rudyvdbrink/CitationDatabase huggingface dataset:
Learning hierarchical sequence representations across human cortex and hippocampus.
Science advances, 2021

Sensory input arrives in continuous sequences that humans experience as segmented units, e.g., words and events. The brain's ability to discover regularities is called statistical learning. Structure can be represented at multiple levels, including transitional probabilities, ordinal position, and identity of units. To investigate sequence encoding in cortex and hippocampus, we recorded from intracranial electrodes in human subjects as they were exposed to auditory and visual sequences containing temporal regularities. We find neural tracking of regularities within minutes, with characteristic profiles across brain areas. Early processing tracked lower-level features (e.g., syllables) and learned units (e.g., words), while later processing tracked only learned units. Learning rapidly shaped neural representations, with a gradient of complexity from early brain areas encoding transitional probability, to associative regions and hippocampus encoding ordinal position and identity of units. These findings indicate the existence of multiple, parallel computational systems for sequence learning across hierarchically organized cortico-hippocampal circuits.
Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation.
Human mutation, 2004

We recently identified mutations of ARX in nine genotypic males with X-linked lissencephaly with abnormal genitalia (XLAG), and in several female relatives with isolated agenesis of the corpus callosum (ACC). We now report 13 novel and two recurrent mutations of ARX, and one nucleotide change of uncertain significance in 20 genotypic males from 16 families. Most had XLAG, but two had hydranencephaly and abnormal genitalia, and three males from one family had Proud syndrome or ACC with abnormal genitalia. We obtained detailed clinical information on all 29 affected males, including the nine previously reported subjects. Premature termination mutations consisting of large deletions, frameshifts, nonsense mutations, and splice site mutations in exons 1 to 4 caused XLAG or hydranencephaly with abnormal genitalia. Nonconservative missense mutations within the homeobox caused less severe XLAG, while conservative substitution in the homeodomain caused Proud syndrome. A nonconservative missense mutation near the C-terminal aristaless domain caused unusually severe XLAG with microcephaly and mild cerebellar hypoplasia. In addition, several less severe phenotypes without malformations have been reported, including mental retardation with cryptogenic infantile spasms (West syndrome), other seizure types, dystonia or autism, and nonsyndromic mental retardation. The ARX mutations associated with these phenotypes have included polyalanine expansions or duplications, missense mutations, and one deletion of exon 5. Together, the group of phenotypes associated with ARX mutations demonstrates remarkable pleiotropy, but also comprises a nearly continuous series of developmental disorders that begins with hydranencephaly, lissencephaly, and agenesis of the corpus callosum, and ends with a series of overlapping syndromes with apparently normal brain structure.
Ipsilateral foetal-type posterior cerebral artery is associated with cognitive decline after carotid revascularisation.
BMC neurology, 2014

Stenosis of the internal carotid artery has been associated with cognitive impairment and decline. However, studies testing the effect of carotid revascularisation on cognition have had conflicting results. This may in part be explained by variation in the flow territory of the carotid artery. In 12 to 36% of the patients, the posterior cerebral artery is mainly or exclusively supplied by the internal carotid artery via a foetal-type posterior cerebral artery. In these patients, ipsilateral carotid artery stenosis is likely to result in a larger area with hypoperfusion than in case of a normal posterior cerebral artery. Patients with a foetal-type posterior cerebral artery could therefore benefit more from revascularisation. We compared the effects of carotid revascularisation on cognition between patients with a foetal-type and those with a normal posterior cerebral artery.
Infant maternal separation impairs adult cognitive performance in BALB/cJ mice.
Psychopharmacology, 2011

Early life adversity, such as early abuse or parental loss, is thought to increase risk for developing psychiatric disorders in adulthood including mood and anxiety disorders. Human retrospective studies also suggest that early life adversity predicts poor response to antidepressants in adulthood.
Cell-specific synaptic plasticity induced by network oscillations.
eLife, 2016

Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner.
Knowledge and beliefs about epilepsy among people with and without epilepsy in urban Suriname.
Epilepsy & behavior : E&B, 2013

Reducing the burden of epilepsy in low- and middle-income countries requires understanding of the cultural aspects of epilepsy. This cross-sectional study among individuals attending a clinic in an urban setting in Paramaribo, Suriname aimed to obtain information on the knowledge of and attitudes towards epilepsy and epilepsy treatment, comparing people with epilepsy (PWE) to those without epilepsy. This study also explored the help-seeking behavior and experience of having epilepsy in PWE. While the results of interviews with 49 PWE and 33 controls compared favorably to studies conducted in similar countries, a significant minority of PWE still rely on traditional remedies. Prejudices regarding social roles, schooling, and occupational choices of PWE also remain prevalent. Currently, the major source of information for both groups is the media, but there could be opportunities for the local epilepsy association to play a larger role. These findings, despite some selection bias, could be useful in bringing conventional medical treatment strategies to more PWE in Suriname, as well as empower patient organizations in designing stigma-reducing interventions.
Repetitive Transcranial Magnetic Stimulation Over the Left Posterior Middle Temporal Gyrus Reduces Wrist Velocity During Emblematic Hand Gesture Imitation.
Brain topography, 2019

Results from neuropsychological studies, and neuroimaging and behavioural experiments with healthy individuals, suggest that the imitation of meaningful and meaningless actions may be reliant on different processing routes. The left posterior middle temporal gyrus (pMTG) is one area that might be important for the recognition and imitation of meaningful actions. We studied the role of the left pMTG in imitation using repetitive transcranial magnetic stimulation (rTMS) and two-person motion-tracking. Participants imitated meaningless and emblematic meaningful hand and finger gestures performed by a confederate actor whilst both individuals were motion-tracked. rTMS was applied during action observation (before imitation) over the left pMTG or a vertex control site. Since meaningless action imitation has been previously associated with a greater wrist velocity and longer correction period at the end of the movement, we hypothesised that stimulation over the left pMTG would increase wrist velocity and extend the correction period of meaningful actions (i.e., due to interference with action recognition). We also hypothesised that imitator accuracy (actor-imitator correspondence) would be reduced following stimulation over the left pMTG. Contrary to our hypothesis, we found that stimulation over the pMTG, but not the vertex, during action observation reduced wrist velocity when participants later imitated meaningful, but not meaningless, hand gestures. These results provide causal evidence for a role of the left pMTG in the imitation of meaningful gestures, and may also be in keeping with proposals that left posterior temporal regions play a role in the production of postural components of gesture.
The course of unilateral intracranial arteriopathy in young adults with arterial ischemic stroke.
Stroke, 2012

Unilateral intracranial focal nonprogressive arteriopathy is often found in children with arterial ischemic stroke. We aimed to investigate the course of unilateral intracranial arteriopathy in young adults.
The Prognostic Performance of Frailty for Delirium and Functional Decline in Vascular Surgery Patients.
Journal of the American Geriatrics Society, 2021

Frailty in older vascular surgery patients is associated with increased mortality, hospital stay, and morbidity. The association of frailty with hospital-acquired geriatric syndromes such as delirium and functional decline has not been well studied.
Do prism and other adaptation paradigms really measure the same processes?
Cortex; a journal devoted to the study of the nervous system and behavior, 2019

Sensorimotor plasticity allows the nervous system to set up appropriate motor and sensory compensations when individuals face changing demands in a given motor task. A much-debated question in neuroscience research is the identification of processes that encompass this capacity of plasticity. Prism adaptation is the oldest experimental paradigm that has been used to achieve this goal (Helmholtz, 1867). Since 1990's, other paradigms have emerged such as visuomotor rotations or dynamical perturbations (inertial Coriolis forces, velocity-dependent force-field). We compared these paradigms with respect to three specific methodological features: application of the perturbation, after-effects, and generalization. This work aimed to shed light on the following central issue: Do all these paradigms involve similar processes? We used generalization properties-a relevant feature associated with the credit assignment problem-to emphasize the involvement of different processes in "adaptation" paradigms. We therefore classified these processes based on the context specificity of elicited transformations. This review reveals that the processes involved are closely linked to paradigm-related experimental conditions. Context-independent processes appear to be favored when errors are attributed to our own sensorimotor performance (prism, Coriolis) whereas context-dependent processes appear to be mostly mediated by attribution of errors to a specific external interface (visuomotor rotation, force-field). This work encourages researchers to consider the methodological aspects specific to each paradigm for future investigations of sensorimotor plasticity.
Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432.
The Journal of pharmacology and experimental therapeutics, 2014

In the central nervous system, the ATP-gated Purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is expressed in glial cells and modulates neurophysiology via release of gliotransmitters, including the proinflammatory cytokine interleukin (IL)-1β. In this study, we characterized JNJ-42253432 [2-methyl-N-([1-(4-phenylpiperazin-1-yl)cyclohexyl]methyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide] as a centrally permeable (brain-to-plasma ratio of 1), high-affinity P2X7 antagonist with desirable pharmacokinetic and pharmacodynamic properties for in vivo testing in rodents. JNJ-42253432 is a high-affinity antagonist for the rat (pKi 9.1 ± 0.07) and human (pKi 7.9 ± 0.08) P2X7 channel. The compound blocked the ATP-induced current and Bz-ATP [2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate tri(triethylammonium)]-induced release of IL-1β in a concentration-dependent manner. When dosed in rats, JNJ-42253432 occupied the brain P2X7 channel with an ED50 of 0.3 mg/kg, corresponding to a mean plasma concentration of 42 ng/ml. The compound blocked the release of IL-1β induced by Bz-ATP in freely moving rat brain. At higher doses/exposure, JNJ-42253432 also increased serotonin levels in the rat brain, which is due to antagonism of the serotonin transporter (SERT) resulting in an ED50 of 10 mg/kg for SERT occupancy. JNJ-42253432 reduced electroencephalography spectral power in the α-1 band in a dose-dependent manner; the compound also attenuated amphetamine-induced hyperactivity. JNJ-42253432 significantly increased both overall social interaction and social preference, an effect that was independent of stress induced by foot-shock. Surprisingly, there was no effect of the compound on either neuropathic pain or inflammatory pain behaviors. In summary, in this study, we characterize JNJ-42253432 as a novel brain-penetrant P2X7 antagonist with high affinity and selectivity for the P2X7 channel.
Direct and indirect connections with upper limb motoneurons from the primate reticulospinal tract.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

Although the reticulospinal tract is a major descending motor pathway in mammals, its contribution to upper limb control in primates has received relatively little attention. Reticulospinal connections are widely assumed to be responsible for coordinated gross movements primarily of proximal muscles, whereas the corticospinal tract mediates fine movements, particularly of the hand. In this study, we used intracellular recording in anesthetized monkeys to examine the synaptic connections between the reticulospinal tract and antidromically identified cervical ventral horn motoneurons, focusing in particular on motoneurons projecting distally to wrist and digit muscles. We found that motoneurons receive monosynaptic and disynaptic reticulospinal inputs, including monosynaptic excitatory connections to motoneurons that innervate intrinsic hand muscles, a connection not previously known to exist. We show that excitatory reticulomotoneuronal connections are as common and as strong in hand motoneuron groups as in forearm or upper arm motoneurons. These data suggest that the primate reticulospinal system may form a parallel pathway to distal muscles, alongside the corticospinal tract. Reticulospinal neurons are therefore in a position to influence upper limb muscle activity after damage to the corticospinal system as may occur in stroke or spinal cord injury, and may be a target site for therapeutic interventions.
Eddy-current compensated diffusion weighting with a single refocusing RF pulse.
Magnetic resonance in medicine, 2009

A modification of the Stejskal-Tanner diffusion-weighting preparation with a single refocusing RF pulse is presented which involves three gradient lobes that can be adjusted to null eddy currents with any given decay rate to reduce geometric distortions in diffusion-weighted echo-planar imaging (EPI). It has a very similar compensation performance as the commonly used double-spin-echo preparation but (i) is less sensitive to flip angle imperfections, e.g. along the slice profile, and B(1) inhomogeneities and (ii) can yield shorter echo times for moderate b values, notably for longer echo trains as required for higher spatial resolution. It therefore can provide an increased signal-to-noise ratio as is simulated numerically and demonstrated experimentally in water phantoms and the human brain for standard EPI (2.0 x 2.0 mm(2)) and high-resolution EPI of inner field-of-views using 2D-selective RF excitations (0.5 x 1.0 mm(2)). Thus, the presented preparation may help to overcome current limitations of diffusion-weighted EPI, in particular at high static magnetic fields.
Identification of hippocampus-dependent and hippocampus independent memory components in step-down inhibitory avoidance tasks.
Behavioural brain research, 2010

The aim of this study was to determine if the memory of the association between a step-down response and a foot-shock can be dissociated from the memory of the context in which the shocking experience occurred. To test this, two versions of the step-down inhibitory avoidance task were used: a standard version, in which animals were given one trial with a weak exposure to the context and a new version, in which animals were given a stronger exposure to the context. A retention test was performed with the platform placed either in the same conditioning chamber as during the acquisition phase or in a new context. Our results demonstrate that the step-down inhibitory avoidance can actually be solved without a functional hippocampus. Specifically, the results show that hippocampus-lesioned mice and sham controls can express similar level of memory performance but use two different strategies which were distinguished by assessing retention in a new context. Hippocampus-lesioned mice and mice injected with forskolin (adenylyl cyclase activator) 3h after acquisition use a memory strategy which is independent of the context of acquisition. In addition, our results confirm that the cAMP signaling pathway is a key step in memory consolidation processing.
Glutamatergic hypofunction in medication-free major depression: Secondary effects of affective diagnosis and relationship to peripheral glutaminase.
Journal of affective disorders, 2018

There is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations.
Attentional Fluctuations, Cognitive Flexibility, and Bilingualism in Kindergarteners.
Behavioral sciences (Basel, Switzerland), 2019

The idea of a bilingual advantage in aspects of cognitive control-including cognitive flexibility, inhibition, working memory, and attention-is disputed. Using a sample of kindergarten children, the present study investigated associations between bilingualism and cognitive flexibility-a relationship that has shown mixed findings in prior literature. We also extend prior work by exploring relationships between bilingualism and attentional fluctuations, which represent consistency in attentional control and contribute to cognitive performance. To our knowledge, no previous study has explored this association. Theoretically, attentional fluctuations might mediate or moderate the relationship between bilingualism and cognitive flexibility. However, given evidence of null findings from extant literature when confounding variables are adequately controlled and tasks are standardized, we did not expect to find a bilingual advantage in either cognitive flexibility or attentional fluctuations. Our results supported this hypothesis when considering bilingualism both continuously and categorically. The importance of expanding upon mechanistic accounts connecting bilingualism to cognitive improvements is discussed.
Hippocampal and prefrontal contributions to memory retrieval: Examination of immediate early gene, NMDA receptor and environmental interactions.
The European journal of neuroscience, 2020

Animals can use a range of strategies to recall important locations. These include simple stimulus-response strategies and more complex spatial (place) strategies, which are thought to have distinct neural substrates. The hippocampus-and NMDA receptor activation therein-is considered to be crucial for spatial, but not response strategies. The medial prefrontal cortex has also been implicated in memory retrieval; however, evidence concerning its specific role is equivocal. Both hippocampal and prefrontal regions have been associated with flexible behavioural responding (e.g. when task demands change). Here, we investigated the use of spatial and non-spatial strategies in the Morris water maze and their associated brain areas in rats using immediate early gene (IEG) imaging of Zif268 and c-Fos. Specifically, we charted the involvement of hippocampal and prefrontal subregions during retrieval of spatial and non-spatial memories. Behavioural flexibility was also examined using intact and partial cue configurations during recall. Results indicated that regions of both the hippocampus (area CA3) and prefrontal cortex (anterior cingulate cortex) were preferentially engaged in spatial memory recall compared to response learning. In addition, both spatial and non-spatial memories were dependent on NMDA receptor activation. MK801 impaired recall performance across all groups and reduced IEG activation across hippocampal and prefrontal regions. Finally, IEG results revealed divergent patterns of Zif268 and c-Fos activity and support the suggestion that Zif268 plays a functional role in the recall of long-term memories.
Roadmap for a competency-based educational curriculum in epileptology: report of the Epilepsy Education Task Force of the International League Against Epilepsy.
Epileptic disorders : international epilepsy journal with videotape, 2019

Teaching competency in the diagnosis and clinical management of epilepsy is of utmost importance for the ILAE. To achieve this mission, the Task Force for Epilepsy Education (EpiEd) developed a competency-based curriculum for epileptology, covering the spectrum of skills and knowledge for best medical practice. The curriculum encompasses seven domains, 42 competencies, and 124 learning objectives, divided into three levels: entry (Level 1), proficiency (Level 2), and advanced proficiency (Level 3). A survey of the currently existing ILAE-endorsed teaching activities identified a significant gap in education of basic knowledge of epileptology (Level 1). To bridge this gap, a web-based educational tool is being developed. A virtual campus will be constructed around the curriculum, integrating the various educational activities of the ILAE. This paper describes the development of the curriculum and future tasks necessary to achieve the educational goal of the ILAE.
Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.
Cell, 2013

Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER. We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice. Cloning of a short-period circadian mutant, Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation. While loss of function of FBXL3 leads to period lengthening, mutation of Fbxl21 causes period shortening. FBXL21 forms an SCF E3 ligase complex that slowly degrades CRY in the cytoplasm but antagonizes the stronger E3 ligase activity of FBXL3 in the nucleus. FBXL21 plays a dual role: protecting CRY from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm. Thus, the balance and cellular compartmentalization of competing E3 ligases for CRY determine circadian period of the clock in mammals.