This paper presents a neurocomputational model using the ACT‐R cognitive architecture that simulates intrusive memory retrieval following a potentially traumatic event and predicts hippocampal volume changes observed in Post‐Traumatic Stress Disorder.

Elucidating distinct morphological atrophy patterns of Alzheimer’s disease and its prodromal stage, namely, mild cognitive impairment helps to improve early diagnosis and medical intervention of AD. On that account, we aimed to obtain distinct patterns of voxel-wise morphological atrophy and its further perturbation on structural covariance network in AD and MCI compared with healthy controls. T1-weighted anatomical images of matched AD, MCI, and HCs were included in this study. Gray matter volume was obtained using voxel-based morphometry and compared among (...) three groups. In addition, structural covariance network of identified brain regions exhibiting morphological difference was constructed and compared between pairs of three groups. Thus, patients with AD have a reduced hippocampal volume and an increased rate of atrophy compared with MCI and HCs. MCI exhibited a decreased trend in bilateral hippocampal volume compared with HCs and the accelerated right hippocampal atrophy rate than HCs. In AD, the hippocampus further exhibited increased structural covariance connected to reward related brain regions, including the anterior cingulate cortex, the putamen, the caudate, and the insula compared with HCs. In addition, the patients with AD exhibited increased structural covariance of left hippocampus with the bilateral insula, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum than MCI. These results reveal distinct patterns of morphological atrophy in AD and MCI, providing new insights into pathology of AD. (shrink)

The hippocampus is known to be comprised of several subfields, but the developmental trajectories of these subfields are under debate. In this study, we analyzed magnetic resonance imaging data from a cross-sectional sample using an automated segmentation tool to delineate the development of the hippocampal subregions from 6 to 26 years of age. We also examined whether gender and hemispheric differences influence the development of these subregions. For the whole hippocampus, the trajectory of development was observed to be an (...) inverse-u. A significant increase in volume with age was found for most of the subregions, except for the L/R-parasubiculum, L/R-fimbria, and L-HATA. Gender-related differences were also found in the development of most subregions, especially for the hippocampal tail, CA1, molecular layer HP, GC-DG, CA3, and CA4, which showed a consistent increase in females and an early increase followed by a decrease in males. A comparison of the average volumes showed that the right whole hippocampus was significantly larger, along with the R-presubiculum, R-hippocampal-fissure, L/R-CA1, and L/R-molecular layer HP in males in comparison to females. Additionally, the average volume of the right hemisphere was shown to be significantly larger for the hippocampal tail, CA1, molecular layer HP, GC-DG, CA3, and CA4. However, for the presubiculum, parasubiculum, and fimbria, the left side was shown to be larger. In conclusion, the hippocampal subregions appear to develop in various ways from childhood to adulthood, with both gender and hemispheric differences affecting their development. (shrink)

Psychiatric disorders share an excess of seasonal birth in winter and spring, suggesting an increase of neurodevelopmental risks. Evidence suggests season of birth can serve as a proxy of harmful environmental factors. Given that prenatal exposure of these factors may trigger pathologic processes in the neurodevelopment, they may consequently lead to brain volume alterations. Here we tested the effects of season of birth on gray matter volume in a transdiagnostic sample of patients with schizophrenia and depression compared to (...) healthy controls. We found a significant effect of season of birth on gray matter volume with reduced right hippocampal volume in summer-born compared to winter-born patients with depression. In addition, the volume of the right hippocampus was reduced independent from season of birth in schizophrenia. Our results support the potential impact of season of birth on hippocampal volume in depression. (shrink)

Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier function in schizophrenia pathogenesis. However, direct evidence demonstrating an impaired BBB function is missing. In this preliminary study, we used immunohistochemistry and serum immunoglobulin G antibodies to investigate the state of BBB function in formalin-fixed postmortem samples from the hippocampus and surrounding temporal cortex of patients with schizophrenia and (...) controls without schizophrenia matched for age, sex, and race. Since a functional BBB prevents the extravasation of IgGs, detection of IgGs in the parenchyma is used as direct evidence of BBB breakdown. We also developed a semi-quantitative approach to quantify the extent of IgG leak and therein BBB breach. Analysis of our immunohistochemistry data demonstrated a significantly higher incidence of IgG leak in patients with schizophrenia compared to controls. Further, BBB permeability was significantly higher in advanced-age patients with schizophrenia than both advanced-age controls and middle-aged patients with schizophrenia. Male patients with schizophrenia also demonstrated a significant increase in IgG permeability compared to control males. Interestingly, the extravasated IgGs also demonstrated selective immunoreactivity for neurons. Based on these observations, we suggest that BBB dysfunction and IgG autoantibodies could be two key missing pathoetiological links underwriting schizophrenia hippocampal damage. (shrink)

Brain‐derived neurotrophic factor (BDNF) is the most‐abundant neurotrophin in the brain. In mammals, it is synthesized as a precursor called proBDNF, which is proteolytically cleaved to generate mature BDNF. The BDNF gene is located on chromosome 11p13, and a functional single nucleotide polymorphism (SNP) of this gene has been shown to produce a valine (Val)‐to‐methionine (Met) substitution in the proBDNF protein at codon 66 (Val66Met). Several papers suggest that this SNP is related to decreased hippocampal volume and hippocampus‐mediated (...) memory performance in humans. Recently, Chen et al.1 generated a variant BDNF mouse (BDNFMet/Met) that reproduces the phenotypic hallmarks in humans with a variant Met allele. In the behavioral analysis, BDNFMet/Met mice show increased anxiety‐related behaviors. This mini‐review examines the impact of Met substitution of proBDNF on anxiety‐related behaviors. BioEssays 29: 116–119, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Ample research demonstrates that parents’ experience-based mental representations of attachment—cognitive models of close relationships—relate to their children’s social-emotional development. However, no research to date has examined how parents’ attachment representations relate to another crucial domain of children’s development: brain development. The present study is the first to integrate the separate literatures on attachment and developmental social cognitive neuroscience to examine the link between mothers’ attachment representations and 3- to 8-year-old children’s brain structure. We hypothesized that mothers’ attachment representations would relate (...) to individual differences in children’s brain structures involved in stress regulation—specifically, amygdala and hippocampal volumes—in part via mothers’ responses to children’s distress. We assessed 52 mothers’ attachment representations and children’s brain structure. Mothers’ secure base script knowledge was significantly related to children’s smaller left amygdala volume but was unrelated to hippocampal volume; we found no indirect links via maternal responses to children’s distress. Exploratory analyses showed associations between mothers’ attachment representations and white matter and thalamus volumes. Together, these preliminary results suggest that mothers’ attachment representations may be linked to the development of children’s neural circuitry related to stress regulation. (shrink)

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults from the DZNE-Longitudinal Cognitive Impairment and Dementia Study study. Participants reporting having played a musical instrument across three life periods were compared to controls without a history of musical instrument playing, well-matched for reserve proxies of education, (...) intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion. (shrink)

This study compared 30 older musicians and 30 age-matched non-musicians to investigate the association between lifelong musical instrument training and age-related cognitive decline and brain atrophy. Although previous research has demonstrated that young musicians have larger gray matter volume in the auditory-motor cortices and cerebellum than non-musicians, little is known about older musicians. Music imagery in young musicians is also known to share a neural underpinning [the supramarginal gyrus and cerebellum] with music performance. Thus, we hypothesized that older musicians (...) would show superiority to non-musicians in some of the abovementioned brain regions. Behavioral performance, GMV, and brain activity, including functional connectivity during melodic working memory tasks, were evaluated in both groups. Behaviorally, musicians exhibited a much higher tapping speed than non-musicians, and tapping speed was correlated with executive function in musicians. Structural analyses revealed larger GMVs in both sides of the cerebellum of musicians, and importantly, this was maintained until very old age. Task-related FC analyses revealed that musicians possessed greater cerebellar-hippocampal FC, which was correlated with tapping speed. Furthermore, musicians showed higher activation in the SMG during MWM tasks; this was correlated with earlier commencement of instrumental training. These results indicate advantages or heightened coupling in brain regions associated with music performance and imagery in musicians. We suggest that lifelong instrumental training highly predicts the structural maintenance of the cerebellum and related cognitive maintenance in old age. (shrink)

As we move around in our environment, and interact with it, many of the most important problems we face involve the processing of spatial information. We have to be able to navigate by perceiving and remembering the locations and orientations of the objects around us relative to ourself; we have to sense and act upon these objects; and we need to move through space to position ourselves in favourable locations or to avoid dangerous ones. While this appears so simple that (...) we don't even think about it, the difficulty of solving these problems has been shown in the repeated failure of artificial systems to perform these kinds of tasks efficiently. In contrast, humans and other animals routinely overcome these problems every single day. This book examines some of the neural substrates and mechanisms that support these remarkable abilities. The hippocampus and the parietal cortex have been implicated in various core spatial behaviours, such as the ability to localise an object and navigate to it. Damage to these areas in humans and animals leads to impairment of these spatial functions. This collection of papers, written by internationally recognized experts in the field, reviews the evidence that each area is involved in spatial cognition, examines the mechanisms underlying the generation of spatial behaviours, and considers the relative roles of the parietal and hippocampal areas, including how each interacts with the other. The papers integrate a wide range of theoretical and experimental approaches, and touch on broader issues relating to memory and imagery. As such, this book represents the state of the art of current research into the neural basis of spatial cognition. It should be of interest to anyone - researchers or graduate students - working in the areas of cognitive neuroscience, neuroanatomy, neuropsychology, and cognition generally. (shrink)

Goal-directed spatial decision making video games combine spatial mapping, memory, and reward; all of which can involve hippocampal excitation through suppression of an inhibitory neurotransmitter, γ-aminobutyric acid. In this study, GABA was measured before and after 30 min of video game play within a voxel around the hippocampus. It was predicted that all participants would experience a decrease in GABA during gaming as a result of in-game rewards; and, those who were most competitive with the goal-directed spatial decision making (...) game would display lower hippocampal GABA concentrations after gaming. Those who were not competitive, because they were too skilled or not skilled enough, would demonstrate higher hippocampal GABA concentrations after gaming. While there were no significant differences in hippocampal GABA before and after gaming for gamers and non-gamers alike, there was a significant quadratic regression between performance on a spatial working memory task and post-gaming hippocampal GABA concentrations. (shrink)

Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI). Methods: Human patients undergoing Phase II invasive monitoring for (...) intractable epilepsy were implanted with depth electrodes capable of recording neurophysiological signals. Subjects performed a delayed-match-to-sample (DMS) memory task while hippocampal ensembles from CA1 and CA3 cell layers were recorded to estimate a multi-input, multi-output (MIMO) model of CA3-to-CA1 neural encoding and a memory decoding model (MDM) to decode memory information from CA3 and CA1 neuronal signals. After model estimation, subjects again performed the DMS task while either MIMO-based or MDM-based patterned stimulation was delivered to CA1 electrode sites during the encoding phase of the DMS trials. Each subject was sorted (post hoc) by prior experience of repeated and/or mild-to-moderate brain injury (RMBI), TBI, or no history (control) and scored for percentage successful delayed recognition (DR) recall on stimulated vs. non-stimulated DMS trials. The subject’s medical history was unknown to the experimenters until after individual subject memory retention results were scored. Results: When examined compared to control subjects, both TBI and RMBI subjects showed increased memory retention in response to both MIMO and MDM-based hippocampal stimulation. Furthermore, effects of stimulation were also greater in subjects who were evaluated as having pre-existing mild-to-moderate memory impairment. Conclusion: These results show that hippocampal stimulation for memory facilitation was more beneficial for subjects who had previously suffered a brain injury (other than epilepsy), compared to control (epilepsy) subjects who had not suffered a brain injury. This study demonstrates that the epilepsy/intracranial recording model can be extended to test the ability of DBS to restore memory function in subjects who previously suffered a brain injury other than epilepsy, and support further investigation into the beneficial effect of DBS in TBI patients. (shrink)