during childhood to 28% for those with deficits in memory. The three variables had low deficit rates in the offspring of the other two parental groups and were not associated with other psychiatric disorders in any group.



Schizophrenia-related psychoses in adulthood are distinguished in subjects at risk for schizophrenia by childhood deficits in verbal memory, gross motor skills, and attention. The findings suggest that deficits in these variables are relatively specific to schizophrenia risk and may be indicators of the genetic liability to schizophrenia.

title: The endophenotype concept in psychiatry: etymology and strategic intentions.
abstract: Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.

title: Recall in Infancy
abstract: Relations between developments in neural structures and changes in memory in infancy are a relatively recent focus of research. Greater knowledge about brain development, as well as methodological advances such as combined use of behavioral and electrophysiological techniques, have led to the generation and testing of specific hypotheses regarding sources of age-related change. Theory and data converge to suggest that the early-stage processes of encoding and consolidation are a significant source of age-related variability in memory early in life. Additional research is needed to determine how these processes change and interact with myriad other determinants of recall.

title: The role of associative strength in children's false memory illusions
abstract: The effects of associative strength on rates of 7- and 11-year-old children's true and false memories were examined when category and Deese-Roediger-McDermott (DRM) lists were used to cue the same critical lure. Backward associative strength (BAS) was varied such that the category and DRM lists had the same strength (DRM=category), DRM lists had more BAS (DRM>category), or category lists had more BAS (DRM<category). If BAS drives children's false memories then BAS, not the type of relation across items in a list, should determine false memory production. The results confirmed this prediction using both recall and recognition measures: (1) both true and false memories increased with age, (2) true memory was better for category than DRM lists but there were no differences for false memory, and (3) at all ages, false memories varied predictably with changes in BAS but were unaffected by list-type manipulations. These findings are discussed in the context of models of false memory development.

title: Parameters of remembering and forgetting in the transition from infancy to early childhood.
abstract: The ability to recall is something that most intact adults take for granted. For much of the last century, this feature of mental life was not considered to extend to very young children. There now is evidence that 1- to 2-year-olds are able to recall specific events after delays of several months. Over the short term, 1- to 2-year-olds' recall is affected by the same factors that affect older children's recall; it is not clear whether similar effects are apparent over the long term. Moreover, although age-related increases in long-term recall are assumed, there have been few empirical tests of the question. We examined recall by 14- to 32-month-olds for events experienced at 13 to 20 months. Using elicited imitation of novel multistep event sequences we examined effects of (a) delay length, (b) age at the time of experience, (c) temporal structure of events, (d) mode of experience of events, and (e) availability of verbal reminders, on long-term recall. Participants were 360 children enrolled at 13 (n = 90), 16 (n = 180), and 20 (n = 90) months. All of the 13-month-olds and half of the 16-month-olds were tested on 3-step event sequences; all of the 20-month-olds and half of the 16-month-olds were tested on 4-step event sequences. Within each age and step-length group, equal numbers of children were tested after intervals of 1, 3, 6, 9, and 12 months (n = 18 per cell). Children were tested on a variety of sequence types. For half of the events, imitation was permitted prior to the delay; for the other half, children were not permitted imitation. At delayed testing, children experienced a recall period during which they were cued by the event-related props alone, followed by a period in which recall was cued both by the event-related props and by verbal labels for the event sequences. Within step-length groups, the length of time for which older and younger children showed evidence of memory did not differ. Nevertheless, when the children were prompted by the event-related props alone, there were age-related differences in the robustness of children's memories (as indexed by higher levels of recall for older children relative to younger children). When the children were prompted by the props and by verbal labels for the event sequences, at the longer retention intervals, there were age-related differences in the robustness of children's memories and in the reliability with which recall was evidenced (as indexed by the larger numbers of older children evincing recall). Age-related effects were particularly apparent on children's ordered recall. Across the entire age range, the children were similarly affected by the variables of sequence type, opportunity for imitation, and verbal reminding.

title: Age-related changes in verbal and nonverbal memory during early childhood.
abstract: In the present experiment, age-related changes in verbal and nonverbal memory performance by 2- to 4-year-old children were assessed. All children participated in the same unique event, and their memory of that event was assessed after a 24-hr delay. Overall, children's performance on each memory measure increased as a function of age. Furthermore, children's performance on both the verbal and nonverbal memory tests was related to their language ability; children with more advanced language skills reported more during the verbal interview and exhibited superior nonverbal memory relative to children with less advanced language skills. Finally, children's verbal recall of the event lagged behind both their nonverbal recall and their general verbal skill. It is hypothesized that despite large strides in language acquisition. preschool-age children continue to rely primarily on nonverbal representations of past events. The findings have important implications for the phenomenon of childhood amnesia.

title: Behavioral measurement of remembering phenomenologies: so simple a child can do it.
abstract: Two remembering phenomenologies, vivid recollection and vague familiarity, have been extensively studied in adults using introspective self-report tasks, such as remember-know. Because such tasks are beyond the capabilities of young children, there is no database on how these phenomenologies first develop and what factors affect them. In experiments with 5- to 14-year-olds, a child-appropriate behavioral methodology (conjoint recognition) was used to measure these phenomenologies. For both true and false memory, there were marked age increases in vivid recollective experiences, coupled with only slight increases in vague familiarity experiences. Thus, there is a vague-to-vivid developmental shift in the mental states that accompany remembering, a finding that is predicted by fuzzy-trace theory's explanation of recollection and familiarity.

title: The development of recollection and familiarity in childhood and adolescence: evidence from the dual-process signal detection model.
abstract: Two experiments examined the development of recollection (recalling qualitative details about an event) and familiarity (recognizing the event) using the dual-process signal detection model. In Experiment 1 (n = 117; ages 6, 8, 10, 14, and 18 years), recollection improved from childhood to adolescence after semantic encoding but not after perceptual encoding and familiarity improved from ages 6 to 8 regardless of encoding condition. In Experiment 2 (n = 56; ages 6, 8, and 10 years), long duration compared to short duration of semantic encoding increased familiarity but not recollection. Age-related differences replicated those of Experiment 1, except no age difference in familiarity was found with long study duration. Overall, recollection and familiarity showed distinct developmental and functional characteristics. The dual-process signal detection model proved promising for developmental investigations.

title: Development of subjective recollection: understanding of and introspection on memory States.
abstract: The development of subjective recollection was investigated in participants aged 6-18 years. In Experiment 1 (N = 90), age-related improvements were found in understanding of the subjective experience of recollection, although robust levels of understanding were observed even in the youngest group. In Experiment 2 (N = 100), age-related differences were found in subjective recollection during a memory task, suggesting development not only in the ability to reflect on memory states, but also in the informational basis of subjective recollection. Lower understanding of memory states was associated with increased propensity to claim recollection. These results indicate that subjective recollection develops considerably during childhood and suggest that the development of metamemory supports this capacity.

title: The development of verbal memory in childhood and adolescence: Findings from the Munich Longitudinal Study.
abstract: The authors assessed developmental changes in verbal memory from the beginning of elementary school to late adolescence on the basis of data from the Munich Longitudinal Study. Major issues concern the stability of individual differences in strategy use as well as interrelationships among different components of verbal memory and the impact of educational context on verbal memory development. Long-term stability of strategic memory was low to moderate in late childhood and adolescence. Interrelations among the verbal memory components were also moderate and did not change much over time. Unexpectedly, no impact of educational context was found. Overall, individual differences in verbal memory performance develop very early in life and are relatively unaffected by differences in educational experiences.

title: Memory binding in early childhood: evidence for a retrieval deficit.
abstract: Previous research has suggested that performance for items requiring memory-binding processes improves between ages 4 and 6 (J. Sluzenski, N. Newcombe, & S. L. Kovacs, 2006). The present study suggests that much of this improvement is due to retrieval, as opposed to encoding, deficits for 4-year-olds. Four- and 6-year-old children (N = 48 per age) were given objects, backgrounds, and object + background combinations to remember. Younger children performed equivalently to 6-year-olds during a working memory task for all types of memory questions but were impaired during a long-term memory task for the object + background combinations. Furthermore, this deficit was completely due to differences in false alarm rates, suggesting that separate analyses of hits and false alarms may be preferable to corrected recognition scores when studying memory development.

title: Do school-age children remember or know the personal past?
abstract: The aim of this study was to examine developmental differences in autobiographical memory using a novel test that assesses its semantic and episodic subcomponents. Forty-two children aged 7-13 years were asked to recall semantic information and episodic events from three different time periods (current school year, last school year, and previous school years). For the recalls of all events, sense of remembering or sense of just knowing was measured via the Remember/Know paradigm. Age-related differences were observed for episodic autobiographical memory whereas semantic autobiographical memory was characterized by a relative developmental invariance. The increase with age was also found in the number of "Remember" responses and their justification in terms of the actual contextual information retrieved-factual, spatial, and, more especially, temporal details. These findings highlight developmental differences between the episodic and semantic subcomponents of autobiographical memory and support the view that mental 'time travel' through subjective time, which allows one to re-experience the past through self-awareness, is the last feature of autobiographical memory to become fully operational.

title: Developmental patterns in priming and familiarity in explicit recollection.
abstract: Developmental trajectories of two classes of human memory, implicit and explicit memory, appear to diverge. We examined how developmental differences in perceptual and conceptual priming, two types of implicit memory, coincide with differences between familiarity and recollective responses on explicit memory tests that employ the Remember/Know paradigm ( Tulving, 1985 ). Both types of priming were characterized by developmental invariance in 52 children and adolescents ages 8-19 years. Contrary to Komatsu, Naito, and Fuke (1996) results, few age-group differences in perceptual priming were observed following a levels-of-processing encoding manipulation. In contrast, age group differences were found for "Remember" but not "Know" responses. Neither levels of awareness nor strategies influenced priming. Adult levels of performance appear earlier in development on perceptual and conceptual priming tests compared to explicit memory tests. Similar developmental dissociations exist between explicit and implicit memory performance as between "Remember" and "Know" recollective responses.

title: "If it happened, I would remember it": strategic use of event memorability in the rejection of false autobiographical events.
abstract: The present research investigated the link between perceived event memorability and false-event rejection. In 2 studies, event salience, plausibility, and recency were manipulated. Study 1 showed that high-salience events elicited higher memorability ratings than low-salience events for 5-, 7-, 9-year-olds and adults. Plausibility and recency affected only 9-year-olds' and adults' judgments. Study 2 demonstrated that younger versus older children and adults were less likely to reject false events, and that older children and adults were more likely to reject false events based on salience than were younger children. High-recency false events were more likely to be rejected than low-recency false events. Consistent with prediction, recency moderated the effect of salience. The development of metamemorial awareness and rejection strategies is discussed.

title: Knowing about not remembering: developmental dissociations in lack-of-memory monitoring.
abstract: Children aged 7 and younger encounter great difficulty in assessing whether lack of memory for an event indicates that the event was not experienced. The present research investigated whether this difficulty results from a general inability to evaluate memory absence or from a specific inability to monitor one feature of memory absence that has been examined in previous studies, namely expected memorability. Seven-, 8- and 9-year-olds, and adults (N = 72) enacted, imagined and confabulated about bizarre and common actions. Two weeks later, participants were asked to recognize the actions that had been enacted. Even 7-year-olds monitored the relative familiarity of rejected distracters (i.e. reported higher confidence for the rejection of novel versus imagined and confabulated distracters). However, only older children and adults exhibited the ability to monitor expected memorability (e.g. reported higher confidence for the rejection of bizarre versus common distracters). These results suggest that young children exhibit specific, rather than general, deficits in monitoring memory absence, and provide an indication of the specific domains in which lack-of-memory monitoring improves during childhood.

title: The influence of prior knowledge and repeated questioning on children's long-term retention of the details of a pediatric examination.
abstract: Children's recall of the details of pediatric examinations was examined over the course of a 6-month interval. Although the 83 4- to 7-year-old participants reported a substantial amount of information at each assessment, performance declined over time, dropping sharply over the course of 3 months but then remaining constant out to the final interview at 6 months. As expected, older children provided more total information than younger children did and reported a greater proportion of the event components in response to general rather than specific questions. However, comparable patterns of remembering and forgetting over time were observed at each age level. In addition, no effects of repeated questioning--in the form of an interview at 3 months for half of the children--were observed on performance at the 6-month assessment. Moreover, children's prior knowledge about routine doctor visits was assessed before the checkup for half of the participants at each age and was associated with initial but not delayed recall. Although knowledge increased with age as expected, it nonetheless affected recall over and above the influence of age.

title: Helping Children to Remember: The Influence of Object Cues on Children's Accounts of a Real Event
abstract: The authors examined the effects of reinstating objects from an event on 6- and 9-year-old children's reports of the event in which they had either participated or observed. Half of the 95 children were interviewed twice, 10 days and 10 weeks after the event (Group 1), and the remaining children were interviewed a single time, 10 weeks after (Group 2). Following free recall, prompted recall and direct questions were accompanied by objects from the event and distractors for half the children. The effect of the delay on free recall was ameliorated by the prior interview for older but not younger children. Objects attenuated age differences in prompted recall for participants and enhanced accuracy in response to questions. Objects also led to more errors at the long delay. Analyses based on signal detection theory indicated that both response strategy and memory-related factors contributed to developmental changes in compliance with misleading questions. It is now widely recognized that children cannot be categorized as competent or incompetent witnesses on the basis of age alone. Many factors influence children's accounts of events, and an interactional perspective on children's eye witness testimony, according to which the skills demonstrated by the child are jointly determined by the child and the environmental context, is beginning to emerge. Such a perspective highlights the importance of the interviewer's behavior (e.g., Stellar, 1991) which, in turn, points to the need to develop innovative interviewing techniques so that "children can be empowered to become their most reliable selves" (McGough, 1991, p. 167). In recent studies, a number of procedures designed to improve children's event reports have been examined, including interviewer style (Goodman, Bottoms, Schwartz-Kenney, & Rudy, 1991), preparation and training prior to interviews (Saywitz & Snyder, 1993), procedures from Fisher and Geiselman's (1992) cognitive interview (Memon, Cronin, Eaves, & Bull, 1993; Saywitz, Geiselman, & Bornstein, 1992), and the use of nonverbal props (DeLoache, Kolstad, & Anderson, 1991; Goodman & Aman, 1990; Pipe, Gee, & Wilson, 1993). In the present study we ex

title: The emergence of strategic knowledge activation in categorical clustering during retrieval.
abstract: Elementary school children's free recall clustering has recently been explained as an automatic by-product of their developing knowledge base. In contrast, it is claimed that as children get older they become aware of the usefulness of category organization as a memory strategy that enables them to strategically activate category knowledge even during retrieval. To test this hypothesis an experimental procedure was developed where Ss first had to learn items in a noncategorical order to the criterion of two perfect serial recall trials. After a 12- to 15-min retention interval Ss unexpectedly received either serial or free recall (or--in Experiment 1--cued recall) instructions. In three experiments with second and fourth graders it was shown that (1) fourth graders' recall exceeded that of second graders only in the free, but not in the serial (or cued), recall condition, (2) higher levels of clustering were observed for fourth graders in the free recall condition, and (3) the grade effect on free recall data was eliminated when the influence of metamemory and categorical clustering statistically was partialled out (Experiments 1 and 3). This pattern of results proved robust against variants in which a metamemory question was asked or omitted prior to recall (Experiment 2) and manipulations in which age differences in categorical knowledge were minimized (Experiment 3). The results were interpreted as demonstrating fourth graders' strategic competence in activating category knowledge during retrieval and second graders' automatic knowledge activation.

title: Capacity, strategies, and metamemory: tests of a three-factor model of memory development.
abstract: Multiple measures of three of the factors (capacity, strategies, and metamemory) hypothesized to cause improvements in memory with age were obtained from 179 children in kindergarten to second grade (younger: ages 5-8) or third and fourth grade (older: ages 8-11) during nine sessions of testing. Confirmatory factor analysis was computed separately for each age group. Results suggested that the fit of the three-factor model was statistically significantly better than a one-factor, general memory model for both age groups. However, the fit indices were borderline, and there was not sufficient evidence for a metamemory factor for younger children. The factors that influence memory performance may differ with age.

title: Metacognitive monitoring and control processes involved in primary school children's test performance.
abstract: Within the context of students' self-regulated learning, the interplay between learners' individual characteristics and the context of testing have been emphasized for assessing learning outcomes.



The present study examined metacognitive monitoring and control processes in elementary schoolchildren's test taking behaviour and explored the impacts of these metacognitive skills for the accuracy and the quantity of test performance.



A total of 133 participants from third and fifth grade did a cloze test about a previously learned science topic, gave confidence judgments for every answer, and were then allowed to cross-out answers if they wished. Two different mock scoring schemes for test performance were compared with a control group.



Results revealed well-developed monitoring skills indicating that by the age of 9 children can reliably distinguish between correct and incorrect answers. As for control skills, 11- and 12-year-olds proved to be better able to improve their test performance by selectively withdrawing answers that would have been incorrect than the 9- to 10-year-olds.



The study offers evidence for the impact of metacognitive processes in students' learning outcomes and documents strategic behaviour during test taking, as well as developmental progression in the involved skills.

title: Brain activity underlying encoding and retrieval of source memory.
abstract: Neural activity elicited during the encoding and retrieval of source information was investigated with event-related functional magnetic resonance imaging (efMRI). During encoding, 17 subjects performed a natural/artificial judgement on pictures of common objects which were presented randomly in one of the four quadrants of the display. At retrieval, old pictures were mixed with new ones and subjects judged whether each picture was new or old and, if old, indicated in which quadrant it was presented at encoding. During encoding, study items that were later recognized and assigned a correct source judgement elicited greater activity than recognized items given incorrect judgements in a variety of regions, including right lateral occipital and left prefrontal cortex. At retrieval, regions showing greater activity for recognized items given correct versus incorrect source judgements included the right hippocampal formation and the left prefrontal cortex. These findings indicate a role for these regions in the encoding and retrieval of episodic information beyond that required for simple item recognition.

title: Multiple routes to memory: Distinct medial temporal lobe processes build item and source memories
abstract: A central function of memory is to permit an organism to distinguish between stimuli that have been previously encountered and those that are novel. Although the medial temporal lobe (which includes the hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortices) is known to be crucial for recognition memory, controversy remains regarding how the specific subregions within the medial temporal lobe contribute to recognition. We used event-related functional MRI to examine the relation between activation in distinct medial temporal lobe subregions during memory formation and the ability (i) to later recognize an item as previously encountered (item recognition) and (ii) to later recollect specific contextual details about the prior encounter (source recollection). Encoding activation in hippocampus and in posterior parahippocampal cortex predicted later source recollection, but was uncorrelated with item recognition. In contrast, encoding activation in perirhinal cortex predicted later item recognition, but not subsequent source recollection. These outcomes suggest that the subregions within the medial temporal lobe subserve distinct, but complementary, learning mechanisms.

title: From Conditioning to Conscious Recollection Memory Systems of the Brain. Oxford Psychology Series, Volume 35.
abstract: The authors conceptualize these memory systems from both behavioural and neurobiological perspectives, guided by three related principles: * First, that our understanding of a wide range of memory phenomena can be advanced by breaking down memory into multiple forms with different operating characteristics.  Second, that different forms of memory representation are supported by distinct brain pathways with circuitry and neural coding properties.  Third, that the contributions of different brain systems can be compared and contrasted by distinguishing between dedicated (or specific) and elaborate (or general) memory systems. A primary goal of this work is to relate the neurobiological properties of dedicated and elaborate systems to their neuropsychological counterparts, and in so doing, account for the phenomenology of memory, from conditioning to conscious recollection.

title: Relational Memory and the Hippocampus: Representations and Methods
abstract: Since the discovery of the importance of the hippocampus for normal memory, considerable research has endeavored to characterize the precise role played by the hippocampus. Previously we have offered the relational memory theory, which posits that the hippocampus forms representations of arbitrary or accidentally occurring relations among the constituent elements of experience. In a recent report we emphasized the role of the hippocampus in all manner of relations, supporting this claim with the finding that amnesic patients with hippocampal damage were similarly impaired on probes of memory for spatial, sequential, and associative relations. In this review we place these results in the context of the broader literature, including how different kinds of relational or source information are tested, and consider the importance of specifying hippocampal function in terms of the representations it supports.

title: Imaging recollection and familiarity in the medial temporal lobe: a three-component model
abstract: The medial temporal lobe (MTL) plays a crucial role in supporting memory for events, but the functional organization of regions in the MTL remains controversial, especially regarding the extent to which different subregions support recognition based on familiarity or recollection. Here we review results from functional neuroimaging studies showing that, whereas activity in the hippocampus and posterior parahippocampal gyrus is disproportionately associated with recollection, activity in the anterior parahippocampal gyrus is disproportionately associated with familiarity. The results are consistent with the idea that the parahippocampal cortex (located in the posterior parahippocampal gyrus) supports recollection by encoding and retrieving contextual information, whereas the hippocampus supports recollection by associating item and context information. By contrast, perirhinal cortex (located in the anterior parahippocampal gyrus) supports familiarity by encoding and retrieving specific item information. We discuss the implications of a 'binding of item and context' (BIC) model for studies of recognition memory. This model argues that there is no simple mapping between MTL regions and recollection and familiarity, but rather that the involvement of MTL regions in these processes depends on the specific demands of the task and the type of information involved. We highlight several predictions for future imaging studies that follow from the BIC model.

title: A unified framework for the functional organization of the medial temporal lobes and the phenomenology of episodic memory
abstract: There is currently an intense debate about the nature of recognition memory and about the roles of medial temporal lobe subregions in recognition memory processes. At a larger level, this debate has been about whether it is appropriate to propose unified theories to explain memory at neural, functional, and phenomenological levels of analysis. Here, I review findings from physiology, functional imaging, and lesion studies in humans, monkeys, and rodents relevant to the roles of medial temporal lobe subregions in recognition memory, as well as in short‐term memory and perception. The results from these studies are consistent with the idea that there is functional heterogeneity in the medial temporal lobes, although the differences among medial temporal lobe subregions do not precisely correspond to different types of memory tasks, cognitive processes, or states of awareness. Instead, the evidence is consistent with the idea that medial temporal lobe subregions differ in terms of the kind of information they process and represent, and that these regions collectively support episodic memory by binding item and context information.

title: Evidence for a specific role of the anterior hippocampal region in successful associative encoding
abstract: It has been well established that the hippocampal formation plays a critical role in the formation of memories. However, functional specialization within the hippocampus remains controversial. Using functional magnetic resonance imaging (fMRI) during a face‐name associative encoding task, followed by a postscan recognition test for face memory and face‐name pair memory, we investigated the roles of anterior and posterior hippocampal regions in successful encoding of associations and items. Whole‐brain and region of interest (ROI) analyses revealed that the anterior hippocampal formation showed increased activation for subsequently remembered face‐name associations compared with pairs that were forgotten. In contrast, the posterior hippocampal formation showed activation above baseline during attempted encoding of face‐name pairs, but no evidence of differential activation based on subsequent memory. Furthermore, exploratory whole‐brain analyses revealed that a parahippocampal region, most likely corresponding to perirhinal cortex, showed subsequent memory effects for faces. These data provide evidence for functional specialization within the hippocampal formation based on the associative nature of the stimuli and subsequent memory.

title: Decoding Individual Episodic Memory Traces in the Human Hippocampus
abstract: In recent years, multivariate pattern analyses have been performed on functional magnetic resonance imaging (fMRI) data, permitting prediction of mental states from local patterns of blood oxygen-level-dependent (BOLD) signal across voxels [1, 2]. We previously demonstrated that it is possible to predict the position of individuals in a virtual-reality environment from the pattern of activity across voxels in the hippocampus . Although this shows that spatial memories can be decoded, substantially more challenging, and arguably only possible to investigate in humans [4], is whether it is feasible to predict which complex everyday experience, or episodic memory, a person is recalling. Here we document for the first time that traces of individual rich episodic memories are detectable and distinguishable solely from the pattern of fMRI BOLD signals across voxels in the human hippocampus. In so doing, we uncovered a possible functional topography in the hippocampus, with preferential episodic processing by some hippocampal regions over others. Moreover, our results imply that the neuronal traces of episodic memories are stable (and thus predictable) even over many re-activations. Finally, our data provide further evidence for functional differentiation within the medial temporal lobe, in that we show the hippocampus contains significantly more episodic information than adjacent structures.

title: Distinct hippocampal regions make unique contributions to relational memory
abstract: Neuroscientific research has shown that the hippocampus is important for binding or linking together the various components of a learning event into an integrated memory. In a prior study, we demonstrated that the anterior hippocampus is involved in memory for the relations among informational elements to a greater extent that it is involved in memory for individual elements (Giovanello et al., 2004. Hippocampus 14:5–8). In the current study, we extend those findings by further specifying the role of anterior hippocampus during relational memory retrieval. Specifically, anterior hippocampal activity was observed during flexible retrieval of learned associations, whereas posterior hippocampal activity was detected during reinstatement of study episodes. These findings suggest a functional dissociation across the long axis of human hippocampus based on the nature of the mnemonic process rather than the stage of memory processing or type of stimulus.

title: Neural Correlates of Relational Memory: Successful Encoding and Retrieval of Semantic and Perceptual Associations
abstract: Using event-related functional magnetic resonance imaging, we identified brain regions involved in successful relational memory (RM) during encoding and retrieval for semantic and perceptual associations or in general, independent of phase and content. Participants were scanned while encoding and later retrieving associations between pairs of words (semantic RM) or associations between words and fonts (perceptual RM). Encoding success activity (ESA) was identified by comparing study-phase activity for items subsequently remembered (hits) versus forgotten (misses) and retrieval success activity (RSA) by comparing test-phase activity for hits versus misses. The study yielded three main sets of findings. First, ESA-RSA differences were found within the medial temporal lobes (MTLs) and within the prefrontal cortex (PFC). Within the left MTL, ESA was greater in the anterior hippocampus, and RSA was greater in the posterior parahippocampal cortex/hippocampus. This finding is consistent with the notion of an encoding-retrieval gradient along the longitudinal MTL axis. Within the left PFC, ESA was greater in ventrolateral PFC, and RSA was greater in dorsolateral and anterior PFC. This is the first evidence of a dissociation in successful encoding and retrieval activity within left PFC. Second, consistent with the transfer-appropriate processing principle, some ESA regions were reactivated during RSA in a content-specific manner. For semantic RM, these regions included the left ventrolateral PFC, whereas for perceptual RM, they included occipitoparietal and right parahippocampal regions. Finally, only one region in the entire brain was associated with RM in general (i.e., for both semantic and perceptual ESA and RSA): the left hippocampus. This finding highlights the fundamental role of the hippocampus in RM.

title: Left ventrolateral prefrontal cortex and the cognitive control of memory
abstract: Cognitive control mechanisms permit memory to be accessed strategically, and so aid in bringing knowledge to mind that is relevant to current goals and actions. In this review, we consider the contribution of left ventrolateral prefrontal cortex (VLPFC) to the cognitive control of memory. Reviewed evidence supports a two-process model of mnemonic control, supported by a double dissociation among rostral regions of left VLPFC. Specifically, anterior VLPFC (approximately BA 47; inferior frontal gyrus pars orbitalis) supports controlled access to stored conceptual representations, whereas mid-VLPFC (approximately BA 45; inferior frontal gyrus pars triangularis) supports a domain-general selection process that operates post-retrieval to resolve competition among active representations. We discuss the contribution of these control mechanisms across a range of mnemonic domains, including semantic retrieval, recollection of contextual details about past events, resolution of proactive interference in working memory, and task switching. Finally, we consider open directions for future research into left VLPFC function and the cognitive control of memory.

title: Prefrontal Cortex and Long-Term Memory Encoding: An Integrative Review of Findings from Neuropsychology and Neuroimaging
abstract: Recent findings have led to a growing appreciation of the role of the lateral prefrontal cortex (PFC) in episodic long-term memory (LTM). Here, the authors will review results from neuropsychological and neuroimaging studies of humans and present a framework to explain how different regions of the PFC contribute to successful LTM formation. Central to this framework is the idea that different regions within the PFC implement different control processes that augment memory by enhancing or attenuating memory for certain aspects of a particular item or event. Evidence reviewed here suggests that ventrolateral regions of the PFC contribute to the ability to select goal-relevant item information, and that this processing strengthens the representation of goal-relevant features of items during LTM encoding. Dorsolateral regions of the PFC may contribute to the ability to organize multiple pieces of information in working memory, thereby enhancing memory for associations among items in LTM. Thus, dorsolateral and ventrolateral regions of the PFC may implement different control processes that support LTM formation in a complementary fashion.  2007.

title: Mechanisms of spontaneous confabulations: a strategic retrieval account.
abstract: The 'temporality' hypothesis of confabulation posits that confabulations are true memories displaced in time, while the 'strategic retrieval' hypothesis suggests a general retrieval failure of which temporal confusion is a common symptom. Four confabulating patients with rupture of an anterior communicating artery (ACoA) aneurysm, eight non-confabulating ACoA controls and 16 normal controls participated in three experiments designed to test the two hypotheses. In Experiment 1, participants were tested on two continuous recognition tasks, one requiring temporal context distinctions, previously shown to be sensitive to confabulation and another that only requires content distinctions. Both manipulations were sensitive to confabulation, but not specific to it. Temporal context and content confusions (TCCs and CCs) can be explained as failures to make fine-grained distinctions within memory. In Experiment 2, free recall of semantic narratives that require strategic retrieval but are independent of temporal context was used to induce confabulations associated with remote memory, acquired before the onset of amnesia. Confabulators produced significantly more errors. Thus, when retrieval demands are equated, confabulations can be induced in the absence of temporal confusions. Only confabulators conflated semantic content from different remote semantic narratives and introduced idiosyncratic content, suggesting that qualitatively different mechanisms are responsible for distortions due to normal memory failure and for confabulation. Lesion analyses revealed that damage to ventromedial prefrontal cortex is sufficient for temporal context errors to occur, but additional orbitofrontal damage is crucial for spontaneous confabulation. In Experiment 3, we tested whether failure in memory monitoring is crucial for confabulation. Recognition of details from semantic and autobiographical narratives was used to minimize the initiation and search components of strategic retrieval. Only confabulators made more false alarms on both tasks, endorsed even highly implausible lures related to autobiographical events and were indiscriminately confident about their choices. These findings support a strategic retrieval account of confabulation of which monitoring is a critical component. Post-retrieval monitoring has at least two components: one is early, rapid and pre-conscious and the other is conscious and elaborate. Failure of at least the former is necessary and sufficient for confabulation. Other deficits, including TCC and CC, may be required for spontaneous confabulations to arise. The confluence of different sub-components of strategic retrieval would determine the content of confabulation and exacerbate its occurrence.

title: Selecting for Memory? The Influence of Selective Attention on the Mnemonic Binding of Contextual Information
abstract: Not all of what is experienced is remembered later. Behavioral evidence suggests that the manner in which an event is processed influences which aspects of the event will later be remembered. The present experiment investigated the neural correlates of “selective encoding,” or the mechanisms that support the encoding of some elements of an event in preference to others. Event-related MRI data were acquired while volunteers selectively attended to one of two different contextual features of study items (color or location). A surprise memory test for the items and both contextual features was subsequently administered to determine the influence of selective attention on the neural correlates of contextual encoding. Activity in several cortical regions indexed later memory success selectively for color or location information, and this encoding-related activity was enhanced by selective attention to the relevant feature. Critically, a region in the hippocampus responded selectively to attended source information (whether color or location), demonstrating encoding-related activity for attended but not for nonattended source features. Together, the findings suggest that selective attention modulates the magnitude of activity in cortical regions engaged by different aspects of an event, and hippocampal encoding mechanisms seem to be sensitive to this modulation. Thus, the information that is encoded into a memory representation is biased by selective attention, and this bias is mediated by cortical–hippocampal interactions.

title: Posterior parietal cortex and episodic encoding: Insights from fMRI subsequent memory effects and dual-attention theory
abstract: The formation of episodic memories--memories for life events--is affected by attention during event processing. A leading neurobiological model of attention posits two separate yet interacting systems that depend on distinct regions in lateral posterior parietal cortex (PPC). From this dual-attention perspective, dorsal PPC is thought to support the goal-directed allocation of attention, whereas ventral PPC is thought to support reflexive orienting to information that automatically captures attention. To advance understanding of how parietal mechanisms may impact event encoding, we review functional MRI studies that document the relationship between lateral PPC activation during encoding and subsequent memory performance (e.g., later remembering or forgetting). This review reveals that (a) encoding-related activity is frequently observed in human lateral PPC, (b) increased activation in dorsal PPC is associated with later memory success, and (c) increased activation in ventral PPC predominantly correlates with later memory failure. From a dual-attention perspective, these findings suggest that allocating goal-directed attention during event processing increases the probability that the event will be remembered later, whereas the capture of reflexive attention during event processing may have negative consequences for event encoding. The prevalence of encoding-related activation in parietal cortex suggests that neurobiological models of episodic memory should consider how parietal-mediated attentional mechanisms regulate encoding.

title: The parietal cortex and episodic memory: an attentional account
abstract: The contribution of the parietal cortex to episodic memory is a fascinating scientific puzzle. On the one hand, parietal lesions do not normally yield severe episodic-memory deficits; on the other hand, parietal activations are seen frequently in functional-neuroimaging studies of episodic memory. A review of these two categories of evidence suggests that the answer to the puzzle requires us to distinguish between the contributions of dorsal and ventral parietal regions and between the influence of top-down and bottom-up attention on memory.

title: Parietal lobe contributions to episodic memory retrieval
abstract: Although the parietal lobe is not traditionally thought to support declarative memory, recent event-related fMRI studies of episodic retrieval have consistently revealed a range of memory-related influences on activation in lateral posterior parietal cortex (PPC) and precuneus extending into posterior cingulate and retrosplenial cortex. This article surveys the fMRI literature on PPC activation during remembering, a literature that complements earlier electroencephalography data. We consider these recent memory-related fMRI responses within the context of classical ideas about parietal function that emphasize space-based attention and motor intention. We conclude by proposing three hypotheses concerning how parietal cortex might contribute to memory.

title: LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS
abstract: In 1954 Scoville described a grave loss of recent memory which he had observed as a sequel to bilateral medial temporal-lobe resection in one psychotic patient and one patient with intractable seizures. In both cases the operations had been radical ones, undertaken only when more conservative forms of treatment had failed. The removals extended posteriorly along the mesial surface of the temporal lobes for a distance of approximately 8 cm. from the temporal tips and probably destroyed the anterior two-thirds of the hippocampus and hippocampal gyrus bilaterally, as well as the uncus and amygdala. The unexpected and persistent memory deficit which resulted seemed to us to merit further investigation. We have therefore carried out formal memory and intelligence testing of these two patients and also of eight other patients who had undergone similar, but less radical, bilateral medial temporallobe resections. The present paper gives the results of these studies which point to the importance of the hippocampal complex for normal memory function. Whenever the hippocampus and hippocampal gyrus were damaged bilaterally in these operations some memory deficit was found, but not otherwise. We have chosen to report these findings in full, partly for their theoretical significance, and partly as a warning to others of the risk to memory involved in bilateral surgical lesions of the hippocampal region.

title: Item, context and relational episodic encoding in humans
abstract: Recent functional imaging work supports the view that item and relational memory depend upon distinct encoding operations within the medial temporal lobe. Specifically, emerging findings demonstrate that the level of engagement of perirhinal cortex predicts later memory for individual items, whereas the level of hippocampal processing correlates with later relational memory, or recovery of additional episodic details. Furthermore, recent functional magnetic resonance imaging evidence in humans suggests that medial temporal lobe cortical input structures, the perirhinal and posterior parahippocampal cortices, differentially participate in the encoding of objects and their context, providing domain-specific input to the hippocampus. Taken together, these data help to construct a working model of how distinct medial temporal lobe structures participate in episodic memory formation with domain-general relational binding mechanisms supported by the hippocampus and provide emerging evidence for domain-specificity within the perirhinal and parahippocampal cortices.

title: The hippocampus as a "stupid," domain-specific module: Implications for theories of recent and remote memory, and of imagination.
abstract: The hippocampus and surrounding regions of the medial temporal lobe play a central role in all neuropsychological theories of memory. It is still a matter of debate, however, how best to characterise the functions of these regions, the hippocampus in particular. In this article, I examine the proposal that the hippocampus is a "stupid" module whose specific domain is consciously apprehended information. A number of interesting consequences for the organisation of memory and the brain follow from this proposal and the assumptions it entails. These, in turn, have important implications for neuropsychological theories of recent and remote episodic, semantic, and spatial memory and for the functions that episodic memory may serve in perception, comprehension, planning, imagination, and problem solving. I consider these implications by selectively reviewing the literature and primarily drawing on research my collaborators and I have conducted.

title: Dynamic mapping of normal human hippocampal development
abstract: The hippocampus, which plays an important role in memory functions and emotional responses, has distinct subregions subserving different functions. Because the volume and shape of the hippocampus are altered in many neuropsychiatric disorders, it is important to understand the trajectory of normal hippocampal development. We present the first dynamic maps to reveal the anatomical sequence of normal human hippocampal development. A novel hippocampal mapping technique was applied to a database of prospectively obtained brain magnetic resonance imaging (MRI) scans (100 scans in 31 children and adolescents), scanned every 2 yr for 6–10 yr between ages 4 and 25. Our results establish that the structural development of the human hippocampus is remarkably heterogeneous, with significant differences between posterior (increase over time) and anterior (loss over time) subregions. These distinct developmental trajectories of hippocampal subregions may parallel differences in their functional development.

title: Postnatal development and synaptic connections of hilar mossy cells in the hippocampal dentate gyrus of rhesus monkeys
abstract: Mossy cells of the hippocampal dentate gyrus were analyzed through postnatal development. At birth, a few thorny excrescences were found on the proximal dendrites of mossy cells, whereas distal dendrites displayed pedunculate spines. Thorny excrescences increased in number and complexity until the third month. After that age, the complexity of thorny excrescences is so great that an increase in spine density can be seen only in electron microscopic preparations. An increase in the number of pedunculate spines per unit length of distal dendrite was detected via light microscopy during the first 9 postnatal months. The somata and dendrites of mossy cells displayed adult‐like characteristics after the ninth postnatal month.

title: Glutamate receptor binding in the human hippocampus and adjacent cortex during development and aging
abstract: Distinct patterns of age-related alterations in NMDA (MK801 binding) and non-NMDA, AMPA (CNQX), and kainate binding have been identified in human hippocampus and parahippocampal gyrus in normal individuals with no evidence of degenerative brain disease ranging in age from 24 gestational weeks to 94 years. Whereas MK801 binding did not alter substantially over this age range, CNQX binding rose from low levels in the fetus to maximum levels between neonate and middle age, and kainate binding declined extensively from the perinatal to adult stage. Following maturity, there were no significant changes in kainate binding, although MK801 binding increased in CA1 and CA3 and CNQX binding declined in several regions, particularly CA2 and subiculum. For each receptor binding the timing of these fluctuations ocurring during development and aging varied within different regions of the dentate gyrus, hippocampus proper, subicular complex, and entorhinal cortex examined. The transient peaks of receptor binding are likely to reflect processes of synaptogenesis and pruning and may provide clues regarding the role of the different glutamate receptor subtypes in various pathologies of the hippocampus and adjacent cortex associated with developmental disorders (of genetic origin or due to perinatal trauma or insult). The absence of substantial changes in any subtype examined from middle to old age suggests alterations in transmitter binding to these glutamate receptors are not involved in senescent neurodegeneration.

title: A quantitative analysis of synaptogenesis in the molecular layer of the dentate gyrus in the rhesus monkey.
abstract: Quantitative electron microscopy was used to study synapse formation in the molecular layer of the dentate gyrus in rhesus monkeys ranging in age from embryonic day 62 to adult. Four to eight radial probes, consisting of a series of overlapping electronmicrographs and extending across the full thickness of the molecular layer were made in each specimen. Synaptic density (normalized to volume of neuropil) increased significantly during the last half of gestation, reaching adult levels at the time of birth. However, new synapses were added during infancy, resulting in an apparent peak in density at between 4 and 5 months of age. This increase was followed by a decline in the synaptic density over the next 5 months, to levels comparable to that of the newborn. In addition to synaptic density, synapse type (symmetric, asymmetric), location (on dendritic shafts or spines), and laminar distribution in the developing molecular layer was determined. The decrease in synaptic density is unlikely to be due to 'dilution' caused by an increase in molecular layer volume since no increase in the volume of the dentate gyrus could be detected during this period. Our calculations suggest that a selective overproduction of asymmetrical, axo-spinous synapses occurs during infancy. Finally, synaptic density was significantly greater in the middle third of the molecular layer suggesting that synaptic exuberance may be related to entorhinal input.

title: Postnatal development of the human hippocampal formation.
abstract: The postnatal development of the human hippocampal formation (HF) is subject of increasing interest due to its implication in important pathologies that hamper the normal development of children. In this work, we present a glimpse of the main events that constitute important milestones in the development and shaping of some of the most important psychological capabilities such as autobiographical memory. We analyzed a total of 21 brains ranging from 27 gestational weeks to 14 years. Although we examined some cases in the last trimester of gestation, our description starts at birth, around 40 gestational weeks. Serial sections stained with thionin for Nissl analysis revealed that all fields of the HF were present and identifiable at birth. However, the relative growth of the cortical mantle was much higher relative to the HF. The main structural changes took place during the first postnatal year, in particular in the dentate gyrus and in the entorhinal cortex. At subsequent ages, a growth in size was noted in all components of the HF. This growth was more evident at the body and tail of the hippocampus, as evidenced by measurements of the neuroanatomical series. In addition, we examined in some cases the MRI appearance of the HF at different postnatal ages obtained by postmortem imaging. MRI neuroanatomical series provided anatomically identified landmarks useful for the MRI identification of different components of the HF during postnatal development.

title: Dissociating memory processes in the developing brain: the role of hippocampal volume and cortical thickness in recall after minutes versus days.
abstract: Retention of information over extended time periods places special demands on the brain. The neural correlates of memory performance after a short delay of 30 min and a long delay of 1 week are likely partly different, but we do not know how structural maturation of the brain contributes to the differential development of these functions. This question was investigated in a sample of 107 children and adolescents aged 8-19 years. Measures used were structural magnetic resonance imaging and the Rey Complex Figure Test copy, organizational strategy, and 30-min and 1-week recall. While the amount of details copied and later recalled after both 30 min and 1 week increased with age, the relative saving over 1 week (1-week/30-min ratio score) did not increase with age. Thirty minutes recall performance was related to thinner left orbitofrontal cortex independently of age and organizational strategy measured during copy, possibly reflecting executive components of retrieval or encoding processes. In contrast, the 1-week/30-min ratio, likely reflecting consolidation of memory traces, was related to larger bilateral hippocampal volume. This indicates that differential developmental effects on memory for short and long periods of time are related to differentially developing brain structures.

title: Improved memory functioning and frontal lobe maturation between childhood and adolescence: A structural MRI study
abstract: Previous studies conducted by our group have provided evidence for age-related reductions in cortical thickness in dorsal frontal and parietal regions between childhood and adulthood, and gray matter volume increases of mesial temporal and anterior diencephalic structures. The purpose of this study was to describe neurobehavioral correlates of these brain maturational changes using morphometric analyses of brain magnetic resonance images (MRI) and two tests of cognitive abilities. Participants were 35 normal children roughly stratified by age (7 to 16 years) and sex (20 boys and 15 girls) and frontal and mesial temporal regions were anatomically defined in each subjects' MRI data. The California Verbal Learning Test–Children's Version and the Rey-Osterrieth Complex Figure test were used as measures of verbal and visuospatial memory and organizational abilities. Analyses designed to show regionally specific relationships between the brain and behavioral measures revealed interesting results. Specifically, frontal lobe gray matter thinning was more strongly predictive of delayed verbal memory functioning than was the mesial temporal lobe gray matter volume, and this relationship did not appear to be mediated by factors indexed in chronological age. Similar, but less regionally specific relationships were observed for measures of visuospatial memory abilities and frontal lobe maturation. Functional imaging studies in the literature consistently report activation in frontal regions in adults during retrieval tasks. The relationship between frontal lobe maturation and delayed recall observed here may be reflective of the children's development towards the more adult-like frontal lobe function revealed in the functional imaging studies. (JINS, 2001, 7, 312–322.

title: Cognitive Correlates of Medial Temporal Lobe Development across Adolescence: A Magnetic Resonance Imaging Study
abstract: Adolescent development involves progressive changes in brain structure and cognitive function, but relatively few studies have documented the cognitive correlates of differences in structural brain volumes in this age group. We examined the relations among age, cognitive processing, and mesial temporal lobe volume in 37 children and adolescents. Participants completed a brief cognitive assessment battery and underwent volumetric structural magnetic resonance imaging. For the sample as a whole, amygdala volume correlated positively with age, and larger volumes of both the left and right amygdala were significantly associated with better performance on several cognitive tasks assessing academic skills and acquired knowledge in long-term memory. In contrast, hippocampal volumes did not correlate with adolescents' age and were less frequently correlated with cognitive performance. Amygdala volumes were most predictive of cognitive abilities in boys, whereas for girls, the volume of the hippocampus contributed more frequently to the prediction of cognitive abilities. These data suggest that mensurable differences in mesial temporal volumes during adolescence are reliably associated with long-term cognitive abilities, particularly academic skills and the acquisition of intellectual knowledge, and that these relationships may differ as a function of the sex of the child.

title: A Hippocampal Marker of Recollection Memory Ability among Healthy Young Adults: Contributions of Posterior and Anterior Segments
abstract: The hippocampus is known to support recollection memory, but the relation between its structure and recollection in healthy adults has not been established. Here we show that the hippocampus (including subiculum, DG, and CA1-CA4), when separated into posterior and anterior segments, can reliably predict recollection in healthy young adults. Better memory was associated with larger posterior and smaller anterior segments, as evaluated relative to the uncal apex. Overall hippocampal volume, however, did not predict memory. This pattern was confirmed in four separate data sets from different studies and laboratories. The relationship between the posterior hippocampus and memory was mediated by the structure's functional connectivity with a neocortical network identified during a postencoding resting-state scan. The relationship was also weakest in an experiment involving no appreciable study-test interval. These findings suggest that enhanced posterior-hippocampal postencoding processes may account for the memory benefit associated with larger posterior hippocampi.

title: Developmental Differences in Medial Temporal Lobe Function during Memory Encoding
abstract: The ability to recollect details about past events improves during childhood. Most researchers favor the view that this improvement depends largely on the development of the prefrontal cortex, which is thought to have a protracted course of development relative to the medial temporal lobes (MTL). The primary goal of the present study was to test the hypothesis that the development of detail recollection is also associated with changes in MTL function. We collected functional magnetic resonance imaging data during an incidental encoding task in 80 participants, divided equally across four age groups: 8-year-olds, 10- to 11-year-olds, 14-year-olds, and young adults. Developmental differences in MTL activation profiles were observed. Fourteen-year-olds and adults engaged regions of the hippocampus and posterior parahippocampal gyrus selectively for subsequent detail recollection, whereas 8- and 10- to 11-year-olds did not. In 8-year-olds, these regions were recruited indiscriminately for detail recollection and item recognition; in 10- to 11-year-olds, activation in these regions did not consistently predict subsequent memory. These results suggest there are changes in the functional organization of the MTL, such that the hippocampus and posterior parahippocampal gyrus become increasingly specialized for recollection; these changes may be in part responsible for long-term memory improvements during childhood.

title: Developmental fMRI study of episodic verbal memory encoding in children
abstract: Understanding the maturation and organization of cognitive function in the brain is a central objective of both child neurology and developmental cognitive neuroscience. This study focuses on episodic memory encoding of verbal information by children, a cognitive domain not previously studied using fMRI.  Children from 7 to 19 years of age were scanned at 1.5-T field strength using event-related fMRI while performing a novel verbal memory encoding paradigm in which words were incidentally encoded. A subsequent memory analysis was performed. SPM2 was utilized for whole brain and region-of-interest analyses of data. Both whole-sample intragroup analyses and intergroup analyses of the sample divided into 2 subgroups by age were conducted.  Importantly, behavioral memory performance was equal across the age range of children studied. Encoding-related activation in the left hippocampus and bilateral basal ganglia declined as age increased. In addition, while robust blood oxygen level–dependent signal was found in left prefrontal cortex with task performance, no encoding-related age-modulated prefrontal activation was observed in either hemisphere.  These data are consistent with a developmental pattern of verbal memory encoding function in which left hippocampal and bilateral basal ganglionic activations are more robust earlier in childhood but then decline with age. No encoding-related activation was found in prefrontal cortex which may relate to this region's recognized delay in biologic maturation in humans. These data represent the first fMRI demonstration of verbal encoding function in children and are relevant developmentally and clinically.

title: Neurodevelopmental Correlates of True and False Recognition
abstract: The Deese/Roediger–McDermott (DRM) false-memory effect has been extensively documented in psychological research. People falsely recognize critical lures or nonstudied items that are semantically associated with studied items. Behavioral research has provided evidence for age-related increases in the DRM false-recognition effect. The present event-related functional magnetic resonance imaging study was aimed at investigating neurodevelopmental changes in brain regions associated with true- and false-memory recognition in 8-year olds, 12-year olds, and adults. Relative to 8-year olds, adults correctly endorsed more studied items as “old” but also mistakenly endorsed more critical lures. Age-related increases in recollection were associated with changes in the medial temporal lobe (MTL) activation profile. Additionally, age-related increases in false alarms (FAs) to semantically related lures were associated with changes in the activation profile of left ventrolateral prefrontal cortex, a region associated with semantic processing. Additional regions exhibiting age-related changes include posterior parietal and anterior prefrontal cortices. In summary, concomitant changes in the MTL, prefrontal cortex, and parietal cortex underlie developmental increases in true and false recognition during childhood and adolescence.

title: Imaging the developing brain: what have we learned about cognitive development?
abstract: The human brain undergoes significant changes in both its structural architecture and functional organization across the life span. Advances in neuroimaging techniques over the past decade have allowed us to track these changes safely in the human in vivo. We review the imaging literature on the neurobiology of cognitive development, focusing specifically on cognitive task-dependent changes observed in brain physiology and anatomy across childhood and adolescence. The findings suggest that cortical function becomes fine-tuned with development. Brain regions associated with more basic functions such as sensory and motor processes mature first, followed by association areas involved in top-down control of behavior.

title: Relationships between brain activation and brain structure in normally developing children.
abstract: Dynamic changes in brain structure, activation, and cognitive abilities co-occur during development, but little is known about how changes in brain structure relate to changes in cognitive function or brain activity. By using cortical pattern matching techniques to correlate cortical gray matter thickness and functional brain activity over the entire brain surface in 24 typically developing children, we integrated structural and functional magnetic resonance imaging data with cognitive test scores to identify correlates of mature performance during orthographic processing. Fast-naming individuals activated the right fronto-parietal attention network in response to novel fonts more than slow-naming individuals, and increased activation of this network was correlated with more mature brain morphology in the same fronto-parietal region. These relationships remained even after effects of age or general cognitive ability were statistically controlled. These results localized cortical regions where mature morphology corresponds to mature patterns of activation, and may suggest a role for experience in mediating brain structure-activation relationships.

title: Retrieval variability: The inefficient use of retrieval cues by young children ☆
abstract: The hypothesis of this study is that the inefficient use of retrieval cues by young children is due to retrieval variability: the variable encoding of semantic information in cue stimuli at input and retrieval and the inability to reinterpret cue information to ensure cue-trace compatibility. The critical manipulations involved the use of semantic orienting questions at both input and retrieval. Second and fourth graders and college adults were given moderately associated word pairs (Knife-Axe). Encoding was constrained or free between groups at both input and retrieval. The retrieval questions biased the Same interpretation of the cue as at input (weapon), a uniquely Different interpretation (utensil), or an inappropriate Negative interpretation. Both cued recall and recognition of the target items was tested. The results showed systematic developmental increases both in the distinctiveness of the semantic encoding of stimulus information, and in the ability to reinterpret cue information to ensure cue-trace compatibility. The second graders encoded more variably than the older subjects, and were less able to shift from an incompatible encoding of cue information.

title: Development of the declarative memory system in the human brain
abstract: Brain regions that are involved in memory formation, particularly medial temporal lobe (MTL) structures and lateral prefrontal cortex (PFC), have been identified in adults, but not in children. We investigated the development of brain regions involved in memory formation in 49 children and adults (ages 8–24), who studied scenes during functional magnetic resonance imaging. Recognition memory for vividly recollected scenes improved with age. There was greater activation for subsequently remembered scenes than there was for forgotten scenes in MTL and PFC regions. These activations increased with age in specific PFC, but not in MTL, regions. PFC, but not MTL, activations correlated with developmental gains in memory for details of experiences. Voxel-based morphometry indicated that gray matter volume in PFC, but not in MTL, regions reduced with age. These results suggest that PFC regions that are important for the formation of detailed memories for experiences have a prolonged maturational trajectory.

title: The hippocampal formation participates in novel picture encoding: evidence from functional magnetic resonance imaging.
abstract: Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory.

title: Making memories: brain activity that predicts how well visual experience will be remembered.
abstract: Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.

title: Dissociable correlates of recollection and familiarity within the medial temporal lobes
abstract: Regions in the medial temporal lobes (MTL) have long been implicated in the formation of new memories for events, however, it is unclear whether different MTL subregions support different memory processes. Here, we used event-related functional magnetic resonance imaging (fMRI) to examine the degree to which two recognition memory processes-recollection and familiarity-were supported by different MTL subregions. Results showed that encoding activity in the rhinal cortex selectively predicted familiarity-based recognition, whereas, activity in the hippocampus and posterior parahippocampal cortex selectively predicted recollection. Collectively, these results support the view that different subregions within the MTL memory system implement unique encoding processes that differentially support familiarity and recollection.

title: Differential development of high-level visual cortex correlates with category-specific recognition memory
abstract: High-level visual cortex in humans includes functionally defined regions that preferentially respond to objects, faces and places. It is unknown how these regions develop and whether their development relates to recognition memory. We used functional magnetic resonance imaging to examine the development of several functionally defined regions including object (lateral occipital complex, LOC)-, face ('fusiform face area', FFA; superior temporal sulcus, STS)- and place ('parahippocampal place area', PPA)-selective cortices in children (ages 7–11), adolescents (12–16) and adults. Right FFA and left PPA volumes were substantially larger in adults than in children. This development occurred by expansion of FFA and PPA into surrounding cortex and was correlated with improved recognition memory for faces and places, respectively. In contrast, LOC and STS volumes and object-recognition memory remained constant across ages. Thus, the ventral stream undergoes a prolonged maturation that varies temporally across functional regions, is determined by brain region rather than stimulus category, and is correlated with the development of category-specific recognition memory.

title: Scene Complexity: Influence on Perception, Memory, and Development in the Medial Temporal Lobe
abstract: Regions in the medial temporal lobe (MTL) and prefrontal cortex (PFC) are involved in memory formation for scenes in both children and adults. The development in children and adolescents of successful memory encoding for scenes has been associated with increased activation in PFC, but not MTL, regions. However, evidence suggests that a functional subregion of the MTL that supports scene perception, located in the parahippocampal gyrus (PHG), goes through a prolonged maturation process. Here we tested the hypothesis that maturation of scene perception supports the development of memory for complex scenes. Scenes were characterized by their levels of complexity defined by the number of unique object categories depicted in the scene. Recognition memory improved with age, in participants ages 8–24, for high-, but not low-, complexity scenes. High-complexity compared to low-complexity scenes activated a network of regions including the posterior PHG. The difference in activations for high- versus low-complexity scenes increased with age in the right posterior PHG. Finally, activations in right posterior PHG were associated with age-related increases in successful memory formation for high-, but not low-, complexity scenes. These results suggest that functional maturation of the right posterior PHG plays a critical role in the development of enduring long-term recollection for high-complexity scenes.

title: Recognition and source memory for pictures in children and adults
abstract: The present experiment investigated the developmental aspects of source compared to item memory. College students and 7-8-year-old children viewed pictures drawn in red or green during a study phase, and were asked either to remember the pictures for a subsequent recognition test, or to remember both the pictures and their associated colors for a subsequent source memory test. In the test phase, new and old pictures were presented in black. In the recognition task, participants were asked to make binary old/new recognition judgments, while in the source task, they were asked to make trinary old-green/old-red/new source judgements. Performance on all tasks improved with increasing age, but the age difference for source was much larger than that for item memory. It has been suggested that the frontal lobes play a critical role in the retrieval of source information, and that this brain region relative to the medial temporal lobes continues to develop into late adolescence. Thus, it is possible that immaturity of the frontal lobes may be causally related to the children's lower performance on the source memory task.

title: Associative and strategic components of episodic memory: a life-span dissociation.
abstract: The authors investigated the strategic component (i.e., elaboration and organization of episodic features) and the associative component (i.e., binding processes) of episodic memory and their interactions in 4 age groups (10-12, 13-15, 20-25, and 70-75 years of age). On the basis of behavioral and neural evidence, the authors hypothesized that the two components are functionally related but follow different life-span gradients. In a fully crossed design, age differences in recognition memory for single words versus word pairs (associative demand manipulation) were examined under instructions that emphasized item, pair, or elaborative-pair encoding (strategy manipulation). As predicted, the results showed that the strategic and associative components follow different life-span trajectories. Relative to younger adults, children's difficulties in episodic memory primarily reflected lower levels of strategic functioning. In contrast, older adults showed impairments in both strategic and associative components. The authors conclude that the comparison of strategic and associative components of episodic memory across the life span helps to delineate the two components' unique and interactive contributions to episodic memory performance.

title: Episodic memory across the lifespan: The contributions of associative and strategic components
abstract: The structural and functional brain circuitries supporting episodic memory undergo profound reorganization in childhood and old age. We propose a two-component framework that combines and integrates evidence from child development and aging. It posits that episodic memory builds on two interacting components: (a) the strategic component, which refers to memory control operations, and (b) the associative component, which refers to mechanisms that bind different features of a memory episode into a compound representation. We hypothesize that: (a) children's difficulties in episodic memory primarily originate from low levels of strategic operations, and reflect the protracted development of the prefrontal cortex (PFC); (b) deficits in episodic memory performance among older adults originate from impairments in both strategic and associative components, reflecting senescent changes in the PFC and the medio-temporal lobes (MTL). Initial behavioral and neural evidence is consistent with both hypotheses. The two-component framework highlights the specificities of episodic memory in different age periods, helps to identify and dissociate its components, and contributes to understanding the interplay among maturation, learning, and senescence.

title: Structural Magnetic Resonance Imaging of the Adolescent Brain
abstract: Magnetic resonance imaging (MRI) provides accurate anatomical brain images without the use of ionizing radiation, allowing longitudinal studies of brain morphometry during adolescent development. Results from an ongoing brain imaging project being conducted at the Child Psychiatry Branch of the National Institute of Mental Health indicate dynamic changes in brain anatomy throughout adolescence. White matter increases in a roughly linear pattern, with minor differences in slope in the four major lobes (frontal, parietal, temporal, occipital). Cortical gray matter follows an inverted U‐shape developmental course with greater regional variation than white matter. For instance, frontal gray matter volume peaks at about age 11.0 years in girls and 12.1 years in boys, whereas temporal gray matter volume peaks at about age at 16.7 years in girls and 16.2 years in boys. The dorsal lateral prefrontal cortex, important for controlling impulses, is among the latest brain regions to mature without reaching adult dimensions until the early 20s. The details of the relationships between anatomical changes and behavioral changes, and the forces that influence brain development, have not been well established and remain a prominent goal of ongoing investigations.

title: Imaging the brain before, during, and after transcranial magnetic stimulation
abstract: This article provides a brief overview of current trends in combining neuroimaging and transcranial magnetic stimulation (TMS). First, I outline the utility of magnetic-resonance imaging (MRI) and frameless stereotaxy for planning, monitoring and documenting the location of the TMS coil relative to the subject's brain. Second, I describe two novel methods, based on the combination of TMS with positron emission tomography (PET) or with electroencephalography (EEG), for the assessment of connectivity and excitability of the human cerebral cortex. Finally, I point out the utility of PET and MRI for evaluating possible long-term effects of repetitive TMS.

title: Mapping Changes in the Human Cortex throughout the Span of Life
abstract: In this review, the authors summarize the literature on brain morphological changes that occur throughout the human life span from childhood into old age. They examine changes observed postmortem and in vivo where various brain MRI analytic methods have been applied. They evaluate brain changes observed with volumetric image analytic methods and voxel-based morphometric methods that may be used to better localize where changes occur. The primary focus of the review is on recent studies using state-of-the-art cortical pattern-matching techniques to assess age-related changes in cortical asymmetries, gray matter distribution, and brain growth across various age spans. The authors attempt to integrate findings from the in vivo studies with results from postmortem studies and analyze the complicated question of when brain maturation stops and brain aging begins. Analyzing the regional patterns of change initiated at various ages may help elucidate relationships between changing brain morphology and changing cognitive functions that occur throughout life. Long-range longitudinal studies, correlations between imaging and postmortem data, and more advanced image acquisition and analysis technologies will be needed to fully interpret brain morphological changes observed in vivo in relation to development and aging.

title: Memory Development Between Two and Twenty
abstract: Preface to the First Edition. Preface to the Second Edition. Memory Development Since We Wrote Last Time: Much Ado About Children's Autobiographical Memories. A Brief History of Memory Development Research. Basic Memory Capacities and Mechanisms. The Knowledge Base. Development of Encoding and Retrieval Strategies. Metamemory. Good Information Processing: A General Model, A Specific Example, and Comments on How to Do Research on the Development of Information-Processing Proficiency. Is Good Strategy Use Possible?

title: Neurocognitive development of the ability to manipulate information in working memory.
abstract: The ability to manipulate information in working memory is a key factor in cognitive development. Here, we used event-related functional MRI to test the hypothesis that developmental improvements in manipulation, relative to pure maintenance, are associated with increased recruitment of dorsolateral (DL) prefrontal cortex (PFC) and superior parietal cortex. Three age groups (8-12 years old, 13-17 years old, and 18-25 years old) performed an object-working memory task with separate maintenance and manipulation conditions. We found that 8- to 12-year-olds did not perform the task as well as adolescents or adults, particularly on trials requiring manipulation in addition to maintenance. In this study, no age differences were observed in the activation profile of ventrolateral PFC, a region associated with online maintenance. In contrast, unlike the older participants, 8- to 12-year-olds failed to recruit right DL PFC and bilateral superior parietal cortex during the delay period for manipulation relative to maintenance. This group difference was observed specifically during the delay period, while participants reordered items in working memory, and could not be accounted for by group differences in performance. Across participants, activation levels in right DL PFC and superior parietal cortex, but not ventrolateral PFC, were positively correlated with performance on manipulation trials. These results indicate that increased recruitment of right DL PFC and bilateral parietal cortex during adolescence is associated with improvements in the ability to work with object representations.

title: Source monitoring 15 years later: what have we learned from fMRI about the neural mechanisms of source memory?
abstract: Focusing primarily on functional magnetic resonance imaging (fMRI), this article reviews evidence regarding the roles of subregions of the medial temporal lobes, prefrontal cortex, posterior representational areas, and parietal cortex in source memory. In addition to evidence from standard episodic memory tasks assessing accuracy for neutral information, the article considers studies assessing the qualitative characteristics of memories, the encoding and remembering of emotional information, and false memories, as well as evidence from populations that show disrupted source memory (older adults, individuals with depression, posttraumatic stress disorder, or schizophrenia). Although there is still substantial work to be done, fMRI is advancing understanding of source memory and highlighting unresolved issues. A continued 2-way interaction between cognitive theory, as illustrated by the source monitoring framework (M. K. Johnson, S. Hashtroudi, & D. S. Lindsay, 1993), and evidence from cognitive neuroimaging studies should clarify conceptualization of cognitive processes (e.g., feature binding, retrieval, monitoring), prior knowledge (e.g., semantics, schemas), and specific features (e.g., perceptual and emotional information) and of how they combine to create true and false memories.

title: MR imaging of the temporal stem: anatomic dissection tractography of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation.
abstract: The MR anatomy of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation, which traverse the temporal stem, is not well known. The purpose of this investigation was to study these structures in the anterior temporal lobe and the external and extreme capsules and to correlate the dissected anatomy with the cross-sectional MR anatomy.



Progressive dissection was guided by three-dimensional MR renderings and cross-sectional images. Dissected segments of the tracts and the temporal stem were traced and projected onto reformatted images. The method of dissection tractography is detailed in a companion article.



The temporal stem extends posteriorly from the level of the amygdala to the level of the lateral geniculate body. The uncinate and inferior occipitofrontal fasciculi pass from the temporal lobe into the extreme and external capsules via the temporal stem. Meyer's loop extends to the level of the amygdala, adjacent to the uncinate fasciculus and anterior commissure. These anatomic features were demonstrated on correlative cross-sectional MR images and compared with clinical examples.



This study clarified the MR anatomy of the uncinate and inferior occipitofrontal fasciculi and Meyer's loop in the temporal stem and in the external and extreme capsules, helping to explain patterns of tumor spread. The inferior occipitofrontal fasciculus is an important yet previously neglected tract. These results provide a solid anatomic foundation for diffusion tractography of the normal temporal stem and its tracts, as well as their abnormalities in brain disorders such as epilepsy, postoperative complications, trauma, schizophrenia, and Alzheimer disease.

title: Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey
abstract: The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

title: Some observations on the course and composition of the cingulum bundle in the rhesus monkey
abstract: The course and composition of the cingulum bundle was examined by using the autoradiographic tracer technique in the rhesus monkey. The cingulum bundle is observed to consist of three major fiber components originating from thalamus, cingulate gyrus, and cortical association areas. Following isotope injections in the anterior and lateral dorsal thalamic nuclei, labelled fibers form an arch in the white matter behind the cingulate sulcus and occupy the ventral sector of the cingulum bundle. The fibers from the anterior thalamic nucleus coursing in the cingulum bundle extended rostrally to the frontal cortex and caudally to area 23 and the retrosplenial cortex. In contrast, the fibers from lateral dorsal nucleus reached the retrosplenial cortex as well as the parahippocampal gyrus and presubiculum. Efferent fibers from the cingulate gyrus occupy a dorsolateral sector of the cingulum bundle. Those fibers from area 24 of the cingulate gyrus are directed to the premotor and prefrontal regions as well as area 23 and retrosplenial cortex. The fibers from area 23 extend rostrally to the prefrontal cortex and caudoventrally to the presubiculum and parahippocampal gyrus. Finally, an association component originates mainly from prefrontal cortex and posterior parietal region. These fibers occupy a more dorsal and lateral periphery in the cingulate white matter. Cingulum bundle fibers from the prefrontal cortex extend up to the retrosplenial cortex while those from the posterior parietal cortex extend caudally to the parahippocampal gyrus and presubiculum, and rostrally up to the prefrontal cortex.

title: In-vivo investigation of the human cingulum bundle using the optimization of MR diffusion spectrum imaging.
abstract: Diffusion spectrum imaging (DSI) is a generalization of diffusion tensor imaging to map fibrous structure of white matter and potentially very sensitive to alterations of the cingulum bundles in dementia. In this in-vivo 4T study, DSI parameters especially spatial resolution and diffusion encoding bandwidth were optimized on humans to segment the cingulum bundles for tract level measurements of diffusion. The careful tailoring of the DSI acquisitions in conjunction with fiber tracking provided an optimal DSI setting for a reliable quantification of the cingulum bundle tracts. The optimization of tracking the cingulum bundle was verified using fiber tract quantifications, including coefficients of variability of DSI measurements along the fibers between and within healthy subjects in back-to-back studies and variogram analysis of spatial correlations between diffusion orientation distribution functions (ODF) along the cingulum bundle tracts. The results demonstrate that the identification of the cingulum bundle in human brain is reproducible using an optimized DSI parameter for maximum b-value and high spatial resolution of the DSI acquisition with a feasible acquisition time of whole brain in clinical practice. This optimized DSI setting should be useful for detecting alterations along the cingulum bundle in Alzheimer disease and related neurodegenerative disorders.

title: Structural dissociation of attentional control and memory in adults with and without mild traumatic brain injury.
abstract: Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether microstructural integrity of white matter, as measured by fractional anisotropy (FA) within a small set of individually localized regions of interest (ROIs), is associated with these cognitive domains in normal adults and adults with mild TBI. Results in a sample of 23 normal controls reveal a significant correlation between attentional control and FA within a ROI in the left hemisphere anterior corona radiata. Furthermore, the controls demonstrate a correlation between memory performance and FA in a ROI placed in the uncinate fasciculus. Next, to examine whether these relationships are found in the pathological ranges of attention, memory and microstructural white matter integrity associated with mild TBI, these analyses were applied to a group of 43 mild TBI patients. , which generally demonstrated a wider range of attention, memory and FA scores, replicated the correlation between attentional control and FA in left hemisphere anterior corona radiata, as well as the correlation between memory performance and FA in the uncinate fasciculus. These two sets of brain-behaviour relationships were highly specific, as shown by a lack of correlation between attention and uncinate fasciculus FA and the lack of correlation between memory performance and anterior corona radiata FA. Furthermore, a 'correlational double dissociation' was demonstrated to exist between two distinct frontal structures independently associated with attention and memory, respectively, via a series of multiple regression analyses in both normal controls and adults with mild TBI. The results of the multiple regression analyses provide direct evidence that tract-specific variation in microstructural white matter integrity among normal controls and among mild TBI patients can account for much of the variation in performance in specific cognitive domains. More generally, such findings suggest that diffusion anisotropy measurement can be used as a quantitative biomarker for neurocognitive function and dysfunction.

title: A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory
abstract: Uncovering the functional relationship between temporal lobe amnesia and diencephalic amnesia depends on determining the role of the fornix, the major interlinking fiber tract. In this study relating fornix volume with memory, we made magnetic resonance imaging–based volume estimates of 13 brain structures in 38 individuals with surgically removed colloid cysts. Fornix status was assessed directly by overall volume and indirectly by mammillary body volume (which atrophies after fornix damage). Mammillary body volume significantly correlated with 13 out of 14 tests of episodic memory recall, but correlated poorly with recognition memory. Furthermore, as the volumes of the left fornix and the left mammillary bodies decreased, the difference between recall and recognition scores increased. No other structure was consistently associated with memory. These findings support models of diencephalic memory mechanisms that require hippocampal inputs for recall, but not for key elements of recognition.

title: Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain
abstract: Understanding the contribution of the brain white matter pathways to declarative verbal memory processes has been hindered by the lack of an adequate model in humans. An attractive and underexplored approach to study white matter region functionality in the living human brain is through the use of non-aprioristic models which specifically search disrupted white matter pathways. For this purpose, we employed voxel-based lesion-function mapping to correlate white matter lesions on the magnetic resonance images of 46 multiple sclerosis patients with their performance on declarative verbal memory storage and retrieval. White matter correlating with storage was in the temporal lobe-particularly lateral to the hippocampus and in the anterior temporal stem-, in the thalamic region and in the anterior limb of the internal capsule, all on the left hemisphere, and also in the right anterior temporal stem. The same volumes were relevant for retrieval, but to them were added temporo-parieto-frontal paramedian bundles, particularly the cingulum and the fronto-occipital fasciculus. These 3D maps indicate the white matter regions most critically involved in declarative verbal memory in humans.

title: Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease
abstract: In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.

title: Microstructural maturation of the human brain from childhood to adulthood
abstract: Brain maturation is a complex process that continues well beyond infancy, and adolescence is thought to be a key period of brain rewiring. To assess structural brain maturation from childhood to adulthood, we charted brain development in subjects aged 5 to 30 years using diffusion tensor magnetic resonance imaging, a novel brain imaging technique that is sensitive to axonal packing and myelination and is particularly adept at virtually extracting white matter connections. Age-related changes were seen in major white matter tracts, deep gray matter, and subcortical white matter, in our large (n=202), age-distributed sample. These diffusion changes followed an exponential pattern of maturation with considerable regional variation. Differences observed in developmental timing suggest a pattern of maturation in which areas with fronto-temporal connections develop more slowly than other regions. These in vivo results expand upon previous postmortem and imaging studies and provide quantitative measures indicative of the progression and magnitude of regional human brain maturation.

title: Longitudinal Development of Human Brain Wiring Continues from Childhood into Adulthood
abstract: Healthy human brain development is a complex process that continues during childhood and adolescence, as demonstrated by many cross-sectional and several longitudinal studies. However, whether these changes end in adolescence is not clear. We examined longitudinal white matter maturation using diffusion tensor tractography in 103 healthy subjects aged 5–32 years; each volunteer was scanned at least twice, with 221 total scans. Fractional anisotropy (FA) and mean diffusivity (MD), parameters indicative of factors including myelination and axon density, were assessed in 10 major white matter tracts. All tracts showed significant nonlinear development trajectories for FA and MD. Significant within-subject changes occurred in the vast majority of children and early adolescents, and these changes were mostly complete by late adolescence for projection and commissural tracts. However, association tracts demonstrated postadolescent within-subject maturation of both FA and MD. Diffusion parameter changes were due primarily to decreasing perpendicular diffusivity, although increasing parallel diffusivity contributed to the prolonged increases of FA in association tracts. Volume increased significantly with age for most tracts, and longitudinal measures also demonstrated postadolescent volume increases in several association tracts. As volume increases were not directly associated with either elevated FA or reduced MD between scans, the observed diffusion parameter changes likely reflect microstructural maturation of brain white matter tracts rather than just gross anatomy.

title: The relations between white matter and declarative memory in older children and adolescents
abstract: Neural communication between the temporal and frontal cortex underlies mature declarative memory skills. The integrity of white matter pathways connecting these regions is likely critical in supporting this communication. Little is known about the relationship between white matter and declarative memory in older children and adolescents, an age period when advanced function in this domain is established. We acquired diffusion tensor imaging (DTI) data for 22 participants (9-15 years). Multiple DTI indices were calculated for the uncinate fasciculus - the major white matter tract connecting temporal and prefrontal regions. Indices were also calculated for compartments of lobar and posterior fossa white matter. Measures of visual-perceptual and auditory-verbal memory were administered. Correlation analyses were used to examine the relations between age, DTI indices, and memory. Voxel-wise analyses were also conducted. Age-related increases in FA were evident for frontal, parietal, and temporal hemispheric white matter. Proficiency in auditory-verbal memory was related to white matter integrity in the left uncinate fasciculus as well as parietal and cerebellar white matter. Proficiency in recall of a complex design was related to integrity within parietal and temporal regions. Our findings support the role of white matter in facilitating connectivity between cerebral regions important for declarative memory.

title: Evaluating the relationship between memory functioning and cingulum bundles in acute mild traumatic brain injury using diffusion tensor imaging.
abstract: Compromised memory functioning is one of the commonly reported cognitive sequelae seen following mild traumatic brain injury (mTBI). Diffusion tensor imaging (DTI) has been shown to be sufficiently sensitive at detecting early microstructural pathological alterations after mTBI. Given its location and shape, the cingulate, which is comprised of the cingulate gyrus (gray matter) and cingulum bundles (white matter), is selectively vulnerable to mTBI. In this study we examined the integrity of cingulum bundles using DTI, and the relationship between cingulum bundles and memory functioning. Twelve adolescents with mTBI and 11 demographically-matched healthy controls were studied. All participants with mTBI had a Glasgow Coma Scale score of 15, and were without intracranial findings on CT scan. Brain scans were performed on average 2.92 days post-injury, and all participants were administered the Verbal Selective Reminding Test (VSRT), an episodic verbal learning and memory task. Participants with mTBI had a significantly lower apparent diffusion coefficient (ADC) bilaterally than controls (p < 0.001). Despite the marginal significance of the group difference in fractional anisotropy (FA), the effect size between groups was moderate (d = 0.66). Cognitively, healthy controls performed better than the TBI group on immediate and delayed recall; however, the difference did not reach statistical significance. In the mTBI group, FA of the left cingulum bundle was significantly correlated with 30-min delayed recall (r = -0.56, p = 0.05). A marginally significant correlation was found between ADC of the left cingulum bundle and the total words of immediate recall (r = 0.59, p = 0.07). No significant correlation was found between DTI metrics and memory functioning for the control group. These preliminary findings indicate that cingulate injury likely contributes to the cognitive sequelae seen during the early phase post-mTBI.

title: Development of distinct control networks through segregation and integration
abstract: Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to support the formation and maintenance of neural networks. Such mechanisms may encourage tighter “integration” of some regions into networks over time while “segregating” other sets of regions into separate networks. Here we use resting state functional connectivity MRI, which measures correlations in spontaneous blood oxygenation level-dependent signal fluctuations between brain regions to compare previously identified control networks between children and adults. We find that development of the proposed adult control networks involves both segregation (i.e., decreased short-range connections) and integration (i.e., increased long-range connections) of the brain regions that comprise them. Delay/disruption in the developmental processes of segregation and integration may play a role in disorders of control, such as autism, attention deficit hyperactivity disorder, and Tourette's syndrome.

title: Hierarchical relational binding in the medial temporal lobe: The strong get stronger
abstract: Controversy exists over the functional role of the medial temporal lobe (MTL) in episodic memory. Some have suggested that the hippocampus plays a unique and qualitatively different role than other MTL regions, whereas others suggest that the entire MTL has one functional role, which is to support the consolidation of declarative memories. Hierarchical relational binding theory (hRBT) purports that the functional role of the entire MTL is the binding of features associated with an episodic experience. As the hippocampus sits at the top of this hierarchy, binding at this level is particularly efficient in reinstating event features at the time of retrieval. Thus, this theory offers a unified account of MTL that yields outcomes similar to theories that suggest a special role of the hippocampus. In this way, hRBT captures features of both single‐ and dual‐process models of MTL and reconciles controversies about the nature of episodic recollection.

title: Can medial temporal lobe regions distinguish true from false? An event-related functional MRI study of veridical and illusory recognition memory
abstract: To investigate the types of memory traces recovered by the medial temporal lobe (MTL), neural activity during veridical and illusory recognition was measured with the use of functional MRI (fMRI). Twelve healthy young adults watched a videotape segment in which two speakers alternatively presented lists of associated words, and then the subjects performed a recognition test including words presented in the study lists (True items), new words closely related to studied words (False items), and new unrelated words (New items). The main finding was a dissociation between two MTL regions: whereas the hippocampus was similarly activated for True and False items, suggesting the recovery of semantic information, the parahippocampal gyrus was more activated for True than for False items, suggesting the recovery of perceptual information. The study also yielded a dissociation between two prefrontal cortex (PFC) regions: whereas bilateral dorsolateral PFC was more activated for True and False items than for New items, possibly reflecting monitoring of retrieved information, left ventrolateral PFC was more activated for New than for True and False items, possibly reflecting semantic processing. Precuneus and lateral parietal regions were more activated for True and False than for New items. Orbitofrontal cortex and cerebellar regions were more activated for False than for True items. In conclusion, the results suggest that activity in anterior MTL regions does not distinguish True from False, whereas activity in posterior MTL regions does.

title: Functional-Anatomic Correlates of Memory Retrieval That Suggest Nontraditional Processing Roles for Multiple Distinct Regions within Posterior Parietal Cortex
abstract: Current theories of posterior parietal cortex (PPC) function emphasize space-based attention and motor intention. Imaging studies of long-term memory have demonstrated PPC activation during successful memory retrieval. Here, we explored the relationship between memory processes and classical notions of PPC function. Study 1 investigated old-new recognition using picture and sound stimuli to test whether PPC memory effects were dependent on visuospatial attention. A region lateral to the intraparietal sulcus [inferior parietal lobule complex (IPLC)] and two regions in the medial PPC [precuneus complex (PCC) and posterior cingulate/retrosplenial cortex (pC/Rsp)] showed strong retrieval success effects for both picture and sound stimuli. Study 2 explored a recognition task with varied response contingencies to investigate whether these retrieval success effects are dependent on motor intentions. In one condition, subjects responded to both old and new items. In two other conditions, subjects responded only to old or only to new items. IPLC, PCC, and pC/Rsp continued to show retrieval success effects with similar magnitudes for all response contingencies, including a condition in which no responses were made to old items. In a third study, IPLC and PCC activity was modulated at retrieval based on levels of processing at study, suggesting sensitivity to memory demands. These studies demonstrate that retrieval success effects in lateral and medial PPC regions are not affected by manipulations predicted by classical theories of PPC function but can be modulated by memory-related manipulations. PPC regions thus have prominent response properties associated with memory, which may arise through interactions with medial temporal cortex.

title: A sensory signature that distinguishes true from false memories
abstract: Human behavioral studies show that there is greater sensory/perceptual detail associated with true memories than false memories. We therefore hypothesized that true recognition of abstract shapes would elicit greater visual cortical activation than would false recognition. During functional magnetic resonance imaging (fMRI), participants studied exemplar shapes and later made recognition memory decisions (“old” or “new”) concerning studied exemplars (old shapes), nonstudied lures (related shapes) and new shapes. Within visual processing regions, direct contrasts between true recognition (“old” response to an old shape; old-hit) and false recognition (“old” response to a related shape; related-false alarm) revealed preferential true recognition–related activity in early visual processing regions (Brodmann area (BA)17, BA18). By comparison, both true and false recognition were associated with activity in early and late (BA19, BA37) visual processing regions, the late regions potentially supporting “old” responses, independent of accuracy. Further analyses suggested that the differential early visual processing activity reflected repetition priming, a type of implicit memory. Thus, the sensory signature that distinguishes true from false recognition may not be accessible to conscious awareness.

title: Retrieval Success is Accompanied by Enhanced Activation in Anterior Prefrontal Cortex During Recognition Memory: An Event-Related fMRI Study
abstract: Neural regions associated with retrieval success were identified using event-related fMRI procedures and randomly ordered trials on a recognition memory test. Differences between hits and correct rejections (CRs) occurred in multiple regions, including bilateral anterior and right dorsolateral prefrontal cortex, bilateral inferior parietal cortex, and right superior parietal cortex (all hits > CRs), and right occipital cortex (CRs > hits). The hit > CR pattern is not compromised by time-on-task explanations because response latencies for correctly rejected words exceeded those for hits. Converging evidence for the claim that the hit > CR pattern identified neural correlates of retrieval success was obtained by unconfounding item history and retrieval success. That is, we implemented a third condition in which nonstudied words were presented, yet retrieval success was hypothesized to facilitate CRs of these lures. Specifically, when confronted with a familiar, yet nonstudied word, (e.g., nosedive after studying nosebleed and skydive), subjects might adopt a strategy whereby they recall the studied word(s) that gave rise to the familiarity (nosebleed, skydive) and thereby reject the lure. This method of instantiating retrieval success under conditions in which the target word had not been studied offers converging evidence for the claim that anterior-prefrontal cortex (among other regions) demonstrates enhanced activation during retrieval success.

title: Neural processing associated with true and false memory retrieval
abstract: We investigated the neural bases for false memory with fMRI by examining neural activity during retrieval processes that yielded true or false memories. We used a reality monitoring paradigm in which participants saw or imagined pictures of concrete objects. (A subsequent misinformation task was also used to increase false memory rates.) At test, fMRI data were collected as the participants determined whether they had seen or had only imagined the object at study. True memories were of seen pictures accurately endorsed as seen, and for false memories were of imagined pictures falsely endorsed as seen. Three distinct patterns of activity were observed: Left frontal and parietal activity was not different for true and for false memories, whereas activity was greater for true than for false memories in occipital visual regions and posterior portions of the parahippocampal gyrus, and activity was greater for false than for true memories in right anterior cingulate gyrus. Possible interpretations are discussed.

title: Functional Dissociation among Components of Remembering: Control, Perceived Oldness, and Content
abstract: Remembering is the ability to bring back to mind episodes from one's past and is presumably accomplished by multiple, interdependent processes. In the present functional magnetic resonance imaging study, neural correlates of three hypothesized components of remembering were explored, including those associated with control, perceived oldness, and retrieved content. Levels of each component were separately manipulated by varying study procedures and sorting trials by subject response. Results suggest that specific regions in the left prefrontal cortex, including anterior-ventral Brodmann's Area (BA) 45/47 and more dorsal BA 44, increase activity when high levels of control are required but do not necessarily modulate on the basis of perceived oldness. Parietal and frontal regions, particularly the left parietal cortex near BA 40/39, associate with the perception that information is old and generalize across levels of control and retrieved content. Activity in the parietal cortex correlated with perceived oldness even when judgments were in error. The inferior temporal cortex near BA 19/37 associated differentially with retrieval of visual object content. Within the ventral visual processing stream, content-based modulation was specific to late object-responsive regions, suggesting an efficient retrieval process that spares areas that process more primitive retinotopically mapped visual features. Taken collectively, the results identify neural correlates of distinct components of remembering and provide evidence for a functional dissociation. Frontal regions may contribute to control processes that interact with different posterior regions that contribute a signal that information is old and support the contents of retrieval.

title: Parietal Lobe and Episodic Memory: Bilateral Damage Causes Impaired Free Recall of Autobiographical Memory
abstract: Does the parietal lobe have a critical role in memory? The neuroimaging literature indicates that it has an important role, especially in episodic memory. However, the neuropsychological literature suggests that its role is more limited to attentional, spatial, or imagery aspects of memory. Here, we present data to adjudicate this disagreement. Two patients with bilateral parietal lobe damage received detailed assessments of their autobiographical memories. The results show that although both patients easily recalled various memories, their freely recalled memories were relatively impoverished, lacking in detail. This deficit was ubiquitous, and not limited to spatial or perceptual aspects of memory. The memory deficit disappeared when memory was specifically probed by asking pointed questions. Additional tests show that it is unlikely that their free recall deficit can be explained by general mental imagery problems. In sum, the parietal lobe appears to have a critical role in recollection aspects of episodic memory.

title: Some surprising findings on the involvement of the parietal lobe in human memory
abstract: The posterior parietal lobe is known to play some role in a far-flung list of mental processes: linking vision to action (saccadic eye movements, reaching, grasping), attending to visual space, numerical calculation, and mental rotation. Here, we review findings from humans and monkeys that illuminate an untraditional function of this region: memory. Our review draws on neuroimaging findings that have repeatedly identified parietal lobe activations associated with short-term or working memory and episodic memory. We also discuss recent neuropsychological findings showing that individuals with parietal lobe damage exhibit both working memory and long-term memory deficits. These deficits are not ubiquitous; they are only evident under certain retrieval demands. Our review elaborates on these findings and evaluates various theories about the mechanistic role of the posterior parietal lobe in memory. The available data point towards the conclusion that the posterior parietal lobe plays an important role in memory retrieval irrespective of elapsed time. However, the available data do not support simple dichotomies such as recall versus recognition, working versus long-term memory. We conclude by formalizing several open questions that are intended to encourage future research in this rapidly developing area of memory research.

title: The episodic buffer: a new component of working memory?
abstract: In 1974, Baddeley and Hitch proposed a three-component model of working memory. Over the years, this has been successful in giving an integrated account not only of data from normal adults, but also neuropsychological, developmental and neuroimaging data. There are, however, a number of phenomena that are not readily captured by the original model. These are outlined here and a fourth component to the model, the episodic buffer, is proposed. It comprises a limited capacity system that provides temporary storage of information held in a multimodal code, which is capable of binding information from the subsidiary systems, and from long-term memory, into a unitary episodic representation. Conscious awareness is assumed to be the principal mode of retrieval from the buffer. The revised model differs from the old principally in focussing attention on the processes of integrating information, rather than on the isolation of the subsystems. In doing so, it provides a better basis for tackling the more complex aspects of executive control in working memory.

title: The relationship between electrophysiological correlates of recollection and amount of information retrieved
abstract: The electrophysiological correlates of recollection were investigated with a modified Remember/Know task in which subjects signaled whether they fully or partially recollected visual object information in each study episode. A positive-going ERP deflection--the left parietal old/new effect--was sensitive to the amount of information recollected, demonstrating greater amplitude when elicited by test items associated with full relative to partial recollection. These findings support prior proposals that the left parietal ERP old/new effect is sensitive to the amount of information recollected from episodic memory. An early-onsetting (ca. 150 ms), left frontal old/new effect differentiated items accorded correct old versus correct new responses regardless of whether the items were endorsed as familiar or recollected. This finding extends the range of circumstances under which early, frontally distributed old/new effects occur, and adds weight to previous suggestions that these effects are a neural correlate of familiarity-driven recognition memory.

title: Memory retrieval and the parietal cortex: A review of evidence from a dual-process perspective
abstract: Although regions of the parietal cortex have been consistently implicated in episodic memory retrieval, the functional roles of these regions remain poorly understood. The present review presents a meta-analysis of findings from event-related fMRI studies reporting the loci of retrieval effects associated with familiarity- and recollection-related recognition judgments. The results of this analysis support previous suggestions that retrieval-related activity in lateral parietal cortex dissociates between superior regions, where activity likely reflects the task relevance of different classes of recognition test items, and more inferior regions where retrieval-related activity appears closely linked to successful recollection. It is proposed that inferior lateral parietal cortex forms part of a neural network supporting the 'episodic buffer' [Baddeley, A. D. (2000). The episodic buffer: A new component of working memory? Trends in Cognitive Sciences, 4, 417-423].

title: Role of parietal regions in episodic memory retrieval: The dual attentional processes hypothesis
abstract: Although parietal cortex is frequently activated during episodic memory retrieval, damage to this region does not markedly impair episodic memory. To account for these and other findings, a new dual attentional processes (DAP) hypothesis is proposed. According to this hypothesis, dorsal parietal cortex (DPC) contributes top-down attentional processes guided by retrieval goals, whereas ventral parietal cortex (VPC) contributes bottom-up attentional processes captured by the retrieval output. Consistent with this hypothesis, DPC activity increases with retrieval effort whereas VPC activity increases with confidence in old and new responses. The DAP hypothesis can also account for the overlap of parietal activations across different cognitive domains and for opposing effects of parietal activity on encoding vs. retrieval. Finally, the DAP hypothesis explains why VPC lesions yield a memory neglect syndrome: a deficit in spontaneously reporting relevant memory details but not in accessing the same details when guided by specific questions.

title: Top-down and bottom-up attention to memory: A hypothesis (AtoM) on the role of the posterior parietal cortex in memory retrieval
abstract: Recent neuroimaging studies have implicated the posterior parietal cortex in episodic memory retrieval, but there is uncertainty about its specific role. Research in the attentional domain has shown that superior parietal lobe (SPL) regions along the intraparietal sulcus are implicated in the voluntary orienting of attention to relevant aspects of the environment, whereas inferior parietal lobe (IPL) regions at the temporo-parietal junction mediate the automatic allocation of attention to task-relevant information. Here we propose that the SPL and the IPL play conceptually similar roles in episodic memory retrieval. We hypothesize that the SPL allocates top-down attention to memory retrieval, whereas the IPL mediates the automatic, bottom-up attentional capture by retrieved memory contents. By reviewing the existing fMRI literature, we show that the posterior intraparietal sulcus of SPL is consistently active when the need for top-down assistance to memory retrieval is supposedly maximal, e.g., for memories retrieved with low vs. high confidence, for familiar vs. recollected memories, for recognition of high vs. low frequency words. On the other hand, the supramarginal gyrus of IPL is consistently active when the attentional capture by memory contents is supposedly maximal, i.e., for strong vs. weak memories, for vividly recollected vs. familiar memories, for memories retrieved with high vs. low confidence. We introduce a model of episodic memory retrieval that characterizes contributions of posterior parietal cortex.

title: Parietal contributions to recollection: Electrophysiological evidence from aging and patients with parietal lesions
abstract: There has been much recent investigation into the role of parietal cortex in memory retrieval. Proposed hypotheses include attention to internal memorial representations, an episodic working memory-type buffer, and an accumulator of retrieved memorial information. The current investigation used event-related potentials (ERPs) to test the episodic buffer hypothesis, and to assess the memorial contribution of parietal cortex in younger and older adults, and in patients with circumscribed lateral parietal lesions. In a standard recognition memory paradigm, subjects studied color pictures of common objects. One-third of the test items were presented in the same viewpoint as the study phase, one-third were presented in a 90 degrees rotated viewpoint, and one-third were presented in a noncanonical viewpoint. Conflicting with the episodic buffer hypothesis, results revealed that the duration of the parietal old/new effect was longest for the canonical condition and shortest for the noncanonical condition. Results also revealed that older adults demonstrated a diminished parietal old/new effect relative to younger adults. Consistent with previous data reported by Simons et al., patients with lateral parietal lesions showed no behavioral impairment compared to controls. Behavioral and ERP data from parietal lesion patients are presented and discussed. From these results, the authors speculate that the parietal old/new effect may be the neural correlate of an individual's subjective recollective experience.

title: Dissociation Between Memory Accuracy and Memory Confidence Following Bilateral Parietal Lesions
abstract: Numerous functional neuroimaging studies have observed lateral parietal lobe activation during memory tasks: a surprise to clinicians who have traditionally associated the parietal lobe with spatial attention rather than memory. Recent neuropsychological studies examining episodic recollection after parietal lobe lesions have reported differing results. Performance was preserved in unilateral lesion patients on source memory tasks involving recollecting the context in which stimuli were encountered, and impaired in patients with bilateral parietal lesions on tasks assessing free recall of autobiographical memories. Here, we investigated a number of possible accounts for these differing results. In 3 experiments, patients with bilateral parietal lesions performed as well as controls at source recollection, confirming the previous unilateral lesion results and arguing against an explanation for those results in terms of contralesional compensation. Reducing the behavioral relevance of mnemonic information critical to the source recollection task did not affect performance of the bilateral lesion patients, indicating that the previously observed reduced autobiographical free recall might not be due to impaired bottom-up attention. The bilateral patients did, however, exhibit reduced confidence in their source recollection abilities across the 3 experiments, consistent with a suggestion that parietal lobe lesions might lead to impaired subjective experience of rich episodic recollection.

title: Parietal activation during retrieval of abstract and concrete auditory information
abstract: Successful memory retrieval has been associated with a neural circuit that involves prefrontal, precuneus, and posterior parietal regions. Specifically, these regions are active during recognition memory tests when items correctly identified as "old" are compared with items correctly identified as "new." Yet, as nearly all previous fMRI studies have used visual stimuli, it is unclear whether activations in posterior regions are specifically associated with memory retrieval or if they reflect visuospatial processing. We focus on the status of parietal activations during recognition performance by testing memory for abstract and concrete nouns presented in the auditory modality with eyes closed. Successful retrieval of both concrete and abstract words was associated with increased activation in left inferior parietal regions (BA 40), similar to those observed with visual stimuli. These results demonstrate that activations in the posterior parietal cortex during retrieval cannot be attributed to bottom-up visuospatial processes but instead have a more direct relationship to memory retrieval processes.

title: Functional-anatomic correlates of remembering and knowing
abstract: Neural correlates of remembering were examined using event-related functional MRI (fMRI) in 20 young adults. A recognition paradigm based on the remember/know (RK) procedure was used to separately classify studied items that were correctly identified and accompanied by a conscious recollection of details about the study episode from studied items that were correctly identified in the absence of conscious recollection. To facilitate exploration of the basis of remember decisions, studied items were paired with pictures and sounds to encourage retrieval of specific content during scanned testing. Analyses using a priori regions of interest indicated that remembering recruited both regions that associate with the perception and/or decision that information is old and regions that associate preferentially with visual content, while knowing recruited regions associated with oldness, but did not recruit visual content regions. Exploratory analyses further indicated a functional dissociation across regions of parietal cortex that may aid to reconcile several divergent results in the literature. Lateral parietal regions responded preferentially to remember decisions, while a slightly medial region responded robustly to both remember and know decisions. Taken collectively, these results suggest that remembering and knowing associate with common processes supporting a perception and/or the decision that information is old. Remembering additionally recruits regions specific to retrieved content, which may participate to convey the vividness typical of recollective experience.

title: A Parcellation Scheme for Human Left Lateral Parietal Cortex
abstract: The parietal lobe has long been viewed as a collection of architectonic and functional subdivisions. Though much parietal research has focused on mechanisms of visuospatial attention and control-related processes, more recent functional neuroimaging studies of memory retrieval have reported greater activity in left lateral parietal cortex (LLPC) when items are correctly identified as previously studied ("old") versus unstudied ("new"). These studies have suggested functional divisions within LLPC that may provide distinct contributions toward recognition memory judgments. Here, we define regions within LLPC by developing a parcellation scheme that integrates data from resting-state functional connectivity MRI and functional MRI. This combined approach results in a 6-fold parcellation of LLPC based on the presence (or absence) of memory-retrieval-related activity, dissociations in the profile of task-evoked time courses, and membership in large-scale brain networks. This parcellation should serve as a roadmap for future investigations aimed at understanding LLPC function.

title: Parcellation in left lateral parietal cortex is similar in adults and children.
abstract: A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity.

title: Developmental relationships among metamemory, elaborative strategy use, and associative memory☆
abstract: Two experiments examined the relationships among metamemory knowledge, the use of associative memory strategies like elaboration, and cued-recall memory. In Experiment 1, 5th and 12th graders verbalized their strategies while studying noun pairs; their cued-recall memory of those pairs was then tested. Metamemory knowledge was assessed before or after this task. ANOVAs revealed developmental increases in associative strategies, cued recall, and metamemory. Multiple regression indicated the increase in associative strategies predicted all but 4% of the increase in cued recall; metamemory development in turn predicted all but 4% of the increase in associative strategies. Metamemory was a better predictor than a nonverbal measure of intelligence. The strong relationships were due partly to methodological refinements, including a counterbalanced design, a direct strategy measure, a reliable composite rather than single-item metamemory measure, ordinal rather than dichotomous scoring of metamemory items, and regression rather than χ 2 analyses. The results of Experiment 1 were replicated in Experiment 2. Metamemory development also predicted most of the grade difference in cued recall that remained after study strategies were equated by elaboration instructions, suggesting it may explain improvements in retrieval strategies as well.

title: Adolescent Brain Development: A Period of Vulnerabilities and Opportunities. Keynote Address
abstract: This article introduces and summarizes the goals of the symposium. It also provides an overview of a conceptual framework for understanding adolescence, which emphasizes how the very nature of this developmental transition requires an interdisciplinary approach—one that focuses on brain/behavior/social‐context interactions during this important maturational period. More specifically it describes a set of neurobehavioral changes that appear to be linked to pubertal development, which appear to have a significant effect on motivation and emotion, and considers these puberty‐specific changes in affect in relation to a much larger set of developmental changes in adolescence. This framework is used to argue for the need for a transdisciplinary dialogue that brings together work in several areas of neuroscience (including animal models) and normal development with clinical and social policy research aimed at early intervention and prevention strategies.

title: Beyond What Develops When
abstract: There is no single methodology that can fully explain the nature of human development and learning. Yet, headway is being made on how cognitive milestones are achieved during development with the use of magnetic resonance imaging (MRI) technology. With this methodology, it is possible to assess changes in brain structure, function, and connectivity. Recent findings suggest that both progressive and regressive processes—as opposed to simple linear patterns of change—underlie changes in cognitive abilities. Functional MRI studies suggest that both biological maturation and learning correspond to a fine-tuning of neural systems with enhanced recruitment of task-relevant regions. This fine-tuning of cortical systems corresponds with their enhanced connectivity with cortical and subcortical circuitry. In sum, imaging has helped to move the field of cognitive development beyond questions of what develops and when, to how these changes may occur.

title: Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity.
abstract: Sex differences in age- and puberty-related maturation of human brain structure have been observed in typically developing age-matched boys and girls. Because girls mature 1-2 years earlier than boys, the present study aimed at assessing sex differences in brain structure by studying 80 adolescent boys and girls matched on sexual maturity, rather than age. We evaluated pubertal influences on medial temporal lobe (MTL), thalamic, caudate, and cortical gray matter volumes utilizing structural magnetic resonance imaging and 2 measures of pubertal status: physical sexual maturity and circulating testosterone. As predicted, significant interactions between sex and the effect of puberty were observed in regions with high sex steroid hormone receptor densities; sex differences in the right hippocampus, bilateral amygdala, and cortical gray matter were greater in more sexually mature adolescents. Within sex, we found larger volumes in MTL structures in more sexually mature boys, whereas smaller volumes were observed in more sexually mature girls. Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys, which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.

title: Sex differences and the impact of steroid hormones on the developing human brain.
abstract: Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

title: Environmental stimulation, parental nurturance and cognitive development in humans.
abstract: The effects of environmental stimulation and parental nurturance on brain development have been studied extensively in animals. Much less is known about the relations between childhood experience and cognitive development in humans. Using a longitudinally collected data set with ecologically valid in-home measures of childhood experience and later in-laboratory behavioral measures of cognitive ability, we were able to test hypotheses concerning the effects of environmental stimulation and parental nurturance. A double dissociation was found: On the one hand, there was a selective relation between parental nurturance and memory development, consistent with the animal literature on maternal buffering of stress hormone effects on hippocampal development. On the other hand, there was a selective relation between environmental stimulation and language development. The relevance of these findings to socioeconomic gradients in cognitive ability is discussed.

title: Epigenetics and the biological definition of gene x environment interactions.
abstract: Variations in phenotype reflect the influence of environmental conditions during development on cellular functions, including that of the genome. The recent integration of epigenetics into developmental psychobiology illustrates the processes by which environmental conditions in early life structurally alter DNA, providing a physical basis for the influence of the perinatal environmental signals on phenotype over the life of the individual. This review focuses on the enduring effects of naturally occurring variations in maternal care on gene expression and phenotype to provide an example of environmentally driven plasticity at the level of the DNA, revealing the interdependence of gene and environmental in the regulation of phenotype.

title: A Review of Adversity, The Amygdala and the Hippocampus: A Consideration of Developmental Timing
abstract: A review of the human developmental neuroimaging literature that investigates outcomes following exposure to psychosocial adversity is presented with a focus on two subcortical structures – the hippocampus and the amygdala. Throughout this review, we discuss how a consideration of developmental timing of adverse experiences and age at measurement might provide insight into the seemingly discrepant findings across studies. We use findings from animal studies to suggest some mechanisms through which timing of experiences may result in differences across time and studies. The literature suggests that early life may be a time of heightened susceptibility to environmental stressors, but that expression of these effects will vary by age at measurement.

title: Epigenetics and the biological basis of gene x environment interactions.
abstract: Child and adolescent psychiatry is rife with examples of the sustained effects of early experience on brain function. The study of behavioral genetics provides evidence for a relation between genomic variation and personality and with the risk for psychopathology. A pressing challenge is that of conceptually integrating findings from genetics into the study of personality without regressing to arguments concerning the relative importance of genomic variation versus nongenomic or environmental influences.



Epigenetics refers to functionally relevant modifications to the genome that do not involve a change in nucleotide sequence. This review examines epigenetics as a candidate biological mechanism for gene x environment interactions, with a focus on environmental influences that occur during early life and that yield sustained effects on neural development and function.



The studies reviewed suggest that epigenetic remodeling occurs in response to the environmental activation of cellular signalling pathways associated with synaptic plasticity, epigenetic marks are actively remodeled during early development in response to environmental events that regulate neural development and function, and epigenetic marks are subject to remodeling by environmental influences even at later stages in development.



Epigenetic remodeling might serve as an ideal mechanism for phenotypic plasticity--the process whereby the environment interacts with the genome to produce individual differences in the expression of specific traits.

title: Socioeconomic status and the brain: mechanistic insights from human and animal research
abstract: Human brain development occurs within a socioeconomic context and childhood socioeconomic status (SES) influences neural development — particularly of the systems that subserve language and executive function. Research in humans and in animal models has implicated prenatal factors, parent–child interactions and cognitive stimulation in the home environment in the effects of SES on neural development. These findings provide a unique opportunity for understanding how environmental factors can lead to individual differences in brain development, and for improving the programmes and policies that are designed to alleviate SES-related disparities in mental health and academic achievement.

title: Maternal support in early childhood predicts larger hippocampal volumes at school age
abstract: Early maternal support has been shown to promote specific gene expression, neurogenesis, adaptive stress responses, and larger hippocampal volumes in developing animals. In humans, a relationship between psychosocial factors in early childhood and later amygdala volumes based on prospective data has been demonstrated, providing a key link between early experience and brain development. Although much retrospective data suggests a link between early psychosocial factors and hippocampal volumes in humans, to date there has been no prospective data to inform this potentially important public health issue. In a longitudinal study of depressed and healthy preschool children who underwent neuroimaging at school age, we investigated whether early maternal support predicted later hippocampal volumes. Maternal support observed in early childhood was strongly predictive of hippocampal volume measured at school age. The positive effect of maternal support on hippocampal volumes was greater in nondepressed children. These findings provide prospective evidence in humans of the positive effect of early supportive parenting on healthy hippocampal development, a brain region key to memory and stress modulation.

title: Early parental care is important for hippocampal maturation: Evidence from brain morphology in humans
abstract: The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

title: Memory plasticity across the life span: uncovering children's latent potential.
abstract: Memory plasticity, or the ability to improve one's memory performance through instruction and training, is known to decline during adulthood. However, direct comparisons among middle childhood, adulthood, and old age are lacking. The authors examined memory plasticity in an age-comparative multisession training study. One hundred and eight participants ages 9-10, 11-12, 20-25, and 65-78 years learned and practiced an imagery-based mnemonic technique to encode and retrieve words by location cues. Individuals of all ages were able to acquire and optimize use of the technique. Older adults and children showed similar baseline performance and improvement through mnemonic instruction. However, in line with tenets from life-span psychology (P. B. Baltes, 1987), children profited more from mnemonic practice and reached higher levels of final performance than did older adults.

title: Hundred Days of Cognitive Training Enhance Broad Cognitive Abilities in Adulthood: Findings from the COGITO Study
abstract: We examined whether positive transfer of cognitive training, which so far has been observed for individual tests only, also generalizes to cognitive abilities, thereby carrying greater promise for improving everyday intellectual competence in adulthood and old age. In the COGITO Study, 101 younger and 103 older adults practiced six tests of perceptual speed (PS), three tests of working memory (WM), and three tests of episodic memory (EM) for over 100 daily 1-h sessions. Transfer assessment included multiple tests of PS, WM, EM, and reasoning. In both age groups, reliable positive transfer was found not only for individual tests but also for cognitive abilities, represented as latent factors. Furthermore, the pattern of correlations between latent change factors of practiced and latent change factors of transfer tasks indicates systematic relations at the level of broad abilities, making the interpretation of effects as resulting from unspecific increases in motivation or self-concept less likely.

title: Spatial navigation training protects the hippocampus against age-related changes during early and late adulthood
abstract: It is unknown whether lifestyle, including mental stimulation, and appropriate training interventions, may directly improve spatial navigation performance and its underlying neural substrates. Here we report that healthy younger and older men performing a cognitively demanding spatial navigation task every other day over 4 months display navigation-related gains in performance and stable hippocampal volumes that were maintained 4 months after termination of training. In contrast, control groups displayed volume decrements consistent with longitudinal estimates of age-related decline. Hippocampal barrier density, as indicated by mean diffusivity estimated from diffusion tensor imaging, showed a quadratic shape of increased density after training followed by a return to baseline in the right hippocampus, but declined in the control groups and in the left hippocampus. We conclude that sustained experiential demands on spatial ability protect hippocampal integrity against age-related decline. These results provide the first longitudinal evidence indicating that spatial navigation experience modifies hippocampal volumes in humans, and confirm epidemiological results suggesting that mental stimulation may have direct effects on neural integrity.

title: Differential cognitive effects of cycling versus stretching/coordination training in middle-aged adults.
abstract: Physical exercise has been linked to higher cognitive functioning and enhanced brain plasticity in aging humans. The most consistent positive effects have been reported for executive functions associated with frontal brain regions. In rodents, however, running has been shown to induce functional and structural changes in the hippocampus, a brain region known to be important for memory. It is still a matter of debate which cognitive functions are susceptible to exercise and whether an increase in cardiovascular fitness is beneficial for cognitive functioning. Moreover, little is known about the impact of exercise on cognition in middle-aged humans.



Sixty-eight sedentary men and women between 40 and 56 years of age were randomly assigned to one of two training programs: aerobic endurance training (cycling) or nonendurance training (stretching/coordination). Both groups exercised twice a week for six months. Additionally, a sedentary control group was tested. At baseline and after six months, episodic memory, perceptual speed, executive functions, and spatial reasoning were assessed with standardized psychometric tests, and all participants underwent a cardiovascular fitness test.



Significant improvements in memory were observed in both the cycling and the stretching/coordination group as compared with the sedentary control group. The improvement in episodic memory correlated positively with the increase in cardiovascular fitness. The stretching/coordination training particularly improved selective attention as compared with the cycling training.



The results suggest that cardiovascular fitness has beneficial effects even in high-functioning middle-aged participants, but that these benefits are very specific to memory functions rather than a wider range of cognitive functions.

title: Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males
abstract: Physical activity has been reported to improve cognitive function in humans and rodents, possibly via a brain-derived neurotrophic factor (BDNF)-regulated mechanism. In this study of human subjects, we have assessed the effects of acute and chronic exercise on performance of a face-name matching task, which recruits the hippocampus and associated structures of the medial temporal lobe, and the Stroop word-colour task, which does not, and have assessed circulating concentrations of BDNF and IGF-1 in parallel. The results show that a short period of high-intensity cycling results in enhancements in performance of the face-name matching, but not the Stroop, task. These changes in cognitive function were paralleled by increased concentration of BDNF, but not IGF-1, in the serum of exercising subjects. 3 weeks of cycling training had no effect on cardiovascular fitness, as assessed by VO2 scores, cognitive function, or serum BDNF concentration. Increases in fitness, cognitive function and serum BDNF response to acute exercise were observed following 5 weeks of aerobic training. These data indicate that both acute and chronic exercise improve medial temporal lobe function concomitant with increased concentrations of BDNF in the serum, suggesting a possible functional role for this neurotrophic factor in exercise-induced cognitive enhancement in humans.

title: Brain sensitivity to print emerges when children learn letter–speech sound correspondences
abstract: The acquisition of reading skills is a major landmark process in a human's cognitive development. On the neural level, a new functional network develops during this time, as children typically learn to associate the well-known sounds of their spoken language with unfamiliar characters in alphabetic languages and finally access the meaning of written words, allowing for later reading. A critical component of the mature reading network located in the left occipito-temporal cortex, termed the “visual word-form system” (VWFS), exhibits print-sensitive activation in readers. When and how the sensitivity of the VWFS to print comes about remains an open question. In this study, we demonstrate the initiation of occipito-temporal cortex sensitivity to print using functional MRI (fMRI) (n = 16) and event-related potentials (ERP) (n = 32) in a controlled, longitudinal training study. Print sensitivity of fast (<250 ms) processes in posterior occipito-temporal brain regions accompanied basic associative learning of letter–speech sound correspondences in young (mean age 6.4 ± 0.08 y) nonreading kindergarten children, as shown by concordant ERP and fMRI results. The occipito-temporal print sensitivity thus is established during the earliest phase of reading acquisition in childhood, suggesting that a crucial part of the later reading network first adopts a role in mapping print and sound.

title: Training and plasticity of working memory
abstract: Working memory (WM) capacity predicts performance in a wide range of cognitive tasks. Although WM capacity has been viewed as a constant trait, recent studies suggest that it can be improved by adaptive and extended training. This training is associated with changes in brain activity in frontal and parietal cortex and basal ganglia, as well as changes in dopamine receptor density. Transfer of the training effects to non-trained WM tasks is consistent with the notion of training-induced plasticity in a common neural network for WM. The observed training effects suggest that WM training could be used as a remediating intervention for individuals for whom low WM capacity is a limiting factor for academic performance or in everyday life.

title: At the nexus of neuroscience and education
abstract: Research on how the brain develops and learns has he potential to have a profound impact on education. ndeed, understanding the brain mechanisms that underlie earning and memory, and the effects of age, genetics, the nvironment, emotion and motivation on learning could ransform educational strategies and enable us to design rograms that optimise learning for people of all ages and f all needs. Neuroscience can already offer some undertanding of how the brain learns new information and rocesses this information throughout life (Blakemore and rith, 2005; Goswami, 2006; Shonkoff and Levitt, 2010). he potential link between neuroscience findings and eduational practice and policy is the focus of this special issue f Developmental Cognitive Neuroscience on Neuroscience nd Education. Developmental cognitive neuroscience is contributing o our basic understanding of how the brain develops nd changes with experience from infancy onward, as ell as the neural mechanisms underlying school-based earning and how these can go wrong. As such, develpmental cognitive neuroscience has the potential to ontribute to education policy. Indeed, to say that neuoscience is relevant to education is an understatement. y definition, education changes the brain; the brain hanges every time a child – or an adult – learns somehing new. Thus a deeper understanding of how the brain rocesses and learns shapes and sounds, letters and numers, the neural processes underlying the maintenance and anipulation of task-relevant information, individual diferences in learning, motivation and memory, and so on, is rofoundly relevant to education. Understanding the bioogical basis of the developmental disorders that affect hildren’s educational attainment is a critical step in develping interventions. Inroads are being made: There are already multi-way ialogues between the fields of neuroscience and educaion. Educators and parents are learning about the brain, nd neuroscientists are moving their research into the chools and engaging with policymakers in an effort to pdate educational policies as a function of what we have

title: The two-component model of memory development, and its potential implications for educational settings
abstract: We recently introduced a two-component model of the mechanisms underlying age differences in memory functioning across the lifespan. According to this model, memory performance is based on associative and strategic components. The associative component is relatively mature by middle childhood, whereas the strategic component shows a maturational lag and continues to develop until young adulthood. Focusing on work from our own lab, we review studies from the domains of episodic and working memory informed by this model, and discuss their potential implications for educational settings. The episodic memory studies uncover the latent potential of the associative component in childhood by documenting children's ability to greatly improve their memory performance following mnemonic instruction and training. The studies on working memory also point to an immature strategic component in children whose operation is enhanced under supportive conditions. Educational settings may aim at fostering the interplay between associative and strategic components. We explore possible routes towards this goal by linking our findings to recent trends in research on instructional design.