Parts of the Brain - Memory & the Brain - The Human Memory MEMORY & THE BRAIN Neurons & Synapses PARTS OF THE BRAIN The human brain is hugely interconnected but three major components can be identified: the cerebrum, the cerebellum and the brain stem. The brainstem which includes the medulla, the pons and the midbrain, controls breathing, digestion, heart rate and other autonomic processes, as well as connecting the brain with the spinal cord and the rest of the body. The cerebellum plays an important role in balance, motor control, but is also involved in some cognitive functions such as attention, language, emotional functions (such as regulating fear and pleasure responses) and in the processing of procedural memories . The cerebrum (or forebrain), which makes up 75% of the brain by volume and 85% by weight, is divided by a large groove, known as the longitudinal fissure, into two distinct hemispheres.

The left and right hemispheres ("left" and "right" refer to the owner's point of view, not an outside viewer's) are linked by a large bundle of nerve fibres called the corpus callosum, and also by other smaller connections called commissures. Most of the important elements of the cerebrum, are split into symmetrical pairs in the left and right hemispheres. Thus, we often speak of the temporal lobes, hippocampi, etc (in the plural), although this website generally follows the convention of speaking of the temporal lobe, hippocampus, etc (in the singular), which should therefore be taken to mean both sides, within both hemispheres. The two hemispheres look similar, but are slightly different in structure and perform different functions. The right hemisphere generally controls the left side of the body, and vice versa, although popular notions that logic, creativity, etc, are restricted to the left or right hemispheres are largely simplistic and unfounded.

Lobes of the cerebral cortex Picture from Wikipedia ( The cerebrum is covered by a sheet of neural tissue known as the cerebral cortex (or neocortex), which envelops other brain organs such as the thalamus (which evolved to help relay information from the brain stem and spinal cord to the cerebral cortex) and the hypothalamus and pituitary gland (which control visceral functions, body temperature and behavioural responses such as feeding, drinking, sexual response, aggression and pleasure). The cerebral cortex itself is only 2 - 4 mm thick, and contains six distinct but interconnected layers. It is intricately grooved and folded into the familiar convoluted pattern of folds, or gyri, allowing a large surface area (typically almost 2m2) to fit within the confines of the skull. Consequently, more than two-thirds of the cerebral cortex is buried in the grooves, or sulci. About 90% of all the brain�s neurons are located in the cerebral cortex, mainly in the "grey matter", which makes up the surface regions of the cerebral cortex, while the inner "white matter" consists mainly of myelinated axons, over 170,000 km of them.

As many as five times that number of glial cells exist to support the active nerve cells. The cerebral cortex plays a key role in memory, attention, perceptual awareness, thought, language and consciousness. It is divided into four main regions or lobes, which cover both hemispheres: the frontal lobe (involved in conscious thought and higher mental functions such as decision-making, particularly in that part of the frontal lobe known as the prefrontal cortex, and plays an important part in processing short-term memories and retaining longer term memories which are not task-based); the parietal lobe (involved in integrating sensory information from the various senses, and in the manipulation of objects in determining spatial sense and navigation); the temporal lobe (involved with the senses of smell and sound, the processing of semantics in both speech and vision, including the processing of complex stimuli like faces and scenes, and plays a key role in the formation of long-term memory ); and the occipital lobe (mainly involved with the sense of sight).

The Limbic System and Basal Ganglia Picture from How Stuff Works ( swearing.htm/printable) The medial temporal lobe (the inner part of the temporal lobe, near the divide between the left and right hemispheres) in particular is thought to be involved in declarative and episodic memory . Deep inside the medial temporal lobe is the region of the brain known as the limbic system, which includes the hippocampus, the amygdala, the cingulate gyrus, the thalamus, the hypothalamus, the epithalamus, the mammillary body and other organs, many of which are of particular relevance to the processing of memory. The hippocampus, for example, is essential for memory function, particularly the transference from short- to long-term memory and control of spatial memory and behaviour. The hippocampus is one of the few areas of the brain capable actually growing new neurons , although this ability is impaired by stress-related glucocorticoids. The amygdala also performs a primary role in the processing and memory of emotional reactions and social and sexual behaviour, as well as regulating the sense of smell.

Another sub-cortical systems (inside the cerebral cortex) which is essential to memory function is the basal ganglia system, particularly the striatum (or neostriatum) which is important in the formation and retrieval of procedural memory . THE BRAIN FROM TOP TO BOTTOM How Different Parts of the Brain Co-operate Suppose you are in a museum admiring a painting. Your retinas capture the image of this painting and route it, in the form of nerve impulses, to the visual zone of your brain, which reconstructs the overall image. These impulses are then routed to your hippocampus, which acts as the gatekeeper and decides whether or not to accept the information and pass it on to your long-term memory. If your hippocampus does not let this information in, you will probably forget the image of the painting within a minute. But if your hippocampus does accept this information, it will eventually be returned to the area it came from: the visual cortex. There the image of the painting will be placed in long-term memory, point by point, in the form of thousands of strengthened connections between neurons. The hippocampus appears to play a fundamental role in spatial memory in many animal species, including humans.

For example, in a British study, the researchers asked taxi drivers to imagine their travels through the city of London, while their brain activity was monitored by positron emission tomography (PET scan). This task, which was so familiar to these subjects, caused a specific activation of their right hippocampus. In human beings, the hippocampus may therefore contribute to the construction of episodic memory by providing a spatial framework for each memory that lets it be reconstituted accurately. LONG-TERM MEMORY The hippocampus, the cortical structures surrounding it, and the neural pathways that connect them to the cortex as a whole are all heavily involved in declarative memory –the memory of facts and events. For example, after you’ve had a fine dinner with some friends, your memories of their faces, the taste of the wine, and the music that was playing are distributed in the various visual, olfactory, and auditory areas of the brain, but they are all connected together by the hippocampus to form an "episode", rather than remaining a collection of separate memories. The hippocampus thus plays a fundamental role in episodic memory , the kind that will let you remember this especially pleasant dinner party years later.

In fact, it seems to be the hippocampus that enables you to “play the scene back”, by reactivating this particular activity pattern in the various regions of the cortex. This phenomenon would be very important during dreams, and would explain the incorporation of events from the last few days into them. But after a while, these various cortical regions activated during an event would become so strongly linked with one another that they would no longer need the hippocampus to act as their link. Thanks to this linkage, the memory of a piece of music that was playing that night could be enough to bring back the entire scene of the dinner party. Each of these elements could act as an index entry that lets you retrieve all the others to your consciousness. Thus, information that has been encoded in long-term memory for a lengthy period of time no longer requires the intervention of the hippocampus. This is the case in particular for general knowledge in semantic memory , which instead activates the frontal and temporal cortexes. The activity in the temporal lobe would correspond to the activation of the fact in question, while the activity in the frontal cortex would correspond to its reaching consciousness. Unlike our memory of facts and events, however, our spatial memory appears to be confined to the hippocampus.

And more specifically to the right hippocampus. This structure seems to be able to create a mental map of space, thanks to certain cells called place cells . Some very intense personal memories that bring what is sometimes called emotional memory into play appear to involve another structure of the limbic system besides the hippocampus. This structure is the amygdala , which is already known to manage our reactions to fear. Many other structures in the limbic system also help to encode our long-term memories. Lastly, procedural memory, such as knowing how to ride a bike, does not appear to involve the hippocampus at all. Instead, procedural memory appears to be associated with modifications in the cerebellum , the basal ganglia , and the motor cortex , all of which are involved in motor control. As evidence to this effect, procedural memory is not affected by amnesia caused by lesions to the hippocampus, but is affected by damage to the cerebellum and by neurodegenerative diseases that alter the basal ganglia, such as Huntington’s disease.

A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis Original Research Article A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis S Y Shu1, Y M Wu1, X M Bao1, Z B Wen2, F H Huang2, S X Li1, Q Z Fu1 and Q Ning1 1Institute for Neuroscience of the First Military Medical University, Zhu-Jiang Hospital, Guangzhou, China 2Department of Radiology of Zhu-Jiang Hospital, Guangzhou, China Correspondence to: Professor S-Y Shu, Institute for Neuroscience, First Military Medical University, Zhu-jiang Hospital, Guangzhou, 510282, China. E-mail: shusybao@gdvnet.com Abstract Previous studies identified a new brain area, the marginal division (MrD), at the caudomedial border of the neostriatum in the brain of the rat, cat and monkey. The MrD was distinguishable from the rest of the striatum by the presence of spindle-shaped neurons, specific connections, and dense immunoreactivity for neuropeptides and monoamines in fibers, terminals and neuronal somata.

Behavioral testing demonstrated that the MrD contributes to learning and memory in the rat. In the present study, the structure and the function of the MrD were investigated in the human brain. The presence of spindle-shaped neurons and the distribution of neurotransmitters in the MrD were evaluated by immunocytochemical methods. The function of the MrD was identified with functional magnetic resonance imaging (fMRI) of healthy volunteers tested with an auditory digital working memory task. Highly active areas were observed in the prefrontal cortex and MrD with left sided predominance during performance of the task, but other parts of the neostriatum were not excited and the MrD was not activated in a control test of non-working memory. The results of the present investigation therefore indicate the existence of a new area associated with learning and memory function in the human brain. The MrD probably plays an important role in the execution of digital working memory and appears to link the limbic system and the basal nucleus of Meynert. The MrD may also be involved in the mechanism of Alzheimer's disease. Molecular Psychiatry (2002) 7, 1018-1022.

doi:10.1038/sj.mp.4001155 Keywords marginal division; neostriatum; functional magnetic resonance imaging; learning and memory; digital working memory; human brain; immunohistochemistry In previous studies we discovered a structure we termed the marginal division (MrD) on the basis of its location at the caudomedial margin of the neostriatum surrounding the rostral border of the globus pallidus in rat, 1 cat 2 and monkey 3 brains. A three dimensional reconstruction from Nissl-stained sections of the rat brain showed that the MrD is a flat, pan-shaped structure. The MrD was easily distinguishable from the rest of the striatum by the presence of spindle-shaped neurons and a variety of intensely expressed neuropeptides and monoamines in nerve fibers, terminals and neuronal somata. 4 Most of the neuropeptides in the MrD have been considered to be functionally involved in learning and memory. 5 , 6 Functional neuronal connections between the MrD and the hippocampus, amygdala and basal nucleus of Meynert (NBM) were identified by chemically induced c-fos protein (c-Fos) expression.

7 The MrD was shown to contribute to learning and memory in the rat with the double-blind Y-maze test. 8 The presence of the MrD in the neostriatum was confirmed by other investigators in immunohistochemical and physiological studies. Talley et al reported a higher level of expression of 2A adrenergic receptors in the marginal division than in the rest of the striatum. 9 Lavoie and Parent demonstrated that pedunculopontine nuclear projections to the basal ganglia terminated exclusively in the MrD, 10 distinguishing it from other parts of the striatum. Nociceptive neurons were reported localized solely in the MrD of the rat striatum, using neurophysiological techniques, 11 and the MrD was described as part of the ventral striatal area by Heimer and coworkers. 12, , 13 In the present study we wished to determine whether the MrD is also present in the human brain and to assess its possible function in vivo with a non-invasive imaging technique.

Neuroanatomical and immunocytochemical studies were carried out on brains autopsied from 12 children and five adults to assess any differences between the young and the mature brain; no staining differences between them were observed. Brains were dissected and sectioned to study the structure of the neostriatum. The cytoarchitecture of brain sections was investigated with Nissl staining. Neurotransmitter distribution was identified with primary and secondary antibodies using the Avidin-Biotin Complex (ABC) technique and a glucose oxidase and nickel ammonium sulfate-intensified diaminobenzidine (GDN) staining method. 14 A cellular zone consisting of fusiform neurons situated between the neostriatum (putamen) and the globus pallidus was detected in these sections of the human brain. The long axes of the neurons in this region ran dorsoventrally, parallel to the border between the putamen and the globus pallidus, in a fashion similar to that seen in other mammalian species.

Numerous Leu-enkephalin- (L-Enk), neurotensin- (NT) and substance P- (SP) positive fibers and cells were found in this area ( Figure 1 ). The results of these studies confirmed that a new area, recognized by the presence of spindle-shaped neurons with dense expression of a variety of neuropeptides, is also present in the medial margin of the neostriatum (putamen) in the human brain. The MrD appears thicker and more developed in primate than in rodent brains, and is most highly developed in the human brain. The elaboration of the MrD in the human brain suggested that it could have a significant function. Is the MrD of the human brain also involved in learning and memory as it is in the rat? Non-invasive methods are required to explore the function of the human brain in vivo. Functional imaging techniques, and particularly fMRI, provide a powerful and non-invasive means of linking brain function to structure in vivo.

Because of its high spatial and rapid temporal resolution, fMRI is especially useful in detecting and localizing neural activity in the human brain, and was therefore used in the present study to investigate whether the MrD contributes to the function of learning and memory in human subjects. Thirteen volunteers undertook both an auditory digital working memory task and a non-working memory control task separately monitored by fMRI. The working memory task required subjects to actively maintain and identify several stimuli at a time, while the non-working memory task only required subjects to perform an instant judgment. Eleven of 13 subjects achieved criterion performance on the working memory task with an average score of 22.7 (of a possible score of 30; SD = 1.74). Data from two male subjects with scores below 20 were excluded because of their failure to achieve a criterion performance in the task. In these 11 subjects highly activated areas were observed bilaterally in the prefrontal cortex (PFC, McNemar Test P < 0.001) and left MrD (P < 0.001) during execution of the auditory digital working memory task ( Figure 2b ,d).

Most of the activity in the PFC exhibited left predominance. However, the right MrD in one male subject was highly activated as well ( Figure 2f ), although other parts of his right striatum were not. Other areas, such as the right internal capsule (IC, P > 0.05), right thalamus (Th, P > 0.05), left temporal lobe (TL, P > 0.05) and genu of corpus callosum (GCC, P > 0.05) were occasionally activated in some subjects ( Table 1 ). The PFC and MrD were not activated when these subjects were executing the non-working memory control task ( Figure 2c, e, g ). It is widely accepted that the PFC is an important center for working memory, involved in the integration and temporary storage of information. Research on the PFC of monkeys and humans indicates that this region contributes to many mental processes and complex behaviors. 15 fMRI studies have identified the role of the PFC in working memory and indicated that the mnemonic content of the task affects the relative weighting of hemispheric activation.

When results from a group of previously reported human functional brain imaging studies were plotted onto a standardized brain, the hemispheric organization of the PFC was found to depend on the type of material held in working memory. 16 Activity of the left PFC was greater during tasks involving nonspatial working memory (such as digital working memory) than during tasks using spatial working memory. This analysis was supported by other studies. 17 , 18 In the present investigation, 11 of 13 subjects showed activation of the PFC with left predominance during the execution of auditory digital working memory. These results therefore support a prominent role of the PFC in working memory, while other cortical regions, such as the supplementary motor area, lateral premotor and the parietal cortex, appear to play subservient roles. 16 There are few previous studies examining activation of subcortical regions of the brain using fMRI during tasks involving working memory. The results of the present investigation show that both the MrD and the PFC are activated during the execution of auditory digital working memory.

The MrD was not activated in the same individuals during execution of the control task, suggesting that the MrD was not activated by auditory stimuli or finger movements during the auditory digital working memory task. The MrD thus appears to be activated by working memory itself. It is interesting to note that the MrD showed obvious left predominance in 10 of the 11 subjects, which was the same hemispheric predominance of the PFC in these individuals. This suggests that the MrD should not be considered as merely a transfer station on the afferent or efferent pathways involved in working memory but as a subcortical center for learning and memory. C-Fos immunohistochemistry labels functionally connected neurons activated by a variety of stimuli 19 and was used to trace the functional connections of the MrD in our previous study. 7 C-Fos-immunoreactive neurons were observed in the hippocampus, dentate gyrus, amygdala, NBM and the PFC following stereotaxic injection of 0.01% kainic acid into the MrD of the rat brain.

C-Fos immunoreactivity was also expressed in neurons of the MrD, hippocampus, dentate gyrus, amygdala and PFC after injecting 0.01% kainic acid into the NBM. The positive expression of c-Fos was stained in a purple-black color with the ABC-GDN immunohistochemical staining method. The purple-black stained nuclei of activated neurons were observed only in the caudal margin of the striatum without expression in other parts of this structure. The c-Fos positive stained nuclei of activated neurons accumulated in a rainbow-shaped zone clearly distinguished the MrD from the rest of the striatum, following chemical stimulation of the NBM ( Figure 3 ). The hippocampus, dentate gyrus and amygdala are considered to be part of the limbic system and important for learning and memory. 20 Pathological changes in the NBM induced an obvious decrease in cholinergic fiber density in the cortex, which could be of relevance to the changes in cognitive function seen in Alzheimer's disease. 21 The efferent projections from the MrD were further identified by electron microscopy to synapse on the cholinergic cell bodies of the NBM.

A reduction in learning and memory was recorded following terminal degeneration of the MrD-NBM projection after a lesion of the MrD. 22 These studies thus identify functional connections among the NBM, the MrD and the limbic system. The MrD was formerly considered as part of the limbic motor circuit 23 and thought to represent neurons of passage from the central division of the extended amygdala in the rat brain. 24 In the present study, functional connections between the MrD and the limbic system are demonstrated. Thus the MrD functions as a link between the NBM and the limbic system, and appears likely to modulate learning and memory in both parts of the brain ( Figure 4 ). In conclusion, the present study demonstrates the presence of the MrD in the human brain and provides direct evidence that the MrD contributes to learning and memory in vivo. The MrD as well as the PFC may play an important role in the execution of digital working memory. In addition, the MrD constitutes a link between NBM and the limbic system, suggesting involvement in the mechanism of Alzheimer's disease.

Materials and methods Immunohistochemical techniques Autopsy brains were obtained from 12 children, ages 9 to 12, and from five adults, ages 21-38, within 12 h of death from acute, non-nervous system diseases such as pneumonia. Standard protocols were followed for approval by relatives of the deceased and by the human subjects review committee of the hospital. Brains were removed from the skull and fixed with 4% paraformaldehyde for 14-20 days at 4°C. The neostriatum and globus pallidus were dissected and sectioned frontally at 50- m thickness with a Cryostat microtome (Cryocut 1800, Leica Instruments, Germany). Polyclonal anti-enkephalin (Enk) (1:3000; INCSTAR, Stillwater, MN, USA), anti-substance P (SP) (1:6000; INCSTAR) and anti-neurotensin (NT) (1:2000; INCSTAR) were used to examine peptide expression.

Sections were processed with the ABC method with ABC kits (Vector Laboratories, Burlingame, CA, USA) and stained with a glucose oxidase and nickel ammonium sulfate-intensified diaminobenzidine (GDN) method. 14 Positively stained structures exhibited purple-black reaction product in the sections. Control sections were processed without the primary antibody; these sections were not stained. C-Fos immunocytochemistry experiments were performed on rats. A low concentration of kainic acid solution was used as the chemical stimulus to induce C-Fos expression in the brains of 61 animals. A total of 0.1-0.2 l of 0.01% kainic acid was stereotaxically microinjected into the NBM or MrD. Animals were killed 6 or 8 h after injection by anaesthesia with Nembutal and perfused with 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4) through the aorta. Brains were removed and sectioned frontally at 40- m thickness with a Cryostat microtome.

Sections were reacted with an antibody to c-Fos (1:1000; Santa Cruz Biotechnology, Santa Cruz, CA, USA). ABC and GDN methods were used to demonstrate the expression of c-Fos in the brain. Thirty brains with correct injection sites were analyzed. c-Fos-positive neurons exhibited purple black nuclear stain. No nuclear staining of neurons was observed when the primary antibody to c-Fos was omitted in reaction of control sections. Behavioral tasks Thirteen right-handed healthy volunteers (nine males and four females, aged 21-35 years) were asked to participate in both the auditory digital working memory task and the non-working memory control task. All subjects were undergraduates and graduates from the First Military Medical University of PLA, Guangzhou, China. They had no history of medical, neurological or psychiatric illness, nor were taking any type of prescription medication immediately prior to or during the period of the test. They gave their written, informed consent in accordance with the Declaration of Helsinki. Stimuli consisted of a series of two-digit numbers, which were read by a man at a speed of one number per second followed by a 1-s interval. Each series was divided into two groups: a memory group and a test group.

Each group had five numbers. In each series, two or three numbers in each group were the same while the others were different. The experiment contained six cycles, each of which consisted of a 20-s block of the memory task, alternating with a 20-s block of the interval phase. In each auditory working memory task cycle, subjects heard a randomly chosen series of stimuli. The subjects were instructed to memorize the numbers in the memory group and then determine whether the numbers in the corresponding test group had been presented. 'Yes' was indicated by raising the right thumb and 'no' was indicated by raising the left thumb, respectively. The score was recorded as the number of correct answers out of a total possible score of 30. Data from two male subjects, whose score was lower than 20, were excluded from analysis. In the non-working memory control task group the stimuli and process were the same as those in the auditory digital working memory task group; however, subjects were instructed to judge whether each number was greater than 50, instead of memorizing them and comparing them with numbers in the test group. Subjects were asked to perform the digital task first followed by the non-working memory control task.

fMRI techniques Imaging was carried out on a 1.5 T SIGNA scanner (GE Medical Systems, Milwaukee, USA) equipped with a fast gradient system for echo-planar imaging. A standard radio frequency head coil was used and the head motion was restricted. High-resolution sagittal T1-weighted images were obtained from every subject prior to localization experiments. A gradient echo, echoplanar sequence (repetition time = 2000 ms, echo time = 60 ms, flip angle = 90°) was used to acquire data sensitive to the blood-oxygen-level-dependent (BOLD) signal. Resolution was 128 ´ 128 lattice in each plane and 0 mm between planes (four plane slices). Activated areas were visualized after processing by the Functool program (supplied by GE Medical Systems) using the correlation coefficient algorithm method. Regions of interest were analyzed by the McNemar test (a nonparametric test for two related samples). Acknowledgements We thank Dr Brian Leonard very much for his advice during the course of this project and for very helpful comments. We thank Dr Nicholas Spitzer very much for his helpful comments and editing the English presentation of the manuscript.

We thank Dr Lajtha and Dr Zaborsky for their helpful suggestions. We express our gratitude to the volunteers for their participation in the fMRI tests and to the relatives of the deceased patients for their contribution to this medical research. References 24 Gore P, Alheid GF, Shammah-Lagnado SJ, Beltramino CA, Yang M, Marksteiner J et al. Peripallidal portions of the extended amygdala in the rat: the supracapsular and marginal zones. Abstr Soc Neurosci 1996; 22: 2049. Figures Figure 1 Neurons and neurotransmitters in the human marginal division (MrD). (a) The schematic drawing shows the MrD of the human brain as a narrow band located between the putamen (Put) and the external segment of the globus pallidus (GPe). The rectangle at lower right displays a high magnification view of Nissl-stained fusiform neurons in the MrD. Scale bar is 50 m.

(b-d) Enkephalin- (Enk), Substance P- (SP), and Neurotensin- (NT) immunoreactive fibers, terminals and fusiform neurons in the MrD visualized with ABC-GDN staining. Scale bar for (b-d) is 50 m. Figure 2 Selective activation of the human MrD during auditory digital working memory task, visualized with functional MRI (fMRI). (a) A T2 MRI image demonstrates the positions of the prefrontal cortex (PFC), the putamen (Put), the external segment of the globus pallidus (GPe) and the marginal division (MrD) in the normal human brain. (b) A T2* fMRI image shows a highly activated area in the bilateral PFC with left predominance and in the left MrD in the first subject's brain while he was performing the auditory digital working memory task. (c) The T2* fMRI image reveals no activation in the MrD in the same subject's brain (b) while he was performing the non-working memory control task. (d,e) Similar results to (c,d) in the second subject's brain.

(f,g) Results similar to those in (b,c) and (d,e) demonstrating selective activation of areas in the left PFC and bilateral MrD of the third subject's brain. Figure 3 Sagittal section of the rat brain illustrating c-Fos expression in the marginal division following stimulation of the basal nucleus of Meynert with kainic acid. The MrD was distinguished from the rest of the striatum by a rainbow-shaped zone of c-Fos-positive nuclei at the caudal border of the striatum. Scale bar is 100 m. The bottom right corner shows a high magnification view of c-Fos-reactive nuclei of the MrD in the rectangular area above. NBM: basal nucleus of Meynert; GP: globus pallidus; IC: internal capsule; MrD: marginal division; St: striatum; Th: thalamus. Figure 4 Schematic drawing illustrating the functional connections between the marginal division (MrD), basal nucleus of Meynert (NBM) and the limbic system. The MrD is shown as a linking area between the limbic system and the NBM.

Afferent impulses from the prefrontal cortex (PFC), bed nucleus of stria terminalis (BST), amygdala (A) and hippocampus (Hi) provide input to the MrD. Efferent impulses from the MrD travel to the NBM, which sends efferent impulses to the limbic system and the cortex. AD: Alzheimer's disease; +: excitatory influence; (+): assumed excitatory influence. Tables Table 1 Summary of brain areas activated during the working memory task Received 24 October 2001; revised 12 March 2002; accepted 3 April 2002 2002, Volume 7, Number 9, Pages 1018-1022 Regular exercise changes the brain to improve memory, thinking skills - Harvard Health Blog - Harvard Health Publications Regular exercise changes the brain to improve memory, thinking skills Heidi Godman , Executive Editor, Harvard Health Letter There are plenty of good reasons to be physically active. Big ones include reducing the odds of developing heart disease, stroke, and diabetes. Maybe you want to lose weight, lower your blood pressure, prevent depression, or just look better.

Here’s another one, which especially applies to those of us (including me) experiencing the brain fog that comes with age: exercise changes the brain in ways that protect memory and thinking skills. In a study done at the University of British Columbia, researchers found that regular aerobic exercise, the kind that gets your heart and your sweat glands pumping, appears to boost the size of the hippocampus, the brain area involved in verbal memory and learning. Resistance training, balance and muscle toning exercises did not have the same results. The finding comes at a critical time. Researchers say one new case of dementia is detected every four seconds globally. They estimate that by the year 2050, more than 115 million people will have dementia worldwide. Exercise and the brain Exercise helps memory and thinking through both direct and indirect means. The benefits of exercise come directly from its ability to reduce insulin resistance, reduce inflammation, and stimulate the release of growth factors—chemicals in the brain that affect the health of brain cells, the growth of new blood vessels in the brain, and even the abundance and survival of new brain cells. Indirectly, exercise improves mood and sleep, and reduces stress and anxiety. Problems in these areas frequently cause or contribute to cognitive impairment.

Many studies have suggested that the parts of the brain that control thinking and memory (the prefrontal cortex and medial temporal cortex) have greater volume in people who exercise versus people who don’t. “Even more exciting is the finding that engaging in a program of regular exercise of moderate intensity over six months or a year is associated with an increase in the volume of selected brain regions,” says Dr. Scott McGinnis, a neurologist at Brigham and Women’s Hospital and an instructor in neurology at Harvard Medical School. Put it to the test So what should you do? Start exercising! We don’t know exactly which exercise is best. Almost all of the research has looked at walking, including the latest study. “It’s likely that other forms of aerobic exercise that get your heart pumping might yield similar benefits,” says Dr. McGinnis. How much exercise is required to improve memory? These study participants walked briskly for one hour, twice a week. That’s 120 minutes of moderate intensity exercise a week. Standard recommendations advise half an hour of moderate physical activity most days of the week, or 150 minutes a week.

If that seems daunting, start with a few minutes a day, and increase the amount you exercise by five or 10 minutes every week until you reach your goal. If you don’t want to walk, consider other moderate-intensity exercises, such as swimming, stair climbing, tennis, squash, or dancing. Don’t forget that household activities can count as well, such as intense floor mopping, raking leaves, or anything that gets your heart pumping so much that you break out in a light sweat. Don’t have the discipline to do it on your own? Try any or all of these ideas: Join a class or work out with a friend who’ll hold you accountable. Track your progress, which encourages you to reach a goal. If you’re able, hire a personal trainer. (Paying an expert is good motivation.) Whatever exercise and motivators you choose, commit to establishing exercise as a habit, almost like taking a prescription medication. After all, they say that exercise is medicine, and that can go on the top of anyone’s list of reasons to work out.

Brain Anatomy, Anatomy of the Human Brain Anatomy of the Brain Overview The brain is an amazing three-pound organ that controls all functions of the body, interprets information from the outside world, and embodies the essence of the mind and soul. Intelligence, creativity, emotion, and memory are a few of the many things governed by the brain. Protected within the skull, the brain is composed of the cerebrum, cerebellum, and brainstem. The brainstem acts as a relay center connecting the cerebrum and cerebellum to the spinal cord. The brain receives information through our five senses: sight, smell, touch, taste, and hearing - often many at one time. It assembles the messages in a way that has meaning for us, and can store that information in our memory. The brain controls our thoughts, memory and speech, movement of the arms and legs, and the function of many organs within our body. It also determines how we respond to stressful situations (such as taking a test, losing a job, or suffering an illness) by regulating our heart and breathing rate. Nervous system The nervous system is divided into central and peripheral systems. The central nervous system (CNS) is composed of the brain and spinal cord.

The peripheral nervous system (PNS) is composed of spinal nerves that branch from the spinal cord and cranial nerves that branch from the brain. The PNS includes the autonomic nervous system, which controls vital functions such as breathing, digestion, heart rate, and secretion of hormones. Skull The purpose of the bony skull is to protect the brain from injury. The skull is formed from 8 bones that fuse together along suture lines. These bones include the frontal, parietal (2), temporal (2), sphenoid, occipital and ethmoid (Fig. 1). The face is formed from 14 paired bones including the maxilla, zygoma, nasal, palatine, lacrimal, inferior nasal conchae, mandible, and vomer. Figure 1. Eight bones form the skull and fourteen bones form the face. Inside the skull are three distinct areas: anterior fossa, middle fossa, and posterior fossa (Fig. 2). Doctors sometimes refer to a tumor’s location by these terms, e.g., middle fossa meningioma. Figure 2. The inside of the skull is divided into three areas called the anterior, middle, and posterior fossae.

Similar to cables coming out the back of a computer, all the arteries, veins and nerves exit the base of the skull through holes, called foramina. The big hole in the middle (foramen magnum) is where the spinal cord exits. Brain The brain is composed of the cerebrum, cerebellum, and brainstem (Fig. 3). Figure 3. The brain is composed of three parts: the brainstem, cerebellum, and cerebrum. The cerebrum is divided into four lobes: frontal, parietal, temporal, and occipital. The cerebrum is the largest part of the brain and is composed of right and left hemispheres. It performs higher functions like interpreting touch, vision and hearing, as well as speech, reasoning, emotions, learning, and fine control of movement. The cerebellum is located under the cerebrum. Its function is to coordinate muscle movements, maintain posture, and balance. The brainstem includes the midbrain, pons, and medulla. It acts as a relay center connecting the cerebrum and cerebellum to the spinal cord.

It performs many automatic functions such as breathing, heart rate, body temperature, wake and sleep cycles, digestion, sneezing, coughing, vomiting, and swallowing. Ten of the twelve cranial nerves originate in the brainstem. The surface of the cerebrum has a folded appearance called the cortex. The cortex contains about 70% of the 100 billion nerve cells. The nerve cell bodies color the cortex grey-brown giving it its name – gray matter (Fig. 4). Beneath the cortex are long connecting fibers between neurons, called axons, which make up the white matter. Figure 4. The surface of the cerebrum is called the cortex. The cortex contains neurons (grey matter), which are interconnected to other brain areas by axons (white matter). The cortex has a folded appearance. A fold is called a gyrus and the groove between is a sulcus. The folding of the cortex increases the brain’s surface area allowing more neurons to fit inside the skull and enabling higher functions. Each fold is called a gyrus, and each groove between folds is called a sulcus. There are names for the folds and grooves that help define specific brain regions.

Right brain – left brain The right and left hemispheres of the brain are joined by a bundle of fibers called the corpus callosum that delivers messages from one side to the other. Each hemisphere controls the opposite side of the body. If a brain tumor is located on the right side of the brain, your left arm or leg may be weak or paralyzed. Not all functions of the hemispheres are shared. In general, the left hemisphere controls speech, comprehension, arithmetic, and writing. The right hemisphere controls creativity, spatial ability, artistic, and musical skills. The left hemisphere is dominant in hand use and language in about 92% of people. Lobes of the brain The cerebral hemispheres have distinct fissures, which divide the brain into lobes. Each hemisphere has 4 lobes: frontal, temporal, parietal, and occipital (Fig 3). Each lobe may be divided, once again, into areas that serve very specific functions. It’s important to understand that each lobe of the brain does not function alone. There are very complex relationships between the lobes of the brain and between the right and left hemispheres.

Frontal lobe Hearing Sequencing and organization Messages within the brain are carried along pathways. Messages can travel from one gyrus to another, from one lobe to another, from one side of the brain to the other, and to structures found deep in the brain (e.g. thalamus, hypothalamus). Deep structures Hypothalamus - is located in the floor of the third ventricle and is the master control of the autonomic system. It plays a role in controlling behaviors such as hunger, thirst, sleep, and sexual response. It also regulates body temperature, blood pressure, emotions, and secretion of hormones. Pituitary gland - lies in a small pocket of bone at the skull base called the sella turcica. The pituitary gland is connected to the hypothalamus of the brain by the pituitary stalk. Known as the “master gland,” it controls other endocrine glands in the body. It secretes hormones that control sexual development, promote bone and muscle growth, respond to stress, and fight disease. Pineal gland - is located behind the third ventricle. It helps regulate the body’s internal clock and circadian rhythms by secreting melatonin. It has some role in sexual development.

Thalamus - serves as a relay station for almost all information that comes and goes to the cortex (Fig. 5). It plays a role in pain sensation, attention, alertness and memory. Figure 5. Coronal cross-section showing the basal ganglia. Basal ganglia - includes the caudate, putamen and globus pallidus. These nuclei work with the cerebellum to coordinate fine motions, such as fingertip movements. Limbic system - is the center of our emotions, learning, and memory. Included in this system are the cingulate gyri, hypothalamus, amygdala (emotional reactions) and hippocampus (memory). Cranial nerves The brain communicates with the body through the spinal cord and twelve pairs of cranial nerves (Fig. 6). Ten of the twelve pairs of cranial nerves that control hearing, eye movement, facial sensations, taste, swallowing and movement of the face, neck, shoulder and tongue muscles originate in the brainstem. The cranial nerves for smell and vision originate in the cerebrum. Figure 6. The Roman numeral, name, and main function of the twelve cranial nerves.

moves tongue Meninges The brain and spinal cord are covered and protected by three layers of tissue called meninges. From the outermost layer inward they are: the dura mater, arachnoid mater, and pia mater. The dura mater is a strong, thick membrane that closely lines the inside of the skull; its two layers, the periosteal and meningeal dura, are fused and separate only to form venous sinuses. The dura creates little folds or compartments. There are two special dural folds, the falx and the tentorium. The falx separates the right and left hemispheres of the brain and the tentorium separates the cerebrum from the cerebellum. The arachnoid mater is a thin, web-like membrane that covers the entire brain. The arachnoid is made of elastic tissue. The space between the dura and arachnoid membranes is called the subdural space. The pia mater hugs the surface of the brain following its folds and grooves. The pia mater has many blood vessels that reach deep into the brain. The space between the arachnoid and pia is called the subarachnoid space.

It is here where the cerebrospinal fluid bathes and cushions the brain. Ventricles and cerebrospinal fluid The brain has hollow fluid-filled cavities called ventricles (Fig. 7). Inside the ventricles is a ribbon-like structure called the choroid plexus that makes clear colorless cerebrospinal fluid (CSF). CSF flows within and around the brain and spinal cord to help cushion it from injury. This circulating fluid is constantly being absorbed and replenished. Figure 7. CSF is produced inside the ventricles deep within the brain. CSF fluid circulates inside the brain and spinal cord and then outside to the subarachnoid space. Common sites of obstruction: 1) foramen of Monro, 2) aqueduct of Sylvius, and 3) obex. There are two ventricles deep within the cerebral hemispheres called the lateral ventricles. They both connect with the third ventricle through a separate opening called the foramen of Monro. The third ventricle connects with the fourth ventricle through a long narrow tube called the aqueduct of Sylvius.

From the fourth ventricle, CSF flows into the subarachnoid space where it bathes and cushions the brain. CSF is recycled (or absorbed) by special structures in the superior sagittal sinus called arachnoid villi. A balance is maintained between the amount of CSF that is absorbed and the amount that is produced. A disruption or blockage in the system can cause a build up of CSF, which can cause enlargement of the ventricles (hydrocephalus) or cause a collection of fluid in the spinal cord (syringomyelia). Blood supply Blood is carried to the brain by two paired arteries, the internal carotid arteries and the vertebral arteries (Fig. 8). The internal carotid arteries supply most of the cerebrum. Figure 8. The common carotid artery courses up the neck and divides into the internal and external carotid arteries. The brain’s anterior circulation is fed by the internal carotid arteries (ICA) and the posterior circulation is fed by the vertebral arteries (VA). The two systems connect at the Circle of Willis (green circle). The vertebral arteries supply the cerebellum, brainstem, and the underside of the cerebrum.

After passing through the skull, the right and left vertebral arteries join together to form the basilar artery. The basilar artery and the internal carotid arteries “communicate” with each other at the base of the brain called the Circle of Willis (Fig. 9). The communication between the internal carotid and vertebral-basilar systems is an important safety feature of the brain. If one of the major vessels becomes blocked, it is possible for collateral blood flow to come across the Circle of Willis and prevent brain damage. Figure 9. Top view of the Circle of Willis. The internal carotid and vertebral-basilar systems are joined by the anterior communicating and posterior communicating arteries. The venous circulation of the brain is very different than the rest of the body. Usually arteries and veins run together as they supply and drain specific areas of the body. So one would think there would be a pair of vertebral veins and internal carotid veins. However, this is not the case in the brain. The major vein collectors are integrated into the dura to form venous sinuses (Fig. 10) - not to be confused with the air sinuses in the face and nasal region.

The venous sinuses collect the blood from the brain and pass it to the internal jugular veins. The superior and inferior sagittal sinuses drain the cerebrum, the cavernous sinuses drains the anterior skull base. All sinuses eventually drain to the sigmoid sinuses, which exit the skull and form the jugular veins. These two jugular veins are essentially the only drainage of the brain. Figure 10. Three quarter view of the dural covering of the brain depicts the two major dural folds, the falx and tentorium along with the venous sinuses. Language In general, the left hemisphere of the brain is responsible for language and speech and is called the "dominant" hemisphere. The right hemisphere plays a large part in interpreting visual information and spatial processing. In about one third of individuals who are left-handed, speech function may be located on the right side of the brain. Left-handed individuals may need special testing to determine if their speech center is on the left or right side prior to any surgery in that area. Aphasia is a disturbance of language affecting production, comprehension, reading or writing, due to brain injury – most commonly from stroke or trauma. The type of aphasia depends on the brain area affected.

Broca’s area lies in the left frontal lobe (Fig 3). If this area is damaged, one may have difficulty moving the tongue or facial muscles to produce the sounds of speech. The individual can still read and understand spoken language but has difficulty in speaking and writing (i.e. forming letters and words, doesn't write within lines) – called Broca's aphasia. Wernicke's area lies in the left temporal lobe (Fig 3). Damage to this area causes Wernicke's aphasia. The individual may speak in long sentences that have no meaning, add unnecessary words, and even create new words. They can make speech sounds, however they have difficulty understanding speech and are therefore unaware of their mistakes. Memory Memory is a complex process that includes three phases: encoding (deciding what information is important), storing, and recalling. Different areas of the brain are involved in memory depending on the type of memory. Short-term memory, also called working memory, occurs in the prefrontal cortex. It stores information for about one minute and its capacity is limited to about 7 items. For example, it enables you to dial a phone number someone just told you.

It also intervenes during reading, to memorize the sentence you have just read, so that the next one makes sense. Long-term memory is processed in the hippocampus of the temporal lobe and is activated when you want to memorize something for a longer time. This memory has unlimited content and duration capacity. It contains personal memories as well as facts and figures. Skill memory is processed in the cerebellum, which relays information to the basal ganglia. It stores automatic learned memories like tying a shoe, playing an instrument, or riding a bike. Cells of the brain The brain is made up of two types of cells: nerve cells (neurons) and glia cells. Nerve cells There are many sizes and shapes of neurons, but all consist of a cell body, dendrites and an axon. The neuron conveys information through electrical and chemical signals. Try to picture electrical wiring in your home. An electrical circuit is made up of numerous wires connected in such a way that when a light switch is turned on, a light bulb will beam. A neuron that is excited will transmit its energy to neurons within its vicinity. Neurons transmit their energy, or “talk”, to each other across a tiny gap called a synapse (Fig.

11). A neuron has many arms called dendrites, which act like antennae picking up messages from other nerve cells. These messages are passed to the cell body, which determines if the message should be passed along. Important messages are passed to the end of the axon where sacs containing neurotransmitters open into the synapse. The neurotransmitter molecules cross the synapse and fit into special receptors on the receiving nerve cell, which stimulates that cell to pass on the message. Figure 11. Nerve cells consist of a cell body, dendrites and axon. Neurons communicate with each other by exchanging neurotransmitters across a tiny gap called a synapse. Glia cells Glia (Greek word meaning glue) are the cells of the brain that provide neurons with nourishment, protection, and structural support. There are about 10 to 50 times more glia than nerve cells and are the most common type of cells involved in brain tumors. Astroglia or astrocytes transport nutrients to neurons, hold neurons in place, digest parts of dead neurons, and regulate the blood brain barrier. Oligodendroglia cells provide insulation (myelin) to neurons.

Ependymal cells line the ventricles and secrete cerebrospinal fluid (CSF). Microglia digest dead neurons and pathogens. Sources & links If you have more questions, please contact Mayfield Brain & Spine at 800-325-7787 or 513-221-1100. Links updated > 4.2016 reviewed by > Tonya Hines, CMI, Mayfield Clinic / University of Cincinnati Department of Neurosurgery, Ohio Mayfield Certified Health Info materials are written and developed by the Mayfield Clinic. We comply with the HONcode standard for trustworthy health information. This information is not intended to replace the medical advice of your health care provider. Mayfield services During the past 10 to 15 years medical science has made a quantum leap in our understanding of the human brain and spinal cord. These revelations have been fueled by advances in imaging technology and neurobiology. Whether they are studying genetic biomarkers in basic science laboratories or perusing functional MRI scans at an advanced imaging center, Mayfield researchers are making new discoveries about how nerve cells work, grow, die, and repair themselves.

Every day, we are working to translate new research discoveries into better treatments for our patients. Learn more about our brain research at the UC Department of Neurosurgery. To make an appointment call 513-221-1100. Neural Correlates of Memory Storage About Watch and Favorite Watch Watching this resources will notify you when proposed changes or new versions are created so you can keep track of improvements that have been made. Favorite Favoriting this resource allows you to save it in the “My Resources” tab of your account. There, you can easily access this resource later when you’re ready to customize it or assign it to your students. Neural Correlates of Memory Storage Although the physical location of memory remains relatively unknown, it is thought to be distributed in neural networks throughout the brain. Learning Objective Discuss the physical characteristics of memory storage Key Points It is theorized that memories are stored in neural networks in various parts of the brain associated with different types of memory, including short-term memory, sensory memory , and long-term memory. Memory traces , or engrams , are physical neural changes associated with memories. Scientists have gained knowledge about these neuronal codes from studies on neuroplasticity .

Encoding of episodic memory involves lasting changes in molecular structures , which alter communication between neurons . Recent functional-imaging studies have detected working-memory signals in the medial temporal lobe and the prefrontal cortex . Both the frontal lobe and prefrontal cortex are associated with long- and short-term memory, suggesting a strong link between these two types of memory. The hippocampus is integral in consolidating memories but does not seem to store memories itself. Terms Register for FREE to remove ads and unlock more features! Learn more Full Text Many areas of the brain have been associated with the processes of memory storage. Lesion studies and case studies of individuals with brain injuries have allowed scientists to determine which areas of the brain are most associated with which kinds of memory. However, the actual physical location of memories remains relatively unknown. It is theorized that memories are stored in neural networks in various parts of the brain associated with different types of memory, including short-term memory, sensory memory, and long-term memory. Keep in mind, however, that it is not sufficient to describe memory as solely dependent on specific brain regions, although there are areas and pathways that have been shown to be related to certain functions.

Memory Traces Memory traces, or engrams, are the physical neural changes associated with memory storage. The big question of how information and mental experiences are coded and represented in the brain remains unanswered. However, scientists have gained much knowledge about neuronal codes from studies on neuroplasticity, the brain's capacity to change its neural connections. Most of this research has been focused on simple learning and does not clearly describe changes involved in more complex examples of memory. Encoding of working memory involves the activation of individual neurons induced by sensory input. These electric spikes continue even after the sensation stops. Encoding of episodic memory (i.e., memories of experiences) involves lasting changes in molecular structures that alter communication between neurons. Recent functional-magnetic-resonance-imaging (fMRI) studies detected working memory signals in the medial temporal lobe and the prefrontal cortex. These areas are also associated with long-term memory, suggesting a strong relationship between working memory and long-term memory. Brain Areas Associated with Memory Imaging research and lesion studies have led scientists to conclude that certain areas of the brain may be more specialized for collecting, processing, and encoding specific types of memories. Activity in different lobes of the cerebral cortex have been linked to the formation of memories.

Short Term Memory , Hippocampus Newswise — Research in animals has revealed new information about how animals and humans may store and retrieve short-term memories, say researchers from Wake Forest University Baptist Medical Center. "For the first time, we've found that two different areas of the brain share the function of storing and remembering events for short-term memory," said Sam Deadwyler, Ph.D., lead researcher. "These new findings broaden our understanding of how memory works." Deadwyler and co-investigator Robert Hampson, Ph.D., showed that the hippocampus, a structure long believed to be important for short-term memory, shares this function with another adjacent brain area, the subiculum. The research, reported in the current issue of Neuron, shows that both structures are required to process information correctly. Knowing more about memory " and what goes wrong in conditions such as Alzheimer's disease " could lead to more sensitive tests for early diagnosis, as well as new drugs to enhance and recover memory, said Deadwyler. In addition, the findings that two brain areas act together to establish and retrieve short-term memories suggests the possibility that humans could be retrained to use one area if the other is damaged or diseased.

"Surprisingly, we found that the shortest memories were controlled almost exclusively by the subiculum, which is exactly opposite from what was previously believed," said Deadwyler. "For the first 10 to 15 seconds of the task used to examine this in rats, we found that the memory function of the hippocampus actually shuts off." Using multiple electrodes smaller than the size of a human hair, the researchers recorded activity in the hippocampus and subiculum as rats performed a memory task. The results showed that both brain structures "encode" or "remember" information, but they do it at different times. For the memory task, rats were randomly presented either a "right" of "left" lever. With food as an incentive, the rat pressed the lever and then had to perform another behavior on the opposite side of the cage for 1 second to 30 seconds as a distraction. When the animal returned after the delay, both the "right" and "left" levers were showing. To get the task correct, the rat now had to press the lever opposite from the one selected at the beginning of the trial.

Electrode recordings of cell activity in both brain areas unexpectedly showed that when the imposed delay was less than 15 seconds, only the subiculum recorded the information. But, when the delay was longer, the subiculum became inactive while the hippocampus switched on and took over control of the memory requirements of the task. The research also revealed another important finding about the hippocampus. When it switched on to complete the trial, the memory was biased by past experience. This strategy allowed the hippocampus to anticipate future events based on past outcomes. With the rat trials, the hippocampus did not start from scratch. Because of this strategy in some cases it would "expect" the trials to alternate "left," then "right," and fired cells to remember the alternate lever even before the trial began. "When the hippocampus relies on previous experience, and doesn't use current events, the rat can get the task wrong because the anticipatory firing is actually controlling the animal's behavior," said Hampson. In humans, this is similar to someone who takes the same highway exit each day to get to work. He may end up taking that route even when he's not supposed to " such as on a day he needed to go to the dentist before work.

"When this happens, you're using a behavioral pattern that is remembered by your hippocampus," said Deadwyler. "When you get in your car in the morning, you trigger that pattern and your hippocampus then takes over. Based on familiar landmarks, it then guides you toward your destination. But, you're acting in accordance with what your 'memory' is telling you instead of what is actually going on in the real world around you, and you miss the turn." The researchers hope to continue the work to learn more about how the hippocampus and subiculum work together with other brain regions to establish more permanent memories. The research was funded by grants from the National Institutes of Health (National Institute on Drug Abuse and National Institute of Mental Health). About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University School of Medicine. It is licensed to operate 1,282 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.

Question: In the brain what area is especially associated with memory?
Answer: HIPPOCAMPUS