Relationship between visuospatial neglect and kinesthetic deficits after stroke.

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Semrau, Jennifer A; Wang, Jeffery C; Herter, Troy M; Scott, Stephen H; Dukelow, Sean P

2015-05-01

After stroke, visuospatial and kinesthetic (sense of limb motion) deficits are common, occurring in approximately 30% and 60% of individuals, respectively. Although both types of deficits affect aspects of spatial processing necessary for daily function, few studies have investigated the relationship between these 2 deficits after stroke. We aimed to characterize the relationship between visuospatial and kinesthetic deficits after stroke using the Behavioral Inattention Test (BIT) and a robotic measure of kinesthetic function. Visuospatial attention (using the BIT) and kinesthesia (using robotics) were measured in 158 individuals an average of 18 days after stroke. In the kinesthetic matching task, the robot moved the participant's stroke-affected arm at a preset direction, speed, and magnitude. Participants mirror-matched the robotic movement with the less/unaffected arm as soon as they felt movement in their stroke affected arm. We found that participants with visuospatial inattention (neglect) had impaired kinesthesia 100% of the time, whereas only 59% of participants without neglect were impaired. For those without neglect, we observed that a higher percentage of participants with lower but passing BIT scores displayed impaired kinesthetic behavior (78%) compared with those participants who scored perfect or nearly perfect on the BIT (49%). The presence of visuospatial neglect after stroke is highly predictive of the presence of kinesthetic deficits. However, the presence of kinesthetic deficits does not necessarily always indicate the presence of visuospatial neglect. Our findings highlight the importance of assessment and treatment of kinesthetic deficits after stroke, especially in patients with visuospatial neglect. © The Author(s) 2014.

Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

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Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

2006-10-01

Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study

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Tsai, Ping-Fang; Yang, Chi-Cheng; Chuang, Chi-Cheng; Huang, Ting-Yi; Wu, Yi-Ming; Pai, Ping-Ching; Tseng, Chen-Kan; Wu, Tung-Ho; Shen, Yi-Liang; Lin, Shinn-Yn

2015-01-01

Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT). Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD 2 ) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study. Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD 2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that

Visuospatial memory in patients with obsessive-compulsive disorder

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Anamika Sahu

2017-01-01

Full Text Available Background: Obsessive-compulsive disorder (OCD is a clinically heterogeneous disorder. The previous studies have been conducted to elucidate visuospatial and nonverbal memory deficits in OCD patients. However, they did not reach equivocal results which need to be replicated. Objectives: The current study examines the visuospatial memory in male patients with OCD as compared to normal healthy controls. Materials and Methods: It is a cross-sectional hospital-based study, in which 15 OCD patients and 15 age-, sex-, and education-matched normal healthy controls were chosen by purposive sampling technique. All the participants underwent the Extended Complex Figure Test (ECFT for the assessment of visuospatial memory. Results: Significant difference was found between OCD patients and normal healthy controls on various domains of ECFT. OCD patients performed poorly on copy condition (t = −4.46; P< 0.001, immediate recall (t = −5.20; P< 0.001, delayed recall (t = −5.18; P< 0.001, recognition task (P < 0.001, and matching task (P < 0.001 than the controls. Conclusion: Visuospatial memory was significantly impaired in OCD that included disturbed encoding and impaired visuospatial functioning. Hence, it is important to understand the significance of visuospatial memory in the pathophysiology for OCD diagnosis and therapeutic decision.

Hippocampal volumes are important predictors for memory function in elderly women

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Adolfsdottir Steinunn

2009-08-01

Full Text Available Abstract Background Normal aging involves a decline in cognitive function that has been shown to correlate with volumetric change in the hippocampus, and with genetic variability in the APOE-gene. In the present study we utilize 3D MR imaging, genetic analysis and assessment of verbal memory function to investigate relationships between these factors in a sample of 170 healthy volunteers (age range 46–77 years. Methods Brain morphometric analysis was performed with the automated segmentation work-flow implemented in FreeSurfer. Genetic analysis of the APOE genotype was determined with polymerase chain reaction (PCR on DNA from whole-blood. All individuals were subjected to extensive neuropsychological testing, including the California Verbal Learning Test-II (CVLT. To obtain robust and easily interpretable relationships between explanatory variables and verbal memory function we applied the recent method of conditional inference trees in addition to scatterplot matrices and simple pairwise linear least-squares regression analysis. Results APOE genotype had no significant impact on the CVLT results (scores on long delay free recall, CVLT-LD or the ICV-normalized hippocampal volumes. Hippocampal volumes were found to decrease with age and a right-larger-than-left hippocampal asymmetry was also found. These findings are in accordance with previous studies. CVLT-LD score was shown to correlate with hippocampal volume. Multivariate conditional inference analysis showed that gender and left hippocampal volume largely dominated predictive values for CVLT-LD scores in our sample. Left hippocampal volume dominated predictive values for females but not for males. APOE genotype did not alter the model significantly, and age was only partly influencing the results. Conclusion Gender and left hippocampal volumes are main predictors for verbal memory function in normal aging. APOE genotype did not affect the results in any part of our analysis.

Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

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Caitlin M. Vander Weele

2013-06-01

Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

Unpacking the cognitive map: the parallel map theory of hippocampal function.

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Jacobs, Lucia F; Schenk, Françoise

2003-04-01

In the parallel map theory, the hippocampus encodes space with 2 mapping systems. The bearing map is constructed primarily in the dentate gyrus from directional cues such as stimulus gradients. The sketch map is constructed within the hippocampus proper from positional cues. The integrated map emerges when data from the bearing and sketch maps are combined. Because the component maps work in parallel, the impairment of one can reveal residual learning by the other. Such parallel function may explain paradoxes of spatial learning, such as learning after partial hippocampal lesions, taxonomic and sex differences in spatial learning, and the function of hippocampal neurogenesis. By integrating evidence from physiology to phylogeny, the parallel map theory offers a unified explanation for hippocampal function.

Relation between hippocampal damage and cerebral cortical function in Alzheimer's disease

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Hanyu, Haruo; Asano, Tetsuichi; Kogure, Daiji; Sakurai, Hirofumi; Iwamoto, Toshihiko; Takasaki, Masaru

2000-01-01

We investigated the relation between hippocampal damage and cerebral cortical dysfunction in Alzheimer's disease (AD) using MRI and SPECT. Nineteen patients with AD and 10 control subjects were studied. Hippocampal damage (including hippocampal formation, entorhinal cortex, and parahippocampal white matter) was assessed to evaluate the severity of atrophy and the magnetization transfer ratio (MTR) and cerebral cortical dysfunction was evaluated by quantitative cerebral blood flow (CBF) measurements using SPECT with 99mTc-ECD. Compared with controls, patients with AD had significantly more atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus and parahippocampus. There were significant correlations between the severity of hippocampal damage and regional CBF in temporoparietal lobes. Mini-Mental State Examination scores significantly correlated with the severity of hippocampal damage and regional CBFs in temporoparietal lobes. These results suggest that the functional effect of hippocampal damage occurs in temporoparietal lobes in AD, probably due to neuronal disconnections between hippocampal areas (including the entorhinal cortex) and temporoparietal lobes. (author)

Visuospatial Functioning in Cerebral Amyloid Angiopathy : A Pilot Study

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Valenti, Raffaella; Charidimou, Andreas; Xiong, Li; Boulouis, Gregoire; Fotiadis, Panagiotis; Ayres, Alison; Riley, Grace; Kuijf, Hugo J.; Reijmer, Yael D.; Pantoni, Leonardo; Gurol, M. Edip; Davidsdottir, Sigurros; Greenberg, Steven M.; Viswanathan, Anand

2017-01-01

Cerebral amyloid angiopathy (CAA) is a contributor to cognitive impairment in the elderly. We hypothesized that the posterior cortical predilection of CAA would cause visual-processing impairment. We systematically evaluated visuospatial abilities in 22 non-demented CAA patients. Neurocognitive

The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource.

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Rönnberg, Jerker; Hygge, Staffan; Keidser, Gitte; Rudner, Mary

2014-01-01

The UK Biobank offers cross-sectional epidemiological data collected on >500,000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138,098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three groups: poor, insufficient and normal hearers. We found negative relationships between functional hearing loss and both visuospatial working memory (i.e., a card pair matching task) and visuospatial, episodic long-term memory (i.e., a prospective memory task), with the strongest association for episodic long-term memory. The use of hearing aids showed a small positive effect for working memory performance for the poor hearers, but did not have any influence on episodic long-term memory. Age also showed strong main effects for both memory tasks and interacted with gender and education for the long-term memory task. Broader theoretical implications based on a memory systems approach will be discussed and compared to theoretical alternatives.

The Effect of Functional Hearing Loss and Age on Long- and Short-term Visuospatial Memory: Evidence from the UK Biobank Resource

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Jerker eRönnberg

2014-12-01

Full Text Available The UK Biobank offers cross-sectional epidemiological data collected on > 500 000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138 098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three groups: poor, insufficient and normal hearers. We found negative relationships between functional hearing loss and both visuospatial working memory (i.e., a card pair matching task and visuospatial, episodic long-term memory (i.e., a prospective memory task, with the strongest association for episodic long-term memory. The use of hearing aids showed a small positive effect for working memory performance for the poor hearers, but did not have any influence on episodic long-term memory. Age also showed strong main effects for both memory tasks and interacted with gender and education for the long-term memory task. Broader theoretical implications based on a memory systems approach will be discussed and compared to theoretical alternatives.

Anticlockwise or Clockwise? A Dynamic Perception-Action-Laterality Model for Directionality Bias in Visuospatial Functioning

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Karim, A.K.M. Rezaul; Proulx, Michael J.; Likova, Lora T.

2016-01-01

Reviewing the relevant literature in visual psychophysics and visual neuroscience we propose a three-stage model of directionality bias in visuospatial functioning. We call this model the ‘Perception-Action-Laterality’ (PAL) hypothesis. We analyzed the research findings for a wide range of visuospatial tasks, showing that there are two major directionality trends: clockwise versus anticlockwise. It appears these preferences are combinatorial, such that a majority of people fall in the first category demonstrating a preference for stimuli/objects arranged from left-to-right rather than from right-to-left, while people in the second category show an opposite trend. These perceptual biases can guide sensorimotor integration and action, creating two corresponding turner groups in the population. In support of PAL, we propose another model explaining the origins of the biases– how the neurogenetic factors and the cultural factors interact in a biased competition framework to determine the direction and extent of biases. This dynamic model can explain not only the two major categories of biases, but also the unbiased, unreliably biased or mildly biased cases in visuosptial functioning. PMID:27350096

Midlife managerial experience is linked to late life hippocampal morphology and function.

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Suo, C; Gates, N; Fiatarone Singh, M; Saigal, N; Wilson, G C; Meiklejohn, J; Sachdev, P; Brodaty, H; Wen, W; Singh, N; Baune, B T; Baker, M; Foroughi, N; Wang, Y; Valenzuela, Michael J

2017-04-01

An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

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Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

2017-09-01

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

Comparison of fMRI paradigms assessing visuospatial processing: Robustness and reproducibility.

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Verena Schuster

Full Text Available The development of brain imaging techniques, in particular functional magnetic resonance imaging (fMRI, made it possible to non-invasively study the hemispheric lateralization of cognitive brain functions in large cohorts. Comprehensive models of hemispheric lateralization are, however, still missing and should not only account for the hemispheric specialization of individual brain functions, but also for the interactions among different lateralized cognitive processes (e.g., language and visuospatial processing. This calls for robust and reliable paradigms to study hemispheric lateralization for various cognitive functions. While numerous reliable imaging paradigms have been developed for language, which represents the most prominent left-lateralized brain function, the reliability of imaging paradigms investigating typically right-lateralized brain functions, such as visuospatial processing, has received comparatively less attention. In the present study, we aimed to establish an fMRI paradigm that robustly and reliably identifies right-hemispheric activation evoked by visuospatial processing in individual subjects. In a first study, we therefore compared three frequently used paradigms for assessing visuospatial processing and evaluated their utility to robustly detect right-lateralized brain activity on a single-subject level. In a second study, we then assessed the test-retest reliability of the so-called Landmark task-the paradigm that yielded the most robust results in study 1. At the single-voxel level, we found poor reliability of the brain activation underlying visuospatial attention. This suggests that poor signal-to-noise ratios can become a limiting factor for test-retest reliability. This represents a common detriment of fMRI paradigms investigating visuospatial attention in general and therefore highlights the need for careful considerations of both the possibilities and limitations of the respective fMRI paradigm-in particular

Associations Between the Self-Reported Frequency of Hearing Chemical Alarms in Theater and Visuospatial Function in Gulf War Veterans.

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Chao, Linda L

2016-10-01

The aim of this study was to examine the relationship between the self-reported frequencies of hearing chemical alarms during deployment and visuospatial function in Gulf War (GW) veterans. The relationship between the self-reported frequency of hearing chemical alarms, neurobehavioral, and volumetric brain imaging data was examined with correlational, regression, and mediation analyses. The self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on a visuospatial task (ie, Block Design) over and above potentially confounding variables, including concurrent, correlated GW-related exposures. This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume. Exposure to substances that triggered chemical alarms during GW deployment likely had adverse effects on veterans' brain structure and function, warranting further investigation of whether these GW veterans are at an increased risk for dementia.

Hippocampal sleep features: relations to human memory function

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Michele eFerrara

2012-04-01

Full Text Available The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific pattern of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, NREM sleep in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep

Hippocampal Sleep Features: Relations to Human Memory Function

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Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

2012-01-01

The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate

The Neuroanatomical Basis for Posterior Superior Parietal Lobule Control Lateralization of visuospatial Attention

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Yan eWu

2016-03-01

Full Text Available The right hemispheric dominance in visuospatial attention in human brain has been well established. Converging evidence has documented that ventral posterior parietal cortex (PPC plays an important role in visuospatial attention. The role of dorsal PPC subregions, especially the superior parietal lobule (SPL in visuospatial attention is still controversial. In the current study, we used repetitive transcranial magnetic stimulation (rTMS and diffusion magnetic resonance imaging (MRI techniques to test the role of posterior SPL in visuospatial attention and to investigate the potential neuroanatomical basis for right hemisphere dominance in visuospatial function. TMS results unraveled that the right SPL predominantly mediated visuospatial attention compared to left SPL. Anatomical connections analyses between the posterior SPL and the intrahemispheric frontal subregions and the contralateral PPC revealed that right posterior SPL has stronger anatomical connections with the ipsilateral middle frontal gyrus, with the ipsilateral inferior frontal gyrus, and with contralateral PPC than that of the left posterior SPL. Furthermore, these asymmetric anatomical connections were closely related to behavioral performances. Our findings indicate that SPL plays a crucial role in regulating visuospatial attention, and dominance of visuospatial attention results from unbalanced interactions between the bilateral fronto-parietal networks and the interhemispheric parietal network.

Set shifting and visuospatial organization deficits in body dysmorphic disorder.

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Greenberg, Jennifer L; Weingarden, Hilary; Reuman, Lillian; Abrams, Dylan; Mothi, Suraj S; Wilhelm, Sabine

2017-11-24

Individuals with body dysmorphic disorder (BDD) over-attend to perceived defect(s) in their physical appearance, often becoming "stuck" obsessing about perceived flaws and engaging in rituals to hide flaws. These symptoms suggest that individuals with BDD may experience deficits in underlying neurocognitive functions, such as set-shifting and visuospatial organization. These deficits have been implicated as risk and maintenance factors in disorders with similarities to BDD but have been minimally investigated in BDD. The present study examined differences in neurocognitive functions among BDD participants (n = 20) compared to healthy controls (HCs; n = 20). Participants completed neuropsychological assessments measuring set-shifting (Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set Shift [IED] task) and visuospatial organization and memory (Rey-Osterrieth Complex Figure Test [ROCF]). Results revealed a set-shifting deficit among BDD participants compared to HCs on the IED. On the ROCF, BDD participants exhibited deficits in visuospatial organization compared to HCs, but they did not differ in visuospatial memory compared to HCs. Results did not change when accounting for depression severity. Findings highlight neurocognitive deficits as potential endophenotype markers of clinical features (i.e., delusionality). Understanding neuropsychological deficits may clarify similarities and differences between BDD and related disorders and may guide targets for BDD treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The pharmacology of visuospatial attention and inhibition

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Logemann, H.N.A.

2013-01-01

Attention and inhibition are of vital importance in everyday functioning. Problems of attention and inhibition are central to disorders such as Attention Deficit/Hyperactivity Disorder (ADHD). Both bias and disengagement key components of visuospatial attention. Bias refers to neuronal signals that

Memory function and hippocampal volumes in preterm born very-low-birth-weight (VLBW) young adults.

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Aanes, Synne; Bjuland, Knut Jørgen; Skranes, Jon; Løhaugen, Gro C C

2015-01-15

The hippocampi are regarded as core structures for learning and memory functions, which is important for daily functioning and educational achievements. Previous studies have linked reduction in hippocampal volume to working memory problems in very low birth weight (VLBW; ≤ 1500 g) children and reduced general cognitive ability in VLBW adolescents. However, the relationship between memory function and hippocampal volume has not been described in VLBW subjects reaching adulthood. The aim of the study was to investigate memory function and hippocampal volume in VLBW young adults, both in relation to perinatal risk factors and compared to term born controls, and to look for structure-function relationships. Using Wechsler Memory Scale-III and MRI, we included 42 non-disabled VLBW and 61 control individuals at age 19-20 years, and related our findings to perinatal risk factors in the VLBW-group. The VLBW young adults achieved lower scores on several subtests of the Wechsler Memory Scale-III, resulting in lower results in the immediate memory indices (visual and auditory), the working memory index, and in the visual delayed and general memory delayed indices, but not in the auditory delayed and auditory recognition delayed indices. The VLBW group had smaller absolute and relative hippocampal volumes than the controls. In the VLBW group inferior memory function, especially for the working memory index, was related to smaller hippocampal volume, and both correlated with lower birth weight and more days in the neonatal intensive care unit (NICU). Our results may indicate a structural-functional relationship in the VLBW group due to aberrant hippocampal development and functioning after preterm birth. Copyright © 2014 Elsevier Inc. All rights reserved.

Visuospatial perception in children born preterm with no major neurological disorders.

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Butcher, Phillipa R; Bouma, Anke; Stremmelaar, Elisabeth F; Bos, Arend F; Smithson, Michael; Van Braeckel, Koenraad N J A

2012-11-01

Many investigations have found deficits in visuospatial perception in children born preterm, however, it is not clear whether the deficits are specific to visuospatial perception or the consequences of deficits in other functional areas, which often accompany preterm birth. This study investigated whether children born preterm show a specific deficit in visuospatial perception. Fifty-six 7- to 11-year-old preterm born children (gestational age children completed four computerized tasks tapping different levels and types of visuospatial perception. Accuracy and speed of responses were recorded. Task formats were designed to reduce demands on attentional deployment. Measures of intelligence and parental education were included in the analysis. Children born preterm performed less accurately and/or less rapidly on all tasks. Their poorer performance did not reflect differences in speed-accuracy trade-off. Parental education and IQ, both significantly lower in the preterm children, contributed positively to performance on all tasks. IQ mediated the association between preterm birth and visuospatial performance on the most cognitively demanding task. Children born preterm performed more poorly than full-term controls on four visuospatial perceptual tasks. Although intelligence and parental education were also associated with performance, preterm birth contributed independently of these factors on three of four tasks. Many children born preterm are thus multiply disadvantaged on visuospatial tasks: the lower IQ scores and parental educational levels frequently found in this group increase the deficit associated with preterm birth. (c) 2012 APA, all rights reserved.

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis.

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Jin, Seung-Hyun; Chung, Chun Kee

2015-10-01

Little is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance. Resting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE=22; right mTLE=19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS. Connectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE. Our results suggest that right hippocampal-left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between

Visuo-spatial construction in patients with frontal and parietal lobe lesions

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Himani Kashyap

2011-04-01

Full Text Available Visuospatial construction, traditionally viewed as a putative parietal function, also requires sustained attention, planning, organization strategies and error correction, and hence frontal lobe mediation. The relative contributions of the frontal and parietal lobes are poorly understood. To examine the contributions of parietal, frontal lobes, as well as right and left cerebral hemispheres to visuospatial construction. The Stick Construction Test for two-dimensional construction and the Block Construction Test for three-dimensional construction were administered pre-surgically to patients with lesions in the parietal lobe (n =9 and the frontal lobe (n=11, along with normal control subjects (n =20 matched to the patients on age (+/- 3 years, gender, education (+/- 3 years and handedness. The patients were significantly slower than the controls on both two-dimensional and three-dimensional tests. Patients with parietal lesions were slower than those with frontal lesions on the test of three-dimensional construction. Within each lobe patients with right and left sided lesions did not differ significantly. It appears that tests of three-dimensional construction might be most sensitive to visuospatial construction deficits. Visuospatial construction involves the mediation of both frontal and parietal lobes. The function does not appear to be lateralized. The networks arising from the parieto-occipital areas and projecting to the frontal cortices (e.g., occipito-frontal fasciculus may be the basis of the mediation of both lobes in visuospatial construction. The present findings need replication from studies with larger sample sizes.

Hippocampal declarative memory supports gesture production: Evidence from amnesia.

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Hilverman, Caitlin; Cook, Susan Wagner; Duff, Melissa C

2016-12-01

Spontaneous co-speech hand gestures provide a visuospatial representation of what is being communicated in spoken language. Although it is clear that gestures emerge from representations in memory for what is being communicated (De Ruiter, 1998; Wesp, Hesse, Keutmann, & Wheaton, 2001), the mechanism supporting the relationship between gesture and memory is unknown. Current theories of gesture production posit that action - supported by motor areas of the brain - is key in determining whether gestures are produced. We propose that when and how gestures are produced is determined in part by hippocampally-mediated declarative memory. We examined the speech and gesture of healthy older adults and of memory-impaired patients with hippocampal amnesia during four discourse tasks that required accessing episodes and information from the remote past. Consistent with previous reports of impoverished spoken language in patients with hippocampal amnesia, we predicted that these patients, who have difficulty generating multifaceted declarative memory representations, may in turn have impoverished gesture production. We found that patients gestured less overall relative to healthy comparison participants, and that this was particularly evident in tasks that may rely more heavily on declarative memory. Thus, gestures do not just emerge from the motor representation activated for speaking, but are also sensitive to the representation available in hippocampal declarative memory, suggesting a direct link between memory and gesture production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spatial memory and hippocampal function: Where are we now?

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Mark Good

2002-01-01

Full Text Available The main aim of this paper is to provide an overview of current debates concerning the role of the mammalian hippocampus in learning with a particular emphasis on spatial learning. The review discusses recent debates on (1 the role of the primate hippocampus in recognition memory and object-in-place memory, (2 the role of the hippocampus in spatial navigation in both rats and humans, and (3 the effects of hippocampal damage on processing contextual information. Evidence from these lines of research have led many current theories to posit a function for the hippocampus that has as its organizing principle the association or binding of stimulus representations. Based on this principle, recent theories of hippocampal function have extended their application beyond the spatial domain to capture features of declarative and episodic memory processes.

Domain general sequence operations contribute to pre-SMA involvement in visuo-spatial processing

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E. Charles eLeek

2016-01-01

Full Text Available This study used 3T MRI to elucidate the functional role of supplementary motor area (SMA in relation to visuo-spatial processing. A localizer task contrasting sequential number subtraction and repetitive button pressing was used to functionally delineate non-motor sequence processing in pre-SMA, and activity in SMA-proper associated with motor sequencing. Patterns of BOLD responses in these regions were then contrasted to those from two tasks of visuo-spatial processing. In one task participants performed mental rotation in which recognition memory judgments were made to previously memorized 2D novel patterns across image-plane rotations. The other task involved abstract grid navigation in which observers computed a series of imagined location shifts in response to directional (arrow cues around a mental grid. The results showed overlapping activation in pre-SMA for sequential subtraction and both visuo-spatial tasks. These results suggest that visuo-spatial processing is supported by non-motor sequence operations that involve pre-SMA. More broadly, these data further highlight the functional heterogeneity of pre-SMA, and show that its role extends to processes beyond the planning and online control of movement.

Oscillations during observations: Dynamic oscillatory networks serving visuospatial attention.

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Wiesman, Alex I; Heinrichs-Graham, Elizabeth; Proskovec, Amy L; McDermott, Timothy J; Wilson, Tony W

2017-10-01

The dynamic allocation of neural resources to discrete features within a visual scene enables us to react quickly and accurately to salient environmental circumstances. A network of bilateral cortical regions is known to subserve such visuospatial attention functions; however the oscillatory and functional connectivity dynamics of information coding within this network are not fully understood. Particularly, the coding of information within prototypical attention-network hubs and the subsecond functional connections formed between these hubs have not been adequately characterized. Herein, we use the precise temporal resolution of magnetoencephalography (MEG) to define spectrally specific functional nodes and connections that underlie the deployment of attention in visual space. Twenty-three healthy young adults completed a visuospatial discrimination task designed to elicit multispectral activity in visual cortex during MEG, and the resulting data were preprocessed and reconstructed in the time-frequency domain. Oscillatory responses were projected to the cortical surface using a beamformer, and time series were extracted from peak voxels to examine their temporal evolution. Dynamic functional connectivity was then computed between nodes within each frequency band of interest. We find that visual attention network nodes are defined functionally by oscillatory frequency, that the allocation of attention to the visual space dynamically modulates functional connectivity between these regions on a millisecond timescale, and that these modulations significantly correlate with performance on a spatial discrimination task. We conclude that functional hubs underlying visuospatial attention are segregated not only anatomically but also by oscillatory frequency, and importantly that these oscillatory signatures promote dynamic communication between these hubs. Hum Brain Mapp 38:5128-5140, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

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Debora eCutuli

2014-08-01

Full Text Available As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations found in n-3 PUFA supplemented mice also pointed towards an effective neuroprotection.On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

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Castellano Gabriela

2010-06-01

Full Text Available Abstract Background Mesial temporal lobe epilepsy (MTLE, the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS. Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI. Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE. Results We detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group. Conclusions The findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.

A Compressed Sensing Perspective of Hippocampal Function

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Panagiotis ePetrantonakis

2014-08-01

Full Text Available Hippocampus is one of the most important information processing units in the brain. Input from the cortex passes through convergent axon pathways to the downstream hippocampal subregions and, after being appropriately processed, is fanned out back to the cortex. Here, we review evidence of the hypothesis that information flow and processing in the hippocampus complies with the principles of Compressed Sensing (CS. The CS theory comprises a mathematical framework that describes how and under which conditions, restricted sampling of information (data set can lead to condensed, yet concise, forms of the initial, subsampled information entity (i.e. of the original data set. In this work, hippocampus related regions and their respective circuitry are presented as a CS-based system whose different components collaborate to realize efficient memory encoding and decoding processes. This proposition introduces a unifying mathematical framework for hippocampal function and opens new avenues for exploring coding and decoding strategies in the brain.

Comparison of Visuospatial and Verbal Abilities in First Psychotic Episode of Schizophrenia Spectrum Disorder: Impact on Global Functioning and Quality of Life

Czech Academy of Sciences Publication Activity Database

Rodriquez, M.; Španiel, F.; Konrádová, L.; Sedláková, K.; Dvorská, K.; Prajsová, J.; Kratochvílová, Z.; Levčík, David; Vlček, Kamil; Fajnerová, Iveta

2015-01-01

Roč. 9, Dec 18 (2015), s. 322 ISSN 1662-5153 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : cognitive deficit * first psychotic episode * schizophrenia spectrum disorder * global functioning * quality of life * visuospatial functions * verbal functions * antipsychotic medication Subject RIV: FH - Neurology Impact factor: 3.392, year: 2015

Driving and visuospatial performance in people with hemianopia

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Tant, M.L.; Brouwer, W.H.; Cornelissen, F.W; Kooijman, A.C

2002-01-01

Practical fitness to drive was studied in 28 patients with homonymous hemianopia (HH). More specifically, visual performance during driving and neuropsychological visuospatial test performance were compared and related. Visuospatial tests were a priori classified in four visuospatial sets, and were

17β Estradiol increases resilience and improves hippocampal synaptic function in helpless ovariectomized rats

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Bredemann, Teruko M.; McMahon, Lori L.

2014-01-01

Summary Memory impairment is the most commonly reported cognitive symptom associated with major depressive disorder. Decreased hippocampal volume and neurogenesis in depression link hippocampal dysfunction with deficits in memory. Stress decreases hippocampal dendritic spine density and long-term potentiation (LTP) at glutamate synapses, a cellular correlate of learning and memory. However, elevated plasma levels of 17β estradiol (E2) during proestrus increase hippocampal structure and function, directly opposing the negative consequences of stress. In women, significant fluctuations in ovarian hormones likely increase vulnerability of hippocampal circuits to stress, potentially contributing to the greater incidence of depression compared to men. Using the learned helplessness model of depression and ovariectomized female rats, we investigated whether acquisition of helplessness and hippocampal synaptic dysfunction is differentially impacted by the presence or absence of plasma E2. We find that inescapable shock induces a greater incidence of helplessness in vehicle- versus E2-treated OVX rats. In the vehicle-treated group, LTP was absent at CA3-CA1 synapses in slices only from helpless rats, and CA1 spine density was decreased compared to resilient rats. In contrast, significant LTP was observed in slices from E2-treated helpless rats; importantly, spine density was not different between E2-treated helpless and resilient rats, dissociating spine density from the LTP magnitude. We also find that E2 replacement can reverse previously established helpless behavior. Thus, our results show that E2 replacement in OVX rats increases resilience and improves hippocampal plasticity, suggesting that E2 therapy may increase resilience to stress and preserve hippocampal function in women experiencing large fluctuations in plasma estrogen levels. PMID:24636504

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

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Vinet Jonathan

2012-01-01

Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

Sex differences in visuospatial abilities persist during induced hypogonadism.

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Guerrieri, Gioia M; Wakim, Paul G; Keenan, P A; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J; Rubinow, David R; Schmidt, Peter J

2016-01-29

Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Men (n=16) and women (n=15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 6-8 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus

Movement Interferes with Visuospatial Working Memory during the Encoding: An ERP Study

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Rumeysa Gunduz Can

2017-05-01

Full Text Available The present study focuses on the functional interactions of cognition and manual action control. Particularly, we investigated the neurophysiological correlates of the dual-task costs of a manual-motor task (requiring grasping an object, holding it, and subsequently placing it on a target for working memory (WM domains (verbal and visuospatial and processes (encoding and retrieval. Thirty participants were tested in a cognitive-motor dual-task paradigm, in which a single block (a verbal or visuospatial WM task was compared with a dual block (concurrent performance of a WM task and a motor task. Event-related potentials (ERPs were analyzed separately for the encoding and retrieval processes of verbal and visuospatial WM domains both in single and dual blocks. The behavioral analyses show that the motor task interfered with WM and decreased the memory performance. The performance decrease was larger for the visuospatial task compared with the verbal task, i.e., domain-specific memory costs were obtained. The ERP analyses show the domain-specific interference also at the neurophysiological level, which is further process-specific to encoding. That is, comparing the patterns of WM-related ERPs in the single block and dual block, we showed that visuospatial ERPs changed only for the encoding process when a motor task was performed at the same time. Generally, the present study provides evidence for domain- and process-specific interactions of a prepared manual-motor movement with WM (visuospatial domain during the encoding process. This study, therefore, provides an initial neurophysiological characterization of functional interactions of WM and manual actions in a cognitive-motor dual-task setting, and contributes to a better understanding of the neuro-cognitive mechanisms of motor action control.

Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.

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Shima, Takeru; Matsui, Takashi; Jesmin, Subrina; Okamoto, Masahiro; Soya, Mariko; Inoue, Koshiro; Liu, Yu-Fan; Torres-Aleman, Ignacio; McEwen, Bruce S; Soya, Hideaki

2017-03-01

Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals. The hippocampal glycometabolism in OLETF rats (model of human type 2 diabetes) was assessed and, subsequently, the effects of exercise on memory function and hippocampal glycometabolism were investigated. OLETF rats, which have memory dysfunction, exhibited higher levels of glycogen in the hippocampus than did control rats, and breakdown of hippocampal glycogen with a single bout of exercise remained unimpaired. However, OLETF rats expressed lower levels of hippocampal monocarboxylate transporter 2 (MCT2, a transporter for lactate to neurons). Four weeks of moderate exercise improved spatial memory accompanied by further increase in hippocampal glycogen levels and restoration of MCT2 expression independent of neurotrophic factor and clinical symptoms in OLETF rats. Our findings are the first to describe detailed profiles of glycometabolism in the type 2 diabetic hippocampus and to show that 4 weeks of moderate exercise improves memory dysfunction in type 2 diabetes via amelioration of dysregulated hippocampal glycometabolism. Dysregulated hippocampal lactate-transport-related glycometabolism is a possible aetiology of type-2-diabetes-mediated memory dysfunction.

IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function.

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Pardo, Joaquín; Abba, Martin C; Lacunza, Ezequiel; Ogundele, Olalekan M; Paiva, Isabel; Morel, Gustavo R; Outeiro, Tiago F; Goya, Rodolfo G

2018-03-14

In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28-month-old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.

Visuospatial processing in early Alzheimer’s disease: a multimodal neuroimaging study

NARCIS (Netherlands)

Jacobs, H.I.L.; Gronenschild, E. H. B. M.; Evers, E.A.T.; Ramakers, I.H.G.B.; Hofman, P.A.M.; Backes, W. H.; Jolles, J.; Verhey, F. R. J.

2013-01-01

Introduction: Dorsal pathway dysfunctions are thought to underlie visuospatial processing problems in Alzheimer disease (AD). Prior studies reported compensatory mechanisms in the dorsal or ventral pathway in response to these functional changes. Since functional and structural connectivity are

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

International Nuclear Information System (INIS)

Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van; Smits, Marion; Lugt, Aad van der; Groot, Marius de; Vrooman, Henri A.; Mattace Raso, Francesco U.; Niessen, Wiro J.; Veen, Frederik M. van der; Prins, Niels D.

2017-01-01

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

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Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van [Erasmus MC - University Medical Center Rotterdam, Department of Neurology, Rotterdam (Netherlands); Smits, Marion; Lugt, Aad van der [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Groot, Marius de; Vrooman, Henri A. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Mattace Raso, Francesco U. [Erasmus MC - University Medical Center Rotterdam, Department of Geriatrics, Rotterdam (Netherlands); Niessen, Wiro J. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Veen, Frederik M. van der [Erasmus University Rotterdam, Institute of Psychology, Rotterdam (Netherlands); Prins, Niels D. [VU University Medical Center, Alzheimer Center, Department of Neurology, Amsterdam (Netherlands)

2017-09-15

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

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Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2018-04-17

Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

Does visuo-spatial working memory generally contribute to immediate serial letter recall?

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Fürstenberg, A; Rummer, R; Schweppe, J

2013-01-01

This work contributes to the understanding of the visual similarity effect in verbal working memory, a finding that suggests that the visuo-spatial sketch pad-the system in Baddeley's working memory model specialised in retaining nonverbal visual information-might be involved in the retention of visually presented verbal materials. Crucially this effect is implicitly interpreted by the most influential theory of multimedia learning as evidence for an obligatory involvement of the visuo-spatial sketch pad. We claim that it is only involved when the functioning of the working memory component normally used for processing verbal material is impaired. In this article we review the studies that give rise to the idea of obligatory involvement of the visuo-spatial sketch pad and suggest that some findings can be understood with reference to orthographic rather than visual similarity. We then test an alternative explanation of the finding that is most apt to serve as evidence for obligatory involvement of the visuo-spatial sketch pad. We conclude that, in healthy adults and under normal learning conditions, the visual similarity effect can be explained within the framework of verbal working memory proposed by Baddeley (e.g., 1986, 2000) without additional premises regarding the visuo-spatial sketch.

Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment☆

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Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

2013-01-01

Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9–10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. PMID:23890692

Executive Functioning and Visuospatial Abilities in Bulimia Nervosa with or without a Previous History of Anorexia Nervosa.

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Degortes, Daniela; Tenconi, Elena; Santonastaso, Paolo; Favaro, Angela

2016-03-01

The aim of the present study was to investigate executive functioning and visuospatial abilities in patients with bulimia nervosa (BN), with a particular interest in exploring the impact of a previous diagnosis of anorexia nervosa (AN). Several neuropsychological tasks were administered to 89 BN patients (52 with a previous history of AN and 37 without previous AN) and 160 healthy women. A poorer performance on set-shifting measures (Wisconsin Card Sorting Test) was found only in BN patients with a previous history of AN. Decision-making abilities (Iowa Gambling Task) were significantly impaired in the whole sample of BN patients, but difficulties were more pronounced in the subgroup with previous AN. Finally, we did not find any differences in response inhibition and visuospatial abilities between the two samples of BN patients and healthy women. Our findings support the idea that cognitive abilities in patients with BN are more impaired in the presence of a prior history of AN. The clinical and treatment implications of our findings should be explored in future studies. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Impaired representation of geometric relationships in humans with damage to the hippocampal formation.

Science.gov (United States)

Finke, Carsten; Ostendorf, Florian; Braun, Mischa; Ploner, Christoph J

2011-01-01

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.

[Developmental changes in visuospatial working memory].

Science.gov (United States)

Oka, Makio; Takeuchi, Akihito; Morooka, Teruko; Ogino, Tatsuya; Ohtsuka, Yoko

2010-07-01

We investigated the developmental changes in visuospatial working memory using the Visuospatial Span Task (VST) and the Matrix Visuospatial Working Memory Test (VSWMT). VST is a short-term storage task, while VSWMT is a complex dual task. VSWMT requires the use of storage, processing, and selective attention, all of which are thought to be supported by the central executive (Baddeley). The subjects of this study were 60 typically developing children (43 boys and 17 girls) aged 6-14 years (average 10.4 years). For each task we evaluated span scores and the number of total passed trials, and investigated the changes that occurred with age. To further elucidate age-related changes in visuospatial working memory, we divided the subjects into three age groups (Group A: 6-8 years, Group B: 9-11 years, and Group C: 12-14 years of age), and statistically evaluated the differences between the groups. In both tasks, span scores and the number of total passed trials showed definite age-related changes from 6 to 14 years of age. Span scores and the number of total passed trials in VSMWT continued to increase until adolescence, with significant differences between the three age groups, while those in VST increased significantly between Groups A and B (the number of total passed trials only) and between Groups A and C (span scores and the number of total passed trials); there was no significant difference between Groups B and C, however. These results suggest that the network of the brain involved in visuospatial working memory gradually matures during early school years and adolescence, and that the basic mechanisms of this network exist by 6-7 years of age. Our results also show that VST and VSWMT are suitable tests for the evaluation of visuospatial working memory in childhood and adolescence.

Mapping of the Underlying Neural Mechanisms of Maintenance and Manipulation in Visuo-Spatial Working Memory Using An n-back Mental Rotation Task: A Functional Magnetic Resonance Imaging Study.

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Lamp, Gemma; Alexander, Bonnie; Laycock, Robin; Crewther, David P; Crewther, Sheila G

2016-01-01

Mapping of the underlying neural mechanisms of visuo-spatial working memory (WM) has been shown to consistently elicit activity in right hemisphere dominant fronto-parietal networks. However to date, the bulk of neuroimaging literature has focused largely on the maintenance aspect of visuo-spatial WM, with a scarcity of research into the aspects of WM involving manipulation of information. Thus, this study aimed to compare maintenance-only with maintenance and manipulation of visuo-spatial stimuli (3D cube shapes) utilizing a 1-back task while functional magnetic resonance imaging (fMRI) scans were acquired. Sixteen healthy participants (9 women, M = 23.94 years, SD = 2.49) were required to perform the 1-back task with or without mentally rotating the shapes 90° on a vertical axis. When no rotation was required (maintenance-only condition), a right hemispheric lateralization was revealed across fronto-parietal areas. However, when the task involved maintaining and manipulating the same stimuli through 90° rotation, activation was primarily seen in the bilateral parietal lobe and left fusiform gyrus. The findings confirm that the well-established right lateralized fronto-parietal networks are likely to underlie simple maintenance of visuo-spatial stimuli. The results also suggest that the added demand of manipulation of information maintained online appears to require further neural recruitment of functionally related areas. In particular mental rotation of visuospatial stimuli required bilateral parietal areas, and the left fusiform gyrus potentially to maintain a categorical or object representation. It can be concluded that WM is a complex neural process involving the interaction of an increasingly large network.

Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task.

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Damarla, Saudamini Roy; Keller, Timothy A; Kana, Rajesh K; Cherkassky, Vladimir L; Williams, Diane L; Minshew, Nancy J; Just, Marcel Adam

2010-10-01

Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging, functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high-functioning autism and 13 controls (age-, IQ-, and gender-matched) were scanned while performing an Embedded Figures Task. Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in the left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher-order working memory/executive areas and visuospatial regions (between frontal and parietal-occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal-posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist.

Alterations of White Matter Integrity and Hippocampal Functional Connectivity in Type 2 Diabetes Without Mild Cognitive Impairment

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Qian Sun

2018-03-01

Full Text Available Aims: To investigate the white matter (WM integrity and hippocampal functional connectivity (FC in type 2 diabetes mellitus (T2DM patients without mild cognitive impairment (MCI by using diffusion tensor imaging (DTI and resting-state functional magnetic resonance imaging (rs-fMRI, respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS combining region of interests (ROIs analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA, mean diffusivity (MD, λ1 and λ23 and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE and Montreal Cognitive Assessment (MoCA. Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC. Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2

Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

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Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

2017-08-01

Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

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Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

2015-10-01

Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

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Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

2013-01-01

Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task

OpenAIRE

Damarla, Saudamini Roy; Keller, Timothy A.; Kana, Rajesh K.; Cherkassky, Vladimir L.; Williams, Diane L.; Minshew, Nancy J.; Just, Marcel Adam

2010-01-01

Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance ...

The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource

OpenAIRE

Rönnberg, Jerker; Hygge, Staffan; Keidser, Gitte; Rudner, Mary

2014-01-01

The UK Biobank offers cross-sectional epidemiological data collected on > 500 000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138 098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three g...

Evidence for a possible association of neurotrophin receptor (NTRK-3) gene polymorphisms with hippocampal function and schizophrenia

DEFF Research Database (Denmark)

Otnaess, Mona K; Djurovic, Srdjan; Rimol, Lars M

2009-01-01

of the sample with neuropsychological test battery (n=104 patients and 175 controls) and functional magnetic resonance imaging tests of hippocampal function (n=36 controls). rs999905 was nominally significantly associated with schizophrenia and the haplotype block that included markers rs999905 and rs4887348......Altered neurodevelopment and plasticity are implicated in schizophrenia pathology. Based on the important role of neurotrophic factors in brain development and plasticity as well as their extensive expression in hippocampal areas, we hypothesized that a variation in the neurotrophin receptor 3 gene...... (NTRK-3) is associated to hippocampal function and schizophrenia. Thirty-three tagging NTRK-3 single nucleotide polymorphisms (SNPs) were genotyped in 839 schizophrenia patients and 1473 healthy controls. SNPs that were significantly associated with schizophrenia were evaluated in subgroups...

Visuospatial ability factors and performance variables in laparoscopic simulator training

NARCIS (Netherlands)

Luursema, J.M.; Verwey, Willem B.; Burie, Remke

2012-01-01

Visuospatial ability has been shown to be important to several aspects of laparoscopic performance, including simulator training. Only a limited subset of visuospatial ability factors however has been investigated in such studies. Tests for different visuospatial ability factors differ in stimulus

Male carriers of the FMR1 premutation show altered hippocampal-prefrontal function during memory encoding

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John M Wang

2012-10-01

Full Text Available Previous functional MRI (fMRI studies have shown that fragile X mental retardation 1 (FMR1 premutation allele carriers (FXPCs exhibit decreased hippocampal activation during a recall task and lower inferior frontal activation during a working memory task compared to matched controls. The molecular characteristics of FXPCs includes 55 to 200 CGG trinucleoutide expansions, increased FMR1 mRNA levels, and decreased FMRP levels especially at higher repeat sizes. In the current study, we utilized MRI to examine differences in hippocampal volume and function during an encoding task in young male FXPCs. While no decreases in either hippocampal volume or hippocampal activity were observed during the encoding task in FXPCs, FMRP level (measured in blood correlated with decreases in parahippocampal activation. In addition, activity in the right dorsolateral prefrontal cortex during correctly encoded trials correlated negatively with mRNA levels. These results, as well as the established biological effects associated with elevated mRNA levels and decreased FMRP levels on dendritic maturation and axonal growth, prompted us to explore functional connectivity between the hippocampus, prefrontal cortex, and parahippocampal gyrus using a psychophysiological interaction analysis. In FXPCs, the right hippocampus evinced significantly lower connectivity with right ventrolateral prefrontal cortex (VLPFC and right parahippocampal gyrus. Furthermore, the weaker connectivity between the right hippocampus and VLPFC was associated with reduced FMRP in the FXPC group. These results suggest that while FXPCs show relatively typical brain response during encoding, faulty connectivity between frontal and hippocampal regions may have subsequent effects on recall and working memory.

Linking empathy to visuospatial perspective-taking in gambling addiction.

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Tomei, Alexander; Besson, Jacques; Grivel, Jeremy

2017-04-01

It has been demonstrated that people suffering from substance-related addictions are less empathic than their non-addicted counterparts. Our first aim was to verify if this is also true for behavioral addictions. We hypothesized that problem gamblers are less empathic than healthy controls. Our second aim was to identify a cognitive marker of empathy that could be targeted in cognitive rehabilitation strategies. We propose that a potential cognitive marker of empathy could be visuospatial perspective-taking. Specifically, we hypothesized that visuospatial perspective-taking performances are lower in problem gamblers compared to healthy controls and that these visuospatial performances predict empathy. Thirty-one non-gamblers, 24 healthy gamblers, and 21 problem gamblers performed a visuospatial perspective-taking task before completing the Interpersonal Reactivity Index (IRI; Davis, 1980; Davis, 1983). Problem gamblers had decreased empathy and lower performance at the visuospatial perspective-taking task than non-gamblers and healthy gamblers. Furthermore, we confirmed that visuospatial perspective-taking abilities predict empathy on the IRI dimensions of interpersonal perspective-taking and personal distress. The present study provides new evidence that reduced empathy is not limited to subjects with substance-related addictions; rather, it extends to behavioral addictions. Visuospatial perspective-taking may be a viable cognitive marker for use as a rehabilitation target of empathy. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Impaired representation of geometric relationships in humans with damage to the hippocampal formation.

Directory of Open Access Journals (Sweden)

Carsten Finke

Full Text Available The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.

Visuospatial Working Memory Capacity Predicts Physiological Arousal in a Narrative Task.

Science.gov (United States)

Smithson, Lisa; Nicoladis, Elena

2016-06-01

Physiological arousal that occurs during narrative production is thought to reflect emotional processing and cognitive effort (Bar-Haim et al. in Dev Psychobiol 44:238-249, 2004). The purpose of this study was to determine whether individual differences in visuospatial working memory and/or verbal working memory capacity predict physiological arousal in a narrative task. Visuospatial working memory was a significant predictor of skin conductance level (SCL); verbal working memory was not. When visuospatial working memory interference was imposed, visuospatial working memory was no longer a significant predictor of SCL. Visuospatial interference also resulted in a significant reduction in SCL. Furthermore, listener ratings of narrative quality were contingent upon the visuospatial working memory resources of the narrator. Potential implications for educators and clinical practitioners are discussed.

Inter-relationships among Diet, Obesity and Hippocampal-dependent Cognitive Function

OpenAIRE

Davidson, Terry L.; Hargrave, Sara L.; Swithers, Susan E.; Sample, Camille H.; Fu, Xue; Kinzig, Kimberly P.; Zheng, Wei

2013-01-01

Intake of a Western diet (WD), which is high in saturated fat and sugar, is associated with deficits in hippocampal-dependent learning and memory processes as well as with markers of hippocampal pathology. In the present study, rats were trained to asymptote on hippocampal-dependent serial feature negative (FN) and hippocampal-independent simple discrimination problems. Performance was then assessed following 7 days on ad libitum chow and after 10, 24, 40, 60, and 90 days of maintenance on WD...

Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice.

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Anna Fiorentini

Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD. METHODOLOGY/PRINCIPAL FINDINGS: The double transgenic (Tg CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein, aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3β and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium's ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines as brain Aβ deposition and pathology increases. CONCLUSIONS: Lithium, when given on time, stimulates neurogenesis and counteracts AD-like pathology.

Neural bases of a specific strategy for visuospatial processing in rugby players.

Science.gov (United States)

Sekiguchi, Atsushi; Yokoyama, Satoru; Kasahara, Satoshi; Yomogida, Yukihito; Takeuchi, Hikaru; Ogawa, Takeshi; Taki, Yasuyuki; Niwa, Shin-Ichi; Kawashima, Ryuta

2011-10-01

Rugby is one of the most tactically complex sports. Rugby coaching theory suggests that rugby players need to possess various cognitive abilities. A previous study claimed that rugby players have high visuospatial awareness, which is induced by a strategy described as taking a "bird's eye view." To examine if there were differential cortical networks related to visuospatial processing tasks among top-level rugby players and control novices, we compared brain activities during a visuospatial processing task between 20 male top-level rugby players (Top) and 20 control novice males (Novice) using functional magnetic resonance imaging (fMRI). To avoid the effect of differential behavioral performances on brain activation, we recruited novices whose visuospatial ability was expected to match that of the rugby players. We adopted a 3-D mental rotation task during fMRI scanning as a visuospatial processing task. Significantly greater activations from baseline were observed for the Top group than for the Novice group in the right superior parietal lobe and lateral occipital cortex. Significantly greater deactivations from baseline were observed for the Top group than for the Novice group in the right medial prefrontal cortex. The discrepancy between psychobehavioral outputs and the fMRI results suggested the existence of a cognitive strategy among top-level rugby players that differs from that among control novices. The greater activation of the right superior parietal lobe and lateral occipital cortex in top-level rugby players suggested a strategy involving visuospatial cognitive processing with respect to the bird's eye view. In addition, the right medial prefrontal cortex is known to be a part of the default mode networks, suggesting an additional cognitive load for the Top group when using the bird's-eye-view strategy. This further supported the existence of a specific cognitive strategy among top-level rugby players.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

Science.gov (United States)

Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

2017-03-01

Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2

Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection.

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Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

2017-04-12

Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection with a large cohort of young adult participants (N = 257). Consistent with some previous human studies, we found that parental care in childhood alone had little association with the hippocampal volume in adulthood. However, when parental overprotection was low, parental care was positively correlated with offspring hippocampal volume, whereas there was no association between parental care and offspring hippocampal volume when parental overprotection was high. Thus, an interaction exists between parental care and overprotection in human's hippocampal development, which contributes to the elucidation of the complex relationship between brain structure and environmental factors.

Impaired visuospatial transformation but intact sequence processing in Parkinson disease.

Science.gov (United States)

Leek, E Charles; Kerai, Julie H; Johnston, Stephen J; Hindle, John V; Bracewell, R Martyn

2014-09-01

We examined whether visuospatial deficits in Parkinson disease (PD) can be explained by a domain-general, nonspatial impairment in the sequencing or serial chaining of mental operations. PD has been shown to be associated with impaired visuospatial processing, but the mechanisms of this impairment remain unclear. Thirteen patients with PD and 20 age-matched, neurologically normal controls performed a visuospatial grid navigation task requiring sequential spatial transformations. The participants also performed a control task of serial number subtraction designed to assess their nonvisuospatial sequencing. The tasks were matched in structure and difficulty. The patients were impaired on the visuospatial task but not in serial number subtraction. This finding suggests that visuospatial processing impairments in PD do not derive from a general impairment affecting sequencing or serial chaining. We argue that visuospatial deficits in PD result from impairments to spatial transformation routines involved in the computation of mappings between spatial locations. These routines are mediated by dopaminergic pathways linking the basal ganglia, prefrontal cortex, supplementary motor area, and parietal cortex.

An fMRI study on variation of visuospatial cognitive performance of young male due to highly concentrated oxygen administration

Science.gov (United States)

Chung, Soon Cheol; Kim, Ik Hyeon; Tack, Gye Rae; Sohn, Jin Hun

2004-04-01

This study investigated the effects of 30% oxygen administration on the visuospatial cognitive performance using fMRI. Eight college students (right-handed, average age 23.5) were selected as subjects for this study. Oxygen supply equipment which gives 21% and 30% oxygen at a constant rate of 8L/min was developed for this study. To measure the performance of visuospatial cognition, two questionnaires with similar difficulty containing 20 questions each were also developed. Experiment was designed as two runs: run for visuospatial cognition test with normal air (21% of oxygen) and run for visuospatial cognition test with highly concentrated air (30% of oxygen). Run consists of 4 blocks and each block has 8 control problems and 5 visuospatial problems. Functional brain images were taken from 3T MRI using single-shot EPI method. Activities of neural network due to performing visuospatial cognition test were identified using subtraction procedure, and activation areas while performing visuospatial cognition test were extracted using double subtraction procedure. Activities were observed at occipital lobe, parietal lobe, and frontal lobe when performing visuospatial cognition test following both 21% and 30% oxygen administration. But in case of only 30% oxygen administration there were more activities at left precuneus, left cuneus, right postcentral gyrus, bilateral middle frontal gyri, right inferior frontal gyrus, left superior frontal gyrus, bilateral uvula, bilateral pyramis, and nodule compared with 21% oxygen administration. From results of visuospatial cognition test, accuracy rate increased in case of 30% oxygen administration. Thus it could be concluded that highly concentrated oxygen administration has positive effects on the visuospatial cognitive performance.

Individual differences in proactive interference in verbal and visuospatial working memory.

Science.gov (United States)

Lilienthal, Lindsey

2017-09-01

Proactive interference (PI) has been shown to affect working memory (WM) span as well as the predictive utility of WM span measures. However, most of the research on PI has been conducted using verbal memory items, and much less is known about the role of PI in the visuospatial domain. In order to further explore this issue, the present study used a within-subjects manipulation of PI that alternated clusters of trials with verbal and visuospatial to-be-remembered items. Although PI was shown to build and release across trials similarly in the two domains, important differences also were observed. The ability of verbal WM to predict performance on a measure of fluid intelligence was significantly affected by the amount of PI present, consistent with past research, but this proved not to be the case for visuospatial WM. Further, individuals' susceptibility to PI in one domain was relatively independent of their susceptibility in the other domain, suggesting that, contrary to some theories of executive function, individual differences in PI susceptibility may not be domain-general.

Low-frequency hippocampal-cortical activity drives brain-wide resting-state functional MRI connectivity.

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Chan, Russell W; Leong, Alex T L; Ho, Leon C; Gao, Patrick P; Wong, Eddie C; Dong, Celia M; Wang, Xunda; He, Jufang; Chan, Ying-Shing; Lim, Lee Wei; Wu, Ed X

2017-08-15

The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal-cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in various cortices and hippocampus. Subsequent local field potential recordings revealed an increase in slow oscillations in dorsal hippocampus and visual cortex, interhemispheric visual cortical connectivity, and hippocampal-cortical connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI responses in visual regions also increased during and after low-frequency dDG stimulation. Together, our results indicate that low-frequency activity robustly propagates in the dorsal hippocampal-cortical pathway, drives interhemispheric cortical rsfMRI connectivity, and mediates visual processing.

Hippocampal and posterior parietal contributions to developmental increases in visual short-term memory capacity.

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von Allmen, David Yoh; Wurmitzer, Karoline; Klaver, Peter

2014-10-01

Developmental increases in visual short-term memory (VSTM) capacity have been associated with changes in attention processing limitations and changes in neural activity within neural networks including the posterior parietal cortex (PPC). A growing body of evidence suggests that the hippocampus plays a role in VSTM, but it is unknown whether the hippocampus contributes to the capacity increase across development. We investigated the functional development of the hippocampus and PPC in 57 children, adolescents and adults (age 8-27 years) who performed a visuo-spatial change detection task. A negative relationship between age and VSTM related activity was found in the right posterior hippocampus that was paralleled by a positive age-activity relationship in the right PPC. In the posterior hippocampus, VSTM related activity predicted individual capacity in children, whereas neural activity in the right anterior hippocampus predicted individual capacity in adults. The findings provide first evidence that VSTM development is supported by an integrated neural network that involves hippocampal and posterior parietal regions.

Sex Differences in Cerebral Laterality of Language and Visuospatial Processing

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Clements, A. M.; Rimrodt, S. L.; Abel, J. R.; Blankner, J. G.; Mostofsky, S. H.; Pekar, J. J.; Denckla, M. B.; Cutting, L. E.

2006-01-01

Sex differences on language and visuospatial tasks are of great interest, with differences in hemispheric laterality hypothesized to exist between males and females. Some functional imaging studies examining sex differences have shown that males are more left lateralized on language tasks and females are more right lateralized on visuospatial…

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks.

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Zilles, David; Lewandowski, Mirjana; Vieker, Henning; Henseler, Ilona; Diekhof, Esther; Melcher, Tobias; Keil, Maria; Gruber, Oliver

2016-01-01

Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. These findings provide evidence for a slightly lower capacity in both WM modalities in females. © 2016 S. Karger AG, Basel.

Co-speech iconic gestures and visuo-spatial working memory.

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Wu, Ying Choon; Coulson, Seana

2014-11-01

Three experiments tested the role of verbal versus visuo-spatial working memory in the comprehension of co-speech iconic gestures. In Experiment 1, participants viewed congruent discourse primes in which the speaker's gestures matched the information conveyed by his speech, and incongruent ones in which the semantic content of the speaker's gestures diverged from that in his speech. Discourse primes were followed by picture probes that participants judged as being either related or unrelated to the preceding clip. Performance on this picture probe classification task was faster and more accurate after congruent than incongruent discourse primes. The effect of discourse congruency on response times was linearly related to measures of visuo-spatial, but not verbal, working memory capacity, as participants with greater visuo-spatial WM capacity benefited more from congruent gestures. In Experiments 2 and 3, participants performed the same picture probe classification task under conditions of high and low loads on concurrent visuo-spatial (Experiment 2) and verbal (Experiment 3) memory tasks. Effects of discourse congruency and verbal WM load were additive, while effects of discourse congruency and visuo-spatial WM load were interactive. Results suggest that congruent co-speech gestures facilitate multi-modal language comprehension, and indicate an important role for visuo-spatial WM in these speech-gesture integration processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Memory-related hippocampal functioning in ecstasy and amphetamine users: a prospective fMRI study.

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Becker, Benjamin; Wagner, Daniel; Koester, Philip; Bender, Katja; Kabbasch, Christoph; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Jörg

2013-02-01

Recreational use of ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) has been associated with memory impairments. Functional neuroimaging studies with cross-sectional designs reported altered memory-related hippocampal functioning in ecstasy-polydrug users. However, differences might be pre-existing or related to the concomitant use of amphetamine. To prospectively investigate the specific effects of ecstasy on memory-related hippocampal functioning. We used an associative memory task and functional magnetic resonance imaging (fMRI) in 40 ecstasy and/or amphetamine users at baseline (t1) and after 12 months (t2). At t1, all subjects had very limited amphetamine and/or ecstasy experience (less than 5 units lifetime dose). Based on the reported drug use at t2, subjects with continued ecstasy and/or amphetamine use (n = 17) were compared to subjects who stopped use after t1 (n = 12). Analysis of repeated measures revealed that encoding-related activity in the left parahippocampal gyrus changed differentially between the groups. Activity in this region increased in abstinent subjects from t1 to t2, however, decreased in subjects with continued use. Decreases within the left parahippocampal gyrus were associated with the use of ecstasy, but not amphetamine, during the follow-up period. However, there were no significant differences in memory performance. The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning. However, alternative explanations such as (sub-)acute cannabis effects are conceivable.

Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

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Fjalldal, S; Follin, C; Svärd, D; Rylander, L; Gabery, S; Petersén, Å; van Westen, D; Sundgren, P C; Björkman-Burtscher, I M; Lätt, J; Ekman, B; Johanson, A; Erfurth, E M

2018-06-01

Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. The South Medical Region of Sweden (2.5 million inhabitants). Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Right uncinate fasciculus was significantly altered ( P  ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge ( P  = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP. © 2018 The authors.

Visuo-spatial abilities are key for young children's verbal number skills.

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Cornu, Véronique; Schiltz, Christine; Martin, Romain; Hornung, Caroline

2018-02-01

Children's development of verbal number skills (i.e., counting abilities and knowledge of the number names) presents a milestone in mathematical development. Different factors such as visuo-spatial and verbal abilities have been discussed as contributing to the development of these foundational skills. To understand the cognitive nature of verbal number skills in young children, the current study assessed the relation of preschoolers' verbal and visuo-spatial abilities to their verbal number skills. In total, 141 children aged 5 or 6 years participated in the current study. Verbal number skills were regressed on vocabulary, phonological awareness and visuo-spatial abilities, and verbal and visuo-spatial working memory in a structural equation model. Only visuo-spatial abilities emerged as a significant predictor of verbal number skills in the estimated model. Our results suggest that visuo-spatial abilities contribute to a larger extent to children's verbal number skills than verbal abilities. From a theoretical point of view, these results suggest a visuo-spatial, rather than a verbal, grounding of verbal number skills. These results are potentially informative for the conception of early mathematics assessments and interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Endogenous IL-1 in cognitive function and anxiety: a study in IL-1RI-/- mice.

Directory of Open Access Journals (Sweden)

Carol L Murray

Full Text Available Interleukin-1 (IL-1 is a key pro-inflammatory cytokine, produced predominantly by peripheral immune cells but also by glia and some neuronal populations within the brain. Its signalling is mediated via the binding of IL-1α or IL-1β to the interleukin-1 type one receptor (IL-1RI. IL-1 plays a key role in inflammation-induced sickness behaviour, resulting in depressed locomotor activity, decreased exploration, reduced food and water intake and acute cognitive deficits. Conversely, IL-1 has also been suggested to facilitate hippocampal-dependent learning and memory: IL-1RI(-/- mice have been reported to show deficits on tasks of visuospatial learning and memory. We sought to investigate whether there is a generalised hippocampal deficit in IL-1RI(-/- animals. Therefore, in the current study we compared wildtype (WT mice to IL-1RI(-/- mice using a variety of hippocampal-dependent learning and memory tasks, as well as tests of anxiety and locomotor activity. We found no difference in performance of the IL-1RI(-/- mice compared to WT mice in a T-maze working memory task. In addition, the IL-1RI(-/- mice showed normal learning in various spatial reference memory tasks including the Y-maze and Morris mater maze, although there was a subtle deficit in choice behaviour in a spatial discrimination, beacon watermaze task. IL-1RI(-/- mice also showed normal memory for visuospatial context in the contextual fear conditioning paradigm. In the open field, IL-1RI(-/- mice showed a significant increase in distance travelled and rearing behaviour compared to the WT mice and in the elevated plus-maze spent more time in the open arms than did the WT animals. The data suggest that, contrary to prior studies, IL-1RI(-/- mice are not robustly impaired on hippocampal-dependent memory and learning but do display open field hyperactivity and decreased anxiety compared to WT mice. The results argue for a careful evaluation of the roles of endogenous IL-1 in hippocampal

Memory functions of children born with asymmetric intrauterine growth restriction.

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Geva, Ronny; Eshel, Rina; Leitner, Yael; Fattal-Valevski, Aviva; Harel, Shaul

2006-10-30

Learning difficulties are frequently diagnosed in children born with intrauterine growth restriction (IUGR). Models of various animal species with IUGR were studied and demonstrated specific susceptibility and alterations of the hippocampal formation and its related neural structures. The main purpose was to study memory functions of children born with asymmetric IUGR in a large-scale cohort using a long-term prospective paradigm. One hundred and ten infants diagnosed with IUGR were followed-up from birth to 9 years of age. Their performance was compared with a group of 63 children with comparable gestational age and multiple socioeconomic factors. Memory functions (short-term, super- and long-term spans) for different stimuli types (verbal and visual) were evaluated using Visual Auditory Digit Span tasks (VADS), Rey Auditory Verbal Learning Test (Rey-AVLT), and Rey Osterrieth Complex Figure Test (ROCF). Children with IUGR had short-term memory difficulties that hindered both serial verbal processing system and simultaneous processing of high-load visuo-spatial stimuli. The difficulties were not related to prematurity, neonatal complications or growth catch-up, but were augmented by lower maternal education. Recognition skills and benefits from reiteration, typically affected by hippocampal dysfunction, were preserved in both groups. Memory profile of children born with IUGR is characterized primarily by a short-term memory deficit that does not necessarily comply with a typical hippocampal deficit, but rather may reflect an executive short-term memory deficit characteristic of anterior hippocampal-prefrontal network. Implications for cognitive intervention are discussed.

Structural correlates of impaired working memory in hippocampal sclerosis

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Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S

2013-01-01

Purpose: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. Methods: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Key Findings: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of

Exercise Influence on Hippocampal Function: Possible Involvement of Orexin-A

OpenAIRE

Chieffi, Sergio; Messina, Giovanni; Villano, Ines; Messina, Antonietta; Esposito, Maria; Monda, Vincenzo; Valenzano, Anna; Moscatelli, Fiorenzo; Esposito, Teresa; Carotenuto, Marco; Viggiano, Andrea; Cibelli, Giuseppe; Monda, Marcellino

2017-01-01

In the present article, we provide a brief review of current knowledge regarding the effects induced by physical exercise on hippocampus. Research involving animals and humans supports the view that physical exercise, enhancing hippocampal neurogenesis and function, improves cognition, and regulates mood. These beneficial effects depend on the contribute of more factors including the enhancement of vascularization and upregulation of growth factors. Among these, the BDNF seems to play a signi...

Patterns of frontoparietal activation as a marker for unsuccessful visuospatial processing in healthy aging.

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Drag, Lauren L; Light, Sharee N; Langenecker, Scott A; Hazlett, Kathleen E; Wilde, Elisabeth A; Welsh, Robert; Steinberg, Brett A; Bieliauskas, Linas A

2016-09-01

Visuospatial abilities are sensitive to age-related decline, although the neural basis for this decline (and its everyday behavioral correlates) is as yet poorly understood. fMRI was employed to examine age-related differences in patterns of functional activation that underlie changes in visuospatial processing. All participants completed a brief neuropsychological battery and also a figure ground task (FGT) assessing visuospatial processing while fMRI was recorded. Participants included 16 healthy older adults (OA; aged 69-82 years) and 16 healthy younger adults (YA; aged 20-35 years). We examined age-related differences in behavioral performance on the FGT in relation to patterns of fMRI activation. OA demonstrated reduced performance on the FGT task and showed increased activation of supramarginal parietal cortex as well as increased activation of frontal and temporal regions compared to their younger counterparts. Performance on the FGT related to increased supramarginal gyrus activity and increased medial prefrontal activity in OAs, but not YAs. Our results are consistent with an anterior-posterior compensation model. Successful FGT performance requires the perception and integration of multiple stimuli and thus it is plausible that healthy aging may be accompanied by changes in visuospatial processing that mimic a subtle form of dorsal simultanagnosia. Overall, decreased visuospatial processing in OA relates to an altered frontoparietal neurobiological signature that may contribute to the general phenomenon of increasingly fragmented execution of behavior associated with normal aging.

A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction.

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Mitsui, Shinichi; Osako, Yoji; Yokoi, Fumiaki; Dang, Mai T; Yuri, Kazunari; Li, Yuqing; Yamaguchi, Nozomi

2009-12-01

Motopsin is a mosaic serine protease secreted from neuronal cells in various brain regions, including the hippocampus. The loss of motopsin function causes nonsyndromic mental retardation in humans and impairs long-term memory formation in Drosophila. To understand motopsin's function in the mammalian brain, motopsin knockout (KO) mice were generated. Motopsin KO mice did not have significant deficits in memory formation, as tested using the Morris water maze, passive avoidance and Y-maze tests. A social recognition test showed that the motopsin KO mice had the ability to recognize two stimulator mice, suggesting normal social memory. In a social novelty test, motopsin KO mice spent a longer time investigating a familiar mouse than wild-type (WT) mice did. In a resident-intruder test, motopsin KO mice showed prolonged social interaction as compared with WT mice. Consistent with the behavioral deficit, spine density was significantly decreased on apical dendrites, but not on basal dendrites, of hippocampal pyramidal neurons of motopsin KO mice. In contrast, pyramidal neurons at the cingulate cortex showed normal spine density. Spatial learning and social interaction induced the phosphorylation of cAMP-responsive element-binding protein (CREB) in hippocampal neurons of WT mice, whereas the phosphorylation of CREB was markedly decreased in mutant mouse brains. Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons.

Male-typical visuospatial functioning in gynephilic girls with gender dysphoria — organizational and activational effects of testosterone

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Burke, Sarah M.; Kreukels, Baudewijntje P.C.; Cohen-Kettenis, Peggy T.; Veltman, Dick J.; Klink, Daniel T.; Bakker, Julie

2016-01-01

Background Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activity during a mental rotation task (MRT). Methods Girls with GD underwent fMRI while performing the MRT twice: when receiving medication to suppress their endogenous sex hormones before onset of testosterone treatment, and 10 months later during testosterone treatment. Two age-matched control groups participated twice as well. Results We included 21 girls with GD, 20 male controls and 21 female controls in our study. In the absence of any group differences in performance, control girls showed significantly increased activation in frontal brain areas compared with control boys (pFWE = 0.012). Girls with GD before testosterone treatment differed significantly in frontal brain activation from the control girls (pFWE = 0.034), suggesting a masculinization of brain structures associated with visuospatial cognitive functions. After 10 months of testosterone treatment, girls with GD, similar to the control boys, showed increases in brain activation in areas implicated in mental rotation. Limitations Since all girls with GD identified as gynephilic, their resemblance in spatial cognition with the control boys, who were also gynephilic, may have been related to their shared sexual orientation rather than their shared gender identity. We did not account for menstrual cycle phase or contraceptive use in our analyses. Conclusion Our findings suggest atypical sexual differentiation of the brain in natal girls with GD and provide new evidence for organizational and activational effects of testosterone on visuospatial cognitive functioning. PMID:27070350

Reduced prefrontal efficiency for visuospatial working memory in attention-deficit/hyperactivity disorder.

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Bédard, Anne-Claude V; Newcorn, Jeffrey H; Clerkin, Suzanne M; Krone, Beth; Fan, Jin; Halperin, Jeffrey M; Schulz, Kurt P

2014-09-01

Visuospatial working memory impairments have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, most ADHD research has focused on the neural correlates of nonspatial mnemonic processes. This study examined brain activation and functional connectivity for visuospatial working memory in youth with and without ADHD. Twenty-four youth with ADHD and 21 age- and sex-matched healthy controls were scanned with functional magnetic resonance imaging while performing an N-back test of working memory for spatial position. Block-design analyses contrasted activation and functional connectivity separately for high (2-back) and low (1-back) working memory load conditions versus the control condition (0-back). The effect of working memory load was modeled with linear contrasts. The 2 groups performed comparably on the task and demonstrated similar patterns of frontoparietal activation, with no differences in linear gains in activation as working memory load increased. However, youth with ADHD showed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p 100 voxels). Reanalysis using a more conservative statistical approach (p 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity. Youth with ADHD show decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial position than healthy control youth. Findings should be replicated in larger samples. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance.

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Tam, Shu K E; Hasan, Sibah; Choi, Harry M C; Brown, Laurence A; Jagannath, Aarti; Hughes, Steven; Hankins, Mark W; Foster, Russell G; Vyazovskiy, Vladyslav V; Bannerman, David M; Peirson, Stuart N

2017-03-29

Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light ( r LL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 ( Per1 and Per2 ), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under r LL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under r LL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals. SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by

Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance

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Tam, Shu K.E.; Hasan, Sibah; Brown, Laurence A.; Jagannath, Aarti; Hankins, Mark W.; Foster, Russell G.; Vyazovskiy, Vladyslav V.

2017-01-01

Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light (rLL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 (Per1 and Per2), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under rLL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under rLL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals. SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by

Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

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Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

2014-01-01

Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

Functional anatomy of top-down visuospatial processing in the human brain : evidence from rTMS

NARCIS (Netherlands)

Aleman, A; Schutter, DJLG; Ramsey, NF; van Honk, J; Kessels, RPC; Hoogduin, JM; Postma, A; Kahn, RS; de Haan, EHF

The hypothesis was tested that visuospatial mental imagery relies on processing in the posterior parietal lobe. Using repetitive transcranial magnetic stimulation (rTMS) in a cross-over, sham-controlled design, we compared involvement of right posterior parietal cortex with primary visual cortex.

Phonological and Visuospatial Working Memory in Autism Spectrum Disorders

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Macizo, P.; Soriano, M. F.; Paredes, N.

2016-01-01

We evaluated phonological and visuospatial working memory (WM) in autism spectrum disorders. Autistic children and typically developing children were compared. We used WM tasks that measured phonological and visuospatial WM up to the capacity limit of each children. Overall measures of WM did not show differences between autistic children and…

Sports training enhances visuo-spatial cognition regardless of open-closed typology

Directory of Open Access Journals (Sweden)

Ting-Yu Chueh

2017-05-01

Full Text Available The aim of this study was to investigate the effects of open and closed sport participation on visuo-spatial attention and memory performance among young adults. Forty-eight young adults—16 open-skill athletes, 16 closed-skill athletes, and 16 non-athletes controls—were recruited for the study. Both behavioral performance and event-related potential (ERP measurement were assessed when participants performed non-delayed and delayed match-to-sample task that tested visuo-spatial attention and memory processing. Results demonstrated that regardless of training typology, the athlete groups exhibited shorter reaction times in both the visuo-spatial attention and memory conditions than the control group with no existence of speed-accuracy trade-off. Similarly, a larger P3 amplitudes were observed in both athlete groups than in the control group for the visuo-spatial memory condition. These findings suggest that sports training, regardless of typology, are associated with superior visuo-spatial attention and memory performance, and more efficient neural resource allocation in memory processing.

Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.

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Flore, Gemma; Di Ruberto, Giuseppina; Parisot, Joséphine; Sannino, Sara; Russo, Fabio; Illingworth, Elizabeth A; Studer, Michèle; De Leonibus, Elvira

2017-02-01

The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Visuospatial working memory training facilitates visually-aided explicit sequence learning.

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Chan, John S Y; Wu, Qiaofeng; Liang, Danxia; Yan, Jin H

2015-10-01

Finger sequence learning requires visuospatial working memory (WM). However, the dynamics between age, WM training, and motor skill acquisition are unclear. Therefore, we examined how visuospatial WM training improves finger movement sequential accuracy in younger (n=26, 21.1±1.37years) and older adults (n=22, 70.6±4.01years). After performing a finger sequence learning exercise and numerical and spatial WM tasks, participants in each age group were randomly assigned to either the experimental (EX) or control (CO) groups. For one hour daily over a 10-day period, the EX group practiced an adaptive n-back spatial task while those in the CO group practiced a non-adaptive version. As a result of WM practice, the EX participants increased their accuracy in the spatial n-back tasks, while accuracy remained unimproved in the numerical n-back tasks. In all groups, reaction times (RT) became shorter in most numerical and spatial n-back tasks. The learners in the EX group - but not in the CO group - showed improvements in their retention of finger sequences. The findings support our hypothesis that computerized visuospatial WM training improves finger sequence learning both in younger and in older adults. We discuss the theoretical implications and clinical relevance of this research for motor learning and functional rehabilitation. Copyright © 2015 Elsevier B.V. All rights reserved.

How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

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Frodl, Thomas; O'Keane, Veronica

2013-04-01

There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection

OpenAIRE

Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

2017-01-01

Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection ...

Autobiographical Memory Retrieval and Hippocampal Activation as a Function of Repetition and the Passage of Time

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Lynn Nadel

2007-01-01

Full Text Available Multiple trace theory (MTT predicts that hippocampal memory traces expand and strengthen as a function of repeated memory retrievals. We tested this hypothesis utilizing fMRI, comparing the effect of memory retrieval versus the mere passage of time on hippocampal activation. While undergoing fMRI scanning, participants retrieved remote autobiographical memories that had been previously retrieved either one month earlier, two days earlier, or multiple times during the preceding month. Behavioral analyses revealed that the number and consistency of memory details retrieved increased with multiple retrievals but not with the passage of time. While all three retrieval conditions activated a similar set of brain regions normally associated with autobiographical memory retrieval including medial temporal lobe structures, hippocampal activation did not change as a function of either multiple retrievals or the passage of time. However, activation in other brain regions, including the precuneus, lateral prefrontal cortex, parietal cortex, lateral temporal lobe, and perirhinal cortex increased after multiple retrievals, but was not influenced by the passage of time. These results have important implications for existing theories of long-term memory consolidation.

Scanless functional imaging of hippocampal networks using patterned two-photon illumination through GRIN lenses

KAUST Repository

Moretti, Claudio; Antonini, Andrea; Bovetti, Serena; Liberale, Carlo; Fellin, Tommaso

2016-01-01

functional imaging in rodent hippocampal networks in vivo ~1.2 mm below the brain surface. Our results open the way to the application of patterned illumination approaches to deep regions of highly scattering biological tissues, such as the mammalian brain.

Aerobic fitness relates to learning on a virtual morris water task and hippocampal volume in adolescents

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Herting, Megan M.; Nagel, Bonnie J.

2012-01-01

In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence – a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume, or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory. PMID:22610054

Aerobic fitness relates to learning on a virtual Morris Water Task and hippocampal volume in adolescents.

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Herting, Megan M; Nagel, Bonnie J

2012-08-01

In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence--a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory. Published by Elsevier B.V.

Altered neuronal excitability underlies impaired hippocampal function in an animal model of psychosis

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Thomas eGrüter

2015-05-01

Full Text Available Psychosis is accompanied by severe attentional deficits, and impairments in associational-memory processing and sensory information processing that are ascribed to dysfunctions in prefrontal and hippocampal function. Disruptions of glutamatergic signalling may underlie these alterations: Antagonism of the N-methyl-D-aspartate receptor (NMDAR results in similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans as those that occur in psychosis, raising the question as to whether changes in glutamatergic transmission may be intrinsic to the pathophysiology of the disease. In an animal model of psychosis that comprises treatment with the irreversible NMDAR-antagonist, MK801, we explored the cellular mechanisms that may underlie hippocampal dysfunction in psychosis. MK801-treatment resulted in a profound loss of hippocampal LTP that was evident 4 weeks after treatment. Whereas neuronal expression of the immediate early gene, Arc, was enhanced in the hippocampus by spatial learning in controls, MK801-treated animals failed to show activity-dependent increases in Arc expression. By contrast, a significant increase in basal Arc expression in the absence of learning was evident compared to controls. Paired-pulse facilitation was increased at the 40 ms interval indicating that NMDAR and/or fast GABAergic-mediated neurotransmission was disrupted. In line with this, MK801-treatment resulted in a significant decrease in GABA(A, and increase in GABA(B-receptor-expression in PFC, along with a significant increase of GABA(B- and NMDAR-GluN2B expression in the dentate gyrus. NMDAR-GluN1 or GluN2A subunit expression was unchanged. These data suggest that in psychosis, deficits in hippocampus-dependent memory may be caused by a loss of hippocampal LTP that arises through enhanced hippocampal neuronal excitability, altered GluN2B and GABA receptor expression and an uncoupling of the hippocampus-prefrontal cortex circuitry.

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

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Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively.

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Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J

2018-05-01

Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

Effects of gender and executive function on visuospatial working memory in adult obsessive-compulsive disorder.

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Martoni, Riccardo Maria; Salgari, Giulia; Galimberti, Elisa; Cavallini, Maria Cristina; O'Neill, Joseph

2015-12-01

Visuospatial working memory (VSWM) is the ability of the brain to transiently store and manipulate visual information. VSWM deficiencies have been reported in obsessive-compulsive disorder (OCD), but not consistently, perhaps due to variability in task design and clinical patient factors. To explore this variability, this study assessed effects of the design factors task difficulty and executive organizational strategy and of the clinical factors gender, OCD symptom dimension, and duration of illness on VSWM in OCD. The CANTAB spatial working memory, spatial recognition memory, delayed matching to sample, and stop signal tasks were administered to 42 adult OCD patients and 42 age- and sex-matched healthy controls. Aims were to detect a possible VSWM deficit in the OCD sample, to evaluate influences of the above task and patient factors, to determine the specificity of the deficit to the visuospatial subdomain, and to examine effects of sustained attention as potential neurocognitive confound. We confirmed previous findings of a VSWM deficit in OCD that was more severe for greater memory load (task difficulty) and that was affected by task strategy (executive function). We failed to demonstrate significant deficits in neighboring or confounding neurocognitive subdomains (visual object recognition or visual object short-term memory, sustained attention). Notably, the VSWM deficit was only significant for female patients, adding to evidence for sexual dimorphism in OCD. Again as in prior work, more severe OCD symptoms in the symmetry dimension (but no other dimension) significantly negatively impacted VSWM. Duration of illness had no significant effect on VSWM. VSWM deficits in OCD appear more severe with higher task load and may be mediated through poor task strategy. Such deficits may present mainly in female patients and in (male and female) patients with symmetry symptoms.

Comparison of Hippocampal Volume in Dementia Subtypes

International Nuclear Information System (INIS)

Vijayakumar, Avinash; Vijayakumar, Abhishek

2012-01-01

Aims. To examine the relationship between different types of dementia and hippocampal volume. Methods. Hippocampal volume was measured using FL3D sequence magnetic resonance imaging in 26 Alzheimer's, vascular dementia, mixed dementia, and normal pressure hydrocephalus patients and 15 healthy controls and also hippocampal ratio, analyzed. Minimental scale was used to stratify patients on cognitive function impairments. Results. Hippocampal volume and ratio was reduced by 25% in Alzheimer's disease, 21% in mixed dementia, 11% in vascular dementia and 5% in normal pressure hydrocephalus in comparison to control. Also an asymmetrical decrease in volume of left hippocampus was noted. The severity of dementia increased in accordance to decreasing hippocampal volume. Conclusion. Measurement in hippocampal volume may facilitate in differentiating different types of dementia and in disease progression. There was a correlation between hippocampal volume and severity of cognitive impairment

Developmental gains in visuospatial memory predict gains in mathematics achievement.

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Yaoran Li

Full Text Available Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4 were larger than gains in the capacity of the central executive (d = 1.6 that in turn were larger than gains in phonological memory span (d = 1.1. First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning.

Developmental gains in visuospatial memory predict gains in mathematics achievement.

Science.gov (United States)

Li, Yaoran; Geary, David C

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning.

Developmental Gains in Visuospatial Memory Predict Gains in Mathematics Achievement

Science.gov (United States)

Li, Yaoran; Geary, David C.

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning. PMID:23936154

Effect of Integrated Cognitive Therapy on Hippocampal Functional Connectivity Patterns in Stroke Patients with Cognitive Dysfunction: A Resting-State fMRI Study

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Shanli Yang

2014-01-01

Full Text Available Objective. This study aimed to identify abnormal hippocampal functional connectivity (FC following ischemic stroke using resting-state fMRI. We also explored whether abnormal hippocampal FC could be modulated by integrated cognitive therapy and tested whether these alterations were associated with cognitive performance. Methods. 18 right-handed cognitively impaired ischemic stroke patients and 18 healty control (HC subjects were included in this study. Stroke subjects were scanned at baseline and after integrated cognitive therapy, while HCs were only scanned at baseline, to identify regions that show significant correlations with the seed region. Behavioral and cognitive assessments were obtained before each scan. Results. During the resting state, we found abnormal hippocampal FC associated with temporal regions, insular cortex, cerebellum, and prefrontal cortex in stroke patients compared to HCs. After integrated cognitive therapy, however, the stroke group showed increased hippocampal FC mainly located in the prefrontal gyrus and the default mode network (DMN. Altered hippocampal FC was associated with cognitive improvement. Conclusion. Resting-state fMRI may provide novel insight into the study of functional networks in the brain after stroke. Furthermore, altered hippocampal FC may be a compensatory mechanism for cognitive recovery after ischemic stroke.

Functional connectivity between prefrontal and parietal cortex drives visuo-spatial attention shifts.

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Heinen, Klaartje; Feredoes, Eva; Ruff, Christian C; Driver, Jon

2017-05-01

It is well established that the frontal eye-fields (FEF) in the dorsal attention network (DAN) guide top-down selective attention. In addition, converging evidence implies a causal role for the FEF in attention shifting, which is also known to recruit the ventral attention network (VAN) and fronto-striatal regions. To investigate the causal influence of the FEF as (part of) a central hub between these networks, we applied thetaburst transcranial magnetic stimulation (TBS) off-line, combined with functional magnetic resonance (fMRI) during a cued visuo-spatial attention shifting paradigm. We found that TBS over the right FEF impaired performance on a visual discrimination task in both hemifields following attention shifts, while only left hemifield performance was affected when participants were cued to maintain the focus of attention. These effects recovered ca. 20min post stimulation. Furthermore, particularly following attention shifts, TBS suppressed the neural signal in bilateral FEF, right inferior and superior parietal lobule (IPL/SPL) and bilateral supramarginal gyri (SMG). Immediately post stimulation, functional connectivity was impaired between right FEF and right SMG as well as right putamen. Importantly, the extent of decreased connectivity between right FEF and right SMG correlated with behavioural impairment following attention shifts. The main finding of this study demonstrates that influences from right FEF on SMG in the ventral attention network causally underly attention shifts, presumably by enabling disengagement from the current focus of attention. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones.

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Gould, E; Woolley, C S; McEwen, B S

1991-01-01

The hippocampal formation is of considerable interest due to its proposed role in a number of important functions, including learning and memory processes. Manipulations of thyroid, gonadal and adrenal hormones have been shown to influence hippocampal physiology as well as learning and memory. The cellular events which underlie these hormone-induced functional changes are largely unexplored. However, studies suggest that hormonal manipulations during development and in adulthood result in dramatic morphological changes within the hippocampal formation. Because neuronal physiology has been suggested to depend upon neuronal morphology, we have been determining the morphologic sensitivity of hippocampal neurons to thyroid and steroid hormones in an effort to elucidate possible structural mechanisms to account for differences in hippocampal function. In this review, hormone-induced structural changes in the developing and adult hippocampal formation are discussed, with particular emphasis on their functional relevance. Sex differences, as well as the developmental effects of thyroid hormone and glucocorticoids, are described. Moreover, the effects of ovarian steroids, thyroid hormone and glucocorticoids on neuronal morphology in the hippocampal formation of the adult rat are reviewed. These hormone-induced structural changes may account, at least in part, for previously reported hormone-induced changes in hippocampal function.

Visuospatial and Verbal Short-Term Memory Correlates of Vocabulary Ability in Preschool Children.

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Stokes, Stephanie F; Klee, Thomas; Kornisch, Myriam; Furlong, Lisa

2017-08-16

Recent studies indicate that school-age children's patterns of performance on measures of verbal and visuospatial short-term memory (STM) and working memory (WM) differ across types of neurodevelopmental disorders. Because these disorders are often characterized by early language delay, administering STM and WM tests to toddlers could improve prediction of neurodevelopmental outcomes. Toddler-appropriate verbal, but not visuospatial, STM and WM tasks are available. A toddler-appropriate visuospatial STM test is introduced. Tests of verbal STM, visuospatial STM, expressive vocabulary, and receptive vocabulary were administered to 92 English-speaking children aged 2-5 years. Mean test scores did not differ for boys and girls. Visuospatial and verbal STM scores were not significantly correlated when age was partialed out. Age, visuospatial STM scores, and verbal STM scores accounted for unique variance in expressive (51%, 3%, and 4%, respectively) and receptive vocabulary scores (53%, 5%, and 2%, respectively) in multiple regression analyses. Replication studies, a fuller test battery comprising visuospatial and verbal STM and WM tests, and a general intelligence test are required before exploring the usefulness of these STM tests for predicting longitudinal outcomes. The lack of an association between the STM tests suggests that the instruments have face validity and test independent STM skills.

Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux.

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Zhou, Tianen; Liang, Lian; Liang, Yanran; Yu, Tao; Zeng, Chaotao; Jiang, Longyuan

2017-09-15

Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux. Copyright © 2017. Published by Elsevier Inc.

Stereopsis, Visuospatial Ability, and Virtual Reality in Anatomy Learning.

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Luursema, Jan-Maarten; Vorstenbosch, Marc; Kooloos, Jan

2017-01-01

A new wave of virtual reality headsets has become available. A potential benefit for the study of human anatomy is the reintroduction of stereopsis and absolute size. We report a randomized controlled trial to assess the contribution of stereopsis to anatomy learning, for students of different visuospatial ability. Sixty-three participants engaged in a one-hour session including a study phase and posttest. One group studied 3D models of the anatomy of the deep neck in full stereoptic virtual reality; one group studied those structures in virtual reality without stereoptic depth. The control group experienced an unrelated virtual reality environment. A post hoc questionnaire explored cognitive load and problem solving strategies of the participants. We found no effect of condition on learning. Visuospatial ability however did impact correct answers at F (1) = 5.63 and p = .02. No evidence was found for an impact of cognitive load on performance. Possibly, participants were able to solve the posttest items based on visuospatial information contained in the test items themselves. Additionally, the virtual anatomy may have been complex enough to discourage memory based strategies. It is important to control the amount of visuospatial information present in test items.

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

NARCIS (Netherlands)

Papma, Janne M.; Smits, Marion; De Groot, Marius; Mattace-Raso, Francesco U. S.; van der Lugt, Aad; Vrooman, Henri A.; Niessen, W.J.; Koudstaal, Peter J.; van Swieten, John C.; van der Veen, Frederik M.; Prins, Niels D.

2017-01-01

Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

NARCIS (Netherlands)

J.M. Papma (Janne); M. Smits (Marion); M. de Groot (Mirthe); F.U.S. Mattace Raso (Francesco); A. van der Lugt (Aad); H.A. Vrooman (Henri); W.J. Niessen (Wiro); P.J. Koudstaal (Peter Jan); J.C. van Swieten (John); F.M. van der Veen (Frederik); N.D. Prins (Niels)

2017-01-01

textabstractObjectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

Endogenous IL-1 in Cognitive Function and Anxiety: A Study in IL-1RI−/− Mice

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Murray, Carol L.; Obiang, Pauline; Bannerman, David; Cunningham, Colm

2013-01-01

Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, produced predominantly by peripheral immune cells but also by glia and some neuronal populations within the brain. Its signalling is mediated via the binding of IL-1α or IL-1β to the interleukin-1 type one receptor (IL-1RI). IL-1 plays a key role in inflammation-induced sickness behaviour, resulting in depressed locomotor activity, decreased exploration, reduced food and water intake and acute cognitive deficits. Conversely, IL-1 has also been suggested to facilitate hippocampal-dependent learning and memory: IL-1RI−/− mice have been reported to show deficits on tasks of visuospatial learning and memory. We sought to investigate whether there is a generalised hippocampal deficit in IL-1RI−/− animals. Therefore, in the current study we compared wildtype (WT) mice to IL-1RI−/− mice using a variety of hippocampal-dependent learning and memory tasks, as well as tests of anxiety and locomotor activity. We found no difference in performance of the IL-1RI−/− mice compared to WT mice in a T-maze working memory task. In addition, the IL-1RI−/− mice showed normal learning in various spatial reference memory tasks including the Y-maze and Morris mater maze, although there was a subtle deficit in choice behaviour in a spatial discrimination, beacon watermaze task. IL-1RI−/− mice also showed normal memory for visuospatial context in the contextual fear conditioning paradigm. In the open field, IL-1RI−/− mice showed a significant increase in distance travelled and rearing behaviour compared to the WT mice and in the elevated plus-maze spent more time in the open arms than did the WT animals. The data suggest that, contrary to prior studies, IL-1RI−/− mice are not robustly impaired on hippocampal-dependent memory and learning but do display open field hyperactivity and decreased anxiety compared to WT mice. The results argue for a careful evaluation of the roles of endogenous IL-1 in

Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity

NARCIS (Netherlands)

Hulst, H.E.; Schoonheim, M.M.; van Geest, Q.; Uitdehaag, B.M.J.; Barkhof, F.; Geurts, J.J.G.

2015-01-01

Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and

Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

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Wang, Yonggang; Neumann, Melanie; Hansen, Katharina; Hong, Shuwhey M.; Kim, Sharon; Noble-Haeusslein, Linda J.

2011-01-01

Abstract The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits. PMID:21175261

Similar prefrontal cortical activities between general fluid intelligence and visuospatial working memory tasks in preschool children as revealed by optical topography.

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Kuwajima, Mariko; Sawaguchi, Toshiyuki

2010-10-01

General fluid intelligence (gF) is a major component of intellect in both adults and children. Whereas its neural substrates have been studied relatively thoroughly in adults, those are poorly understood in children, particularly preschoolers. Here, we hypothesized that gF and visuospatial working memory share a common neural system within the lateral prefrontal cortex (LPFC) during the preschool years (4-6 years). At the behavioral level, we found that gF positively and significantly correlated with abilities (especially accuracy) in visuospatial working memory. Optical topography revealed that the LPFC of preschoolers was activated and deactivated during the visuospatial working memory task and the gF task. We found that the spatio-temporal features of neural activity in the LPFC were similar for both the visuospatial working memory task and the gF task. Further, 2 months of training for the visuospatial working memory task significantly increased gF in the preschoolers. These findings suggest that a common neural system in the LPFC is recruited to improve the visuospatial working memory and gF in preschoolers. Efficient recruitment of this neural system may be important for good performance in these functions in preschoolers, and behavioral training using this system would help to increase gF at these ages.

A virtual reality test identifies the visuospatial strengths of adolescents with dyslexia.

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Attree, Elizabeth A; Turner, Mark J; Cowell, Naina

2009-04-01

Research suggests that the deficits characterizing dyslexia may also be associated with superior visuospatial abilities. Other research suggests that superior visuospatial abilities of people with dyslexia may not have been so far identified because of the lack of appropriate tests of real-life spatial ability. A recent small-scale study found that visuospatial superiority was evident in men with dyslexia. This study assessed the visuospatial ability of adolescents with dyslexia in order to determine whether these adolescents performed better on a pseudo real-life visuospatial test than did their nondyslexic peers. Forty-two adolescents took part in the study. There was an equal numerical split between the experimental and control groups. The experimental group all had a diagnosis of dyslexia by an educational psychologist or specialist teacher. Visuospatial ability was assessed using the Recall of Designs and the Pattern Construction subtests from the British Ability Scales (2nd edition; BAS-11) together with a computer-generated virtual environment test. The assessments were administered in a counterbalanced order. Adolescents with dyslexia tended to perform less well than their nondyslexic peers on the BAS-11 tests; however, this difference was not statistically significant. For the computer-generated virtual environment test (pseudo real-life measure), statistically significant higher scores were achieved by the dyslexic group. These findings suggest that adolescents with dyslexia may exhibit superior visuospatial strengths on certain pseudo real-life tests of spatial ability. The usefulness of these findings is discussed in relation to possible implications for assessment and educational intervention programs for adolescents with dyslexia.

Establishing a New Screening System for Mild Cognitive Impairment and Alzheimer's Disease with Mental Rotation Tasks that Evaluate Visuospatial Function.

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Suzuki, Ayuko; Shinozaki, Jun; Yazawa, Shogo; Ueki, Yoshino; Matsukawa, Noriyuki; Shimohama, Shun; Nagamine, Takashi

2018-01-01

The mental rotation task is well-known for the assessment of visuospatial function; however, it has not been used for screening of dementia patients. The aim of this study was to create a simple screening test for patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by focusing on non-amnestic symptoms. Age-matched healthy controls (age 75.3±6.8), patients with MCI (76.5±5.5), and AD (78.2±5.0) participated in this study. They carried out mental rotation tasks targeting geometric graphics or alphabetical characters with three rotating angles (0°, 90°, and 180°) and indicated the correct answer. Response accuracy and reaction time were recorded along with their eye movements using an eye tracker. To quantify their visual processing strategy, the run count ratio (RC ratio) was calculated by dividing the mean number of fixations in incorrect answers by that in correct answers. AD patients showed lower accuracy and longer reaction time than controls. They also showed a significantly greater number of fixation and smaller saccade amplitude than controls, while fixation duration did not differ significantly. The RC ratio was higher for AD, followed by MCI and control groups. By setting the cut-off value to 0.47 in the 180° rotating angle task, we could differentiate MCI patients from controls with a probability of 80.0%. We established a new screening system for dementia patients by evaluating visuospatial function. The RC ratio during a mental rotation task is useful for discriminating MCI patients from controls.

Pregnancy-related anxiety and depressive symptoms are associated with visuospatial working memory errors during pregnancy.

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Kataja, E-L; Karlsson, L; Huizink, A C; Tolvanen, M; Parsons, C; Nolvi, S; Karlsson, H

2017-08-15

Cognitive deficits, especially in memory and concentration, are often reported during pregnancy. Similar cognitive dysfunctions can also occur in depression and anxiety. To date, few studies have investigated the associations between cognitive deficits and psychiatric symptoms during pregnancy. This field is of interest because maternal cognitive functioning, and particularly its higher-order aspects are related to maternal well-being and caregiving behavior, as well as later child development. Pregnant women (N =230), reporting low (n =87), moderate (n =97), or high (n =46) levels of depressive, general anxiety and/or pregnancy-related anxiety symptoms (assessed repeatedly with EPDS, SCL-90/anxiety subscale, PRAQ-R2, respectively) were tested in mid-pregnancy for their cognitive functions. A computerized neuropsychological test battery was used. Pregnant women with high or moderate level of psychiatric symptoms had significantly more errors in visuospatial working memory/executive functioning task than mothers with low symptom level. Depressive symptoms throughout pregnancy and concurrent pregnancy-related anxiety symptoms were significant predictors of the performance in the task. General anxiety symptoms were not related to visuospatial working memory. Cognitive functions were evaluated only at one time-point during pregnancy precluding causal conclusions. Maternal depressive symptoms and pregnancy-related anxiety symptoms were both associated with decrements in visuospatial working memory/executive functioning. Depressive symptoms seem to present more stable relationship with cognitive deficits, while pregnancy-related anxiety was associated only concurrently. Future studies could investigate, how stable these cognitive differences are, and whether they affect maternal ability to deal with demands of pregnancy and later parenting. Copyright © 2017 Elsevier B.V. All rights reserved.

Verbal and visuospatial working memory as predictors of children's reading ability.

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Pham, Andy V; Hasson, Ramzi M

2014-08-01

Children with reading difficulties often demonstrate weaknesses in working memory (WM). This research study explored the relation between two WM systems (verbal and visuospatial WM) and reading ability in a sample of school-aged children with a wide range of reading skills. Children (N = 157), ages 9-12, were administered measures of short-term memory, verbal WM, visuospatial WM, and reading measures (e.g., reading fluency and comprehension). Although results indicated that verbal WM was a stronger predictor in reading fluency and comprehension, visuospatial WM also significantly predicted reading skills, but provided more unique variance in reading comprehension than reading fluency. These findings suggest that visuospatial WM may play a significant role in higher level reading processes, particularly in reading comprehension, than previously thought. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Inter-relationships among diet, obesity and hippocampal-dependent cognitive function.

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Davidson, T L; Hargrave, S L; Swithers, S E; Sample, C H; Fu, X; Kinzig, K P; Zheng, W

2013-12-03

Intake of a Western diet (WD), which is high in saturated fat and sugar, is associated with deficits in hippocampal-dependent learning and memory processes as well as with markers of hippocampal pathology. In the present study, rats were trained to asymptote on hippocampal-dependent serial feature negative (FN) and hippocampal-independent simple discrimination problems. Performance was then assessed following 7 days on ad libitum chow and after 10, 24, 40, 60, and 90 days of maintenance on WD, on ketogenic (KETO) diet, which is high in saturated fat and low in sugar and other carbohydrates, or continued maintenance on chow (CHOW). Confirming and extending previous findings, diet-induced obese (DIO) rats fed WD showed impaired FN performance, increased blood-brain barrier (BBB) permeability, and increased fasting blood glucose levels compared to CHOW controls and to diet-resistant (DR) rats that did not become obese when maintained on WD. For rats fed the KETO diet, FN performance and BBB integrity were more closely associated with level of circulating ketone bodies than with obesity phenotype (DR or DIO), with higher levels of ketones appearing to provide a protective effect. The evidence also indicated that FN deficits preceded and predicted increased body weight and adiposity. This research (a) further substantiates previous findings of WD-induced deficits in hippocampal-dependent FN discriminations, (b) suggests that ketones may be protective against diet-induced cognitive impairment, and (c) provides evidence that diet-induced cognitive impairment precedes weight gain and obesity. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Stereopsis, Visuospatial Ability, and Virtual Reality in Anatomy Learning

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Jan-Maarten Luursema

2017-01-01

Full Text Available A new wave of virtual reality headsets has become available. A potential benefit for the study of human anatomy is the reintroduction of stereopsis and absolute size. We report a randomized controlled trial to assess the contribution of stereopsis to anatomy learning, for students of different visuospatial ability. Sixty-three participants engaged in a one-hour session including a study phase and posttest. One group studied 3D models of the anatomy of the deep neck in full stereoptic virtual reality; one group studied those structures in virtual reality without stereoptic depth. The control group experienced an unrelated virtual reality environment. A post hoc questionnaire explored cognitive load and problem solving strategies of the participants. We found no effect of condition on learning. Visuospatial ability however did impact correct answers at F(1=5.63 and p=.02. No evidence was found for an impact of cognitive load on performance. Possibly, participants were able to solve the posttest items based on visuospatial information contained in the test items themselves. Additionally, the virtual anatomy may have been complex enough to discourage memory based strategies. It is important to control the amount of visuospatial information present in test items.

Assessment of working memory in patients with mesial temporal lobe epilepsy associated with unilateral hippocampal sclerosis.

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Tudesco, Ivanda de Souza Silva; Vaz, Leonardo José; Mantoan, Marcele Araújo Silva; Belzunces, Erich; Noffs, Maria Helena; Caboclo, Luís Otávio Sales Ferreira; Yacubian, Elza Márcia Targas; Sakamoto, Américo Ceiki; Bueno, Orlando Francisco Amodeo

2010-07-01

The aim of the present study was to investigate whether working memory is impaired in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), a controversial and largely unexplored matter. Twenty subjects with left MTLE-HS, 19 with right MTLE-HS, and 21 control right-handed subjects underwent neuropsychological assessment of episodic and semantic memory, executive functions, and specific working memory components. Left and right epileptogenic foci resulted in impairment of verbal and nonverbal episodic memory (verbal memory deficit greater in left MTLE-HS than in right MTLE-HS). In addition, patients with left MTLE-HS were impaired in learning paired associates, verbal fluency, and Trail Making. No differences were seen in the tests carried out to evaluate the working memory components (except visuospatial short-term memory in right MTLE-HS). In this study we did not detect reliable working memory impairment in patients with MTLE-HS with either a left or right focus in most tasks considered as tests of working memory components. Copyright 2010 Elsevier Inc. All rights reserved.

Multimodal assessments of the hippocampal formation in schizophrenia and bipolar disorder: Evidences from neurobehavioral measures and functional and structural MRI

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Christian Knöchel

2014-01-01

Full Text Available A potential clinical and etiological overlap between schizophrenia (SZ and bipolar disorder (BD has long been a subject of discussion. Imaging studies imply functional and structural alterations of the hippocampus in both diseases. Thus, imaging this core memory region could provide insight into the pathophysiology of these disorders and the associated cognitive deficits. To examine possible shared alterations in the hippocampus, we conducted a multi-modal assessment, including functional and structural imaging as well as neurobehavioral measures of memory performance in BD and SZ patients compared with healthy controls. We assessed episodic memory performance, using tests of verbal and visual learning (HVLT, BVMT in three groups of participants: BD patients (n = 21, SZ patients (n = 21 and matched (age, gender, education healthy control subjects (n = 21. In addition, we examined hippocampal resting state functional connectivity, hippocampal volume using voxel-based morphometry (VBM and fibre integrity of hippocampal connections using diffusion tensor imaging (DTI. We found memory deficits, changes in functional connectivity within the hippocampal network as well as volumetric reductions and altered white matter fibre integrity across patient groups in comparison with controls. However, SZ patients when directly compared with BD patients were more severely affected in several of the assessed parameters (verbal learning, left hippocampal volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus. The results of our study suggest a graded expression of verbal learning deficits accompanied by structural alterations within the hippocampus in BD patients and SZ patients, with SZ patients being more strongly affected. Our findings imply that these two disorders may share some common pathophysiological mechanisms. The results could thus help to further advance and integrate current pathophysiological models of SZ and BD.

Development of vicarious trial-and-error behavior in odor discrimination learning in the rat: relation to hippocampal function?

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Hu, D; Griesbach, G; Amsel, A

1997-06-01

Previous work from our laboratory has suggested that hippocampal electrolytic lesions result in a deficit in simultaneous, black-white discrimination learning and reduce the frequency of vicarious trial-and-error (VTE) at a choice-point. VTE is a term Tolman used to describe the rat's conflict-like behavior, moving its head from one stimulus to the other at a choice point, and has been proposed as a major nonspatial feature of hippocampal function in both visual and olfactory discrimination learning. Simultaneous odor discrimination and VTE behavior were examined at three different ages. The results were that 16-day-old pups made fewer VTEs and learned much more slowly than 30- and 60-day-olds, a finding in accord with levels of hippocampal maturity in the rat.

The CRISP theory of hippocampal function in episodic memory

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Cheng, Sen

2013-01-01

Over the past four decades, a “standard framework” has emerged to explain the neural mechanisms of episodic memory storage. This framework has been instrumental in driving hippocampal research forward and now dominates the design and interpretation of experimental and theoretical studies. It postulates that cortical inputs drive plasticity in the recurrent cornu ammonis 3 (CA3) synapses to rapidly imprint memories as attractor states in CA3. Here we review a range of experimental studies and argue that the evidence against the standard framework is mounting, notwithstanding the considerable evidence in its support. We propose CRISP as an alternative theory to the standard framework. CRISP is based on Context Reset by dentate gyrus (DG), Intrinsic Sequences in CA3, and Pattern completion in cornu ammonis 1 (CA1). Compared to previous models, CRISP uses a radically different mechanism for storing episodic memories in the hippocampus. Neural sequences are intrinsic to CA3, and inputs are mapped onto these intrinsic sequences through synaptic plasticity in the feedforward projections of the hippocampus. Hence, CRISP does not require plasticity in the recurrent CA3 synapses during the storage process. Like in other theories DG and CA1 play supporting roles, however, their function in CRISP have distinct implications. For instance, CA1 performs pattern completion in the absence of CA3 and DG contributes to episodic memory retrieval, increasing the speed, precision, and robustness of retrieval. We propose the conceptual theory, discuss its implications for experimental results and suggest testable predictions. It appears that CRISP not only accounts for those experimental results that are consistent with the standard framework, but also for results that are at odds with the standard framework. We therefore suggest that CRISP is a viable, and perhaps superior, theory for the hippocampal function in episodic memory. PMID:23653597

Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

International Nuclear Information System (INIS)

Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas; Schreckenberger, Matthias; Cumming, Paul; Stoeter, Peter; Gerhard, Alex

2011-01-01

Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

The role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function.

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Yu-Chen Wang

Full Text Available BACKGROUND: Dexamethasone (DEX, a synthetic glucocorticoid, is commonly used to prevent or lessen the morbidity of chronic lung disease in preterm infants. However, evidence is now increasing that this clinical practice negatively affects somatic growth and may result in long-lasting neurodevelopmental deficits. We therefore hypothesized that supporting normal somatic growth may overcome the lasting adverse effects of neonatal DEX treatment on hippocampal function. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we developed a rat model using a schedule of tapering doses of DEX similar to that used in premature infants and examined whether the lasting influence of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance are correlated with the deficits in somatic growth. We confirmed that neonatal DEX treatment switched the direction of synaptic plasticity in hippocampal CA1 region, favoring low-frequency stimulation- and group I metabotropic glutamate receptor agonist (S-3,5,-dihydroxyphenylglycine-induced long-term depression (LTD, and opposing the induction of long-term potentiation (LTP by high-frequency stimulation in the adolescent period. The effects of DEX on LTP and LTD were correlated with an increase in the autophosphorylation of Ca(2+/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. Neonatal DEX treatment resulted in a disruption of memory retention subjected to object recognition task and passive avoidance learning. The adverse effects of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance of the animals from litters culled to 4 pups were significantly less than those for the 8-pup litters. However, there was no significant difference in maternal care between groups. CONCLUSION/SIGNIFICANCE: Our results demonstrate that growth retardation plays a crucial role in DEX-induced long-lasting influence of

Visuospatial attention and motor skills in kung fu athletes.

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Muiños, Mónica; Ballesteros, Soledad

2013-01-01

The present study compared the performance of a group of sixteen kung fu athletes with that of a control group of fourteen nonathletes on a speeded visuospatial task and a hand-tapping motor task. In the visuospatial task the results showed that athletes were faster than the control participants when stimuli were presented at the periphery of the visual field at a middle and high presentation speed with short interstimulus intervals. Athletes were also significantly faster than nonathlete participants when performing motor actions such as hand-tapping with their dominant hand but groups did not differ with the nondominant hand. These results support the view that athletes perform some speeded visuospatial and motor tasks faster than nonathletes under certain conditions. The findings suggest that, after several years of practice, kung fu athletes develop certain skills that allow them to perform motor speed maneuvers under time pressure conditions.

Inhibitory effects of caffeine on hippocampal neurogenesis and function.

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Han, Myoung-Eun; Park, Kyu-Hyun; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Kim, Hak-Jin; Oh, Sae-Ock

2007-05-18

Caffeine is one of the most extensively consumed psychostimulants in the world. However, compared to short-term effects of caffeine, the long-term effects of caffeine consumption on learning and memory are poorly characterized. The present study found that long-term consumption of low dose caffeine (0.3 g/L) slowed hippocampus-dependent learning and impaired long-term memory. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls. From these results, we concluded that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis.

A Neural Mechanism for Surprise-related Interruptions of Visuospatial Working Memory.

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Wessel, Jan R

2018-01-01

Surprising perceptual events recruit a fronto-basal ganglia mechanism for inhibition, which suppresses motor activity following surprise. A recent study found that this inhibitory mechanism also disrupts the maintenance of verbal working memory (WM) after surprising tones. However, it is unclear whether this same mechanism also relates to surprise-related interruptions of non-verbal WM. We tested this hypothesis using a change-detection task, in which surprising tones impaired visuospatial WM. Participants also performed a stop-signal task (SST). We used independent component analysis and single-trial scalp-electroencephalogram to test whether the same inhibitory mechanism that reflects motor inhibition in the SST relates to surprise-related visuospatial WM decrements, as was the case for verbal WM. As expected, surprising tones elicited activity of the inhibitory mechanism, and this activity correlated strongly with the trial-by-trial level of surprise. However, unlike for verbal WM, the activity of this mechanism was unrelated to visuospatial WM accuracy. Instead, inhibition-independent activity that immediately succeeded the inhibitory mechanism was increased when visuospatial WM was disrupted. This shows that surprise-related interruptions of visuospatial WM are not effected by the same inhibitory mechanism that interrupts verbal WM, and instead provides evidence for a 2-stage model of distraction. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Preliminary Study of Functional Brain Activation among Marijuana Users during Performance of a Virtual Water Maze Task

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Jennifer Tropp Sneider

2013-01-01

Full Text Available Numerous studies have reported neurocognitive impairments associated with chronic marijuana use. Given that the hippocampus contains a high density of cannabinoid receptors, hippocampal-mediated cognitive functions, including visuospatial memory, may have increased vulnerability to chronic marijuana use. Thus, the current study examined brain activation during the performance of a virtual analogue of the classic Morris water maze task in 10 chronic marijuana (MJ users compared to 18 nonusing (NU comparison subjects. Imaging data were acquired using blood oxygen level-dependent (BOLD functional MRI at 3.0 Tesla during retrieval (hidden platform and motor control (visible platform conditions. While task performance on learning trials was similar between groups, MJ users demonstrated a deficit in memory retrieval. For BOLD fMRI data, NU subjects exhibited greater activation in the right parahippocampal gyrus and cingulate gyrus compared to the MJ group for the Retrieval-Motor Control contrast (NU > MJ. These findings suggest that hypoactivation in MJ users may be due to differences in the efficient utilization of neuronal resources during the retrieval of memory. Given the paucity of data on visuospatial memory function in MJ users, these findings may help elucidate the neurobiological effects of marijuana on brain activation during memory retrieval.

Visuo-Spatial Attention in ADHD Children: Investigating the Asymmetry

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Faranak Aliabadi

2011-04-01

Full Text Available Objectives: The purpose of the present study was comparing visuo-spatial attention between children with Attention Deficit Hyperactivity Disorder-Inattentive (ADHD-I type and normal children. Methods: In this cross-sectional study fifteen (7-10 years of age children were classified with ADHD-I type and 15 normal children were matched for age, sex, and IQ. They were selected trough simple random sampling. Measurement tools were Wechsler Intelligence Scale for children 4th edition (WISC-IV, the Edinburgh Handedness Inventory and the Star Cancellation Test. Results: The results suggest that there is no significant difference between ADHD-I and normal children from the visuo-spatial standpoint (P>0.05. But three ADHD-I children exhibited signs of unilateral neglect. Discussion: Although, in this study the visuo-spatial attention was not different between ADHD-I group and normal group, considering this form of attention as an item in assessment and therapeutic interventions should not be neglected.

Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.

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Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2018-01-01

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger

Developmental Gains in Visuospatial Memory Predict Gains in Mathematics Achievement

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Li, Yaoran; Geary, David C.

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusiv...

Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

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Chen, Li-You; Renn, Ting-Yi; Liao, Wen-Chieh; Mai, Fu-Der; Ho, Ying-Jui; Hsiao, George; Lee, Ai-Wei; Chang, Hung-Ming

2017-09-01

Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [ 14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from

Central coherence, organizational strategy, and visuospatial memory in children and adolescents with anorexia nervosa.

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Rose, Mark; Frampton, Ian J; Lask, Bryan

2014-01-01

The vast majority of studies in anorexia nervosa that have investigated the domains of central coherence, organizational strategy, and visuospatial memory have focused on adult samples. In addition, studies investigating visuospatial memory have focused on free recall. No study to date has reported the association between recognition memory and central coherence or organizational strategy in younger people with this disorder, yet the capacity to recognize previously seen visual stimuli may contribute to overall visuospatial ability. Therefore, we investigate these domains in children and adolescents with anorexia nervosa compared to age- and gender-matched healthy controls. There were no significant group differences in immediate, delayed, or recognition memory, central coherence, or organization strategy. When compared with controls, patients with anorexia nervosa scored significantly higher on accuracy and took significantly longer when copying the Rey Complex Figure Task. Caution must be taken when interpreting these findings due to lower-than-expected scores in memory performance in the control group and because of a potential lack of sensitivity in the measures used when assessing this younger population. For neuropsychological functions where no normative data exist, we need a deeper, more thorough knowledge of the developmental trajectory and its assessment in young people in the general population before drawing conclusions in anorexia nervosa.

The hippocampal network model: A transdiagnostic metaconnectomic approach

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Eithan Kotkowski

Full Text Available Purpose: The hippocampus plays a central role in cognitive and affective processes and is commonly implicated in neurodegenerative diseases. Our study aimed to identify and describe a hippocampal network model (HNM using trans-diagnostic MRI data from the BrainMap® database. We used meta-analysis to test the network degeneration hypothesis (NDH (Seeley et al., 2009 by identifying structural and functional covariance in this hippocampal network. Methods: To generate our network model, we used BrainMap's VBM database to perform a region-to-whole-brain (RtWB meta-analysis of 269 VBM experiments from 165 published studies across a range of 38 psychiatric and neurological diseases reporting hippocampal gray matter density alterations. This step identified 11 significant gray matter foci, or nodes. We subsequently used meta-analytic connectivity modeling (MACM to define edges of structural covariance between nodes from VBM data as well as functional covariance using the functional task-activation database, also from BrainMap. Finally, we applied a correlation analysis using Pearson's r to assess the similarities and differences between the structural and functional covariance models. Key findings: Our hippocampal RtWB meta-analysis reported consistent and significant structural covariance in 11 key regions. The subsequent structural and functional MACMs showed a strong correlation between HNM nodes with a significant structural-functional covariance correlation of r = .377 (p = .000049. Significance: This novel method of studying network covariance using VBM and functional meta-analytic techniques allows for the identification of generalizable patterns of functional and structural abnormalities pertaining to the hippocampus. In accordance with the NDH, this framework could have major implications in studying and predicting spatial disease patterns using network-based assays. Keywords: Anatomic likelihood estimation, ALE, BrainMap, Functional

The impact of blood pressure on hippocampal glutamate and mnestic function.

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Westhoff, T H; Schubert, F; Wirth, C; Joppke, M; Klär, A A; Zidek, W; Gallinat, J

2011-04-01

Hypertension is associated with an increased risk of cognitive decline, which is generally regarded as a consequence of advanced cerebral atherosclerosis. Many hypertensive patients, however, suffer from cognitive decline long before they have any signs of cerebrovascular disease. Therefore, this study examines direct effects of blood pressure on neurotransmitter status in the hippocampus, a vulnerable cerebral structure relevant for memory consolidation. Absolute glutamate concentration and N-acetylaspartate (NAA) concentration as an alternative marker of neuronal integrity were determined in the hippocampus and the cerebral cortex (anterior cingulate cortex; ACC) by 3-T proton magnetic resonance spectroscopy in 16 probands without any history of cerebrovascular disease. Memory function was tested by the auditory verbal learning test (AVLT) and the rivermead behavioural memory test (RBMT). Arterial stiffness was assessed by augmentation index (AI). Mean arterial pressure showed a significant negative age-adjusted correlation to absolute glutamate concentrations in the hippocampus (R=-0.655, P=0.011), but not in the ACC. There was no significant correlation of mean arterial pressure and NAA in either hippocampus or ACC. AI did not affect hippocampal glutamate. Moreover, there was a significant negative correlation between mean arterial pressure and AVLT (r=-0.558, P=0.025) and RBMT score (r=-0.555, P=0.026). There is an inverse relation between blood pressure and the concentration of hippocampal glutamate. Glutamate is essential for long-term potentiation, the neurobiological correlate for memory formation in the hippocampus. Thus, hypertension-associated cognitive decline may not only be mediated by structural atherosclerotic wall changes, but also by functional changes in neurotransmission.

New protocol for dissociating visuospatial working memory ability in reaching space and in navigational space.

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Lupo, Michela; Ferlazzo, Fabio; Aloise, Fabio; Di Nocera, Francesco; Tedesco, Anna Maria; Cardillo, Chiara; Leggio, Maria

2018-04-27

Several studies have demonstrated that the processing of visuospatial memory for locations in reaching space and in navigational space is supported by independent systems, and that the coding of visuospatial information depends on the modality of the presentation (i.e., sequential or simultaneous). However, these lines of evidence and the most common neuropsychological tests used by clinicians to investigate visuospatial memory have several limitations (e.g., they are unable to analyze all the subcomponents of this function and are not directly comparable). Therefore, we developed a new battery of tests that is able to investigate these subcomponents. We recruited 71 healthy subjects who underwent sequential and simultaneous navigational tests by using an innovative sensorized platform, as well as comparable paper tests to evaluate the same components in reaching space (Exp. 1). Consistent with the literature, the principal-component method of analysis used in this study demonstrated the presence of distinct memory for sequences in different portions of space, but no distinction was found for simultaneous presentation, suggesting that different modalities of eye gaze exploration are used when subjects have to perform different types of tasks. For this purpose, an infrared Tobii Eye-Tracking X50 system was used in both spatial conditions (Exp. 2), showing that a clear effect of the presentation modality was due to the specific strategy used by subjects to explore the stimuli in space. Given these findings, the neuropsychological battery established in the present study allows us to show basic differences in the normal coding of stimuli, which can explain the specific visuospatial deficits found in various neurological conditions.

The human hippocampal formation mediates short-term memory of colour-location associations.

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Finke, Carsten; Braun, Mischa; Ostendorf, Florian; Lehmann, Thomas-Nicolas; Hoffmann, Karl-Titus; Kopp, Ute; Ploner, Christoph J

2008-01-31

The medial temporal lobe (MTL) has long been considered essential for declarative long-term memory, whereas the fronto-parietal cortex is generally seen as the anatomical substrate of short-term memory. This traditional dichotomy is questioned by recent studies suggesting a possible role of the MTL for short-term memory. In addition, there is no consensus on a possible specialization of MTL sub-regions for memory of associative information. Here, we investigated short-term memory for single features and feature associations in three humans with post-surgical lesions affecting the right hippocampal formation and in 10 healthy controls. We used three delayed-match-to-sample tasks with two delays (900/5000 ms) and three set sizes (2/4/6 items). Subjects were instructed to remember either colours, locations or colour-location associations. In colour-only and location-only conditions, performance of patients did not differ from controls. By contrast, a significant group difference was found in the association condition at 5000 ms delay. This difference was largely independent of set size, thus suggesting that it cannot be explained by the increased complexity of the association condition. These findings show that the hippocampal formation plays a significant role for short-term memory of simple visuo-spatial associations, and suggest a specialization of MTL sub-regions for associative memory.

The enhancement of visuospatial processing efficiency through Buddhist Deity meditation.

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Kozhevnikov, Maria; Louchakova, Olga; Josipovic, Zoran; Motes, Michael A

2009-05-01

This study examined the effects of meditation on mental imagery, evaluating Buddhist monks' reports concerning their extraordinary imagery skills. Practitioners of Buddhist meditation were divided into two groups according to their preferred meditation style: Deity Yoga (focused attention on an internal visual image) or Open Presence (evenly distributed attention, not directed to any particular object). Both groups of meditators completed computerized mental-imagery tasks before and after meditation. Their performance was compared with that of control groups, who either rested or performed other visuospatial tasks between testing sessions. The results indicate that all the groups performed at the same baseline level, but after meditation, Deity Yoga practitioners demonstrated a dramatic increase in performance on imagery tasks compared with the other groups. The results suggest that Deity meditation specifically trains one's capacity to access heightened visuospatial processing resources, rather than generally improving visuospatial imagery abilities.

Mutant APP and Amyloid beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer's disease.

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Reddy, P Hemachandra; Yin, XiangLin; Manczak, Maria; Kumar, Subodh; Jangampalli Adi, Pradeepkiran; Vijayan, Murali; Reddy, Arubala P

2018-04-25

The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in human mutant APP (mAPP) cDNA transfected with primary mouse hippocampal neurons (HT22). Hippocampal tissues are the best source of studying learning and memory functions in patients with Alzheimer's disease (AD) and healthy controls. However, investigating immortalized hippocampal neurons that express AD proteins provide an excellent opportunity for drug testing. Using quantitative RT-PCR, immunoblotting & immunofluorescence, and transmission electron microscopy, we assessed mRNA and protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and assessed mitochondrial number and length in mAPP-HT22 cells that express Swedish/Indiana mutations. Mitochondrial function was assessed by measuring the levels of hydrogen peroxide, lipid peroxidation, cytochrome c oxidase activity and mitochondrial ATP. Increased levels of mRNA and protein levels of mitochondrial fission genes, Drp1 and Fis1 and decreased levels fusion (Mfn1, Mfn2 and Opa1) biogenesis (PGC1α, NRF1, NRF2 & TFAM), autophagy (ATG5 & LC3BI, LC3BII), mitophagy (PINK1 & TERT, BCL2 & BNIPBL), synaptic (synaptophysin & PSD95) and dendritic (MAP2) genes were found in mAPP-HT22 cells relative to WT-HT22 cells. Cell survival was significantly reduced mAPP-HT22 cells. GTPase-Dp1 enzymatic activity was increased in mAPP-HT22 cells. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells. These findings suggest that hippocampal accumulation of mutant APP and Aβ is responsible for abnormal mitochondrial dynamics and defective biogenesis, reduced MAP2, autophagy, mitophagy and synaptic proteins & reduced dendritic spines and mitochondrial structural and functional changes in mutant APP hippocampal cells. These observations strongly suggest that accumulation of mAPP and A�

Cognitive demands of face monitoring: evidence for visuospatial overload.

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Doherty-Sneddon, G; Bonner, L; Bruce, V

2001-10-01

Young children perform difficult communication tasks better face to face than when they cannot see one another (e.g., Doherty-Sneddon & Kent, 1996). However, in recent studies, it was found that children aged 6 and 10 years, describing abstract shapes, showed evidence of face-to-face interference rather than facilitation. For some communication tasks, access to visual signals (such as facial expression and eye gaze) may hinder rather than help children's communication. In new research we have pursued this interference effect. Five studies are described with adults and 10- and 6-year-old participants. It was found that looking at a face interfered with children's abilities to listen to descriptions of abstract shapes. Children also performed visuospatial memory tasks worse when they looked at someone's face prior to responding than when they looked at a visuospatial pattern or at the floor. It was concluded that performance on certain tasks was hindered by monitoring another person's face. It is suggested that processing of visual communication signals shares certain processing resources with the processing of other visuospatial information.

Towards a visuospatial developmental account of sequence-space synaesthesia

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Mark ePrice

2013-10-01

Full Text Available Sequence-space synaesthetes experience some sequences (e.g. numbers, calendar units as arranged in spatial forms, i.e., spatial patterns in their mind’s eye or even outside their body. Various explanations have been offered for this phenomenon. Here we argue that these spatial forms are continuous with, and share central characteristics with, varieties of non-synaesthetic visuospatial imagery. This includes their dynamic and elaborative nature, their involuntary feel and consistency over time. Drawing from literatures on mental imagery and working memory, we suggest how the initial acquisition and subsequent elaboration of spatial forms could be accounted for in terms of the known developmental trajectory of visuospatial representations. This extends from the formation of image-based representations of verbal material in childhood to the later maturation of dynamic control of imagery. Individual differences in the development of visuospatial style also account for variation in the character of spatial forms, e.g. in terms of distinctions such as visual versus spatial imagery, or ego-centric versus object-based transformations.

Functional magnetic resonance imaging of hippocampal activation during silent mantra meditation.

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Engström, Maria; Pihlsgård, Johan; Lundberg, Peter; Söderfeldt, Birgitta

2010-12-01

The objective of the present study was to investigate whether moderately experienced meditators activate hippocampus and the prefrontal cortex during silent mantra meditation, as has been observed in earlier studies on subjects with several years of practice. Subjects with less than 2 years of meditation practice according to the Kundalini yoga or Acem tradition were examined by functional magnetic resonance imaging during silent mantra meditation, using an on-off block design. Whole-brain as well as region-of-interest analyses were performed. The most significant activation was found in the bilateral hippocampus/parahippocampal formations. Other areas with significant activation were the bilateral middle cingulate cortex and the bilateral precentral cortex. No activation in the anterior cingulate cortex was found, and only small activation clusters were observed in the prefrontal cortex. In conclusion, the main finding in this study was the significant activation in the hippocampi, which also has been correlated with meditation in several previous studies on very experienced meditators. We propose that the hippocampus is activated already after moderate meditation practice and also during different modes of meditation, including relaxation. The role of hippocampal activity during meditation should be further clarified in future studies, especially by investigating whether the meditation-correlated hippocampal activity is related to memory consolidation.

Deficits and recovery in visuospatial memory during head motion after bilateral labyrinthine lesion.

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Wei, Min; Li, Nuo; Newlands, Shawn D; Dickman, J David; Angelaki, Dora E

2006-09-01

To keep a stable internal representation of the environment as we move, extraretinal sensory or motor cues are critical for updating neural maps of visual space. Using a memory-saccade task, we studied whether visuospatial updating uses vestibular information. Specifically, we tested whether trained rhesus monkeys maintain the ability to update the conjugate and vergence components of memory-guided eye movements in response to passive translational or rotational head and body movements after bilateral labyrinthine lesion. We found that lesioned animals were acutely compromised in generating the appropriate horizontal versional responses necessary to update the directional goal of memory-guided eye movements after leftward or rightward rotation/translation. This compromised function recovered in the long term, likely using extravestibular (e.g., somatosensory) signals, such that nearly normal performance was observed 4 mo after the lesion. Animals also lost their ability to adjust memory vergence to account for relative distance changes after motion in depth. Not only were these depth deficits larger than the respective effects on version, but they also showed little recovery. We conclude that intact labyrinthine signals are functionally useful for proper visuospatial memory updating during passive head and body movements.

Visuospatial transformations and personality: evidence of a relationship between visuospatial perspective taking and self-reported emotional empathy.

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Sulpizio, Valentina; Committeri, Giorgia; Metta, Emilia; Lambrey, Simon; Berthoz, Alain; Galati, Gaspare

2015-07-01

In the visuospatial domain, perspective taking is the ability to imagine how a visual scene appears from an external observer's viewpoint, and can be studied by asking subjects to encode object locations in a visual scene where another individual is present and then detecting their displacement when seeing the scene from the other's viewpoint. In the current study, we explored the relationship between visuospatial perspective taking and self-report measures of the cognitive and emotional components of empathy in young adults. To this aim, we employed a priming paradigm, in which the presence of an avatar allowed to anticipate the next perceived perspective on the visual scene. We found that the emotional dimension of empathy was positively correlated with the behavioral advantage provided by the presence of the avatar, relative to unprimed perspective changes. These data suggest a link between the tendency to vicariously experience the others' emotions and the ability to perform self-other spatial transformations.

Fractionation of visuo-spatial memory processes in bipolar depression: a cognitive scaffolding account

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Gallagher, P.; Gray, J.M.; Kessels, R.P.C.

2015-01-01

BACKGROUND: Previous studies of neurocognitive performance in bipolar disorder (BD) have demonstrated impairments in visuo-spatial memory. The aim of the present study was to use an object-location memory (OLM) paradigm to assess specific, dissociable processes in visuo-spatial memory and examine

Fractionation of visuo-spatial memory processes in bipolar depression: a cognitive scaffolding account

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Gallagher, P.; Gray, J.M.; Kessels, R.P.C.

2015-01-01

Background Previous studies of neurocognitive performance in bipolar disorder (BD) have demonstrated impairments in visuo-spatial memory. The aim of the present study was to use an object-location memory (OLM) paradigm to assess specific, dissociable processes in visuo-spatial memory and examine

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

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Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

2014-01-01

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

Visuospatial characteristics of an elderly Chinese population: results from the WAIS-R block design test.

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Yin, Shufei; Zhu, Xinyi; Huang, Xin; Li, Juan

2015-01-01

Visuospatial deficits have long been recognized as a potential predictor of dementia, with visuospatial ability decline having been found to accelerate in later stages of dementia. We, therefore, believe that the visuospatial performance of patients with mild cognitive impairment (MCI) and dementia (Dem) might change with varying visuospatial task difficulties. This study administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Block Design Test (BDT) to determine whether visuospatial ability can help discriminate between MCI patients from Dem patients and normal controls (NC). Results showed that the BDT could contribute to the discrimination between MCI and Dem. Specifically, simple BDT task scores could best distinguish MCI from Dem patients, while difficult BDT task scores could contribute to discriminating between MCI and NC. Given the potential clinical value of the BDT in the diagnosis of Dem and MCI, normative data stratified by age and education for the Chinese elderly population are presented for use in research and clinical settings.

The impact of sleep loss on hippocampal function

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Prince, Toni-Moi; Abel, Ted

2013-01-01

Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep deprivation to impair memory consolidation and plasticity. In this review, we address these topics with a focus on the detrimental effects of post-learning sleep deprivation on memory consolidation. Obtaining adequate sleep is challenging in a society that values “work around the clock.” Therefore, the development of interventions to combat the negative cognitive effects of sleep deprivation is key. However, there are a limited number of therapeutics that are able to enhance cognition in the face of insufficient sleep. The identification of molecular pathways implicated in the deleterious effects of sleep deprivation on memory could potentially yield new targets for the development of more effective drugs. PMID:24045505

Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes.

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Possin, Katherine L; Kim, Hosung; Geschwind, Michael D; Moskowitz, Tacie; Johnson, Erica T; Sha, Sharon J; Apple, Alexandra; Xu, Duan; Miller, Bruce L; Finkbeiner, Steven; Hess, Christopher P; Kramer, Joel H

2017-07-01

Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington's disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-alpha band synchronization across frontal, parietal and visual cortex mediates behavioral and neuronal effects of visuospatial attention.

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Lobier, Muriel; Palva, J Matias; Palva, Satu

2018-01-15

Visuospatial attention prioritizes processing of attended visual stimuli. It is characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual cortex and increased neuronal activity in a network of frontal and parietal areas. It has remained unknown what mechanisms coordinate neuronal processing among frontoparietal network and visual cortices and implement the attention-related modulations of alpha-band amplitudes and behavior. We investigated whether large-scale network synchronization could be such a mechanism. We recorded human cortical activity with magnetoencephalography (MEG) during a visuospatial attention task. We then identified the frequencies and anatomical networks of inter-areal phase synchronization from source localized MEG data. We found that visuospatial attention is associated with robust and sustained long-range synchronization of cortical oscillations exclusively in the high-alpha (10-14 Hz) frequency band. This synchronization connected frontal, parietal and visual regions and was observed concurrently with amplitude suppression of low-alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high-alpha phase synchronization was associated with decreased reaction times to attended stimuli and larger suppression of alpha-band amplitudes. These results thus show that high-alpha band phase synchronization is functionally significant and could coordinate the neuronal communication underlying the implementation of visuospatial attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

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Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); Schreckenberger, Matthias [University Medical Center Mainz, Department of Nuclear Medicine, Mainz (Germany); Cumming, Paul [University of Munich, Department of Nuclear Medicine, Munich (Germany); Stoeter, Peter [University Medical Center Mainz, Institute of Neuroradiology, Mainz (Germany); Gerhard, Alex [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom)

2011-12-15

Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 {+-} 1.7) were studied with [{sup 18}F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

Audiospatial and Visuospatial Working Memory in 6–13 Year Old School Children

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Vuontela, Virve; Steenari, Maija-Riikka; Carlson, Synnöve; Koivisto, Juha; Fjällberg, Mika; Aronen, Eeva T.

2003-01-01

The neural processes subserving working memory, and brain structures underlying this system, continue to develop during childhood. We investigated the effects of age and gender on audiospatial and visuospatial working memory in a nonclinical sample of school-aged children using n-back tasks. The results showed that auditory and visual working memory performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The gender differences found i...

Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides

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Liu Qiang

2012-12-01

Full Text Available Abstract Background β-amyloid (Aβ accumulation is described as a hallmark of Alzheimer’s disease (AD. Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs, which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7β2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aβ exposure. To extend our previous work, we evaluated the expression and pharmacology of α7β2-nAChRs in hippocampal interneurons and their sensitivity to Aβ. Results GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7β2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-β-erythroidine (DHβE, a nAChR β2* subunit selective blocker, and α7 and β2 subunit interaction using immunoprecipitation assay. In addition, α7β2-nAChRs were sensitive to 1 nM oligomeric Aβ. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. Conclusion These findings suggest that Aβ modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7β2-nAChRs could be an early and critical event in Aβ-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.

The effects of environmental support and secondary tasks on visuospatial working memory.

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Lilienthal, Lindsey; Hale, Sandra; Myerson, Joel

2014-10-01

In the present experiments, we examined the effects of environmental support on participants' ability to rehearse locations and the role of such support in the effects of secondary tasks on memory span. In Experiment 1, the duration of interitem intervals and the presence of environmental support for visuospatial rehearsal (i.e., the array of possible memory locations) during the interitem intervals were both manipulated across four tasks. When support was provided, memory spans increased as the interitem interval durations increased, consistent with the hypothesis that environmental support facilitates rehearsal. In contrast, when environmental support was not provided, spans decreased as the duration of the interitem intervals increased, consistent with the hypothesis that visuospatial memory representations decay when rehearsal is impeded. In Experiment 2, the ratio of interitem interval duration to intertrial interval duration was kept the same on all four tasks, in order to hold temporal distinctiveness constant, yet forgetting was still observed in the absence of environmental support, consistent with the decay hypothesis. In Experiment 3, the effects of impeding rehearsal were compared to the effects of verbal and visuospatial secondary processing tasks. Forgetting of locations was greater when presentation of to-be-remembered locations alternated with the performance of a secondary task than when rehearsal was impeded by the absence of environmental support. The greatest forgetting occurred when a secondary task required the processing visuospatial information, suggesting that in addition to decay, both domain-specific and domain-general effects contribute to forgetting on visuospatial working memory tasks.

Cortisol, Cytokines, and Hippocampal Volume in the Elderly

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Keith Daniel Sudheimer

2014-07-01

Full Text Available Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

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Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

2016-07-01

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. Copyright © 2016 Elsevier Inc. All rights reserved.

Updating the lamellar hypothesis of hippocampal organization

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Robert S Sloviter

2012-12-01

Full Text Available In 1971, Andersen and colleagues proposed that excitatory activity in the entorhinal cortex propagates topographically to the dentate gyrus, and on through a trisynaptic circuit lying within transverse hippocampal slices or lamellae [Andersen, Bliss, and Skrede. 1971. Lamellar organization of hippocampal pathways. Exp Brain Res 13, 222-238]. In this way, a relatively simple structure might mediate complex functions in a manner analogous to the way independent piano keys can produce a nearly infinite variety of unique outputs. The lamellar hypothesis derives primary support from the lamellar distribution of dentate granule cell axons (the mossy fibers, which innervate dentate hilar neurons and area CA3 pyramidal cells and interneurons within the confines of a thin transverse hippocampal segment. Following the initial formulation of the lamellar hypothesis, anatomical studies revealed that unlike granule cells, hilar mossy cells, CA3 pyramidal cells, and Layer II entorhinal cells all form axonal projections that are more divergent along the longitudinal axis than the clearly lamellar mossy fiber pathway. The existence of pathways with translamellar distribution patterns has been interpreted, incorrectly in our view, as justifying outright rejection of the lamellar hypothesis [Amaral and Witter. 1989. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571-591]. We suggest that the functional implications of longitudinally-projecting axons depend not on whether they exist, but on what they do. The observation that focal granule cell layer discharges normally inhibit, rather than excite, distant granule cells suggests that longitudinal axons in the dentate gyrus may mediate "lateral" inhibition and define lamellar function, rather than undermine it. In this review, we attempt a reconsideration of the evidence that most directly impacts the physiological concept of hippocampal lamellar

PirB regulates asymmetries in hippocampal circuitry.

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Hikari Ukai

Full Text Available Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B. By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB, an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.

Distinct neural substrates of visuospatial and verbal-analytic reasoning as assessed by Raven's Advanced Progressive Matrices.

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Chen, Zhencai; De Beuckelaer, Alain; Wang, Xu; Liu, Jia

2017-11-24

Recent studies revealed spontaneous neural activity to be associated with fluid intelligence (gF) which is commonly assessed by Raven's Advanced Progressive Matrices, and embeds two types of reasoning: visuospatial and verbal-analytic reasoning. With resting-state fMRI data, using global brain connectivity (GBC) analysis which averages functional connectivity of a voxel in relation to all other voxels in the brain, distinct neural correlates of these two reasoning types were found. For visuospatial reasoning, negative correlations were observed in both the primary visual cortex (PVC) and the precuneus, and positive correlations were observed in the temporal lobe. For verbal-analytic reasoning, negative correlations were observed in the right inferior frontal gyrus (rIFG), dorsal anterior cingulate cortex and temporoparietal junction, and positive correlations were observed in the angular gyrus. Furthermore, an interaction between GBC value and type of reasoning was found in the PVC, rIFG and the temporal lobe. These findings suggest that visuospatial reasoning benefits more from elaborate perception to stimulus features, whereas verbal-analytic reasoning benefits more from feature integration and hypothesis testing. In sum, the present study offers, for different types of reasoning in gF, first empirical evidence of separate neural substrates in the resting brain.

Multisensory Integration Affects Visuo-Spatial Working Memory

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Botta, Fabiano; Santangelo, Valerio; Raffone, Antonino; Sanabria, Daniel; Lupianez, Juan; Belardinelli, Marta Olivetti

2011-01-01

In the present study, we investigate how spatial attention, driven by unisensory and multisensory cues, can bias the access of information into visuo-spatial working memory (VSWM). In a series of four experiments, we compared the effectiveness of spatially-nonpredictive visual, auditory, or audiovisual cues in capturing participants' spatial…

Visuospatial viewpoint manipulation during full-body illusion modulates subjective first-person perspective.

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Pfeiffer, Christian; Schmutz, Valentin; Blanke, Olaf

2014-12-01

Self-consciousness is based on multisensory signals from the body. In full-body illusion (FBI) experiments, multisensory conflict was used to induce changes in three key aspects of bodily self-consciousness (BSC): self-identification (which body 'I' identify with), self-location (where 'I' am located), and first-person perspective (from where 'I' experience the world; 1PP). Here, we adapted a previous FBI protocol in which visuotactile stroking was administered by a robotic device (tactile stroking) and simultaneously rendered on the back of a virtual body (visual stroking) that participants viewed on a head-mounted display as if filmed from a posterior viewpoint of a camera. We compared the effects of two different visuospatial viewpoints on the FBI and thereby on these key aspects of BSC. During control manipulations, participants saw a no-body object instead of a virtual body (first experiment) or received asynchronous versus synchronous visuotactile stroking (second experiment). Results showed that within-subjects visuospatial viewpoint manipulations affected the subjective 1PP ratings if a virtual body was seen but had no effect for viewing a non-body object. However, visuospatial viewpoint had no effect on self-identification, but depended on the viewed object and visuotactile synchrony. Self-location depended on visuospatial viewpoint (first experiment) and visuotactile synchrony (second experiment). Our results show that the visuospatial viewpoint from which the virtual body is seen during FBIs modulates the subjective 1PP and that such viewpoint manipulations contribute to spatial aspects of BSC. We compare the present data with recent data revealing vestibular contributions to the subjective 1PP and discuss the multisensory nature of BSC and the subjective 1PP.

Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat

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Madsen, Torsten Meldgaard; Kristjansen, P.E.G.; Bolwig, Tom Gert

2003-01-01

irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21...... that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy....

Visuospatial bootstrapping: Binding useful visuospatial information during verbal working memory encoding does not require set-shifting executive resources.

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Calia, Clara; Darling, Stephen; Havelka, Jelena; Allen, Richard J

2018-05-01

Immediate serial recall of digits is better when the digits are shown by highlighting them in a familiar array, such as a phone keypad, compared with presenting them serially in a single location, a pattern referred to as "visuospatial bootstrapping." This pattern implies the establishment of temporary links between verbal and spatial working memory, alongside access to information in long-term memory. However, the role of working memory control processes like those implied by the "Central Executive" in bootstrapping has not been directly investigated. Here, we report a study addressing this issue, focusing on executive processes of attentional shifting. Tasks in which information has to be sequenced are thought to be heavily dependent on shifting. Memory for digits presented in keypads versus single locations was assessed under two secondary task load conditions, one with and one without a sequencing requirement, and hence differing in the degree to which they invoke shifting. Results provided clear evidence that multimodal binding (visuospatial bootstrapping) can operate independently of this form of executive control process.

When math operations have visuospatial meanings versus purely symbolic definitions: Which solving stages and brain regions are affected?

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Pyke, Aryn A; Fincham, Jon M; Anderson, John R

2017-06-01

How does processing differ during purely symbolic problem solving versus when mathematical operations can be mentally associated with meaningful (here, visuospatial) referents? Learners were trained on novel math operations (↓, ↑), that were defined strictly symbolically or in terms of a visuospatial interpretation (operands mapped to dimensions of shaded areas, answer = total area). During testing (scanner session), no visuospatial representations were displayed. However, we expected visuospatially-trained learners to form mental visuospatial representations for problems, and exhibit distinct activations. Since some solution intervals were long (~10s) and visuospatial representations might only be instantiated in some stages during solving, group differences were difficult to detect when treating the solving interval as a whole. However, an HSMM-MVPA process (Anderson and Fincham, 2014a) to parse fMRI data identified four distinct problem-solving stages in each group, dubbed: 1) encode; 2) plan; 3) compute; and 4) respond. We assessed stage-specific differences across groups. During encoding, several regions implicated in general semantic processing and/or mental imagery were more active in visuospatially-trained learners, including: bilateral supramarginal, precuneus, cuneus, parahippocampus, and left middle temporal regions. Four of these regions again emerged in the computation stage: precuneus, right supramarginal/angular, left supramarginal/inferior parietal, and left parahippocampal gyrus. Thus, mental visuospatial representations may not just inform initial problem interpretation (followed by symbolic computation), but may scaffold on-going computation. In the second stage, higher activations were found among symbolically-trained solvers in frontal regions (R. medial and inferior and L. superior) and the right angular and middle temporal gyrus. Activations in contrasting regions may shed light on solvers' degree of use of symbolic versus mental

A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.

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McDonald, Robert J; Jones, Jana; Richards, Blake; Hong, Nancy S

2006-09-01

The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.

Assessing Visuospatial Skills in Parkinson's: Comparison of Neuropsychological Assessment Battery Visual Discrimination to the Judgment of Line Orientation.

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Renfroe, Jenna B; Turner, Travis H; Hinson, Vanessa K

2017-02-01

Judgment of Line Orientation (JOLO) test is widely used in assessing visuospatial deficits in Parkinson's disease (PD). The neuropsychological assessment battery (NAB) offers the Visual Discrimination test, with age and education correction, parallel forms, and co-normed standardization sample for comparisons within and between domains. However, NAB Visual Discrimination has not been validated in PD, and may not measure the same construct as JOLO. A heterogeneous sample of 47 PD patients completed the JOLO and NAB Visual Discrimination within a broader neuropsychological evaluation. Pearson correlations assessed relationships between JOLO and NAB Visual Discrimination performances. Raw and demographically corrected scores from JOLO and Visual Discrimination were only weakly correlated. NAB Visual Discrimination subtest was moderately correlated with overall cognitive functioning, whereas the JOLO was not. Despite apparent virtues, results do not support NAB Visual Discrimination as an alternative to JOLO in assessing visuospatial functioning in PD. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modality specificity and integration in working memory: Insights from visuospatial bootstrapping.

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Allen, Richard J; Havelka, Jelena; Falcon, Thomas; Evans, Sally; Darling, Stephen

2015-05-01

The question of how meaningful associations between verbal and spatial information might be utilized to facilitate working memory performance is potentially highly instructive for models of memory function. The present study explored how separable processing capacities within specialized domains might each contribute to this, by examining the disruptive impacts of simple verbal and spatial concurrent tasks on young adults' recall of visually presented digit sequences encountered either in a single location or within a meaningful spatial "keypad" configuration. The previously observed advantage for recall in the latter condition (the "visuospatial bootstrapping effect") consistently emerged across 3 experiments, indicating use of familiar spatial information in boosting verbal memory. The magnitude of this effect interacted with concurrent activity; articulatory suppression during encoding disrupted recall to a greater extent when digits were presented in single locations (Experiment 1), while spatial tapping during encoding had a larger impact on the keypad condition and abolished the visuospatial bootstrapping advantage (Experiment 2). When spatial tapping was performed during recall (Experiment 3), no task by display interaction was observed. Outcomes are discussed within the context of the multicomponent model of working memory, with a particular emphasis on cross-domain storage in the episodic buffer (Baddeley, 2000). (c) 2015 APA, all rights reserved).

Physical exercise prevents cognitive impairment by enhancing hippocampal neuroplasticity and mitochondrial function in doxorubicin-induced chemobrain.

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Park, Hye-Sang; Kim, Chang-Ju; Kwak, Hyo-Bum; No, Mi-Hyun; Heo, Jun-Won; Kim, Tae-Woon

2018-05-01

Although chemotherapy increases the survival rate of patients with various cancers, such treatment can induce acute or long-term cognitive dysfunction a phenomenon known as post-chemotherapy cognitive impairment (PCCI) or "chemobrain." Exercise is known to positively affect brain function. Thus, the present study aimed to determine whether symptoms of chemobrain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise. Wistar rats were separated into the following groups: control, control plus exercise, chemobrain, and chemobrain plus exercise. For chemobrain induction, 2 mg/kg of doxorubicin (DOX) a widely utilized chemotherapeutic agent among patients with breast cancer was dissolved in saline and directly injected to the abdomen once every 4 weeks. The exercise groups were subjected to low-intensity treadmill, 6 days per week for 4 weeks. The Morris water maze and step-down avoidance tests were conducted to evaluate cognitive function, while neuroplasticity and mitochondrial function were assessed in the hippocampus and dentate gyrus. Decreased cognitive function were observed in the chemobrain group, along with decreases in levels of neurogenesis, brain derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Ca 2+ retention in hippocampus. Rats of the chemobrain group also exhibited an increase in apoptosis, H 2 O 2 emission and permeability transition pore by hippocampal mitochondria. However, exercise attenuated impairments in cognitive function, neuroplasticity, and mitochondrial function induced by DOX treatment. Therefore, the findings of the present study indicate that low-intensity exercise may assist in preventing cognitive dysfunction during or after chemotherapy in patients with various cancers, including breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Working memory and the hippocampus.

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Baddeley, Alan; Jarrold, Christopher; Vargha-Khadem, Faraneh

2011-12-01

A number of studies suggest an important role for the hippocampus in tasks involving visuospatial or relational working memory. We test the generality of this proposal across tasks using a battery designed to investigate the various components of working memory, studying the working memory performance of Jon, who shows a bilateral reduction in hippocampal volume of approximately 50%, comparing him to a group of 48 college students. We measure performance on four complex working memory span measures based on combining visuospatial and verbal storage with visuospatial or verbal concurrent processing as well as measuring Jon's ability to carry out the component storage and processing aspects of these tasks. Jon performed at a consistently high level across our range of tasks. Possible reasons for the apparent disparity between our own findings and earlier studies showing a hippocampal deficit are discussed in terms of both the potential differences in the demands placed on relational memory and of the proposed distinction between egocentric and allocentric visuospatial processing.

Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat.

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Meng Chang Ko

Full Text Available The loop diuretic bumetanide (Bumex is thought to have antiepileptic properties via modulate GABAA mediated signaling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signaling, we sought to investigate whether they also affect hippocampal function. The current study was performed to evaluate the possible role of NKCC1 on the hippocampal function. Brain slice extracellular recording, inhibitory avoidance, and western blot were applied in this study. Results showed that hippocampal Long-term potentiation was attenuated by suprafusion of NKCC1 inhibitor bumetanide, in a dose dependent manner. Sequent experiment result showed that Intravenous injection of bumetanide (15.2 mg/kg 30 min prior to the training session blocked inhibitory avoidance learning significantly. Subsequent control experiment's results excluded the possible non-specific effect of bumetanide on avoidance learning. We also found the phosphorylation of hippocampal MAPK was attenuated after bumetanide administration. These results suggested that hippocampal NKCC1 may via MAPK signaling cascade to possess its function.

Prefrontal-hippocampal-fusiform activity during encoding predicts intraindividual differences in free recall ability: an event-related functional-anatomic MRI study.

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Dickerson, B C; Miller, S L; Greve, D N; Dale, A M; Albert, M S; Schacter, D L; Sperling, R A

2007-01-01

The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which prefrontal activity was greater for all items of the list and hippocampal and fusiform activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance.

Visuo-spatial interference affects the identification of emotional facial expressions in unmedicated Parkinson's patients.

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García-Rodríguez, Beatriz; Guillén, Carmen Casares; Barba, Rosa Jurado; io Valladolid, Gabriel Rub; Arjona, José Antonio Molina; Ellgring, Heiner

2012-02-15

There is evidence that visuo-spatial capacity can become overloaded when processing a secondary visual task (Dual Task, DT), as occurs in daily life. Hence, we investigated the influence of the visuo-spatial interference in the identification of emotional facial expressions (EFEs) in early stages of Parkinson's disease (PD). We compared the identification of 24 emotional faces that illustrate six basic emotions in, unmedicated recently diagnosed PD patients (16) and healthy adults (20), under two different conditions: a) simple EFE identification, and b) identification with a concurrent visuo-spatial task (Corsi Blocks). EFE identification by PD patients was significantly worse than that of healthy adults when combined with another visual stimulus. Published by Elsevier B.V.

Imbalance of incidental encoding across tasks: an explanation for non-memory-related hippocampal activations?

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Reas, Emilie T; Brewer, James B

2013-11-01

Functional neuroimaging studies have increasingly noted hippocampal activation associated with a variety of cognitive functions--such as decision making, attention, perception, incidental learning, prediction, and working memory--that have little apparent relation to declarative memory. Such findings might be difficult to reconcile with classical hippocampal lesion studies that show remarkable sparing of cognitive functions outside the realm of declarative memory. Even the oft-reported hippocampal activations during confident episodic retrieval are not entirely congruent with evidence that hippocampal lesions reliably impair encoding but inconsistently affect retrieval. Here we explore the conditions under which the hippocampus responds during episodic recall and recognition. Our findings suggest that anterior hippocampal activity may be related to the imbalance of incidental encoding across tasks and conditions rather than due to retrieval per se. Incidental encoding and hippocampal activity may be reduced during conditions where retrieval requires greater attentional engagement. During retrieval, anterior hippocampal activity decreases with increasing search duration and retrieval effort, and this deactivation corresponds with a coincident impaired encoding of the external environment (Israel, Seibert, Black, & Brewer, 2010; Reas & Brewer, 2013; Reas, Gimbel, Hales, & Brewer, 2011). In light of this emerging evidence, we discuss the proposal that some hippocampal activity observed during memory retrieval, or other non-memory conditions, may in fact be attributable to concomitant encoding activity that is regulated by the attentional demands of the principal task. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Visuospatial impairment in Parkinson's disease: the role of laterality.

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Karádi, Kázmér; Lucza, Tivadar; Aschermann, Zsuzsanna; Komoly, Sámuel; Deli, Gabriella; Bosnyák, Edit; Acs, Péter; Horváth, Réka; Janszky, József; Kovács, Norbert

2015-01-01

Asymmetry is one of the unique and mysterious features of Parkinson's disease (PD). Motor symptoms develop unilaterally either on the left (LPD) or the right side (RPD). Incongruent data are available whether the side of onset has an impact on cognition in PD. The objective of this study is to compare the visuospatial performance of RPD and LPD patients. Seventy-one non-demented, non-depressive and right-handed patients were categorized into RBD (n = 36) and LPD (n = 35) groups. Rey-Osterrieth Complex Figure Test (ROCF) was evaluated by both the Taylor's and Loring's scoring systems. Subsequently, we also performed subgroup analyses on patients having short disease duration (≤5 years, 15 RBD and 15 LPD patients). The standard analysis of ROCF (Taylor's system) did not reveal any differences; however, the utilization of the Loring's system demonstrated that LPD patients had significantly worse visuospatial performance than the RPD subjects (3.0 vs. 2.0 points, median, p = 0.002). Correlation between the number of spatial errors and the degree of asymmetry was significant (r = -0.437, p = 0.001). However, this difference could not be observed in PD patients with short disease duration. LPD patients had worse visuospatial performance than the RPD subjects and the number of errors tightly correlated with the degree of asymmetry and long disease duration.

Gender differences in visuospatial planning: an eye movements study.

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Cazzato, Valentina; Basso, Demis; Cutini, Simone; Bisiacchi, Patrizia

2010-01-20

Gender studies report a male advantage in several visuospatial abilities. Only few studies however, have evaluated differences in visuospatial planning behaviour with regard to gender. This study was aimed at exploring whether gender may affect the choice of cognitive strategies in a visuospatial planning task and, if oculomotor measures could assist in disentangling the cognitive processes involved. A computerised task based on the travelling salesperson problem paradigm, the Maps test, was used to investigate these issues. Participants were required to optimise time and space of a path travelling among a set of sub-goals in a spatially constrained environment. Behavioural results suggest that there are no gender differences in the initial visual processing of the stimuli, but rather during the execution of the plan, with males showing a shorter execution time and a higher path length optimisation than females. Males often showed changes of heuristics during the execution while females seemed to prefer a constant strategy. Moreover, a better performance in behavioural and oculomotor measures seemed to suggest that males are more able than females in either the optimisation of spatial features or the realisation of the planned scheme. Despite inconclusive findings, the results support previous research and provide insight into the level of cognitive processing involved in navigation and planning tasks, with regard to the influence of gender.

Different effects of executive and visuospatial working memory on visual consciousness.

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De Loof, Esther; Poppe, Louise; Cleeremans, Axel; Gevers, Wim; Van Opstal, Filip

2015-11-01

Consciousness and working memory are two widely studied cognitive phenomena. Although they have been closely tied on a theoretical and neural level, empirical work that investigates their relation is largely lacking. In this study, the relationship between visual consciousness and different working memory components is investigated by using a dual-task paradigm. More specifically, while participants were performing a visual detection task to measure their visual awareness threshold, they had to concurrently perform either an executive or visuospatial working memory task. We hypothesized that visual consciousness would be hindered depending on the type and the size of the load in working memory. Results showed that maintaining visuospatial content in working memory hinders visual awareness, irrespective of the amount of information maintained. By contrast, the detection threshold was progressively affected under increasing executive load. Interestingly, increasing executive load had a generic effect on detection speed, calling into question whether its obstructing effect is specific to the visual awareness threshold. Together, these results indicate that visual consciousness depends differently on executive and visuospatial working memory.

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

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Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

Functional clustering in hippocampal cultures: relating network structure and dynamics

International Nuclear Information System (INIS)

Feldt, S; Dzakpasu, R; Olariu, E; Żochowski, M; Wang, J X; Shtrahman, E

2010-01-01

In this work we investigate the relationship between gross anatomic structural network properties, neuronal dynamics and the resultant functional structure in dissociated rat hippocampal cultures. Specifically, we studied cultures as they developed under two conditions: the first supporting glial cell growth (high glial group), and the second one inhibiting it (low glial group). We then compared structural network properties and the spatio-temporal activity patterns of the neurons. Differences in dynamics between the two groups could be linked to the impact of the glial network on the neuronal network as the cultures developed. We also implemented a recently developed algorithm called the functional clustering algorithm (FCA) to obtain the resulting functional network structure. We show that this new algorithm is useful for capturing changes in functional network structure as the networks evolve over time. The FCA detects changes in functional structure that are consistent with expected dynamical differences due to the impact of the glial network. Cultures in the high glial group show an increase in global synchronization as the cultures age, while those in the low glial group remain locally synchronized. We additionally use the FCA to quantify the amount of synchronization present in the cultures and show that the total level of synchronization in the high glial group is stronger than in the low glial group. These results indicate an interdependence between the glial and neuronal networks present in dissociated cultures

Effect of dorsal hippocampal lesion compared to dorsal hippocampal blockade by atropine on reference memory in vision deprived rats.

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Dhume, R A; Noronha, A; Nagwekar, M D; Mascarenhas, J F

1989-10-01

In order to study the primacy of the hippocampus in place learning function 24 male adult albino rats were hippocampally-lesioned in dorsal hippocampus involving fornical damage (group I); sham operated for comparison with group I (group II); cannulated for instillation of atropine sulphate in the same loci as group I (group III); and cannulated for instillation of saline which served as control for group III (group IV). All the animals were enucleated and their reference memory (long-term memory) was tested, using open 4-arm radial maze. There was loss of reference memory in groups I and III. However, hippocampally-lesioned animals, showed recovery of reference memory deficit within a short period of 10 days or so. Whereas atropinized animals showed persistent reference memory deficit as long as the instillation effect continued. The mechanism involved in the recovery of reference memory in hippocampally-lesioned animals and persistent deficit of reference memory in atropinized animals has been postulated to explain the primacy of hippocampus in the place learning function under normal conditions.

Asymmetry of limbic structure (hippocampal formation and amygdaloidal complex at PTSD

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Aida Sarač-Hadžihalilović

2003-05-01

Full Text Available Defining exact position of weak anatomic function which is find in a base of neurological and psychiatric disorder is just became the subject of intensive research interest. For this purposes it is important to implement structural and functional MRI techniques, also for further lightening and seeing subject of this work, more concretely connected to PTSD. Therefore, exactly MRI gives most sensitive volumetric measuring of hippocampal formation and amygdaloidal complex.The goal of this work was to research asymmetry of hippocampal formation and amygdaloidal complex to the PTSD patients.Results showed that at the axial slice length of hippocampal formation on the left and right side of all patients are significantly asymmetric. At the sagittal slice from the left side of hippocampal formation is in many cases longer than right about 50 %. At the coronal slice, there are no significant differences toward patient proportion according to symm. / asymm. of the hippocampal formation width at the right and left side. Difference in volume average of hippocampal formation between right and left side for axial and coronal slice is not statistically significant, but it is significant for sagittal slice. In about amygdaloidal complex patients with PTSD toward symm. / asymm. Amygdaloidal complex at the right and left side of axial and sagittal slice in all three measurement shows asymmetry, what is especially shown at sagittal slice. Difference in average length of amygdaloidal complex at the right and left side is not statistically significant for no one slice.Therefore, results of a new research that are used MRI, showed smaller hippocampal level at PTSD (researched by Van der Kolka 1996, Pitman 1996, Bremner et al., 1995.. Application of MRI technique in research of asymmetry of hippocampal formation and amygdaloidal complex, which we used in our research, we recommend as a template for future researches in a sense of lightening anatomic function that is

Adult hippocampal neurogenesis and cognitive aging

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Román Darío Moreno Fernández

2013-12-01

Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

The effect of the augmentation of cholinergic neurotransmission by nicotine on EEG indices of visuospatial attention

NARCIS (Netherlands)

Logemann, H.N.A.; Bocker, K.B.E.; Deschamps, P.K.H.; Kemner, C.; Kenemans, J.L.

2014-01-01

The cholinergic system has been implicated in visuospatial attention but the exact role remains unclear. In visuospatial attention, bias refers to neuronal signals that modulate the sensitivity of sensory cortex, while disengagement refers to the decoupling of attention making reorienting possible.

Inhibition of hippocampal synaptic transmission by impairment of Ral function

DEFF Research Database (Denmark)

Owe-Larsson, Björn; Chaves-Olarte, Esteban; Chauhan, Ashok

2005-01-01

Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ras......, R-Ras, Rap) both inhibited autaptic responses. In a proportion of the neurons (25%, TcdA-10463; 54%, TcsL-1522), the inhibition was associated with a shift from activity-dependent depression to facilitation, indicating that the synaptic release probability was reduced. Overexpression of a dominant...... negative Ral mutant, Ral A28N, caused a strong inhibition of autaptic responses, which was associated with a shift to facilitation in a majority (80%) of the neurons. These results indicate that Ral, along with at least one other non-Rab GTPase, participates in presynaptic regulation in hippocampal neurons....

An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis

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Alexander eGarthe

2013-05-01

Full Text Available The Morris water maze represents the de-facto standard for testing hippocampal function in laboratory rodents. In the field of adult hippocampal neurogenesis, however, using this paradigm to assess the functional relevance of the new neurons yielded surprisingly inconsistent results. While some authors found aspects of water maze performance to be linked to adult neurogenesis, others obtained different results or could not demonstrate any effect of manipulating adult neurogenesis.In this review we discuss evidence that the large diversity of protocols and setups used is an important aspect in interpreting the differences in the results that have been obtained. Even simple parameters such as pool size, number and configuration of visual landmarks, or number of trials can become highly relevant for getting the new neurons involved at all. Sets of parameters are often chosen with implicit or explicit concepts in mind and these might lead to different views on the function of adult-generated neurons.We propose that the classical parameters usually used to measure spatial learning performance in the water maze might not be particularly well suited to sensitively and specifically detect the supposedly highly specific functional changes elicited by the experimental modulation of adult hippocampal neurogenesis. As adult neurogenesis is supposed to affect specific aspects of information processing only in the hippocampus, any claim for a functional relevance of the new neurons has to be based on hippocampus-specific parameters. We also placed a special emphasis on the fact that the DG facilitates the differentiation between contexts as opposed to just differentiating places.In conclusion, while the Morris water maze has proven to be one of the most effective testing paradigms to assess hippocampus-dependent spatial learning, new and more specific questions ask for new parameters. Therefore, the full potential of the water maze task remains to be tapped.

Extent of hippocampal atrophy predicts degree of deficit in recall.

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Patai, Eva Zita; Gadian, David G; Cooper, Janine M; Dzieciol, Anna M; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-13

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2

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Elodie De Bruyckere

2018-04-01

Full Text Available Structural and functional plasticity of synapses are critical neuronal mechanisms underlying learning and memory. While activity-dependent regulation of synaptic strength has been extensively studied, much less is known about the transcriptional control of synapse maintenance and plasticity. Hippocampal mossy fiber (MF synapses connect dentate granule cells to CA3 pyramidal neurons and are important for spatial memory formation and consolidation. The transcription factor Bcl11b/Ctip2 is expressed in dentate granule cells and required for postnatal hippocampal development. Ablation of Bcl11b/Ctip2 in the adult hippocampus results in impaired adult neurogenesis and spatial memory. The molecular mechanisms underlying the behavioral impairment remained unclear. Here we show that selective deletion of Bcl11b/Ctip2 in the adult mouse hippocampus leads to a rapid loss of excitatory synapses in CA3 as well as reduced ultrastructural complexity of remaining mossy fiber boutons (MFBs. Moreover, a dramatic decline of long-term potentiation (LTP of the dentate gyrus-CA3 (DG-CA3 projection is caused by adult loss of Bcl11b/Ctip2. Differential transcriptomics revealed the deregulation of genes associated with synaptic transmission in mutants. Together, our data suggest Bcl11b/Ctip2 to regulate maintenance and function of MF synapses in the adult hippocampus.

Distinguishing cognitive state with multifractal complexity of hippocampal interspike interval sequences

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Dustin eFetterhoff

2015-09-01

Full Text Available Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether the multifractal properties inherent to hippocampal spike trains reflect active cognitive processing. To examine this possibility, hippocampal neuronal ensembles were recorded from rats before, during and after a spatial working memory task following administration of tetrahydrocannabinol (THC, a memory-impairing component of cannabis. Multifractal detrended fluctuation analysis was performed on hippocampal interspike interval sequences to determine characteristics of monofractal long-range temporal correlations (LRTCs, quantified by the Hurst exponent, and the degree/magnitude of multifractal complexity, quantified by the width of the singularity spectrum. Our results demonstrate that multifractal firing patterns of hippocampal spike trains are a marker of functional memory processing, as they are more complex during the working memory task and significantly reduced following administration of memory impairing THC doses. Conversely, LRTCs are largest during resting state recordings, therefore reflecting different information compared to multifractality. In order to deepen conceptual understanding of multifractal complexity and LRTCs, these measures were compared to classical methods using hippocampal frequency content and firing variability measures. These results showed that LRTCs, multifractality, and theta rhythm represent independent processes, while delta rhythm correlated with multifractality. Taken together, these results provide a novel perspective on memory function by demonstrating that the multifractal nature of spike trains reflects hippocampal microcircuit activity that can be used to detect and quantify cognitive, physiological and pathological states.

Memory reconsolidation mediates the updating of hippocampal memory content

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Jonathan L C Lee

2010-11-01

Full Text Available The retrieval or reactivation of a memory places it into a labile state, requiring a process of reconsolidation to restabilize it. This retrieval-induced plasticity is a potential mechanism for the modification of the existing memory. Following previous data supportive of a functional role for memory reconsolidation in the modification of memory strength, here I show that hippocampal memory reconsolidation also supports the updating of contextual memory content. Using a procedure that separates the learning of pure context from footshock-motivated contextual fear learning, I demonstrate doubly dissociable hippocampal mechanisms of initial context learning and subsequent updating of the neutral contextual representation to incorporate the footshock. Contextual memory consolidation was dependent upon BDNF expression in the dorsal hippocampus, whereas the footshock modification of the contextual representation required the expression of Zif268. These mechanisms match those previously shown to be selectively involved in hippocampal memory consolidation and reconsolidation, respectively. Moreover, memory reactivation is a necessary step in modifying memory content, as inhibition of hippocampal synaptic protein degradation also prevented the footshock-mediated memory modification. Finally, dorsal hippocampal knockdown of Zif268 impaired the reconsolidation of the pure contextual memory only under conditions of weak context memory training, as well as failing to disrupt contextual freezing when a strong contextual fear memory is reactivated by further conditioning. Therefore, an adaptive function of the reactivation and reconsolidation process is to enable the updating of memory content.

β-Adrenergic Control of Hippocampal Function: Subserving the Choreography of Synaptic Information Storage and Memory

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Hagena, Hardy; Hansen, Niels; Manahan-Vaughan, Denise

2016-01-01

Noradrenaline (NA) is a key neuromodulator for the regulation of behavioral state and cognition. It supports learning by increasing arousal and vigilance, whereby new experiences are “earmarked” for encoding. Within the hippocampus, experience-dependent information storage occurs by means of synaptic plasticity. Furthermore, novel spatial, contextual, or associative learning drives changes in synaptic strength, reflected by the strengthening of long-term potentiation (LTP) or long-term depression (LTD). NA acting on β-adrenergic receptors (β-AR) is a key determinant as to whether new experiences result in persistent hippocampal synaptic plasticity. This can even dictate the direction of change of synaptic strength. The different hippocampal subfields play different roles in encoding components of a spatial representation through LTP and LTD. Strikingly, the sensitivity of synaptic plasticity in these subfields to β-adrenergic control is very distinct (dentate gyrus > CA3 > CA1). Moreover, NA released from the locus coeruleus that acts on β-AR leads to hippocampal LTD and an enhancement of LTD-related memory processing. We propose that NA acting on hippocampal β-AR, that is graded according to the novelty or saliency of the experience, determines the content and persistency of synaptic information storage in the hippocampal subfields and therefore of spatial memories. PMID:26804338

Beyond dizziness: virtual navigation, spatial anxiety and hippocampal volume in bilateral vestibulopathy

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Olympia eKremmyda

2016-03-01

Full Text Available Bilateral vestibulopathy (BVP is defined as the impairment or loss of function of either the labyrinths or the eighth nerves. Patients with total BVP due to bilateral vestibular nerve section exhibit difficulties in spatial memory and navigation and show a loss of hippocampal volume. In clinical practice, most patients do not have a complete loss of function but rather an asymmetrical residual functioning of the vestibular system. The purpose of the current study was to investigate navigational ability and hippocampal atrophy in BVP patients with residual vestibular function. Fifteen patients with BVP and a group of age- and gender- matched healthy controls were examined. Self-reported questionnaires on spatial anxiety and wayfinding were used to assess the applied strategy of wayfinding and quality of life. Spatial memory and navigation were tested directly using a virtual Morris Water Maze Task. The hippocampal volume of these two groups was evaluated by voxel-based morphometry. In the patients, the questionnaire showed a higher spatial anxiety and the Morris Water Maze Task a delayed spatial learning performance. MRI revealed a significant decrease in the gray matter mid-hippocampal volume (Left: p = 0.006, Z = 4.58, Right: p < 0.001, Z = 3.63 and posterior parahippocampal volume (Right: p = 0.005, Z = 4.65, Left: p < 0.001, Z = 3.87 compared to those of healthy controls. In addition, a decrease in hippocampal formation volume correlated with a more dominant route-finding strategy. Our current findings demonstrate that even partial bilateral vestibular loss leads to anatomical and functional

What does the functional organization of cortico-hippocampal networks tell us about the functional organization of memory?

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Reagh, Zachariah M; Ranganath, Charan

2018-04-25

Historically, research on the cognitive processes that support human memory proceeded, to a large extent, independently of research on the neural basis of memory. Accumulating evidence from neuroimaging, however, has enabled the field to develop a broader and more integrative perspective. Here, we briefly outline how advances in cognitive neuroscience can potentially shed light on concepts and controversies in human memory research. We argue that research on the functional properties of cortico-hippocampal networks informs us about how memories might be organized in the brain, which, in turn, helps to reconcile seemingly disparate perspectives in cognitive psychology. Finally, we discuss several open questions and directions for future research. Copyright © 2018. Published by Elsevier B.V.

Epigenetic control of hippocampal stem cells: modulation by hyperactivation, glucocorticoids and aging

NARCIS (Netherlands)

Schouten, M.

2015-01-01

The adult brain has the ability to structurally and functionally adapt to changes in its environment. Examples of these adaptations are the addition of new neurons to neurogenic regions such as the hippocampal dentate gyrus, termed adult hippocampal neurogenesis, and alterations in neuronal

The relationship between level of processing and hippocampal-cortical functional connectivity during episodic memory formation in humans.

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Schott, Björn H; Wüstenberg, Torsten; Wimber, Maria; Fenker, Daniela B; Zierhut, Kathrin C; Seidenbecher, Constanze I; Heinze, Hans-Jochen; Walter, Henrik; Düzel, Emrah; Richardson-Klavehn, Alan

2013-02-01

New episodic memory traces represent a record of the ongoing neocortical processing engaged during memory formation (encoding). Thus, during encoding, deep (semantic) processing typically establishes more distinctive and retrievable memory traces than does shallow (perceptual) processing, as assessed by later episodic memory tests. By contrast, the hippocampus appears to play a processing-independent role in encoding, because hippocampal lesions impair encoding regardless of level of processing. Here, we clarified the neural relationship between processing and encoding by examining hippocampal-cortical connectivity during deep and shallow encoding. Participants studied words during functional magnetic resonance imaging and freely recalled these words after distraction. Deep study processing led to better recall than shallow study processing. For both levels of processing, successful encoding elicited activations of bilateral hippocampus and left prefrontal cortex, and increased functional connectivity between left hippocampus and bilateral medial prefrontal, cingulate and extrastriate cortices. Successful encoding during deep processing was additionally associated with increased functional connectivity between left hippocampus and bilateral ventrolateral prefrontal cortex and right temporoparietal junction. In the shallow encoding condition, on the other hand, pronounced functional connectivity increases were observed between the right hippocampus and the frontoparietal attention network activated during shallow study processing. Our results further specify how the hippocampus coordinates recording of ongoing neocortical activity into long-term memory, and begin to provide a neural explanation for the typical advantage of deep over shallow study processing for later episodic memory. Copyright © 2011 Wiley Periodicals, Inc.

Erythropoietin enhances hippocampal response during memory retrieval in humans

DEFF Research Database (Denmark)

Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

2007-01-01

Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment....... This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders....

Visuo-Spatial Imagery Impairment in Posterior Cortical Atrophy: A Cognitive and SPECT Study

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Simona Gardini

2011-01-01

Full Text Available This study investigated the cognitive profile and the cerebral perfusion pattern in a highly educated 70 year old gentleman with posterior cortical atrophy (PCA. Visuo-perceptual abilities, spatial memory, spatial representation and navigation, visuo-spatial mental imagery, semantic and episodic-autobiographical memory were assessed. Regional cerebral blood flow (rCBF was imaged with SPECT. Cognitive testing showed visual-perceptual impairment, apperceptive visual and landmark agnosia, topographical disorientation with way-finding deficits, impaired map learning and poor mental image generation. Semantic memory was normal, while episodic-autobiographical memory was impaired. Reduced rCBF was found mainly in the right hemisphere, in the precentral gyrus, posterior cingulate and middle temporal gyri, cuneus and precuneus, in the left superior temporal and lingual gyri and in the parahippocampus bilaterally. Hypoperfusion in occipito-parietal regions was associated with visuo-spatial deficits, whereas deficits in visuo-spatial mental imagery might reflect dysfunction related to hypoperfusion in the parahippocampus and precuneus, structures which are responsible for spatial and imagery processing. Dissociating performance between preserved semantic memory and poor episodic-autobiographical recall is consistent with a pattern of normal perfusion in frontal and anterior temporal regions but abnormal rCBF in the parahippocampi. The present findings indicate that PCA involves visuo-spatial imagery deficits and provide further validation to current neuro-cognitive models of spatial representation and topographical disorientation.

Functional neuroimaging of visuospatial working memory tasks enables accurate detection of attention deficit and hyperactivity disorder

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Rubi Hammer

2015-01-01

Full Text Available Finding neurobiological markers for neurodevelopmental disorders, such as attention deficit and hyperactivity disorder (ADHD, is a major objective of clinicians and neuroscientists. We examined if functional Magnetic Resonance Imaging (fMRI data from a few distinct visuospatial working memory (VSWM tasks enables accurately detecting cases with ADHD. We tested 20 boys with ADHD combined type and 20 typically developed (TD boys in four VSWM tasks that differed in feedback availability (feedback, no-feedback and reward size (large, small. We used a multimodal analysis based on brain activity in 16 regions of interest, significantly activated or deactivated in the four VSWM tasks (based on the entire participants' sample. Dimensionality of the data was reduced into 10 principal components that were used as the input variables to a logistic regression classifier. fMRI data from the four VSWM tasks enabled a classification accuracy of 92.5%, with high predicted ADHD probability values for most clinical cases, and low predicted ADHD probabilities for most TDs. This accuracy level was higher than those achieved by using the fMRI data of any single task, or the respective behavioral data. This indicates that task-based fMRI data acquired while participants perform a few distinct VSWM tasks enables improved detection of clinical cases.

Cognitive Differences in Pictorial Reasoning between High-Functioning Autism and Asperger's Syndrome

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Sahyoun, Cherif P.; Soulieres, Isabelle; Belliveau, John W.; Mottron, Laurent; Mody, Maria

2009-01-01

We investigated linguistic and visuospatial processing during pictorial reasoning in high-functioning autism (HFA), Asperger's syndrome (ASP), and age and IQ-matched typically developing participants (CTRL), using three conditions designed to differentially engage linguistic mediation or visuospatial processing (visuospatial, V; semantic, S;…

Visuospatial Orientational Shifts: Evidence for Three Independent Mechanisms.

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Noonan, Michael; Axelrod, Seymour

While it is often assumed that a single mechanism underlies varied experimental evidences of selectivity, Berlyne (1969) suggested that attention-like selectivity may take place in a number of quite separate neural systems. This study examined the issue of visuospatial attention by investigating covert orientation or "looking out of the corner of…

Imbalance of incidental encoding across tasks: An explanation for non-memory-related hippocampal activations?

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Reas, Emilie T.; Brewer, James B.

2013-01-01

Functional neuroimaging studies have increasingly noted hippocampal activation associated with a variety of cognitive functions such as decision-making, attention, perception, incidental learning, prediction and working memory, which have little apparent relation to declarative memory. Such findings might be difficult to reconcile with classical hippocampal lesion studies that show remarkable sparing of cognitive functions outside the realm of declarative memory. Even the oft-reported hippoca...

Peripheral Etanercept Administration Normalizes Behavior, Hippocampal Neurogenesis, and Hippocampal Reelin and GABAA Receptor Expression in a Preclinical Model of Depression

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Kyle J. Brymer

2018-02-01

Full Text Available Depression is a serious psychiatric disorder frequently comorbid with autoimmune disorders. Previous work in our lab has demonstrated that repeated corticosterone (CORT injections in rats reliably increase depressive-like behavior, impair hippocampal-dependent memory, reduce the number and complexity of adult-generated neurons in the dentate gyrus, decrease hippocampal reelin expression, and alter markers of GABAergic function. We hypothesized that peripheral injections of the TNF-α inhibitor etanercept could exert antidepressant effects through a restoration of many of these neurobiological changes. To test this hypothesis, we examined the effect of repeated CORT injections and concurrent injections of etanercept on measures of object-location and object-in-place memory, forced-swim test behavior, hippocampal neurogenesis, and reelin and GABA β2/3 immunohistochemistry. CORT increased immobility behavior in the forced swim test and impaired both object-location and object-in-place memory, and these effects were reversed by etanercept. CORT also decreased both the number and complexity of adult-generated neurons, but etanercept restored these measures back to control levels. Finally, CORT decreased the number of reelin and GABA β2/3-ir cells within the subgranular zone of the dentate gyrus, and etanercept restored these to control levels. These novel results demonstrate that peripheral etanercept has antidepressant effects that are accompanied by a restoration of cognitive function, hippocampal neurogenesis, and GABAergic plasticity, and suggest that a normalization of reelin expression in the dentate gyrus could be a key component underlying these novel antidepressant effects.

Individual Differences in Reasoning and Visuospatial Attention are Associated with Prefrontal and Parietal White Matter Tracts in Healthy Older Adults

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Monge, Zachary A.; Greenwood, Pamela M.; Parasuraman, Raja; Strenziok, Maren

2016-01-01

Objective Although reasoning and attention are two cognitive processes necessary for ensuring the efficiency of many everyday activities in older adults, the role of white matter integrity in these processes has been little studied. This is an important question due to the role of white matter integrity as a neural substrate of cognitive aging. Here, we sought to examine the white matter tracts subserving reasoning and visuospatial attention in healthy older adults. Method Sixty-one adults aged 60 and older completed a battery of cognitive tests to assess reasoning and visuospatial attention. In addition, diffusion tensor images were collected to assess Fractional Anisotropy (FA) – a measure of white matter integrity. A principle component analysis of the test scores yielded two components: reasoning and visuospatial attention. Whole-brain correlations between FA and the cognitive components were submitted to probabilistic tractography analyses for visualization of cortical targets of tracts. Results For reasoning, bilateral thalamo-anterior prefrontal, anterior corpus callosum, and corpus callosum body tracts interconnecting the superior frontal cortices and right cingulum bundle were found. For visuospatial attention, a right inferior fronto-parietal tract, and bilateral parietal and temporal connections were found. Conclusions We conclude that in older adults, prefrontal cortex white matter tracts and interhemispheric communication are important in higher order cognitive functioning. On the other hand, right-sided fronto-parietal tracts appear to be critical for supporting control of cognitive processes, such as redirecting attention. Researchers may use our results to develop neuroscience-based interventions for older adults targeting brain mechanisms involved in cognitive plasticity. PMID:26986750

Taxonomic separation of hippocampal networks: principal cell populations and adult neurogenesis

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Roelof Maarten evan Dijk

2016-03-01

Full Text Available While many differences in hippocampal anatomy have been described between species, it is typically not clear if they are specific to a particular species and related to functional requirements or if they are shared by species of larger taxonomic units. Without such information, it is difficult to infer how anatomical differences may impact on hippocampal function, because multiple taxonomic levels need to be considered to associate behavioral and anatomical changes. To provide information on anatomical changes within and across taxonomic ranks, we present a quantitative assessment of hippocampal principal cell populations in 20 species or strain groups, with emphasis on rodents, the taxonomic group that provides most animals used in laboratory research. Of special interest is the importance of adult hippocampal neurogenesis in species-specific adaptations relative to other cell populations. Correspondence analysis of cell numbers shows that across taxonomic units, phylogenetically related species cluster together, sharing similar proportions of principal cell populations. CA3 and hilus are strong separators that place rodent species into a tight cluster based on their relatively large CA3 and small hilus while non-rodent species (including humans and non-human primates are placed on the opposite side of the spectrum. Hilus and CA3 are also separators within rodents, with a very large CA3 and rather small hilar cell populations separating mole-rats from other rodents that, in turn, are separated from each other by smaller changes in the proportions of CA1 and granule cells. When adult neurogenesis is included, the relatively small populations of young neurons, proliferating cells and hilar neurons become main drivers of taxonomic separation within rodents. The observations provide challenges to the computational modeling of hippocampal function, suggest differences in the organization of hippocampal information streams in rodent and non

Planning sentences while doing other things at the same time: effects of concurrent verbal and visuospatial working memory load.

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Klaus, Jana; Mädebach, Andreas; Oppermann, Frank; Jescheniak, Jörg D

2017-04-01

This study investigated to what extent advance planning during sentence production is affected by a concurrent cognitive load. In two picture-word interference experiments in which participants produced subject-verb-object sentences while ignoring auditory distractor words, we assessed advance planning at a phonological (lexeme) and at an abstract-lexical (lemma) level under visuospatial or verbal working memory (WM) load. At the phonological level, subject and object nouns were found to be activated before speech onset with concurrent visuospatial WM load, but only subject nouns were found to be activated with concurrent verbal WM load, indicating a reduced planning scope as a function of type of WM load (Experiment 1). By contrast, at the abstract-lexical level, subject and object nouns were found to be activated regardless of type of concurrent load (Experiment 2). In both experiments, sentence planning had a more detrimental effect on concurrent verbal WM task performance than on concurrent visuospatial WM task performance. Overall, our results suggest that advance planning at the phonological level is more affected by a concurrently performed verbal WM task than advance planning at the abstract-lexical level. Also, they indicate an overlap of resources allocated to phonological planning in speech production and verbal WM.

Role of medial cortical, hippocampal and striatal interactions during cognitive set-shifting.

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Graham, Steven; Phua, Elaine; Soon, Chun Siong; Oh, Tomasina; Au, Chris; Shuter, Borys; Wang, Shih-Chang; Yeh, Ing Berne

2009-05-01

To date, few studies have examined the functional connectivity of brain regions involved in complex executive function tasks, such as cognitive set-shifting. In this study, eighteen healthy volunteers performed a cognitive set-shifting task modified from the Wisconsin card sort test while undergoing functional magnetic resonance imaging. These modifications allowed better disambiguation between cognitive processes and revealed several novel findings: 1) peak activation in the caudate nuclei in the first instance of negative feedback signaling a shift in rule, 2) lowest caudate activation once the rule had been identified, 3) peak hippocampal activation once the identity of the rule had been established, and 4) decreased hippocampal activation during the generation of new rule candidates. This pattern of activation across cognitive set-shifting events suggests that the caudate nuclei play a role in response generation when the identity of the new rule is unknown. In contrast, the reciprocal pattern of hippocampal activation suggests that the hippocampi help consolidate knowledge about the correct stimulus-stimulus associations, associations that become inappropriate once the rule has changed. Functional connectivity analysis using Granger Causality Mapping revealed that caudate and hippocampal regions interacted indirectly via a circuit involving the medial orbitofrontal and posterior cingulate regions, which are known to bias attention towards stimuli based on expectations built up from task-related feedback. Taken together, the evidence suggests that these medial regions may mediate striato-hippocampal interactions and hence affect goal-directed attentional transitions from a response strategy based on stimulus-reward heuristics (caudate-dependent) to one based on stimulus-stimulus associations (hippocampus-dependent).

Hippocampal volume reduction in congenital central hypoventilation syndrome.

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Paul M Macey

Full Text Available Children with congenital central hypoventilation syndrome (CCHS, a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO(2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI scans, with impaired responses in specific hippocampal regions, suggesting localized injury.We assessed total volume and regional variation in hippocampal surface morphology to identify areas affected in the syndrome. We studied 18 CCHS (mean age+/-std: 15.1+/-2.2 years; 8 female and 32 healthy control (age 15.2+/-2.4 years; 14 female children, and traced hippocampi on 1 mm(3 resolution T1-weighted scans, collected with a 3.0 Tesla MRI scanner. Regional hippocampal volume variations, adjusted for cranial volume, were compared between groups based on t-tests of surface distances to the structure midline, with correction for multiple comparisons. Significant tissue losses emerged in CCHS patients on the left side, with a trend for loss on the right; however, most areas affected on the left also showed equivalent right-sided volume reductions. Reduced regional volumes appeared in the left rostral hippocampus, bilateral areas in mid and mid-to-caudal regions, and a dorsal-caudal region, adjacent to the fimbria.The volume losses may result from hypoxic exposure following hypoventilation during sleep-disordered breathing, or from developmental or vascular consequences of genetic mutations in the syndrome. The sites of change overlap regions of abnormal functional responses to respiratory and autonomic challenges. Affected hippocampal areas have roles associated with memory, mood, and indirectly, autonomic regulation; impairments in these behavioral and physiological functions appear in CCHS.

Visuo-Spatial Performance in Autism: A Meta-Analysis

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Muth, Anne; Hönekopp, Johannes; Falter, Christine M.

2014-01-01

Visuo-spatial skills are believed to be enhanced in autism spectrum disorders (ASDs). This meta-analysis tests the current state of evidence for Figure Disembedding, Block Design, Mental Rotation and Navon tasks in ASD and neurotypicals. Block Design (d = 0.32) and Figure Disembedding (d = 0.26) showed superior performance for ASD with large…

Predicting memory performance in normal ageing using different measures of hippocampal size

International Nuclear Information System (INIS)

Lye, T.C.; Creasey, H.; Kril, J.J.; Grayson, D.A.; Piguet, O.; Bennett, H.P.; Ridley, L.J.; Broe, G.A.

2006-01-01

A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life. (orig.)

Differential effects of a visuospatial attention task on measures of postural control in young and older adults.

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Peterson, Jeffrey J; Keenan, Kevin G

2018-02-01

The purpose of this study was to examine the influence of a visuospatial attention task on three measures of postural control in young and older adults. 20 young (19-36  years) and 20 older (67-91 years) adults performed a choice stepping response time (CSRT) task, a submaximal dorsiflexion force steadiness task, and quiet standing in 3 bilateral stances. All tasks were performed with and without a visuospatial (VS) attention task that involved visualizing a star moving within a 2 × 2 grid. CSRT increased with the addition of the VS task in both groups (p   .084). The findings suggest that visuospatial attention differentially affects postural control in young and older adults and the effect is task-specific. These findings suggest the need to include stepping and force control tasks to further determine what role visuospatial attention plays in postural control. Copyright © 2017. Published by Elsevier Ltd.

Choline-mediated modulation of hippocampal sharp wave-ripple complexes in vitro.

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Fischer, Viktoria; Both, Martin; Draguhn, Andreas; Egorov, Alexei V

2014-06-01

The cholinergic system is critically involved in the modulation of cognitive functions, including learning and memory. Acetylcholine acts through muscarinic (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in the hippocampus. Previous evidence indicates that choline, the precursor and degradation product of Acetylcholine, can itself activate nAChRs and thereby affects intrinsic and synaptic neuronal functions. Here, we asked whether the cellular actions of choline directly affect hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma oscillations. In addition, choline reduces synaptic transmission between hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by activation of both mAChRs and α7-containing nAChRs. Most nicotinic effects became only apparent after local, fast application of choline, indicating rapid desensitization kinetics of nAChRs. Effects were still present following block of choline uptake and are, therefore, likely because of direct actions of choline at the respective receptors. Together, choline turns out to be a potent regulator of patterned network activity within the hippocampus. These actions may be of importance for understanding state transitions in normal and pathologically altered neuronal networks. In this study we asked whether choline, the precursor and degradation product of acetylcholine, directly affects hippocampal network activity. Using mouse hippocampal slices we found that choline efficiently suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In addition, choline reduces synaptic transmission between hippocampal subfields. These effects are mediated by direct activation of muscarinic as well as nicotinic cholinergic pathways. Together, choline turns out to be a potent regulator of patterned activity within hippocampal

Video gaming enhances psychomotor skills but not visuospatial and perceptual abilities in surgical trainees.

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Kennedy, A M; Boyle, E M; Traynor, O; Walsh, T; Hill, A D K

2011-01-01

There is considerable interest in the identification and assessment of underlying aptitudes or innate abilities that could potentially predict excellence in the technical aspects of operating. However, before the assessment of innate abilities is introduced for high-stakes assessment (such as competitive selection into surgical training programs), it is essential to determine that these abilities are stable and unchanging and are not influenced by other factors, such as the use of video games. The aim of this study was to investigate whether experience playing video games will predict psychomotor performance on a laparoscopic simulator or scores on tests of visuospatial and perceptual abilities, and to examine the correlation, if any, between these innate abilities. Institutional ethical approval was obtained. Thirty-eight undergraduate medical students with no previous surgical experience were recruited. All participants completed a self-reported questionnaire that asked them to detail their video game experience. They then underwent assessment of their psychomotor, visuospatial, and perceptual abilities using previously validated tests. The results were analyzed using independent samples t tests to compare means and linear regression curves for subsequent analysis. Students who played video games for at least 7 hours per week demonstrated significantly better psychomotor skills than students who did not play video games regularly. However, there was no difference on measures of visuospatial and perceptual abilities. There was no correlation between psychomotor tests and visuospatial or perceptual tests. Regular video gaming correlates positively with psychomotor ability, but it does not seem to influence visuospatial or perceptual ability. This study suggests that video game experience might be beneficial to a future career in surgery. It also suggests that relevant surgical skills may be gained usefully outside the operating room in activities that are not

Hippocampal-Prefrontal Circuit and Disrupted Functional Connectivity in Psychiatric and Neurodegenerative Disorders

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Ming Li

2015-01-01

Full Text Available In rodents, the hippocampus has been studied extensively as part of a brain system responsible for learning and memory, and the prefrontal cortex (PFC participates in numerous cognitive functions including working memory, flexibility, decision making, and rewarding learning. The neuronal projections from the hippocampus, either directly or indirectly, to the PFC, referred to as the hippocampal-prefrontal cortex (Hip-PFC circuit, play a critical role in cognitive and emotional regulation and memory consolidation. Although in certain psychiatric and neurodegenerative diseases, structural connectivity viewed by imaging techniques has been consistently found to be associated with clinical phenotype and disease severity, the focus has moved towards the investigation of connectivity correlates of molecular pathology and coupling of oscillation. Moreover, functional and structural connectivity measures have been emerging as potential intermediate biomarkers for neuronal disorders. In this review, we summarize progress on the anatomic, molecular, and electrophysiological characters of the Hip-PFC circuit in cognition and emotion processes with an emphasis on oscillation and functional connectivity, revealing a disrupted Hip-PFC connectivity and electrical activity in psychiatric and neurodegenerative disorders as a promising candidate of neural marker for neuronal disorders.

Disparities in visuo-spatial constructive abilities in Williams syndrome patients with typical deletion on chromosome 7q11.23.

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Muramatsu, Yukako; Tokita, Yoshihito; Mizuno, Seiji; Nakamura, Miho

2017-02-01

Williams syndrome (WS) is known for its uneven cognitive abilities, especially the difficulty in visuo-spatial cognition, though there are some inter-individual phenotypic differences. It has been proposed that the difficulty in visuo-spatial cognition of WS patients can be attributed to a haploinsufficiency of some genes located on the deleted region in 7q11.23, based on an examination of atypical deletions identified in WS patients with atypical cognitive deficits. According to this hypothesis, the inter-individual differences in visuo-spatial cognitive ability arise from variations in deletion. We investigated whether there were inter-individual differences in the visuo-spatial constructive abilities of five unrelated WS patients with the typical deletion on chromosome 7q11.23 that includes the candidate genes contributing visuo-spatial difficulty in WS patients. We used tests with three-dimensional factors such as Benton's three-dimensional block construction test, which are considered to be more sensitive than those with only two-dimensional factors. There were diverse inter-individual differences in the visuo-spatial constructive abilities among the present participants who shared the same typical genomic deletion of WS. One of the participants showed almost equivalent performances to typically developing adults in those tests. In the present study, we found a wide range of cognitive abilities in visuo-spatial construction even among the patients with a common deletion pattern of WS. The findings suggest that attributing differences in the phenotypes entirely to genetic factors such as an atypical deletion may not be always correct. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Attention and Visuospatial Working Memory Share the Same Processing Resources

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Jing eFeng

2012-04-01

Full Text Available Attention and visuospatial working memory (VWM share very similar characteristics; both have the same upper bound of about four items in capacity and they recruit overlapping brain regions. We examined whether both attention and visuospatial working memory share the same processing resources using a novel dual-task-costs approach based on a load-varying dual-task technique. With sufficiently large loads on attention and VWM, considerable interference between the two processes was observed. A further load increase on either process produced reciprocal increases in interference on both processes, indicating that attention and VWM share common resources. More critically, comparison among four experiments on the reciprocal interference effects, as measured by the dual-task costs, demonstrates no significant contribution from additional processing other than the shared processes. These results support the notion that attention and VWM share the same processing resources.

Relationship between hippocampal subfield volumes and memory deficits in patients with thalamus infarction.

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Chen, Li; Luo, Tianyou; Lv, Fajin; Shi, Dandan; Qiu, Jiang; Li, Qi; Fang, Weidong; Peng, Juan; Li, Yongmei; Zhang, Zhiwei; Li, Yang

2016-09-01

Clinical studies have shown that thalamus infarction (TI) affects memory function. The thalamic nucleus is directly or indirectly connected to the hippocampal system in animal models. However, this connection has not been investigated using structural magnetic resonance imaging (MRI) in humans. From the pathological perspective, TI patients may serve as valid models for revealing the interaction between the thalamus and hippocampus in memory function. In this study, we aim to assess different hippocampal subfield volumes in TI patients and control subjects using MRI and test their associations with memory function. A total of 37 TI patients (TI group), 38 matched healthy control subjects (HC group), and 22 control patients with other stroke location (SC group) underwent 3.0-T MRI scans and clinical memory examinations. Hippocampal subfield volumes were measured and compared by using FreeSurfer software. We examined the correlation between hippocampal subfield volumes and memory scores. Smaller ipsilesional presubiculum and subiculum volumes were observed, and former was related to graphics recall in both left and right TI patients. The left subiculum volume was correlated with short-delayed recall in left TI patients. The right presubiculum volume was correlated with short- and long-delayed recall in right TI patients. TI was found to result in hippocampal abnormality and memory deficits, and its neural mechanisms might be related with and interaction between the thalamus and hippocampus.

Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development.

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Schlichting, Margaret L; Guarino, Katharine F; Schapiro, Anna C; Turk-Browne, Nicholas B; Preston, Alison R

2017-01-01

Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks-both of which require encoding associations that span multiple episodes-in a developmental sample ranging from ages 6 to 30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region's hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development.

A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sprouting

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Gispen, W.H.; Proper, E.A.; Jansen, G.H.; Veelen, C.W. van; Rijen, P.C. van; Graan, P.N.E. de

2001-01-01

Abstract. In patients suffering from temporal lobe epilepsy (TLE) a highly variable degree of hippocampal sclerosis (HS) can be observed. For standard neuropathological evaluation after hippocampal resection, neuronal cell loss in the hippocampal subareas is assessed (Wyler score 0-4) [Wyler et al.

Adult hippocampal neurogenesis in natural populations of mammals.

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Amrein, Irmgard

2015-05-01

This review will discuss adult hippocampal neurogenesis in wild mammals of different taxa and outline similarities with and differences from laboratory animals. It begins with a review of evidence for hippocampal neurogenesis in various mammals, and shows the similar patterns of age-dependent decline in cell proliferation in wild and domesticated mammals. In contrast, the pool of immature neurons that originate from proliferative activity varies between species, implying a selective advantage for mammals that can make use of a large number of these functionally special neurons. Furthermore, rapid adaptation of hippocampal neurogenesis to experimental challenges appears to be a characteristic of laboratory rodents. Wild mammals show species-specific, rather stable hippocampal neurogenesis, which appears related to demands that characterize the niche exploited by a species rather than to acute events in the life of its members. Studies that investigate adult neurogenesis in wild mammals are not numerous, but the findings of neurogenesis under natural conditions can provide new insights, and thereby also address the question to which cognitive demands neurogenesis may respond during selection. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior.

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Sun, Dong; Sun, Xiang-Dong; Zhao, Lu; Lee, Dae-Hoon; Hu, Jin-Xia; Tang, Fu-Lei; Pan, Jin-Xiu; Mei, Lin; Zhu, Xiao-Juan; Xiong, Wen-Cheng

2018-01-08

Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation. Mechanistic studies revealed a role for neogenin to positively regulate Gli1, a crucial downstream transcriptional factor of sonic hedgehog, and expression of Gli1 into neogenin depleted NSCs/NPCs restores their proliferation. Further morphological and functional studies showed additional abnormities, including reduced dendritic branches and spines, and impaired glutamatergic neuro-transmission, in neogenin-depleted new-born DG neurons; and mice with depletion of neogenin in NSCs/NPCs exhibited depressive-like behavior. These results thus demonstrate unrecognized functions of neogenin in adult hippocampal NSCs/NPCs-promoting NSCs/NPCs proliferation and neurogenesis and preventing astrogliogenesis and depressive-like behavior, and suggest neogenin regulation of Gli1 signaling as a possible underlying mechanism.

Good phonetic errors in poor spellers are associated with right-handedness and possible weak utilisation of visuospatial abilities.

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Eglinton, Elizabeth; Annett, Marian

2008-06-01

Poor spellers in normal schools, who were not poor readers, were studied for handedness, visuospatial and other cognitive abilities in order to explore contrasts between poor spellers with and without good phonology. It was predicted by the right shift (RS) theory of handedness and cerebral dominance that those with good phonology would have strong bias to dextrality and relative weakness of the right hemisphere, while those without good phonology would have reduced bias to dextrality and relative weakness of the left hemisphere. Poor spellers with good phonetic equivalent spelling errors (GFEs) included fewer left-handers (2.4%) than poor spellers without GFEs (24.4%). Differences for hand skill were as predicted. Tests of visuospatial processing found no differences between the groups in levels of ability, but there was a marked difference in pattern of correlations between visuospatial test scores and homophonic word discrimination. Whereas good spellers (GS) and poor spellers without GFEs showed positive correlations between word discrimination and visuospatial ability, there were no significant correlations for poor spellers with GFEs. The differences for handedness and possibly for the utilisation of visuospatial skills suggest that surface dyslexics differ from phonological dyslexics in cerebral specialisation and perhaps in the quality of inter-hemispheric relations.

Intermediate levels of hippocampal activity appear optimal for associative memory formation.

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Xiao Liu

Full Text Available BACKGROUND: It is well established that hippocampal activity is positively related to effective associative memory formation. However, in biological systems often optimal levels of activity are contrasted by both sub- and supra-optimal levels. Sub-optimal levels of hippocampal activity are commonly attributed to unsuccessful memory formation, whereas the supra-optimal levels of hippocampal activity related to unsuccessful memory formation have been rarely studied. It is still unclear under what circumstances such supra-optimal levels of hippocampal activity occur. To clarify this issue, we aimed at creating a condition, in which supra-optimal hippocampal activity is associated with encoding failure. We assumed that such supra-optimal activity occurs when task-relevant information is embedded in task-irrelevant, distracting information, which can be considered as noise. METHODOLOGY/PRINCIPAL FINDINGS: In the present fMRI study, we probed neural correlates of associative memory formation in a full-factorial design with associative memory (subsequently remembered versus forgotten and noise (induced by high versus low distraction as factors. Results showed that encoding failure was associated with supra-optimal activity in the high-distraction condition and with sub-optimal activity in the low distraction condition. Thus, we revealed evidence for a bell-shape function relating hippocampal activity with associative encoding success. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that intermediate levels of hippocampal activity are optimal while both too low and too high levels appear detrimental for associative memory formation. Supra-optimal levels of hippocampal activity seem to occur when task-irrelevant information is added to task-relevant signal. If such task-irrelevant noise is reduced adequately, hippocampal activity is lower and thus optimal for associative memory formation.

Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory.

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Abdul Rahman, Nor Zaihana; Greenwood, Sam M; Brett, Ros R; Tossell, Kyoko; Ungless, Mark A; Plevin, Robin; Bushell, Trevor J

2016-02-24

Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer's disease. Thus, there is great interest in understanding the signaling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system, and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show that long-term potentiation is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls whereas neuronal excitability, evoked synaptic transmission, and paired-pulse facilitation remain unaltered. Furthermore, spontaneous EPSC (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2(-/-) mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures, which may account for the increase in sEPSC frequency. In addition, no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2(-/-) mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signaling. Copyright © 2016 Abdul Rahman et al.

No arousal-biased competition in focused visuospatial attention.

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Ásgeirsson, Árni Gunnar; Nieuwenhuis, Sander

2017-11-01

Arousal sometimes enhances and sometimes impairs perception and memory. A recent theory attempts to reconcile these findings by proposing that arousal amplifies the competition between stimulus representations, strengthening already strong representations and weakening already weak representations. Here, we report a stringent test of this arousal-biased competition theory in the context of focused visuospatial attention. Participants were required to identify a briefly presented target in the context of multiple distractors, which varied in the degree to which they competed for representation with the target, as revealed by psychophysics. We manipulated arousal using emotionally arousing pictures (Experiment 1), alerting tones (Experiment 2) and white-noise stimulation (Experiment 3), and validated these manipulations with electroencephalography and pupillometry. In none of the experiments did we find evidence that arousal modulated the effect of distractor competition on the accuracy of target identification. Bayesian statistics revealed moderate to strong evidence against arousal-biased competition. Modeling of the psychophysical data based on Bundesen's (1990) theory of visual attention corroborated the conclusion that arousal does not bias competition in focused visuospatial attention. Copyright © 2017 Elsevier B.V. All rights reserved.

When do humans spontaneously adopt another's visuospatial perspective?

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Freundlieb, Martin; Kovács, Ágnes M; Sebanz, Natalie

2016-03-01

Perspective-taking is a key component of social interactions. However, there is an ongoing controversy about whether, when and how instances of spontaneous visuospatial perspective-taking occur. The aim of this study was to investigate the underlying factors as well as boundary conditions that characterize the spontaneous adoption of another person's visuospatial perspective (VSP) during social interactions. We used a novel paradigm, in which a participant and a confederate performed a simple stimulus-response (SR) compatibility task sitting at a 90° angle to each other. In this set-up, participants would show a spatial compatibility effect only if they adopted the confederate's VSP. In a series of 5 experiments we found that participants reliably adopted the VSP of the confederate, as long as he was perceived as an intentionally acting agent. Our results therefore show that humans are able to spontaneously adopt the differing VSP of another agent and that there is a tight link between perspective-taking and performing actions together. The results suggest that spontaneous VSP-taking can effectively facilitate and speed up spatial alignment processes accruing from dynamic interactions in multiagent environments. (c) 2016 APA, all rights reserved).

Hippocampal gamma oscillations increase with memory load

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Van Vugt, Marieke K.; Schulze-Bonhage, Andreas; Litt, Brian; Brandt, Armin; Kahana, Michael J.

2010-01-01

Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we

Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults.

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Witte, A Veronica; Kerti, Lucia; Margulies, Daniel S; Flöel, Agnes

2014-06-04

Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanisms underlying this effect. Twenty-three healthy overweight older individuals that successfully completed 26 weeks of resveratrol intake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50-75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging. Copyright © 2014 the authors 0270-6474/14/347862-09$15.00/0.

The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

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Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

2015-01-01

Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

Tuning afferent synapses of hippocampal interneurons by neuropeptide Y

DEFF Research Database (Denmark)

Ledri, Marco; Sørensen, Andreas Toft; Erdelyi, Ferenc

2011-01-01

Cholecystokinin (CCK)-expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory-forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective...... are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65-GFP transgenic mice for prospective identification of CCK basket cells and whole-cell patch-clamp recordings, we show...

Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling.

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Lee, Min Chul; Okamoto, Masahiro; Liu, Yu Fan; Inoue, Koshiro; Matsui, Takashi; Nogami, Haruo; Soya, Hideaki

2012-10-15

Although voluntary running has beneficial effects on hippocampal cognitive functions if done abundantly, it is still uncertain whether resistance running would be the same. For this purpose, voluntary resistance wheel running (RWR) with a load is a suitable model, since it allows increased work levels and resultant muscular adaptation in fast-twitch muscle. Here, we examined whether RWR would have potential effects on hippocampal cognitive functions with enhanced hippocampal brain-derived neurotrophic factor (BDNF), as does wheel running without a load (WR). Ten-week-old male Wistar rats were assigned randomly to sedentary (Sed), WR, and RWR (to a maximum load of 30% of body weight) groups for 4 wk. We found that in RWR, work levels increased with load, but running distance decreased by about half, which elicited muscular adaptation for fast-twitch plantaris muscle without causing any negative stress effects. Both RWR and WR led to improved spatial learning and memory as well as gene expressions of hippocampal BDNF signaling-related molecules. RWR increased hippocampal BDNF, tyrosine-related kinase B (TrkB), and cAMP response element-binding (CREB) protein levels, whereas WR increased only BDNF. With both exercise groups, there were correlations between spatial memory and BDNF protein (r = 0.41), p-CREB protein (r = 0.44), and work levels (r = 0.77). These results suggest that RWR plays a beneficial role in hippocampus-related cognitive functions associated with hippocampal BDNF signaling, even with short distances, and that work levels rather than running distance are more determinant of exercise-induced beneficial effects in wheel running with and without a load.

APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

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Melanie Laßek

2016-04-01

Full Text Available The hallmarks of Alzheimer's disease (AD are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network.

Low-intensity daily walking activity is associated with hippocampal volume in older adults.

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Varma, Vijay R; Chuang, Yi-Fang; Harris, Gregory C; Tan, Erwin J; Carlson, Michelle C

2015-05-01

Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low-intensity walking activity, which may be related to leisure-time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher-intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate- to vigorous-intensity activity and self-reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings

Feedback associated with expectation for larger-reward improves visuospatial working memory performances in children with ADHD.

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Hammer, Rubi; Tennekoon, Michael; Cooke, Gillian E; Gayda, Jessica; Stein, Mark A; Booth, James R

2015-08-01

We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

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Bopanna I Kalappa

2010-11-01

Full Text Available The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596.An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the entire pyramidal neuron and occasionally

Impaired Visuospatial Short-Term Memory in Children with ADHD.

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Narimoto, Tadamasa; Matsuura, Naomi; Hiratani, Michio

2018-01-01

Previous studies provide clear evidence that visuospatial memory performance in children with attention-deficit/hyperactivity disorder (ADHD) is significantly lower than in typically developing children. In the present study, we investigated a major cause of their low performance using a spatial span test. Possibly, inattention resulting from lack of motivation or interest causes their low performance so that they do not correctly encode targets to be remembered. On the other hand, a deficit in temporary maintenance per se may cause their low performance; that is, their inefficient use of rehearsal during a retention interval may lead to memory traces' fast decay. Results in this study indicated that children with ADHD could sustain attention during the encoding phase. Furthermore, their performance at delayed recall was significantly lower than immediate recall, but delayed recall did not affect typically developing children's performance. These results provide evidence for the likelihood that a factor causing children with ADHD difficulty in temporarily maintaining visuospatial information is fast decay of memory traces as a result of inefficient use of rehearsal, not inattention in the encoding phase.

Hippocampal dentation: Structural variation and its association with episodic memory in healthy adults.

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Fleming Beattie, Julia; Martin, Roy C; Kana, Rajesh K; Deshpande, Hrishikesh; Lee, Seongtaek; Curé, Joel; Ver Hoef, Lawrence

2017-07-01

While the hippocampus has long been identified as a structure integral to memory, the relationship between morphology and function has yet to be fully explained. We present an analysis of hippocampal dentation, a morphological feature previously unexplored in regard to its relationship with episodic memory. "Hippocampal dentation" in this case refers to surface convolutions, primarily present in the CA1/subiculum on the inferior aspect of the hippocampus. Hippocampal dentation was visualized using ultra-high resolution structural MRI and evaluated using a novel visual rating scale. The degree of hippocampal dentation was found to vary considerably across individuals, and was positively associated with verbal memory recall and visual memory recognition in a sample of 22 healthy adults. This study is the first to characterize the variation in hippocampal dentation in a healthy cohort and to demonstrate its association with aspects of episodic memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

ADHD subtype differences in reinforcement sensitivity and visuospatial working memory

NARCIS (Netherlands)

Dovis, S.; van der Oord, S.; Wiers, R.W.; Prins, P.J.M.

2015-01-01

Both cognitive and motivational deficits are thought to give rise to the problems in the combined (ADHD-C) and inattentive subtype (ADHD-I) of attention-deficit hyperactivity disorder (ADHD). In both subtypes one of the most prominent cognitive weaknesses appears to be in visuospatial working memory

Contribution of cerebellar sensorimotor adaptation to hippocampal spatial memory.

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Jean-Baptiste Passot

Full Text Available Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation.

Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy

International Nuclear Information System (INIS)

Kazda, Tomas; Slampa, Pavel; Laack, Nadia N; Jancalek, Radim; Pospisil, Petr; Sevela, Ondrej; Prochazka, Tomas; Vrzal, Miroslav; Burkon, Petr; Slavik, Marek; Hynkova, Ludmila

2014-01-01

The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques

Jigsaw Puzzles As Cognitive Enrichment (PACE) - the effect of solving jigsaw puzzles on global visuospatial cognition in adults 50 years of age and older: study protocol for a randomized controlled trial.

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Fissler, Patrick; Küster, Olivia C; Loy, Laura S; Laptinskaya, Daria; Rosenfelder, Martin J; von Arnim, Christine A F; Kolassa, Iris-Tatjana

2017-09-06

Neurocognitive disorders are an important societal challenge and the need for early prevention is increasingly recognized. Meta-analyses show beneficial effects of cognitive activities on cognition. However, high financial costs, low intrinsic motivation, logistic challenges of group-based activities, or the need to operate digital devices prevent their widespread application in clinical practice. Solving jigsaw puzzles is a cognitive activity without these hindering characteristics, but cognitive effects have not been investigated yet. With this study, we aim to evaluate the effect of solving jigsaw puzzles on visuospatial cognition, daily functioning, and psychological outcomes. The pre-posttest, assessor-blinded study will include 100 cognitively healthy adults 50 years of age or older, who will be randomly assigned to a jigsaw puzzle group or a cognitive health counseling group. Within the 5-week intervention period, participants in the jigsaw puzzle group will engage in 30 days of solving jigsaw puzzles for at least 1 h per day and additionally receive cognitive health counseling. The cognitive health counseling group will receive the same counseling intervention but no jigsaw puzzles. The primary outcome, global visuospatial cognition, will depict the average of the z-standardized performance scores in visuospatial tests of perception, constructional praxis, mental rotation, processing speed, flexibility, working memory, reasoning, and episodic memory. As secondary outcomes, we will assess the eight cognitive abilities, objective and subjective visuospatial daily functioning, psychological well-being, general self-efficacy, and perceived stress. The primary data analysis will be based on mixed-effects models in an intention-to-treat approach. Solving jigsaw puzzles is a low-cost, intrinsically motivating, cognitive leisure activity, which can be executed alone or with others and without the need to operate a digital device. In the case of positive results

Prefronto–cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder

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Minichino A

2015-08-01

Full Text Available Amedeo Minichino, Francesco Saverio Bersani, Laura Bernabei, Francesco Spagnoli, Lucilla Vergnani, Alessandra Corrado, Ines Taddei, Massimo Biondi, Roberto Delle Chiaie Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Objective: The aim of the study was to improve neuropsychological functioning of euthymic patients with bipolar disorder (BD using transcranial direct current stimulation (tDCS applied to cerebellar and prefrontal cortices.Methods: Twenty-five BD outpatients underwent prefrontal (anodal and cerebellar (cathodal tDCS for 3 consecutive weeks. All participants were assessed through the Rey Complex Figure Test delay and copy and the Neurological Examination Scale at baseline and after therapy with tDCS.Results: After tDCS treatment, patients showed significant improvements in visuospatial memory tasks. Patients with worse baseline cognitive performances also showed a significant improvement in executive functioning tasks. Neurological Examination Scale total score and motor coordination subscale significantly improved.Conclusion: Prefrontal-excitatory and cerebellar-inhibitory stimulations in euthymic BD patients may lead to better neurocognitive performances. This improvement could result from the modulation of prefronto–thalamic–cerebellar circuit activity pattern, which can be disrupted in BD. Keywords: cerebellum, dorsolateral prefrontal cortex, neuropsychology, cognition 

Conservation Abilities, Visuospatial Skills, and Numerosity Processing Speed: Association With Math Achievement and Math Difficulties in Elementary School Children.

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Lambert, Katharina; Spinath, Birgit

The aim of the present study was to investigate the associations between elementary school children's mathematical achievement and their conservation abilities, visuospatial skills, and numerosity processing speed. We also assessed differences in these abilities between children with different types of learning problems. In Study 1 ( N = 229), we investigated second to fourth graders and in Study 2 ( N = 120), third and fourth graders. Analyses revealed significant contributions of numerosity processing speed and visuospatial skills to math achievement beyond IQ. Conservation abilities were predictive in Study 1 only. Children with math difficulties showed lower visuospatial skills and conservation abilities than children with typical achievement levels and children with reading and/or spelling difficulties, whereas children with combined difficulties explicitly showed low conservation abilities. These findings provide further evidence for the relations between children's math skills and their visuospatial skills, conservation abilities, and processing speed and contribute to the understanding of deficits that are specific to mathematical difficulties.

Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats.

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Fukushima, Atsushi; Ogura, Yuji; Furuta, Miyako; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

2015-10-05

A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability. Copyright © 2015 Elsevier B.V. All rights reserved.

Encoding, Consolidation, and Retrieval of Contextual Memory: Differential Involvement of Dorsal CA3 and CA1 Hippocampal Subregions

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Daumas, Stephanie; Halley, Helene; Frances, Bernard; Lassalle, Jean-Michel

2005-01-01

Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting…

Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

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Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu

2016-07-01

Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

A bilateral frontoparietal network underlies visuospatial analogical reasoning.

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Watson, Christine E; Chatterjee, Anjan

2012-02-01

Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies. Copyright © 2011 Elsevier Inc. All rights reserved.

Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.

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Pearson-Leary, J; Jahagirdar, V; Sage, J; McNay, E C

2018-02-15

The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

A Larger Social Network Enhances Novel Object Location Memory and Reduces Hippocampal Microgliosis in Aged Mice

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Smith, Bryon M.; Yao, Xinyue; Chen, Kelly S.; Kirby, Elizabeth D.

2018-01-01

The mammalian hippocampus shows marked decline in function with aging across many species, including humans and laboratory rodent models. This decline frequently manifests in memory impairments that occur even in the absence of dementia pathology. In humans, a number of factors correlate with preserved hippocampal memory in aging, such as exercise, cognitive stimulation and number of social ties. While interventional studies and animal models clearly indicate that exercise and cognitive stimulation lead to hippocampal preservation, there is relatively little research on whether a decline in social ties leads to cognitive decline or vice versa. Even in animal studies of environmental enrichment in aging, the focus typically falls on physical enrichment such as a rotating cast of toys, rather than the role of social interactions. The present studies investigated the hypothesis that a greater number of social ties in aging mice would lead to improved hippocampal function. Aged, female C57/Bl6 mice were housed for 3 months in pairs or large groups (7 mice per cage). Group-housed mice showed greater novel object location memory and stronger preference for a spatial navigation strategy in the Barnes maze, though no difference in escape latency, compared to pair-housed mice. Group-housed mice did not differ from pair-housed mice in basal corticosterone levels or adult hippocampal neurogenesis. Group-housed mice did, however, show reduced numbers of Iba1/CD68+ microglia in the hippocampus. These findings suggest that group housing led to better memory function and reduced markers of neuroinflammation in aged mice. More broadly, they support a causative link between social ties and hippocampal function, suggesting that merely having a larger social network can positively influence the aging brain. Future research should address the molecular mechanisms by which a greater number of social ties alters hippocampal function. PMID:29904345

Episodic autobiographical memory is associated with variation in the size of hippocampal subregions.

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Palombo, Daniela J; Bacopulos, Agnes; Amaral, Robert S C; Olsen, Rosanna K; Todd, Rebecca M; Anderson, Adam K; Levine, Brian

2018-02-01

Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA 2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA 2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA 1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans. © 2017 Wiley Periodicals, Inc.

Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

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Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli

2013-01-01

The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

Is there a relationship between ultrasound scanning ability (sonography) and visuospatial perception or psychomotor ability?

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Hagen, Suzanne; Gallagher, Helen

2016-01-01

Background Competent sonography is thought to include a unique combination of skills not yet fully defined. This presents challenges when recruiting the correct people for training. Skills are thought to include visuospatial perception and psychomotor skills, but little is known about the relationship between these aptitudes and scanning ability. This feasibility study explored such relationships, to identify evaluation techniques which may improve selection and recruitment. Methods A sample of 30 experienced ultrasound practitioners and 30 trainees at commencement and on completion of training were administered eight tests. Results No significant relationships between experienced practitioners’ or trainees’ visuospatial abilities or psychomotor abilities and scanning abilities were found. Results demonstrated that two of the visuospatial perception tests were not influenced by training and therefore, may be measuring the innate skills of ultrasound practitioners. As ultrasound practitioners had not performed any of the tests previously, ranges of scores for each of the eight tests were established for this group. This included measures for psychomotor skills which added to the current body of knowledge for sonography. Conclusions Although no significant correlations were found between participants’ visuospatial perception or psychomotor abilities and scanning ability, performance on the Obstetric Structured Assessment Test (combining all the skills required) pre-training gave the best indication of post-training scanning performance. The Obstetric Structured Assessment Test may prove a useful tool for initial assessment of potential trainees but abilities will require further investigation. PMID:27847536

Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs

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Tveden-Nyborg, Pernille; Vogt, Lucile; Schjoldager, Janne G

2012-01-01

While having the highest vitamin C (VitC) concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study...... investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet. Newborn...... by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P...

Modulation of Hippocampal Neural Plasticity by Glucose-Related Signaling

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Marco Mainardi

2015-01-01

Full Text Available Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression, structural plasticity (i.e., dynamics of dendritic spines, and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

Evidence for a Double Dissociation between Spatial-Simultaneous and Spatial-Sequential Working Memory in Visuospatial (Nonverbal) Learning Disabled Children

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Mammarella, Irene C.; Cornoldi, Cesare; Pazzaglia, Francesca; Toso, Cristina; Grimoldi, Mario; Vio, Claudio

2006-01-01

The paper describes the performance of three children with specific visuospatial working memory (VSWM) impairments (Study 1) and three children with visuospatial (nonverbal) learning disabilities (Study 2) assessed with a battery of working memory (WM) tests and with a number of school achievement tasks. Overall, performance on WM tests provides…

The Differential Contributions of Auditory-Verbal and Visuospatial Working Memory on Decoding Skills in Children Who Are Poor Decoders

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Squires, Katie Ellen

2013-01-01

This study investigated the differential contribution of auditory-verbal and visuospatial working memory (WM) on decoding skills in second- and fifth-grade children identified with poor decoding. Thirty-two second-grade students and 22 fifth-grade students completed measures that assessed simple and complex auditory-verbal and visuospatial memory,…

Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

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Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-21

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

Visuospatial working memory in very preterm and term born children--impact of age and performance.

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Mürner-Lavanchy, I; Ritter, B C; Spencer-Smith, M M; Perrig, W J; Schroth, G; Steinlin, M; Everts, R

2014-07-01

Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7-12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Visuospatial working memory in very preterm and term born children—Impact of age and performance

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I. Mürner-Lavanchy

2014-07-01

Full Text Available Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7–12 years using functional magnetic resonance imaging (fMRI and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.

Increased Alpha-Rhythm Dynamic Range Promotes Recovery from Visuospatial Neglect: A Neurofeedback Study

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Tomas Ros

2017-01-01

Full Text Available Despite recent attempts to use electroencephalogram (EEG neurofeedback (NFB as a tool for rehabilitation of motor stroke, its potential for improving neurological impairments of attention—such as visuospatial neglect—remains underexplored. It is also unclear to what extent changes in cortical oscillations contribute to the pathophysiology of neglect, or its recovery. Utilizing EEG-NFB, we sought to causally manipulate alpha oscillations in 5 right-hemisphere stroke patients in order to explore their role in visuospatial neglect. Patients trained to reduce alpha oscillations from their right posterior parietal cortex (rPPC for 20 minutes daily, over 6 days. Patients demonstrated successful NFB learning between training sessions, denoted by improved regulation of alpha oscillations from rPPC. We observed a significant negative correlation between visuospatial search deficits (i.e., cancellation test and reestablishment of spontaneous alpha-rhythm dynamic range (i.e., its amplitude variability. Our findings support the use of NFB as a tool for investigating neuroplastic recovery after stroke and suggest reinstatement of intact parietal alpha oscillations as a promising target for reversing attentional deficits. Specifically, we demonstrate for the first time the feasibility of EEG-NFB in neglect patients and provide evidence that targeting alpha amplitude variability might constitute a valuable marker for clinical symptoms and self-regulation.

Novel genetic loci associated with hippocampal volume.

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Hibar, Derrek P; Adams, Hieab H H; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L; Hofer, Edith; Renteria, Miguel E; Bis, Joshua C; Arias-Vasquez, Alejandro; Ikram, M Kamran; Desrivières, Sylvane; Vernooij, Meike W; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H; Beiser, Alexa; Bernard, Manon; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Gutman, Boris A; Hass, Johanna; Haukvik, Unn K; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre F; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; McKay, David R; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C; Nyquist, Paul; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Saremi, Arvin; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Craen, Anton J M; De Geus, Eco J C; De Jager, Philip L; De Zubicaray, Greig I; Deary, Ian J; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J A; Van Haren, Neeltje E M; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Vellas, Bruno; Veltman, Dick J; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, Ronald H; Zonderman, Alan B; Martin, Nicholas G; Van Duijn, Cornelia M; Wright, Margaret J; Longstreth, W T; Schumann, Gunter; Grabe, Hans J; Franke, Barbara; Launer, Lenore J; Medland, Sarah E; Seshadri, Sudha; Thompson, Paul M; Ikram, M Arfan

2017-01-18

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

[Effect of Scalp-acupuncture Stimulation on Neurological Function and Expression of ASIC 1 a and ASIC 2 b of Hippocampal CA 1 Region in Cerebral Ischemia Rats].

Science.gov (United States)

Tian, Liang; Wang, Jin-Hai; Zhao, Min; Bao, Ying-Cun; Shang, Jun-Fang; Yan, Qi; Zhang, Zhen-Chang; Du, Xiao-Zheng; Jiang, Hua; Sun, Run-Jie; Yuan, Bo; Zhang, Xing-Hua; Zhang, Ting-Zhuo; Li, Xing-Lan

2016-10-25

To observe the influence of scalp-acupuncture on the expression of acid-sensing ion channels (ASICs) 1 a and 2 b of hippocampal CA 1 region in cerebral ischemia (CI) rats, so as to investigate its mechanism underlying improvement of ischemic stroke. Thirty-two male SD rats were randomly allocated to normal control, model, scalp-acupuncture and Amiloride group ( n =8 in each group). The model of focal CI was established by middle cerebral artery occlusion (MCAO). Scalp acupuncture stimulation was applied to bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), once daily for 7 days. Rats of the Amiloride group were fed with Amiloride solution, twice a day for 7 days, and those of the normal control and model groups were grabbled and fixed in the same way with the acupuncture and Amiloride groups. The neurological deficit score was given according to Longa's method. The expression of hippocampal ASIC 1 a and ASIC 2 b was detected by immunohistochemistry, and the Ca 2+ concentration in the hippocampal tissue assayed using flowing cytometry. After the intervention, the neurological deficit score of both the scalp-acupuncture and Amiloride groups were significantly decreased in comparison with pre-treatment ( P ASIC 1 a and ASIC 2 b in the hippocampal CA 1 region and hip-pocampal Ca 2+ concentration were significantly up-regulated in the model group compared with the normal control group ( P ASIC 1 a and ASIC 2 b expression and Ca 2+ concentration ( P >0.05). Scalp-acupuncture stimulation can improve neurological function in CI rats, which may be related to its effects in suppressing the increased expression of hippocampal ASIC 1 a and ASIC 2 b proteins and in reducing calcium overload in hip-pocampal neurocytes.

Effects of lamotrigine on hippocampal activation in corticosteroid-treated patients.

Science.gov (United States)

Brown, E Sherwood; Zaidel, Liam; Allen, Greg; McColl, Roderick; Vazquez, Miguel; Ringe, Wendy K

2010-11-01

An extensive animal literature suggests that stress or excessive corticosteroid exposure is associated with changes in hippocampal function and memory. These findings are pertinent to psychiatric disorders with elevated cortisol, Cushing's disease and the millions of patients receiving prescription corticosteroids. In animals, agents that decrease glutamate release attenuate the effects of corticosteroids on the hippocampus. Minimal data are available on preventing or reversing the effects of corticosteroids on the human hippocampus. We previously reported improvement in memory in corticosteroid-treated patients given lamotrigine. In this report, we examined the impact of lamotrigine on task-related hippocampal activation in patients taking prescription corticosteroids. A total of 28 outpatients taking long-term oral prednisone for medical conditions, such as renal transplant rejection, were randomized to lamotrigine or placebo for 24 weeks. Hippocampal activation in response to a visual memory task was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). Consistent with a reduction in glutamate release, the right posterior hippocampus showed a significant decrease in task-related activation in the lamotrigine group as compared to the placebo group. The modest sample size and an assessment period of only 24 weeks are study limitations. Between-group differences in hippocampal activation were observed. The results suggest that an agent that modulates glutamate may modify the effects of long-term corticosteroid exposure on the human hippocampus. Copyright © 2010 Elsevier B.V. All rights reserved.

The angular gyrus and visuospatial attention in decision-making under risk.

Science.gov (United States)

Studer, Bettina; Cen, Danlu; Walsh, Vincent

2014-12-01

Recent neuroimaging studies on decision-making under risk indicate that the angular gyrus (AG) is sensitive to the probability and variance of outcomes during choice. A separate body of research has established the AG as a key area in visual attention. The current study used repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers to test whether the causal contribution of the AG to decision-making is independent of or linked to the guidance of visuospatial attention. A within-subject design compared decision making on a laboratory gambling task under three conditions: following rTMS to the AG, following rTMS to the premotor cortex (PMC, as an active control condition) and without TMS. The task presented two different trial types, 'visual' and 'auditory' trials, which entailed a high versus minimal demand for visuospatial attention, respectively. Our results showed a systematic effect of rTMS to the AG upon decision-making behavior in visual trials. Without TMS and following rTMS to the control region, decision latencies reflected the odds of winning; this relationship was disrupted by rTMS to the AG. In contrast, no significant effects of rTMS to the AG (or to the PMC) upon choice behavior in auditory trials were found. Thus, rTMS to the AG affected decision-making only in the task condition requiring visuospatial attention. The current findings suggest that the AG contributes to decision-making by guiding attention to relevant information about reward and punishment in the visual environment. Copyright © 2014. Published by Elsevier Inc.

Novel genetic loci associated with hippocampal volume

OpenAIRE

Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivieres, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf

2017-01-01

International audience; The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal ...

Visuo-Spatial Performance in Autism: A Meta-analysis

OpenAIRE

Muth, Anne; Honekopp, Johannes; Falter, Christine

2014-01-01

Visuo-spatial skills are believed to be enhanced in autism spectrum disorders (ASDs). This meta-analysis tests the current state of evidence for Figure Disembedding, Block Design, Mental Rotation and Navon tasks in ASD and neurotypicals. Block Design (d = 0.32) and Figure Disembedding (d = 0.26) showed superior performance for ASD with large heterogeneity that is unaccounted for. No clear differences were found for Mental Rotation. ASD samples showed a stronger local processing preference for...

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

Science.gov (United States)

Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

2014-01-01

Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

Hippocampal function is not required for the precision of remote place memory

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Kitamura Takashi

2012-02-01

Full Text Available Abstract Background During permanent memory formation, recall of acquired place memories initially depends on the hippocampus and eventually become hippocampus-independent with time. It has been suggested that the quality of original place memories also transforms from a precise form to a less precise form with similar time course. The question arises of whether the quality of original place memories is determined by brain regions on which the memory depends. Results To directly test this idea, we introduced a new procedure: a non-associative place recognition memory test in mice. Combined with genetic and pharmacological approaches, our analyses revealed that place memory is precisely maintained for 28 days, although the recall of place memory shifts from hippocampus-dependent to hippocampus-independent with time. Moreover, the inactivation of the hippocampal function does not inhibit the precision of remote place memory. Conclusion These results indicate that the quality of place memories is not determined by brain regions on which the memory depends.

Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus

NARCIS (Netherlands)

Bagot, R.C.; van Hasselt, F.N.; Champagne, D.L.; Meaney, M.J.; Krugers, H.J.; Joëls, M.

2009-01-01

Maternal care in the rat influences hippocampal development, synaptic plasticity and cognition. Previous studies, however, have examined animals under minimally stressful conditions. Here we tested the hypothesis that maternal care influences hippocampal function differently when this structure is

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

Directory of Open Access Journals (Sweden)

Roman A Sandler

2017-07-01

Full Text Available Much of the research on cannabinoids (CBs has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC, the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

The rise and fall of immediate and delayed memory for verbal and visuospatial information from late childhood to late adulthood

NARCIS (Netherlands)

Murre, J.M.J.; Janssen, S.M.J.; Rouw, R.; Meeter, M.

2013-01-01

Over 100,000 verbal and visuospatial immediate and delayed memory tests were presented via the Internet to over 28,000 participants in the age range of 11 to 80. Structural equation modeling pointed to the verbal versus visuospatial dimension as an important factor in individual differences, but not

The Rise and Fall of Immediate and Delayed Memory for Verbal and Visuospatial Information from Late Childhood to Late Adulthood

NARCIS (Netherlands)

Murre, J.M.J.; Janssen, S.M.J.; Rouw, R.; Meeter, M.

2013-01-01

Over 100,000 verbal and visuospatial immediate and delayed memory tests were presented via the Internet to over 28,000 participants in the age range of 11 to 80. Structural equation modeling pointed to the verbal versus visuospatial dimension as an important factor in individual differences, but not

The Effect of Binaural Beats on Visuospatial Working Memory and Cortical Connectivity.

Directory of Open Access Journals (Sweden)

Christine Beauchene

Full Text Available Binaural beats utilize a phenomenon that occurs within the cortex when two different frequencies are presented separately to each ear. This procedure produces a third phantom binaural beat, whose frequency is equal to the difference of the two presented tones and which can be manipulated for non-invasive brain stimulation. The effects of binaural beats on working memory, the system in control of temporary retention and online organization of thoughts for successful goal directed behavior, have not been well studied. Furthermore, no studies have evaluated the effects of binaural beats on brain connectivity during working memory tasks. In this study, we determined the effects of different acoustic stimulation conditions on participant response accuracy and cortical network topology, as measured by EEG recordings, during a visuospatial working memory task. Three acoustic stimulation control conditions and three binaural beat stimulation conditions were used: None, Pure Tone, Classical Music, 5Hz binaural beats, 10Hz binaural beats, and 15Hz binaural beats. We found that listening to 15Hz binaural beats during a visuospatial working memory task not only increased the response accuracy, but also modified the strengths of the cortical networks during the task. The three auditory control conditions and the 5Hz and 10Hz binaural beats all decreased accuracy. Based on graphical network analyses, the cortical activity during 15Hz binaural beats produced networks characteristic of high information transfer with consistent connection strengths throughout the visuospatial working memory task.

The Effect of Binaural Beats on Visuospatial Working Memory and Cortical Connectivity.

Science.gov (United States)

Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A; Leonessa, Alexander

2016-01-01

Binaural beats utilize a phenomenon that occurs within the cortex when two different frequencies are presented separately to each ear. This procedure produces a third phantom binaural beat, whose frequency is equal to the difference of the two presented tones and which can be manipulated for non-invasive brain stimulation. The effects of binaural beats on working memory, the system in control of temporary retention and online organization of thoughts for successful goal directed behavior, have not been well studied. Furthermore, no studies have evaluated the effects of binaural beats on brain connectivity during working memory tasks. In this study, we determined the effects of different acoustic stimulation conditions on participant response accuracy and cortical network topology, as measured by EEG recordings, during a visuospatial working memory task. Three acoustic stimulation control conditions and three binaural beat stimulation conditions were used: None, Pure Tone, Classical Music, 5Hz binaural beats, 10Hz binaural beats, and 15Hz binaural beats. We found that listening to 15Hz binaural beats during a visuospatial working memory task not only increased the response accuracy, but also modified the strengths of the cortical networks during the task. The three auditory control conditions and the 5Hz and 10Hz binaural beats all decreased accuracy. Based on graphical network analyses, the cortical activity during 15Hz binaural beats produced networks characteristic of high information transfer with consistent connection strengths throughout the visuospatial working memory task.

Gender-related differences in lateralization of hippocampal activation and cognitive strategy.

Science.gov (United States)

Frings, Lars; Wagner, Kathrin; Unterrainer, Josef; Spreer, Joachim; Halsband, Ulrike; Schulze-Bonhage, Andreas

2006-03-20

Gender-related differences in brain activation patterns and their lateralization associated with cognitive functions have been reported in the field of language, emotion, and working memory. Differences have been hypothesized to be due to different cognitive strategies. The aim of the present study was to test whether lateralization of brain activation in the hippocampi during memory processing differs between the sexes. We acquired functional magnetic resonance imaging data from healthy female and male study participants performing a spatial memory task and quantitatively assessed the lateralization of hippocampal activation in each participant. Hippocampal activation was significantly more left lateralized in women, and more right lateralized in men. Correspondingly, women rated their strategy as being more verbal than men did.

Correlation between hypertension and cognitive function in elderly

Science.gov (United States)

Fitri, F. I.; Rambe, A. S.

2018-03-01

Hypertension and cognitive impairment are common disorders among elderly adults, and their prevalences tend to rise as the population ages. This study aimed to determine the correlation between hypertension and cognitive function in elderly. It was a cross-sectional study involving 62 elderly subjects. All subjects underwent physical and neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function. This study included 62 subjects consisted of 26 males (41.9%) and 36 females (58.1%). There were 24 subjects (38.2%) with hypertension and 38 (61.3%) normal elderly subjects. The mean age was 65.71±4.49 years old. There were no significant differences in demographic characteristics, total MoCA-INA scores, and scores based on cognitive domains between two groups, except for visuospatial and executive function (p=0.026). There was a significant correlation between hypertension and visuospatial and executive function (r=0.301, p=0.017). Hypertension is correlated with cognitive impairment mainly on visuospatial and executive function in elderly.

A three-plane architectonic atlas of the rat hippocampal region.

Science.gov (United States)

Boccara, Charlotte N; Kjonigsen, Lisa J; Hammer, Ingvild M; Bjaalie, Jan G; Leergaard, Trygve B; Witter, Menno P

2015-07-01

The hippocampal region, comprising the hippocampal formation and the parahippocampal region, has been one of the most intensively studied parts of the brain for decades. Better understanding of its functional diversity and complexity has led to an increased demand for specificity in experimental procedures and manipulations. In view of the complex 3D structure of the hippocampal region, precisely positioned experimental approaches require a fine-grained architectural description that is available and readable to experimentalists lacking detailed anatomical experience. In this paper, we provide the first cyto- and chemoarchitectural description of the hippocampal formation and parahippocampal region in the rat at high resolution and in the three standard sectional planes: coronal, horizontal and sagittal. The atlas uses a series of adjacent sections stained for neurons and for a number of chemical marker substances, particularly parvalbumin and calbindin. All the borders defined in one plane have been cross-checked against their counterparts in the other two planes. The entire dataset will be made available as a web-based interactive application through the Rodent Brain WorkBench (http://www.rbwb.org) which, together with this paper, provides a unique atlas resource. © 2014 Wiley Periodicals, Inc.

Stress, depression and hippocampal damage

Indian Academy of Sciences (India)

Amongst the prime targets of stress in the brain is the hippocampus, which has high receptor ... effects on different hippocampal subfields (McEwen 1999). ... disorders, and decreases in hippocampal volume have been observed in patients of ...

Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy

Institute of Scientific and Technical Information of China (English)

Chuanjun Liu; Yue Li; Huiying Gao

2006-01-01

BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily.OBJECTTVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult.DESTGN: Completely randomized grouping, controlled experiment.SETTING: Taian Health Center for Women and Children; Taishan Medical College.MATERTALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou.METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability(After test, 5 rats from each group were sacrificed and used for immunohistochemical staining) ② The right common carotid artery of newborn rats of model group was ligated under the sthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③Thalamencephal tissue

Combined effects of marijuana and nicotine on memory performance and hippocampal volume.

Science.gov (United States)

Filbey, Francesca M; McQueeny, Tim; Kadamangudi, Shrinath; Bice, Collette; Ketcherside, Ariel

2015-10-15

Combined use of marijuana (MJ) and tobacco is highly prevalent in today's population. Individual use of either substance is linked to structural brain changes and altered cognitive function, especially with consistent reports of hippocampal volume deficits and poorer memory performance. However, the combined effects of MJ and tobacco on hippocampal structure and on learning and memory processes remain unknown. In this study, we examined both the individual and combined effects of MJ and tobacco on hippocampal volumes and memory performance in four groups of adults taken from two larger studies: MJ-only users (n=36), nicotine-only (Nic-only, n=19), combined marijuana and nicotine users (MJ+Nic, n=19) and non-using healthy controls (n=16). Total bilateral hippocampal volumes and memory performance (WMS-III logical memory) were compared across groups controlling for total brain size and recent alcohol use. Results found MJ and MJ+Nic groups had smaller total hippocampal volumes compared to Nic-only and controls. No significant difference between groups was found between immediate and delayed story recall. However, the controls showed a trend for larger hippocampal volumes being associated with better memory scores, while MJ+Nic users showed a unique inversion, whereby smaller hippocampal volume was associated with better memory. Overall, results suggest abnormalities in the brain-behavior relationships underlying memory processes with combined use of marijuana and nicotine use. Further research will need to address these complex interactions between MJ and nicotine. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Complex regional pain syndrome (CRPS) impairs visuospatial perception,whereas post-herpetic neuralgia does not: possible implications for supraspinal mechanism of CRPS.

Science.gov (United States)

Uematsu, Hironobu; Sumitani, Masahiko; Yozu, Arito; Otake, Yuko; Shibata, Masahiko; Mashimo, Takashi; Miyauchi, Satoru

2009-11-01

Complex regional pain syndrome (CRPS) patients show impaired visuospatial perception in the dark, as compared to normal patients with acute nociceptive pain. The purpose of this study is 2-fold: (i) to ascertain whether this distorted visuospatial perception is related to the chronicity of pain, and (ii) to analyse visuospatial perception of CRPS in comparison with another neuropathic pain condition. We evaluated visual subjective body-midline (vSM) representation in 27 patients with post-herpetic neuralgia (PHN) and 22 with CRPS under light and dark conditions. A red laser dot was projected onto a screen and moved horizontally towards the sagittal plane of the objective body-midline (OM). Each participant was asked to direct the dot to a position where it crossed their vSM. The distance between the vSM and OM was analysed to determine how and in which direction the vSM deviated. Under light condition, all vSM judgments approximately matched the OM. However, in the dark, CRPS patients, but not PHN patients, showed a shifted vSM towards the affected side. We demonstrated that chronic pain does not always impair visuospatial perception. The aetiology of PHN is limited to the peripheral nervous system, whereas the distorted visuospatial perception suggests a supraspinal aetiology of CRPS.

Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.

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Due, Deborah L; Huettel, Scott A; Hall, Warren G; Rubin, David C

2002-06-01

The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.

Near-Independent Capacities and Highly Constrained Output Orders in the Simultaneous Free Recall of Auditory-Verbal and Visuo-Spatial Stimuli

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Cortis Mack, Cathleen; Dent, Kevin; Ward, Geoff

2018-01-01

Three experiments examined the immediate free recall (IFR) of auditory-verbal and visuospatial materials from single-modality and dual-modality lists. In Experiment 1, we presented participants with between 1 and 16 spoken words, with between 1 and 16 visuospatial dot locations, or with between 1 and 16 words "and" dots with synchronized…

Hippocampal effects of neuronostatin on memory, anxiety-like behavior and food intake in rats.

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Carlini, V P; Ghersi, M; Gabach, L; Schiöth, H B; Pérez, M F; Ramirez, O A; Fiol de Cuneo, M; de Barioglio, S R

2011-12-01

A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro-hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra-hippocampally administered at 3.0 nmol/μl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/μl and 3.0 nmol/μl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/μl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Butch-Femme Identity and Visuospatial Performance Among Lesbian and Bisexual Women in China.

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Zheng, Lijun; Wen, Guangju; Zheng, Yong

2018-05-01

Lesbian and bisexual women who self-identify as "butch" show a masculine profile with regard to gender roles, gender nonconformity, and systemizing cognitive style, whereas lesbian and bisexual women who self-identify as "femme" show a corresponding feminine profile and those who self-identify as "androgynes" show an intermediate profile. This study examined the association between butch or femme lesbian or bisexual identity and visuospatial ability among 323 lesbian and bisexual women, compared to heterosexual women (n = 207) and men (n = 125), from multiple cities in China. Visuospatial ability was assessed using a Shepard and Metzler-type mental rotation task and Judgment of Line Angle and Position (JLAP) test on the Internet. Heterosexual men outperformed heterosexual women on both mental rotation and JLAP tasks. Lesbian and bisexual women outperformed heterosexual women on mental rotation, but not on JLAP. There were significant differences in mental rotation performance among women, with butch- and androgyne-identified lesbian/bisexual women outperforming femme-identified and heterosexual women. There were also significant differences in JLAP performance among women, with butch- and androgyne-identified lesbian/bisexual women and heterosexual women outperforming femme-identified lesbian/bisexual women. The butch-femme differences in visuospatial ability indicated an association between cognitive ability and butch-femme identity and suggest that neurobiological underpinnings may contribute to butch-femme identity although alternative explanations exist.

Hippocampal Astrocyte Cultures from Adult and Aged Rats Reproduce Changes in Glial Functionality Observed in the Aging Brain.

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Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

2017-05-01

Astrocytes are dynamic cells that maintain brain homeostasis, regulate neurotransmitter systems, and process synaptic information, energy metabolism, antioxidant defenses, and inflammatory response. Aging is a biological process that is closely associated with hippocampal astrocyte dysfunction. In this sense, we demonstrated that hippocampal astrocytes from adult and aged Wistar rats reproduce the glial functionality alterations observed in aging by evaluating several senescence, glutamatergic, oxidative and inflammatory parameters commonly associated with the aging process. Here, we show that the p21 senescence-associated gene and classical astrocyte markers, such as glial fibrillary acidic protein (GFAP), vimentin, and actin, changed their expressions in adult and aged astrocytes. Age-dependent changes were also observed in glutamate transporters (glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)) and glutamine synthetase immunolabeling and activity. Additionally, according to in vivo aging, astrocytes from adult and aged rats showed an increase in oxidative/nitrosative stress with mitochondrial dysfunction, an increase in RNA oxidation, NADPH oxidase (NOX) activity, superoxide levels, and inducible nitric oxide synthase (iNOS) expression levels. Changes in antioxidant defenses were also observed. Hippocampal astrocytes also displayed age-dependent inflammatory response with augmentation of proinflammatory cytokine levels, such as TNF-α, IL-1β, IL-6, IL-18, and messenger RNA (mRNA) levels of cyclo-oxygenase 2 (COX-2). Furthermore, these cells secrete neurotrophic factors, including glia-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), S100 calcium-binding protein B (S100B) protein, and transforming growth factor-β (TGF-β), which changed in an age-dependent manner. Classical signaling pathways associated with aging, such as nuclear factor erythroid-derived 2-like 2 (Nrf2), nuclear factor kappa B (NFκ

Neuropsychology, autobiographical memory and hippocampal volume in younger and older patients with chronic schizophrenia

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Christina Josefa Herold

2015-04-01

Full Text Available Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM has been scarcely investigated in these patients. Hence less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21 with respect to AM, additional neuropsychological parameters and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analysed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume, executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.

Neuropsychology, autobiographical memory, and hippocampal volume in "younger" and "older" patients with chronic schizophrenia.

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Herold, Christina Josefa; Lässer, Marc Montgomery; Schmid, Lena Anna; Seidl, Ulrich; Kong, Li; Fellhauer, Iven; Thomann, Philipp Arthur; Essig, Marco; Schröder, Johannes

2015-01-01

Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.

Alteration of functional connectivity within visuospatial working memory-related brain network in patients with right temporal lobe epilepsy: a resting-state fMRI study.

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Lv, Zong-xia; Huang, Dong-Hong; Ye, Wei; Chen, Zi-rong; Huang, Wen-li; Zheng, Jin-ou

2014-06-01

This study aimed to investigate the resting-state brain network related to visuospatial working memory (VSWM) in patients with right temporal lobe epilepsy (rTLE). The functional mechanism underlying the cognitive impairment in VSWM was also determined. Fifteen patients with rTLE and 16 healthy controls matched for age, gender, and handedness underwent a 6-min resting-state functional MRI session and a neuropsychological test using VSWM_Nback. The VSWM-related brain network at rest was extracted using multiple independent component analysis; the spatial distribution and the functional connectivity (FC) parameters of the cerebral network were compared between groups. Behavioral data were subsequently correlated with the mean Z-value in voxels showing significant FC difference during intergroup comparison. The distribution of the VSWM-related resting-state network (RSN) in the group with rTLE was virtually consistent with that in the healthy controls. The distribution involved the dorsolateral prefrontal lobe and parietal lobe in the right hemisphere and the partial inferior parietal lobe and posterior lobe of the cerebellum in the left hemisphere (pright superior frontal lobe (BA8), right middle frontal lobe, and right ventromedial prefrontal lobe compared with the controls (pright superior frontal lobe (BA11), right superior parietal lobe, and left posterior lobe of the cerebellum (prights reserved.

Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

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Dietz, Birte; Manahan-Vaughan, Denise

2017-03-15

Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

Abnormal global processing along the dorsal visual pathway in autism: a possible mechanism for weak visuospatial coherence?

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Pellicano, Elizabeth; Gibson, Lisa; Maybery, Murray; Durkin, Kevin; Badcock, David R

2005-01-01

Frith and Happe (Frith, U., & Happe, F. (1994). Autism: Beyond theory of mind. Cognition, 50, 115-132) argue that individuals with autism exhibit 'weak central coherence': an inability to integrate elements of information into coherent wholes. Some authors have speculated that a high-level impairment might be present in the dorsal visual pathway in autism, and furthermore, that this might account for weak central coherence, at least at the visuospatial level. We assessed the integrity of the dorsal visual pathway in children diagnosed with an autism spectrum disorder (ASD), and in typically developing children, using two visual tasks, one examining functioning at higher levels of the dorsal cortical stream (Global Dot Motion (GDM)), and the other assessing lower-level dorsal stream functioning (Flicker Contrast Sensitivity (FCS)). Central coherence was tested using the Children's Embedded Figures Test (CEFT). Relative to the typically developing children, the children with ASD had shorter CEFT latencies and higher GDM thresholds but equivalent FCS thresholds. Additionally, CEFT latencies were inversely related to GDM thresholds in the ASD group. These outcomes indicate that the elevated global motion thresholds in autism are the result of high-level impairments in dorsal cortical regions. Weak visuospatial coherence in autism may be in the form of abnormal cooperative mechanisms in extra-striate cortical areas, which might contribute to differential performance when processing stimuli as Gestalts, including both dynamic (i.e., global motion perception) and static (i.e., disembedding performance) stimuli.

Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory.

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Pearson-Leary, Jiah; McNay, Ewan C

2016-11-23

The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin- and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also expressed in some hippocampal neurons, but its functional role in the brain is unclear. Several established molecular modulators of memory processing regulate hippocampal GluT4 trafficking and hippocampal memory formation is limited by both glucose metabolism and insulin signaling. Therefore, we hypothesized that hippocampal GluT4 might be involved in memory processes. Here, we show that, in male rats, hippocampal GluT4 translocates to the plasma membrane after memory training and that acute, selective intrahippocampal inhibition of GluT4-mediated glucose transport impaired memory acquisition, but not memory retrieval. Other studies have shown that prolonged systemic GluT4 blockade causes insulin resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose transport through GluT4-upregulated markers of hippocampal insulin signaling prevented task-associated depletion of hippocampal glucose and enhanced both working and short-term memory while also impairing long-term memory. These effects were accompanied by increased expression of hippocampal AMPA GluR1 subunits and the neuronal GluT3, but decreased expression of hippocampal brain-derived neurotrophic factor, consistent with impaired ability to form long-term memories. Our findings are the first to show the cognitive impact of brain GluT4 modulation. They identify GluT4 as a key regulator of hippocampal memory processing and also suggest differential regulation of GluT4 in the hippocampus from that in peripheral tissues. The role of insulin-regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current study, we demonstrate that GluT4 is a critical component of hippocampal memory processes. Memory training increased hippocampal GluT4 translocation and memory acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long

Disentangling the cognitive components supporting Austin Maze performance in left versus right temporal lobe epilepsy.

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Hocking, Julia; Thomas, Hannah J; Dzafic, Ilvana; Williams, Rebecca J; Reutens, David C; Spooner, Donna M

2013-12-01

Neuropsychological tests requiring patients to find a path through a maze can be used to assess visuospatial memory performance in temporal lobe pathology, particularly in the hippocampus. Alternatively, they have been used as a task sensitive to executive function in patients with frontal lobe damage. We measured performance on the Austin Maze in patients with unilateral left and right temporal lobe epilepsy (TLE), with and without hippocampal sclerosis, compared to healthy controls. Performance was correlated with a number of other neuropsychological tests to identify the cognitive components that may be associated with poor Austin Maze performance. Patients with right TLE were significantly impaired on the Austin Maze task relative to patients with left TLE and controls, and error scores correlated with their performance on the Block Design task. The performance of patients with left TLE was also impaired relative to controls; however, errors correlated with performance on tests of executive function and delayed recall. The presence of hippocampal sclerosis did not have an impact on maze performance. A discriminant function analysis indicated that the Austin Maze alone correctly classified 73.5% of patients as having right TLE. In summary, impaired performance on the Austin Maze task is more suggestive of right than left TLE; however, impaired performance on this visuospatial task does not necessarily involve the hippocampus. The relationship of the Austin Maze task with other neuropsychological tests suggests that differential cognitive components may underlie performance decrements in right versus left TLE. © 2013.

Evidence of Hippocampal Structural Alterations in Gulf War Veterans With Predicted Exposure to the Khamisiyah Plume.

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Chao, Linda L; Raymond, Morgan R; Leo, Cynthia K; Abadjian, Linda R

2017-10-01

To replicate and expand our previous findings of smaller hippocampal volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah plume. Total hippocampal and hippocampal subfield volumes were quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom had predicted exposure as per the Department of Defense exposure models. Veterans with predicted exposure had smaller total hippocampal and CA3/dentate gyrus volumes compared with unexposed veterans, even after accounting for potentially confounding genetic and clinical variables. Among veterans with predicted exposure, memory performance was positively correlated with hippocampal volume and negatively correlated with estimated exposure levels and self-reported memory difficulties. These results replicate and extend our previous finding that low-level exposure to chemical nerve agents from the Khamisiyah pit demolition has detrimental, lasting effects on brain structure and function.

The rise and fall of immediate and delayed memory for verbal and visuospatial information from late childhood to late adulthood.

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Murre, Jaap M J; Janssen, Steve M J; Rouw, Romke; Meeter, Martijn

2013-01-01

Over 100,000 verbal and visuospatial immediate and delayed memory tests were presented via the Internet to over 28,000 participants in the age range of 11 to 80. Structural equation modeling pointed to the verbal versus visuospatial dimension as an important factor in individual differences, but not the immediate versus delayed dimension. We found a linear decrease of 1% to 3% per year in overall memory performance past the age of 25. For visuospatial tests, this decrease started at age 18 and was twice as fast as the decrease of verbal memory. There were strong effects of education, with the highest educated group sometimes scoring one full standard deviation above the lowest educated group. Gender effects were small but as expected: women outperformed men on the verbal memory tasks; men outperformed women on the visuospatial tasks. We also found evidence of increasing proneness to false memory with age. Memory for recent news events did not show a decrease with age. Copyright © 2012 Elsevier B.V. All rights reserved.

Ghrelin-induced hippocampal neurogenesis and enhancement of cognitive function are mediated independently of GH/IGF-1 axis: lessons from the spontaneous dwarf rats.

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Li, Endan; Kim, Yumi; Kim, Sehee; Park, Seungjoon

2013-01-01

We recently have reported that ghrelin modulates adult hippocampal neurogenesis. However, there is a possibility that the action of ghrelin on hippocampal neurogenesis could be, in part, due to the ability of ghrelin to stimulate the GH/insulin-like growth factor (IGF)-1 axis, where both GH and IGF-1 infusions are known to increase hippocampal neurogenesis. To explore this possibility, we assessed the impact of ghrelin on progenitor cell proliferation and differentiation in the dentate gyrus (DG) of spontaneous dwarf rats (SDRs), a dwarf strain with a mutation of the GH gene resulting in total loss of GH. Double immunohistochemical staining revealed that Ki-67-positive progenitor cells and doublecortin (DCX)-positive neuroblasts in the DG of the SDRs expressed ghrelin receptors. We found that ghrelin treatment in the SDRs significantly increased the number of proliferating cell nuclear antigen- and BrdU-labeled cells in the DG. The number of DCX-labeled cells in the DG of ghrelin-treated SDRs was also significantly increased compared with the vehicle-treated controls. To test whether ghrelin has a direct effect on cognitive performance independently of somatotropic axis, hippocampus-dependent learning and memory were assessed using the Y-maze and novel object recognition (NOR) test in the SDRs. Ghrelin treatment for 4 weeks by subcutaneous osmotic pump significantly increased alternation rates in the Y-maze and exploration time for novel object in the NOR test compared to vehicle-treated controls. Our results indicate that ghrelin-induced adult hippocampal neurogenesis and enhancement of cognitive function are mediated independently of somatotropic axis.

Specific responses of human hippocampal neurons are associated with better memory.

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Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak

2015-08-18

A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.

Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

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Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

2017-08-01

Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hippocampal Sclerosis in Older Patients

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Cykowski, Matthew D.; Powell, Suzanne Z.; Schulz, Paul E.; Takei, Hidehiro; Rivera, Andreana L.; Jackson, Robert E.; Roman, Gustavo; Jicha, Gregory A.; Nelson, Peter T.

2018-01-01

Context Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (~20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology. PMID:28467211

Visuospatial and visual object cognition in early Parkinson's disease

OpenAIRE

Possin, Katherine L.

2007-01-01

Recent evidence suggests that Parkinson's disease (PD) may be associated with greater impairment in visuospatial working memory as compared to visual object working memory. The nature of this selective impairment is not well understood, however, in part because successful performance on working memory tasks requires numerous cognitive processes. For example, the impairment may be limited to either the encoding or maintenance aspects of spatial working memory. Further, it is unknown at this po...

Differences between nicotine-abstinent smokers and non-smokers in terms of visuospatial attention and inhibition before and after single-blind nicotine administration

NARCIS (Netherlands)

Logemann, H. N A; Böcker, K. B E; Deschamps, P. K H; Kemner, C.; Kenemans, J. L.

2014-01-01

The cholinergic system is implicated in visuospatial attention and inhibition, however the exact role is still unclear. Two key mechanisms in visuospatial attention are bias and disengagement. Bias refers to neuronal signals that enhance the sensitivity of the sensory cortex, disengagement is the

Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

Directory of Open Access Journals (Sweden)

Yuqin Ye

2017-01-01

Full Text Available The protective role of electroacupuncture (EA treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4 signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

Reduced hippocampal volume is associated with overgeneralization of negative context in individuals with PTSD.

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Levy-Gigi, Einat; Szabo, Csilla; Richter-Levin, Gal; Kéri, Szabolcs

2015-01-01

Previous studies demonstrated reduced hippocampal volume in individuals with posttraumatic stress disorder (PTSD). However, the functional role the hippocampus plays in PTSD symptomatology is still unclear. The aim of the present study was to explore generalization learning and its connection to hippocampal volume in individuals with and without PTSD. Animal and human models argue that hippocampal deficit may result in failure to process contextual information. Therefore we predicted associations between reduced hippocampal volume and overgeneralization of context in individuals with PTSD. We conducted MRI scans of bilateral hippocampal and amygdala formations as well as intracranial and total brain volumes. Generalization was measured using a novel-learning paradigm, which separately evaluates generalization of cue and context in conditions of negative and positive outcomes. As expected, MRI scans indicated reduced hippocampal volume in PTSD compared to non-PTSD participants. Behavioral results revealed a selective deficit in context generalization learning in individuals with PTSD, F(1, 43) = 8.27, p < .01, η(p)² = .16. Specifically, as predicted, while generalization of cue was spared in both groups, individuals with PTSD showed overgeneralization of negative context. Hence, they could not learn that a previously negative context is later associated with a positive outcome, F(1, 43) = 7.33, p = .01, η(p)² = .15. Most importantly, overgeneralization of negative context significantly correlated with right and left hippocampal volume (r = .61, p = .000; r = .5, p = .000). Finally, bilateral hippocampal volume provided the strongest prediction of overgeneralization of negative context. Reduced hippocampal volume may account for the difficulty of individuals with PTSD to differentiate negative and novel conditions and hence may facilitate reexperiencing symptoms. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Visual perception is dependent on visuospatial working memory and thus on the posterior parietal cortex.

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Pisella, Laure

2017-06-01

Visual perception involves complex and active processes. We will start by explaining why visual perception is dependent on visuospatial working memory, especially the spatiotemporal integration of the perceived elements through the ocular exploration of visual scenes. Then we will present neuropsychology, transcranial magnetic stimulation and neuroimaging data yielding information on the specific role of the posterior parietal cortex of the right hemisphere in visuospatial working memory. Within the posterior parietal cortex, neuropsychology data also suggest that there might be dissociated neural substrates for deployment of attention (superior parietal lobules) and spatiotemporal integration (right inferior parietal lobule). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effect of Insulin on Visuo-Spatial Memory and Histology of Cerebral ...

African Journals Online (AJOL)

olayemitoyin

the neuronal networks, based on long-term potentiation (LTP) ... insulin syringe daily between the hours of 8:00 – 9:00 am. The mice ... findings. Assessment of long-term visuo-spatial learning and ... (Handycam, SONY, Japan) recorded movement of the mice for later .... laboratory methods, and which this work did not seek.

Why trace and delay conditioning are sometimes (but not always) hippocampal dependent: A computational model

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Moustafa, Ahmed A.; Wufong, Ella; Servatius, Richard J.; Pang, Kevin C. H.; Gluck, Mark A.; Myers, Catherine E.

2013-01-01

A recurrent-network model provides a unified account of the hippocampal region in mediating the representation of temporal information in classical eyeblink conditioning. Much empirical research is consistent with a general conclusion that delay conditioning (in which the conditioned stimulus CS and unconditioned stimulus US overlap and co-terminate) is independent of the hippocampal system, while trace conditioning (in which the CS terminates before US onset) depends on the hippocampus. However, recent studies show that, under some circumstances, delay conditioning can be hippocampal-dependent and trace conditioning can be spared following hippocampal lesion. Here, we present an extension of our prior trial-level models of hippocampal function and stimulus representation that can explain these findings within a unified framework. Specifically, the current model includes adaptive recurrent collateral connections that aid in the representation of intra-trial temporal information. With this model, as in our prior models, we argue that the hippocampus is not specialized for conditioned response timing, but rather is a general-purpose system that learns to predict the next state of all stimuli given the current state of variables encoded by activity in recurrent collaterals. As such, the model correctly predicts that hippocampal involvement in classical conditioning should be critical not only when there is an intervening trace interval, but also when there is a long delay between CS onset and US onset. Our model simulates empirical data from many variants of classical conditioning, including delay and trace paradigms in which the length of the CS, the inter-stimulus interval, or the trace interval is varied. Finally, we discuss model limitations, future directions, and several novel empirical predictions of this temporal processing model of hippocampal function and learning. PMID:23178699

Assessing visuospatial abilities in healthy aging: A novel visuomotor task

Directory of Open Access Journals (Sweden)

Natalie eDe Bruin

2016-02-01

Full Text Available This study examined the efficacy of a novel reaching-and-grasping task in determining visuospatial abilities across adulthood. The task required male and female young (18-25 years and older adults (60-82 years to replicate a series of complex models by locating and retrieving the appropriate building blocks from an array. The task allows visuospatial complexity to be manipulated independently from the visuomotor demands. Mental rotation and spatial visualisation abilities were assessed. The results showed that the time taken to complete the tasks increased with increased mental rotation complexity. Patterns of hand use were also influenced by the complexity of the models being constructed with right hand use being greater for the less complex models. In addition, although older adults consistently performed the visuomotor tasks slower than the younger adults, their performance was comparable when expressed as the percent change in task demands. This is suggestive that spatial abilities are preserved in older adults. Given the ecologically validity, the described task is an excellent candidate for investigating (1 developmental, (2 sex-based and (3 pathology-based differences in spatial abilities in the visuomotor domain.

Past, present, and future in hippocampal formation and memory research.

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Muñoz-López, Mónica

2015-06-01

Over 100 years of research on the hippocampal formation has led us understand the consequences of lesions in humans, the functional networks, anatomical pathways, neuronal types and their local circuitry, receptors, molecules, intracellular cascades, and some of the physiological mechanisms underlying long-term spatial and episodic memory. In addition, complex computational models allow us to formulate sophisticated hypotheses; many of them testable with techniques recently developed unthinkable in the past. Although the neurobiology of the cognitive map is starting to be revealed today, we still face a future with many unresolved questions. The aim of this commentary is twofold. First is to point out some of the critical findings in hippocampal formation research and new challenges. Second, to briefly summarize what the anatomy of memory can tell us about how highly processed sensory information from distant cortical areas communicate with different subareas of the entorhinal cortex, dentate gyrus, and hippocampal subfields to integrate and consolidate unique episodic memory traces. © 2015 Wiley Periodicals, Inc.

Nuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis.

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O'Léime, Ciarán S; Cryan, John F; Nolan, Yvonne M

2017-11-01

Hippocampal neurogenesis, the process by which new neurons are born and develop into the host circuitry, begins during embryonic development and persists throughout adulthood. Over the last decade considerable insights have been made into the role of hippocampal neurogenesis in cognitive function and the cellular mechanisms behind this process. Additionally, an increasing amount of evidence exists on the impact of environmental factors, such as stress and neuroinflammation on hippocampal neurogenesis and subsequent impairments in cognition. Elevated expression of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the hippocampus is established as a significant contributor to the neuronal demise evident in many neurological and psychiatric disorders and is now known to negatively regulate hippocampal neurogenesis. In order to prevent the deleterious effects of IL-1β on neurogenesis it is necessary to identify signalling pathways and regulators of neurogenesis within neural progenitor cells that can interact with IL-1β. Nuclear receptors are ligand regulated transcription factors that are involved in modulating a large number of cellular processes including neurogenesis. In this review we focus on the signalling mechanisms of specific nuclear receptors involved in regulating neurogenesis (glucocorticoid receptors, peroxisome proliferator activated receptors, estrogen receptors, and nuclear receptor subfamily 2 group E member 1 (NR2E1 or TLX)). We propose that these nuclear receptors could be targeted to inhibit neuroinflammatory signalling pathways associated with IL-1β. We discuss their potential to be therapeutic targets for neuroinflammatory disorders affecting hippocampal neurogenesis and associated cognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex differences in visuospatial and navigational working memory: the role of mood induced by background music.

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Palmiero, Massimiliano; Nori, Raffaella; Rogolino, Carmelo; D'amico, Simonetta; Piccardi, Laura

2016-08-01

Sex differences in visuospatial abilities are long debated. Men generally outperform women, especially in wayfinding or learning a route or a sequence of places. These differences might depend on women's disadvantage in underlying spatial competences, such as mental rotation, and on the strategies used, as well as on emotions and on self-belief about navigational skills, not related to actual skill-levels. In the present study, sex differences in visuospatial and navigational working memory in emotional contexts were investigated. Participants' mood was manipulated by background music (positive, negative or neutral) while performing on the Corsi Block-tapping Task (CBT) and Walking Corsi (WalCT) test. In order to assess the effectiveness of mood manipulation, participants filled in the Positive and Negative Affect Schedule before and after carrying out the visuospatial tasks. Firstly, results showed that after mood induction, only the positive affect changed, whereas the negative affect remained unconfounded by mood and by sex. This finding is in line with the main effect of 'group' on all tests used: the positive music group scored significantly higher than other groups. Secondly, although men outperformed women in the CBT forward condition and in the WalCT forward and backward conditions, they scored higher than women only in the WalCT with the negative background music. This means that mood cannot fully explain sex differences in visuospatial and navigational working memory. Our results suggest that sex differences in the CBT and WalCT can be better explained by differences in spatial competences rather than by emotional contexts.

Building hippocampal circuits to learn and remember: insights into the development of human memory.

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Lavenex, Pierre; Banta Lavenex, Pamela

2013-10-01

The hippocampal formation is essential for the processing of episodic memories for autobiographical events that happen in unique spatiotemporal contexts. Interestingly, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. From 2 to 7 years of age, there are fewer memories than predicted based on a forgetting function alone, a phenomenon known as childhood amnesia. Here, we discuss the postnatal maturation of the primate hippocampal formation with the goal of characterizing the development of the neurobiological substrates thought to subserve the emergence of episodic memory. Distinct regions, layers and cells of the hippocampal formation exhibit different profiles of structural and molecular development during early postnatal life. The protracted period of neuronal addition and maturation in the dentate gyrus is accompanied by the late maturation of specific layers in different hippocampal regions that are located downstream from the dentate gyrus, particularly CA3. In contrast, distinct layers in several hippocampal regions, particularly CA1, which receive direct projections from the entorhinal cortex, exhibit an early maturation. In addition, hippocampal regions that are more highly interconnected with subcortical structures, including the subiculum, presubiculum, parasubiculum and CA2, mature even earlier. These findings, together with our studies of the development of human spatial memory, support the hypothesis that the differential maturation of distinct hippocampal circuits might underlie the differential emergence of specific "hippocampus-dependent" memory processes, culminating in the emergence of episodic memory concomitant with the maturation of all hippocampal circuits. Copyright © 2013 Elsevier B.V. All rights reserved.

Evidence for a specific defect in hippocampal memory in overt and subclinical hypothyroidism.

LENUS (Irish Health Repository)

Correia, Neuman

2012-02-01

CONTEXT: Declarative memory largely depends upon normal functioning temporal lobes (hippocampal complex) and prefrontal cortex. Animal studies suggest abnormal hippocampal function in hypothyroidism. OBJECTIVE: The aim of the study was to assess declarative memory in overt and subclinical (SCH) hypothyroid patients before and after l-T(4) (LT4) replacement and in matched normal subjects. DESIGN AND SETTING: A prospective, open-labeled interventional study was conducted at a teaching hospital. PARTICIPANTS AND INTERVENTION: Hypothyroid (n = 21) and SCH (n = 17) patients underwent neuropsychological tests at baseline and 3 and 6 months after LT4 replacement. Normal subjects were studied at the same time-points. MAIN OUTCOME: Tests of spatial, verbal, associative, and working memory; attention; and response inhibition and the Hospital Anxiety and Depression Scale were administered. RESULTS: Baseline deficits in spatial, associative, and verbal memory, which rely upon the integrity of the hippocampal and frontal areas, were identified in patients with overt hypothyroidism. Spatial and verbal memory were impaired in SCH patients (P < 0.05). TSH levels correlated negatively (P < 0.05) with these deficits. After LT4 replacement, verbal memory normalized. Spatial memory normalized in the SCH group but remained impaired in the hypothyroid group. Associative memory deficits persisted in the overt hypothyroid group. Hospital Anxiety and Depression Scale scores did not correlate with cognitive function. Measures of attention and response inhibition did not differ from control subjects. CONCLUSION: Cognitive impairment occurs in SCH and more markedly in overt hypothyroidism. These impairments appear predominantly mnemonic in nature, suggesting that the etiology is not indicative of general cognitive slowing. We propose that these deficits may reflect an underlying disruption of normal hippocampal function and\\/or connectivity.

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

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Wen-bin He

2018-01-01

Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

Learning Discloses Abnormal Structural and Functional Plasticity at Hippocampal Synapses in the APP23 Mouse Model of Alzheimer's Disease

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Middei, Silvia; Roberto, Anna; Berretta, Nicola; Panico, Maria Beatrice; Lista, Simone; Bernardi, Giorgio; Mercuri, Nicola B.; Ammassari-Teule, Martine; Nistico, Robert

2010-01-01

B6-Tg/Thy1APP23Sdz (APP23) mutant mice exhibit neurohistological hallmarks of Alzheimer's disease but show intact basal hippocampal neurotransmission and synaptic plasticity. Here, we examine whether spatial learning differently modifies the structural and electrophysiological properties of hippocampal synapses in APP23 and wild-type mice. While…

High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

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Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

2017-08-01

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Visuo-spatial cueing in children with differential reading and spelling profiles.

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Banfi, Chiara; Kemény, Ferenc; Gangl, Melanie; Schulte-Körne, Gerd; Moll, Kristina; Landerl, Karin

2017-01-01

Dyslexia has been claimed to be causally related to deficits in visuo-spatial attention. In particular, inefficient shifting of visual attention during spatial cueing paradigms is assumed to be associated with problems in graphemic parsing during sublexical reading. The current study investigated visuo-spatial attention performance in an exogenous cueing paradigm in a large sample (N = 191) of third and fourth graders with different reading and spelling profiles (controls, isolated reading deficit, isolated spelling deficit, combined deficit in reading and spelling). Once individual variability in reaction times was taken into account by means of z-transformation, a cueing deficit (i.e. no significant difference between valid and invalid trials) was found for children with combined deficits in reading and spelling. However, poor readers without spelling problems showed a cueing effect comparable to controls, but exhibited a particularly strong right-over-left advantage (position effect). Isolated poor spellers showed a significant cueing effect, but no position effect. While we replicated earlier findings of a reduced cueing effect among poor nonword readers (indicating deficits in sublexical processing), we also found a reduced cueing effect among children with particularly poor orthographic spelling (indicating deficits in lexical processing). Thus, earlier claims of a specific association with nonword reading could not be confirmed. Controlling for ADHD-symptoms reported in a parental questionnaire did not impact on the statistical analysis, indicating that cueing deficits are not caused by more general attentional limitations. Between 31 and 48% of participants in the three reading and/or spelling deficit groups as well as 32% of the control group showed reduced spatial cueing. These findings indicate a significant, but moderate association between certain aspects of visuo-spatial attention and subcomponents of written language processing, the causal status of

Visuo-spatial cueing in children with differential reading and spelling profiles.

Directory of Open Access Journals (Sweden)

Chiara Banfi

Full Text Available Dyslexia has been claimed to be causally related to deficits in visuo-spatial attention. In particular, inefficient shifting of visual attention during spatial cueing paradigms is assumed to be associated with problems in graphemic parsing during sublexical reading. The current study investigated visuo-spatial attention performance in an exogenous cueing paradigm in a large sample (N = 191 of third and fourth graders with different reading and spelling profiles (controls, isolated reading deficit, isolated spelling deficit, combined deficit in reading and spelling. Once individual variability in reaction times was taken into account by means of z-transformation, a cueing deficit (i.e. no significant difference between valid and invalid trials was found for children with combined deficits in reading and spelling. However, poor readers without spelling problems showed a cueing effect comparable to controls, but exhibited a particularly strong right-over-left advantage (position effect. Isolated poor spellers showed a significant cueing effect, but no position effect. While we replicated earlier findings of a reduced cueing effect among poor nonword readers (indicating deficits in sublexical processing, we also found a reduced cueing effect among children with particularly poor orthographic spelling (indicating deficits in lexical processing. Thus, earlier claims of a specific association with nonword reading could not be confirmed. Controlling for ADHD-symptoms reported in a parental questionnaire did not impact on the statistical analysis, indicating that cueing deficits are not caused by more general attentional limitations. Between 31 and 48% of participants in the three reading and/or spelling deficit groups as well as 32% of the control group showed reduced spatial cueing. These findings indicate a significant, but moderate association between certain aspects of visuo-spatial attention and subcomponents of written language processing, the

α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons.

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Froula, Jessica M; Henderson, Benjamin W; Gonzalez, Jose Carlos; Vaden, Jada H; Mclean, John W; Wu, Yumei; Banumurthy, Gokulakrishna; Overstreet-Wadiche, Linda; Herskowitz, Jeremy H; Volpicelli-Daley, Laura A

2018-05-01

Neuronal inclusions composed of α-synuclein (α-syn) characterize Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Cognitive dysfunction defines DLB, and up to 80% of PD patients develop dementia. α-Syn inclusions are abundant in the hippocampus, yet functional consequences are unclear. To determine if pathologic α-syn causes neuronal defects, we induced endogenous α-syn to form inclusions resembling those found in diseased brains by treating hippocampal neurons with α-syn fibrils. At seven days after adding fibrils, α-syn inclusions are abundant in axons, but there is no cell death at this time point, allowing us to assess for potential alterations in neuronal function that are not caused by neuron death. We found that exposure of neurons to fibrils caused a significant reduction in mushroom spine densities, adding to the growing body of literature showing that altered spine morphology is a major pathologic phenotype in synucleinopathies. The reduction in spine densities occurred only in wild type neurons and not in neurons from α-syn knockout mice, suggesting that the changes in spine morphology result from fibril-induced corruption of endogenously expressed α-syn. Paradoxically, reduced postsynaptic spine density was accompanied by increased frequency of miniature excitatory postsynaptic currents (EPSCs) and presynaptic docked vesicles, suggesting enhanced presynaptic function. Action-potential dependent activity was unchanged, suggesting compensatory mechanisms responding to synaptic defects. Although activity at the level of the synapse was unchanged, neurons exposed to α-syn fibrils, showed reduced frequency and amplitudes of spontaneous Ca 2+ transients. These findings open areas of research to determine the mechanisms that alter neuronal function in brain regions critical for cognition at time points before neuron death.

Visuospatial Orientation Learning through Virtual Reality for People with Severe Disability

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de la Torre-Luque, Alejandro; Valero-Aguayo, Luis; de la Rubia-Cuestas, Ernesto J.

2017-01-01

This study aims to test how an intervention based on virtual reality (VR) may enhance visuospatial skills amongst people with disability. A quasi-experimental intra-group study was therefore conducted. Participants were 20 people with severe disability (65% males; 34.35 years, on average, and 84.95% of disability rate according to the Andalusian…

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

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Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

2016-05-04

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

Hippocampal sclerosis in advanced age: clinical and pathological features

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Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

2011-01-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar

Hippocampal sclerosis in advanced age: clinical and pathological features.

Science.gov (United States)

Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

2011-05-01

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR

DEVELOPMENTAL HYPOTHYROIDISM IMPAIRS HIPPOCAMPAL LEARNING AND SYNAPTIC TRANSMISSION IN VIVO.

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A number of environmental chemicals have been reported to alter thyroid hormone (TH) function. It is well established that severe hypothyroidism during critical periods of brain development leads to alterations in hippocampal structure and learning deficits, yet evaluation of ...

Visuospatial working memory and mathematical ability at different ages throughout primary school

NARCIS (Netherlands)

van der Ven, S.H.G.; van der Maas, H.L.J.; Straatemeier, M.; Jansen, B.R.J.

2013-01-01

In this study, three aims were addressed: (1) validating a visuospatial working memory task in Math Garden, an adaptive online tool in which item difficulty and person ability are determined on the fly, (2) investigating the contribution of different item characteristics to the difficulty of the

Semantic, executive, and visuospatial abilities in mathematical reasoning of referred college students.

Science.gov (United States)

Cirino, Paul T; Morris, Mary K; Morris, Robin D

2007-03-01

Semantic retrieval (SR) and executive-procedural (EP), but not visuospatial (VS) skills, have been found to be uniquely predictive of mathematical calculation skills in a sample of clinically referred college students. This study set out to cross-validate these results in an independent sample of clinically referred college students (N = 337) as well as extend them by examination of the contributions of these cognitive domains to math reasoning skills. Results indicate that these cognitive domains were able to predict 30% of the variance in calculation skills and 50% of the variance in math reasoning; however, in both cases, only the domains of semantic retrieval and visuospatial skill contributed uniquely. Differences between studies, and the lack of unique contribution of the EP domain to either type of math skill, may be due to measurement and sampling differences, the degree of shared relations among domains, and the choice of measures that represent the EP domain. Implications and future directions are explored.

[Curcumin improves learning and memory function through decreasing hippocampal TNF-α and iNOS levels after subarachnoid hemorrhage in rats].

Science.gov (United States)

Qiu, Zhenwei; Yue, Shuangzhu

2016-03-01

To investigate the effect of curcumin on learning and memory function of rats with subarachnoid hemorrhage (SAH) and the possible mechanism. A total of 30 male Sprague-Dawley rats were randomly divided into three groups: Sham group, SAH group and curcumin (Cur) therapy group. Experimental SAH rat models were established by injecting autologous blood into the cisterna magna. Neurological deficits of rats were examined at different time points. Spatial learning and memory abilities were tested by Morris water maze test. The hippocampal tumor necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) were detected by ELISA. RESULTS Experimental SAH rat models were established successfully. Neurological scores of the SAH rats were significantly lower than those of the sham group. Curcumin therapy obviously improved the neurological deficits of rats compared with the SAH rats. Morris water maze test showed that SAH caused significant cognitive impairment with longer escape latency compared with the sham group. After treatment with curcumin for 4 weeks, the escape latency decreased significantly. The levels of TNF-α and iNOS in the curcumin-treated group were significantly lower than those of the SAH group. SAH can cause learning and memory impairment in rats. Curcumin can recover learning and memory function through down-regulating hippocampal TNF-α and iNOS levels.

Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations.

Science.gov (United States)

Worker, Amanda; Dima, Danai; Combes, Anna; Crum, William R; Streffer, Johannes; Einstein, Steven; Mehta, Mitul A; Barker, Gareth J; C R Williams, Steve; O'daly, Owen

2018-04-01

The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test-retest reliability of hippocampal subregion volumes was assessed using the intra-class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73-0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum

BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

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Vedder, Lindsey C.; Savage, Lisa M.

2017-01-01

Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

Homologous mechanisms of visuospatial working memory maintenance in macaque and human: Properties and sources

Science.gov (United States)

Reinhart, Robert M.G.; Heitz, Richard P.; Purcell, Braden A.; Weigand, Pauline K.; Schall, Jeffrey D.; Woodman, Geoffrey F.

2012-01-01

Although areas of frontal cortex are thought to be critical for maintaining information in visuospatial working memory, the event-related potential (ERP) index of maintenance is found over posterior cortex in humans. In the present study, we reconcile these seemingly contradictory findings. Here we show that macaque monkeys and humans exhibit the same posterior ERP signature of working memory maintenance that predicts the precision of the memory-based behavioral responses. In addition, we show that the specific pattern of rhythmic oscillations in the alpha band, recently demonstrated to underlie the human visual working memory ERP component, is also present in monkeys. Next, we concurrently recorded intracranial local field potentials from two prefrontal and another frontal cortical area to determine their contribution to the surface potential indexing maintenance. The local fields in the two prefrontal areas, but not the cortex immediately posterior, exhibited amplitude modulations, timing, and relationships to behavior indicating that they contribute to the generation of the surface ERP component measured from the distal posterior electrodes. Rhythmic neural activity in the theta and gamma bands during maintenance provided converging support for the engagement of the same brain regions. These findings demonstrate that nonhuman primates have homologous electrophysiological signatures of visuospatial working memory to those of humans and that a distributed neural network, including frontal areas, underlies the posterior ERP index of visuospatial working memory maintenance. PMID:22649249

PMC-12, a traditional herbal medicine, enhances learning memory and hippocampal neurogenesis in mice.

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Park, Hee Ra; Kim, Ju Yeon; Lee, Yujeong; Chun, Hye Jeong; Choi, Young Whan; Shin, Hwa Kyoung; Choi, Byung Tae; Kim, Cheol Min; Lee, Jaewon

2016-03-23

The beneficial effects of traditional Korean medicine are recognized during the treatment of neurodegenerative conditions, such as, Alzheimer's disease and neurocognitive dysfunction, and recently, hippocampal neurogenesis has been reported to be associated with memory function. In this study, the authors investigated the beneficial effects of polygonum multiflorum Thunberg complex composition-12 (PMC-12), which is a mixture of four medicinal herbs, that is, Polygonum multiflorum, Polygala tenuifolia, Rehmannia glutinosa, and Acorus gramineus, on hippocampal neurogenesis, learning, and memory in mice. PMC-12 was orally administered to male C57BL/6 mice (5 weeks old) at 100 or 500 mg/kg daily for 2 weeks. PMC-12 administration significantly was found to increase the proliferation of neural progenitor cells and the survival of newly-generated cells in the dentate gyrus. In the Morris water maze test, the latency times of PMC-12 treated mice (100 or 500 mg/kg) were shorter than those of vehicle-control mice. In addition, PMC-12 increased the levels of BDNF, p-CREB, and synaptophysin, which are known to be associated with neural plasticity and hippocampal neurogenesis. These findings suggest PMC-12 enhances hippocampal neurogenesis and neurocognitive function and imply that PMC-12 ameliorates memory impairment and cognitive deficits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hippocampal proton MR spectroscopy as a novel approach in the assessment of radiation injury and the correlation to neurocognitive function impairment: initial experiences

International Nuclear Information System (INIS)

Pospisil, Petr; Kazda, Tomas; Bulik, Martin; Dobiaskova, Marie; Burkon, Petr; Hynkova, Ludmila; Slampa, Pavel; Jancalek, Radim

2015-01-01

The hippocampus is considered as the main radiosensitive brain structure responsible for postradiotherapy cognitive decline. We prospectively assessed correlation of memory change to hippocampal N-acetylaspartate (h-tNAA) concentration, a neuronal density and viability marker, by 1 H-MR spectroscopy focused on the hippocampus. Patients with brain metastases underwent whole brain radiotherapy (WBRT) to a dose of 30 Gy in ten fractions daily. Pre-radiotherapy 1 H-MR spectroscopy focused on the h-tNAA concentration and memory testing was performed. Memory was evaluated by Auditory Verbal Learning Test (AVLT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Total recall, recognition and delayed recall were reported. The both investigation procedures were repeated 4 months after WBRT and the h-tNAA and memory changes were correlated. Of the 20 patients, ten passed whole protocol. The h-tNAA concentration significantly decreased from pre-WBRT 8.9, 8.86 and 8.88 [mM] in the right, left and both hippocampi to 7.16, 7.65 and 7.4 after WBRT, respectively. In the memory tests a significant decrease was observed in AVLT total-recall, BVMT-R total-recall and BVMT-R delayed-recall. Weak to moderate correlations were observed between left h-tNAA and AVLT recognition and all BVMT-R subtests and between the right h-tNAA and AVLT total-recall. A significant decrease in h-tNAA after WBRT was proven by 1 H-MR spectroscopy as a feasible method for the in vivo investigation of radiation injury. Continuing patient recruitment focusing on other cognitive tests and metabolites is needed

Enriched encoding: reward motivation organizes cortical networks for hippocampal detection of unexpected events.

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Murty, Vishnu P; Adcock, R Alison

2014-08-01

Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical-hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions-a potentially unique contribution of the hippocampus to reward learning. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Linking adult hippocampal neurogenesis with human physiology and disease.

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Bowers, Megan; Jessberger, Sebastian

2016-07-01

We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

How emotional abilities modulate the influence of early life stress on hippocampal functioning.

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Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

2014-07-01

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

ASIC-like, proton-activated currents in rat hippocampal neurons.

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Baron, Anne; Waldmann, Rainer; Lazdunski, Michel

2002-03-01

The expression of mRNA for acid sensing ion channels (ASIC) subunits ASIC1a, ASIC2a and ASIC2b has been reported in hippocampal neurons, but the presence of functional hippocampal ASIC channels was never assessed. We report here the first characterization of ASIC-like currents in rat hippocampal neurons in primary culture. An extracellular pH drop induces a transient Na(+) current followed by a sustained non-selective cation current. This current is highly sensitive to pH with an activation threshold around pH 6.9 and a pH(0.5) of 6.2. About half of the total peak current is inhibited by the spider toxin PcTX1, which is specific for homomeric ASIC1a channels. The remaining PcTX1-resistant ASIC-like current is increased by 300 microM Zn(2+) and, whereas not fully activated at pH 5, it shows a pH(0.5) of 6.0 between pH 7.4 and 5. We have previously shown that Zn(2+) is a co-activator of ASIC2a-containing channels. Thus, the hippocampal transient ASIC-like current appears to be generated by a mixture of homomeric ASIC1a channels and ASIC2a-containing channels, probably heteromeric ASIC1a+2a channels. The sustained non-selective current suggests the involvement of ASIC2b-containing heteromeric channels. Activation of the hippocampal ASIC-like current by a pH drop to 6.9 or 6.6 induces a transient depolarization which itself triggers an initial action potential (AP) followed by a sustained depolarization and trains of APs. Zn(2+) increases the acid sensitivity of ASIC channels, and consequently neuronal excitability. It is probably an important co-activator of ASIC channels in the central nervous system.

Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease.

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Mak, Elijah; Su, Li; Williams, Guy B; Watson, Rosie; Firbank, Michael; Blamire, Andrew; O'Brien, John

2016-02-01

Dementia with Lewy bodies (DLB) is characterized by relative preservation of the medial temporal lobe compared with Alzheimer disease (AD). The differential involvement of the hippocampal subfields in both diseases has not been clearly established, however. We aim to investigate hippocampal subfield differences in vivo in a clinical cohort of DLB and AD subjects. 104 participants (35 DLBs, 36 ADs, and 35 healthy comparison [HC] subjects) underwent clinical assessment and 3T T1-weighted imaging. A Bayesian model implemented in Freesurfer was used to automatically segment the hippocampus and its subfields. We also examined associations between hippocampal subfields and tests of memory function. Both the AD and DLB groups demonstrated significant atrophy of the total hippocampus relative to HC but the DLB group was characterized by preservation of the cornu ammonis 1 (CA1), fimbria, and fissure. In contrast, all the hippocampal subfields except the fissure were significantly atrophied in AD compared with both DLB and HC groups. Among DLB subjects, CA1 was correlated with the Recent Memory score of the CAMCOG and Delayed Recall subscores of the HVLT. DLB is characterized by milder hippocampal atrophy that was accompanied by preservation of the CA1. The CA1 was also associated with memory function in DLB. Our findings highlight the promising role of hippocampal subfield volumetry, particularly that of the CA1, as a biomarker for the distinction between AD and DLB. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Stereopsis, Visuospatial Ability, and Virtual Reality in Anatomy Learning

OpenAIRE

Luursema, Jan-Maarten; Vorstenbosch, Marc; Kooloos, Jan

2017-01-01

A new wave of virtual reality headsets has become available. A potential benefit for the study of human anatomy is the reintroduction of stereopsis and absolute size. We report a randomized controlled trial to assess the contribution of stereopsis to anatomy learning, for students of different visuospatial ability. Sixty-three participants engaged in a one-hour session including a study phase and posttest. One group studied 3D models of the anatomy of the deep neck in full stereoptic virtual ...

Iron mediates N-methyl-D-aspartate receptor-dependent stimulation of calcium-induced pathways and hippocampal synaptic plasticity.

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Muñoz, Pablo; Humeres, Alexis; Elgueta, Claudio; Kirkwood, Alfredo; Hidalgo, Cecilia; Núñez, Marco T

2011-04-15

Iron deficiency hinders hippocampus-dependent learning processes and impairs cognitive performance, but current knowledge on the molecular mechanisms underlying the unique role of iron in neuronal function is sparse. Here, we investigated the participation of iron on calcium signal generation and ERK1/2 stimulation induced by the glutamate agonist N-methyl-D-aspartate (NMDA), and the effects of iron addition/chelation on hippocampal basal synaptic transmission and long-term potentiation (LTP). Addition of NMDA to primary hippocampal cultures elicited persistent calcium signals that required functional NMDA receptors and were independent of calcium influx through L-type calcium channels or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; NMDA also promoted ERK1/2 phosphorylation and nuclear translocation. Iron chelation with desferrioxamine or inhibition of ryanodine receptor (RyR)-mediated calcium release with ryanodine-reduced calcium signal duration and prevented NMDA-induced ERK1/2 activation. Iron addition to hippocampal neurons readily increased the intracellular labile iron pool and stimulated reactive oxygen species production; the antioxidant N-acetylcysteine or the hydroxyl radical trapper MCI-186 prevented these responses. Iron addition to primary hippocampal cultures kept in calcium-free medium elicited calcium signals and stimulated ERK1/2 phosphorylation; RyR inhibition abolished these effects. Iron chelation decreased basal synaptic transmission in hippocampal slices, inhibited iron-induced synaptic stimulation, and impaired sustained LTP in hippocampal CA1 neurons induced by strong stimulation. In contrast, iron addition facilitated sustained LTP induction after suboptimal tetanic stimulation. Together, these results suggest that hippocampal neurons require iron to generate RyR-mediated calcium signals after NMDA receptor stimulation, which in turn promotes ERK1/2 activation, an essential step of sustained LTP.

Effect of Prenatal Protein Malnutrition on Long-Term Potentiation and BDNF Protein Expression in the Rat Entorhinal Cortex after Neocortical and Hippocampal Tetanization

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Alejandro Hernández

2008-01-01

Full Text Available Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC in the adult progeny. Unlike normal eutrophic controls, 55–60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

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Hernández, Alejandro; Burgos, Héctor; Mondaca, Mauricio; Barra, Rafael; Núñez, Héctor; Pérez, Hernán; Soto-Moyano, Rubén; Sierralta, Walter; Fernández, Victor; Olivares, Ricardo; Valladares, Luis

2008-01-01

Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.

Hippocampal activation during face-name associative memory encoding: blocked versus permuted design

International Nuclear Information System (INIS)

De Vogelaere, Frederick; Vingerhoets, Guy; Santens, Patrick; Boon, Paul; Achten, Erik

2010-01-01

The contribution of the hippocampal subregions to episodic memory through the formation of new associations between previously unrelated items such as faces and names is established but remains under discussion. Block design studies in this area of research generally tend to show posterior hippocampal activation during encoding of novel associational material while event-related studies emphasize anterior hippocampal involvement. We used functional magnetic resonance imaging to assess the involvement of anterior and posterior hippocampus in the encoding of novel associational material compared to the viewing of previously seen associational material. We used two different experimental designs, a block design and a permuted block design, and applied it to the same associative memory task to perform valid statistical comparisons. Our results indicate that the permuted design was able to capture more anterior hippocampal activation compared to the block design, which emphasized more posterior hippocampal involvement. These differences were further investigated and attributed to a combination of the polymodal stimuli we used and the experimental design. Activation patterns during encoding in both designs occurred along the entire longitudinal axis of the hippocampus, but with different centers of gravity. The maximal activated voxel in the block design was situated in the posterior half of the hippocampus while in the permuted design this was located in the anterior half. (orig.)

Hippocampal activation during face-name associative memory encoding: blocked versus permuted design

Energy Technology Data Exchange (ETDEWEB)

De Vogelaere, Frederick; Vingerhoets, Guy [Ghent University, Laboratory for Neuropsychology, Department of Neurology, Ghent (Belgium); Santens, Patrick; Boon, Paul [Ghent University Hospital, Department of Neurology, Ghent (Belgium); Achten, Erik [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

2010-01-15

The contribution of the hippocampal subregions to episodic memory through the formation of new associations between previously unrelated items such as faces and names is established but remains under discussion. Block design studies in this area of research generally tend to show posterior hippocampal activation during encoding of novel associational material while event-related studies emphasize anterior hippocampal involvement. We used functional magnetic resonance imaging to assess the involvement of anterior and posterior hippocampus in the encoding of novel associational material compared to the viewing of previously seen associational material. We used two different experimental designs, a block design and a permuted block design, and applied it to the same associative memory task to perform valid statistical comparisons. Our results indicate that the permuted design was able to capture more anterior hippocampal activation compared to the block design, which emphasized more posterior hippocampal involvement. These differences were further investigated and attributed to a combination of the polymodal stimuli we used and the experimental design. Activation patterns during encoding in both designs occurred along the entire longitudinal axis of the hippocampus, but with different centers of gravity. The maximal activated voxel in the block design was situated in the posterior half of the hippocampus while in the permuted design this was located in the anterior half. (orig.)

Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis.

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Reshef, Ronen; Kreisel, Tirzah; Beroukhim Kay, Dorsa; Yirmiya, Raz

2014-10-01

Recent studies demonstrate that microglia play an important role in cognitive and neuroplasticity processes, at least partly via microglial CX3C receptor 1 (CX3CR1) signaling. Furthermore, microglia are responsive to environmental enrichment (EE), which modulates learning, memory and neurogenesis. In the present study we examined the role of microglial CX3CR1 signaling in hippocampal- and olfactory-bulb (OB)-related memory and neurogenesis in homozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient mice displayed better hippocampal-dependent memory functioning and olfactory recognition, along with increased number and soma size of hippocampal microglia, suggestive of mild activation status, but no changes in OB microglia. A similar increase in hippocampal-dependent memory functioning and microglia number was also induced by pharmacological inhibition of CX3CR1 signaling, using chronic (2weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE improved hippocampal-dependent memory and neurogenesis, and increased hippocampal microglia number and soma size, whereas odor enrichment (OE) improved olfactory recognition and OB neurogenesis without changing OB microglia status. In CX3CR1-deficient mice, EE and OE did not produce any further improvement in memory functioning or neurogenesis and had no effect on microglial status. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans.

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van Kesteren, Marlieke T R; Fernández, Guillén; Norris, David G; Hermans, Erno J

2010-04-20

The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process. Thus, hippocampal-vmPFC crosstalk may support integration of new memories, particularly in the absence of a relevant prior schema. To address this issue, we used functional magnetic resonance imaging (fMRI) and prior schema manipulation to track hippocampal-vmPFC connectivity during encoding and postencoding rest. We manipulated prior schema knowledge by exposing 30 participants to the first part of a movie that was temporally scrambled for 15 participants. The next day, participants underwent fMRI while encoding the movie's final 15 min in original order and, subsequently, while resting. Schema knowledge and item recognition performance show that prior schema was successfully and selectively manipulated. Intersubject synchronization (ISS) and interregional partial correlation analyses furthermore show that stronger prior schema was associated with more vmPFC ISS and less hippocampal-vmPFC interregional connectivity during encoding. Notably, this connectivity pattern persisted during postencoding rest. These findings suggest that additional crosstalk between hippocampus and vmPFC is required to compensate for difficulty integrating novel information during encoding and provide tentative support for the notion that functionally relevant hippocampal-neocortical crosstalk persists during off-line periods after learning.

Scanless functional imaging of hippocampal networks using patterned two-photon illumination through GRIN lenses

KAUST Repository

Moretti, Claudio

2016-09-12

Patterned illumination through the phase modulation of light is increasingly recognized as a powerful tool to investigate biological tissues in combination with two-photon excitation and light-sensitive molecules. However, to date two-photon patterned illumination has only been coupled to traditional microscope objectives, thus limiting the applicability of these methods to superficial biological structures. Here, we show that phase modulation can be used to efficiently project complex two-photon light patterns, including arrays of points and large shapes, in the focal plane of graded index (GRIN) lenses. Moreover, using this approach in combination with the genetically encoded calcium indicator GCaMP6, we validate our system performing scanless functional imaging in rodent hippocampal networks in vivo ~1.2 mm below the brain surface. Our results open the way to the application of patterned illumination approaches to deep regions of highly scattering biological tissues, such as the mammalian brain.

Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

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Jardim, Anaclara Prada; Corso, Jeana Torres; Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Comper, Sandra Mara; Lancellotti, Carmen Lúcia Penteado; Centeno, Ricardo Silva; Carrete, Henrique; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

2016-12-01

To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS. Copyright © 2016 Elsevier B.V. All rights reserved.

Persistence of Gender Related-Effects on Visuo-Spatial and Verbal Working Memory in Right Brain-Damaged Patients.

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Piccardi, Laura; Matano, Alessandro; D'Antuono, Giovanni; Marin, Dario; Ciurli, Paola; Incoccia, Chiara; Verde, Paola; Guariglia, Paola

2016-01-01

The aim of the present study was to verify if gender differences in verbal and visuo-spatial working memory would persist following right cerebral lesions. To pursue our aim we investigated a large sample (n. 346) of right brain-damaged patients and healthy participants (n. 272) for the presence of gender effects in performing Corsi and Digit Test. We also assessed a subgroup of patients (n. 109) for the nature (active vs. passive) of working memory tasks. We tested working memory (WM) administering the Corsi Test (CBT) and the Digit Span (DS) using two different versions: forward (fCBT and fDS), subjects were required to repeat stimuli in the same order that they were presented; and backward (bCBT and bDS), subjects were required to repeat stimuli in the opposite order of presentation. In this way, passive storage and active processing of working memory were assessed. Our results showed the persistence of gender-related effects in spite of the presence of right brain lesions. We found that men outperformed women both in CBT and DS, regardless of active and passive processing of verbal and visuo-spatial stimuli. The presence of visuo-spatial disorders (i.e., hemineglect) can affect the performance on Corsi Test. In our sample, men and women were equally affected by hemineglect, therefore it did not mask the gender effect. Generally speaking, the persistence of the men's superiority in visuo-spatial tasks may be interpreted as a protective factor, at least for men, within other life factors such as level of education or kind of profession before retirement.

Alzheimer's Disease Diagnostic Performance of a Multi-Atlas Hippocampal Segmentation Method using the Harmonized Hippocampal Protocol

DEFF Research Database (Denmark)

Anker, Cecilie Benedicte; Sørensen, Lauge; Pai, Akshay

PURPOSE Hippocampal volumetry is the most widely used structural MRI biomarker of Alzheimer’s disease (AD), and state-of-the-art, automatic hippocampal segmentation can be obtained using longitudinal FreeSurfer. In this study, we compare the diagnostic AD performance of a single time point, multi...

Neuropsychology, Autobiographical Memory, and Hippocampal Volume in “Younger” and “Older” Patients with Chronic Schizophrenia

Science.gov (United States)

Herold, Christina Josefa; Lässer, Marc Montgomery; Schmid, Lena Anna; Seidl, Ulrich; Kong, Li; Fellhauer, Iven; Thomann, Philipp Arthur; Essig, Marco; Schröder, Johannes

2015-01-01

Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution. PMID:25954208

Long-term potentiation expands information content of hippocampal dentate gyrus synapses.

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Bromer, Cailey; Bartol, Thomas M; Bowden, Jared B; Hubbard, Dusten D; Hanka, Dakota C; Gonzalez, Paola V; Kuwajima, Masaaki; Mendenhall, John M; Parker, Patrick H; Abraham, Wickliffe C; Sejnowski, Terrence J; Harris, Kristen M

2018-03-06

An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

βCaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting αCaMKII to synapses.

Science.gov (United States)

Borgesius, Nils Z; van Woerden, Geeske M; Buitendijk, Gabrielle H S; Keijzer, Nanda; Jaarsma, Dick; Hoogenraad, Casper C; Elgersma, Ype

2011-07-13

The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the αCaMKII and βCaMKII isoforms. Yet, in contrast to αCaMKII, the role of βCaMKII in hippocampal synaptic plasticity and learning has not been investigated. Here, we compare two targeted Camk2b mouse mutants to study the role of βCaMKII in hippocampal function. Using a Camk2b(-/-) mutant, in which βCaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateral-CA1 long-term potentiation (LTP) are highly dependent upon the presence of βCaMKII. We further show that βCaMKII is required for proper targeting of αCaMKII to the synapse, indicating that βCaMKII regulates the distribution of αCaMKII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of αCaMKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2b(A303R) mutant, in which the calcium/calmodulin-dependent activation of βCaMKII is prevented, while the F-actin binding and bundling property is preserved. This indicates that the calcium/calmodulin-dependent kinase activity of βCaMKII is fully dispensable for hippocampal learning, LTP, and targeting of αCaMKII, but implies a critical role for the F-actin binding and bundling properties of βCaMKII in synaptic function. Together, our data provide compelling support for a model of CaMKII function in which αCaMKII and βCaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning.

Hippocampal MR volumetry

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Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.

1994-09-01

Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR

Comparing and Contrasting the Cognitive Effects of Hippocampal and Ventromedial Prefrontal Cortex Damage: A Review of Human Lesion Studies.

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McCormick, Cornelia; Ciaramelli, Elisa; De Luca, Flavia; Maguire, Eleanor A

2018-03-15

The hippocampus and ventromedial prefrontal cortex (vmPFC) are closely connected brain regions whose functions are still debated. In order to offer a fresh perspective on understanding the contributions of these two brain regions to cognition, in this review we considered cognitive tasks that usually elicit deficits in hippocampal-damaged patients (e.g., autobiographical memory retrieval), and examined the performance of vmPFC-lesioned patients on these tasks. We then took cognitive tasks where performance is typically compromised following vmPFC damage (e.g., decision making), and looked at how these are affected by hippocampal lesions. Three salient motifs emerged. First, there are surprising gaps in our knowledge about how hippocampal and vmPFC patients perform on tasks typically associated with the other group. Second, while hippocampal or vmPFC damage seems to adversely affect performance on so-called hippocampal tasks, the performance of hippocampal and vmPFC patients clearly diverges on classic vmPFC tasks. Third, although performance appears analogous on hippocampal tasks, on closer inspection, there are significant disparities between hippocampal and vmPFC patients. Based on these findings, we suggest a tentative hierarchical model to explain the functions of the hippocampus and vmPFC. We propose that the vmPFC initiates the construction of mental scenes by coordinating the curation of relevant elements from neocortical areas, which are then funneled into the hippocampus to build a scene. The vmPFC then engages in iterative re-initiation via feedback loops with neocortex and hippocampus to facilitate the flow and integration of the multiple scenes that comprise the coherent unfolding of an extended mental event. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB.

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Rolando, Chiara; Erni, Andrea; Grison, Alice; Beattie, Robert; Engler, Anna; Gokhale, Paul J; Milo, Marta; Wegleiter, Thomas; Jessberger, Sebastian; Taylor, Verdon

2016-11-03

Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gliogenesis. We further find that Drosha directly targets NFIB to repress its expression independently of Dicer and microRNAs. Knockdown of NFIB in Drosha-deficient hippocampal NSCs restores neurogenesis, suggesting that the Drosha/NFIB mechanism robustly prevents oligodendrocyte fate acquisition in vivo. Taken together, our findings establish that adult hippocampal NSCs inherently possess multilineage potential but that Drosha functions as a molecular barrier preventing oligodendrogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

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Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

2016-01-01

In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

Stereotype Threat and Gender Differences in Performance on a Novel Visuospatial Task

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Campbell, Susan Miller; Collaer, Marcia L.

2009-01-01

Stereotype threat research has shown that being a member of a negatively stereotyped group may result in impaired performance on tests of skills thought to be relevant to the stereotype. This study investigated whether stereotype threat influences gender differences in performance on a novel test of visuospatial ability. Undergraduates (N = 194)…

Covert is better than overt when rehearsing Visuo-Spatial information in working memory

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Godijn, R.J.; Theeuwes, J.

2012-01-01

In the present study, we examined whether eye movements facilitate retention of visuo-spatial information in working memory. In two experiments, participants memorised the sequence of the spatial locations of six digits across a retention interval. In some conditions, participants were free to move

Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development

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Schachtschneider, Kyle M.; Liu, Yingkai; Rund, Laurie A.; Madsen, Ole; Johnson, Rodney W.; Groenen, Martien A.M.; Schook, Lawrence B.

2016-01-01

Background

Iron deficiency is a common childhood micronutrient deficiency that results in altered hippocampal function and cognitive disorders. However, little is known about the mechanisms through which neonatal iron deficiency results in long lasting alterations in hippocampal gene

Integrating incremental learning and episodic memory models of the hippocampal region.

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Meeter, M.; Myers, C.E; Gluck, M.A.

2005-01-01

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic

Hippocampal sclerosis in children younger than 2 years

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Kadom, Nadja [Children' s National Medical Center, Department of Diagnostic Imaging and Radiology, Washington, DC (United States); Tsuchida, Tammy; Gaillard, William D. [Children' s National Medical Center, Department of Neurology, Washington, DC (United States)

2011-10-15

Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

Hippocampal sclerosis in children younger than 2 years

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Kadom, Nadja; Tsuchida, Tammy; Gaillard, William D.

2011-01-01

Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

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Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

2015-05-01

Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Relation between sleep and visuospatial skills in students from a public school

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Danilo de Freitas Araújo

2013-03-01

Full Text Available The relation between the sleep and the visuospatial skills was evaluated in 31 students from a public school. For the analysis of sleep, the parents of volunteers answered a sleep evaluation questionnaire and the sleep diary. The visuospatial performance was evaluated by Wechsler Intelligence Scale for Children (WISC-III, through the subtest Picture Completion, the Perceptual Organization Index and the Performance IQ Scale. In accordance with the results, 72% of the students presented regular sleep and good sleep length. The visuospatial performance was deficient in subtest Picture Completion for 56% of the students, and on the Performance IQ Scale for 60% of the students. Significant correlations were verified between early sleep onset (rho = -0.40, p Avaliou-se a relação entre o sono e a visuoespacialidade em 31 estudantes de uma escola pública. Para a análise do sono, foram preenchidos, pelos pais dos voluntários, uma ficha de avaliação do sono e o diário do sono. O desempenho visuoespacial foi avaliado pela Escala de Inteligência Wechsler para Crianças (WISC-III, utilizando o subteste Completar Figuras, o índice fatorial Organização Perceptual e a Escala QIde Execução. De acordo com os resultados, 72% dos estudantes apresentaram sono regular e boa duração. O desempenho visuoespacial foi deficiente no subteste Completar Figuras para 56% dos estudantes, e na Escala QI de Execução para 60% dos alunos. Foram verificadas correlações significativas entre início do sono cedo (rho = -0,40, p < 0,05 e sono regular (rho = -0,39, p < 0,05 com o desempenho visuoespacial. Conclui-se que dormir mais cedo e ter um sono regular podem contribuir para um melhor desempenho visuoespacial.

Dynamic reorganization of human resting-state networks during visuospatial attention.

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Spadone, Sara; Della Penna, Stefania; Sestieri, Carlo; Betti, Viviana; Tosoni, Annalisa; Perrucci, Mauro Gianni; Romani, Gian Luca; Corbetta, Maurizio

2015-06-30

Fundamental problems in neuroscience today are understanding how patterns of ongoing spontaneous activity are modified by task performance and whether/how these intrinsic patterns influence task-evoked activation and behavior. We examined these questions by comparing instantaneous functional connectivity (IFC) and directed functional connectivity (DFC) changes in two networks that are strongly correlated and segregated at rest: the visual (VIS) network and the dorsal attention network (DAN). We measured how IFC and DFC during a visuospatial attention task, which requires dynamic selective rerouting of visual information across hemispheres, changed with respect to rest. During the attention task, the two networks remained relatively segregated, and their general pattern of within-network correlation was maintained. However, attention induced a decrease of correlation in the VIS network and an increase of the DAN→VIS IFC and DFC, especially in a top-down direction. In contrast, within the DAN, IFC was not modified by attention, whereas DFC was enhanced. Importantly, IFC modulations were behaviorally relevant. We conclude that a stable backbone of within-network functional connectivity topography remains in place when transitioning between resting wakefulness and attention selection. However, relative decrease of correlation of ongoing "idling" activity in visual cortex and synchronization between frontoparietal and visual cortex were behaviorally relevant, indicating that modulations of resting activity patterns are important for task performance. Higher order resting connectivity in the DAN was relatively unaffected during attention, potentially indicating a role for simultaneous ongoing activity as a "prior" for attention selection.

The neural correlates of visuo-spatial working memory in children with autism spectrum disorder: effects of cognitive load.

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Vogan, Vanessa M; Morgan, Benjamin R; Lee, Wayne; Powell, Tamara L; Smith, Mary Lou; Taylor, Margot J

2014-01-01

Research on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI). We used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7-13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load. Performance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends. Children with ASD showed differences in activation in the frontal and parietal lobes-both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

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He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

ViSA: a neurodynamic model for visuo-spatial working memory, attentional blink, and conscious access.

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Simione, Luca; Raffone, Antonino; Wolters, Gezinus; Salmas, Paola; Nakatani, Chie; Belardinelli, Marta Olivetti; van Leeuwen, Cees

2012-10-01

Two separate lines of study have clarified the role of selectivity in conscious access to visual information. Both involve presenting multiple targets and distracters: one simultaneously in a spatially distributed fashion, the other sequentially at a single location. To understand their findings in a unified framework, we propose a neurodynamic model for Visual Selection and Awareness (ViSA). ViSA supports the view that neural representations for conscious access and visuo-spatial working memory are globally distributed and are based on recurrent interactions between perceptual and access control processors. Its flexible global workspace mechanisms enable a unitary account of a broad range of effects: It accounts for the limited storage capacity of visuo-spatial working memory, attentional cueing, and efficient selection with multi-object displays, as well as for the attentional blink and associated sparing and masking effects. In particular, the speed of consolidation for storage in visuo-spatial working memory in ViSA is not fixed but depends adaptively on the input and recurrent signaling. Slowing down of consolidation due to weak bottom-up and recurrent input as a result of brief presentation and masking leads to the attentional blink. Thus, ViSA goes beyond earlier 2-stage and neuronal global workspace accounts of conscious processing limitations. PsycINFO Database Record (c) 2012 APA, all rights reserved.

CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

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Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

2006-10-01

Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

Large and Small Dendritic Spines Serve Different Interacting Functions in Hippocampal Synaptic Plasticity and Homeostasis

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Joshua J. W. Paulin

2016-01-01

Full Text Available The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca2+ influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes.

Hippocampal leptin signaling reduces food intake and modulates food-related memory processing.

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Kanoski, Scott E; Hayes, Matthew R; Greenwald, Holly S; Fortin, Samantha M; Gianessi, Carol A; Gilbert, Jennifer R; Grill, Harvey J

2011-08-01

The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 μg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 μg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

Persistence of Gender Related-Effects on Visuo-Spatial and Verbal Working Memory in Right Brain-Damaged Patients

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Piccardi, Laura; Matano, Alessandro; D’Antuono, Giovanni; Marin, Dario; Ciurli, Paola; Incoccia, Chiara; Verde, Paola; Guariglia, Paola

2016-01-01

The aim of the present study was to verify if gender differences in verbal and visuo-spatial working memory would persist following right cerebral lesions. To pursue our aim we investigated a large sample (n. 346) of right brain-damaged patients and healthy participants (n. 272) for the presence of gender effects in performing Corsi and Digit Test. We also assessed a subgroup of patients (n. 109) for the nature (active vs. passive) of working memory tasks. We tested working memory (WM) administering the Corsi Test (CBT) and the Digit Span (DS) using two different versions: forward (fCBT and fDS), subjects were required to repeat stimuli in the same order that they were presented; and backward (bCBT and bDS), subjects were required to repeat stimuli in the opposite order of presentation. In this way, passive storage and active processing of working memory were assessed. Our results showed the persistence of gender-related effects in spite of the presence of right brain lesions. We found that men outperformed women both in CBT and DS, regardless of active and passive processing of verbal and visuo-spatial stimuli. The presence of visuo-spatial disorders (i.e., hemineglect) can affect the performance on Corsi Test. In our sample, men and women were equally affected by hemineglect, therefore it did not mask the gender effect. Generally speaking, the persistence of the men’s superiority in visuo-spatial tasks may be interpreted as a protective factor, at least for men, within other life factors such as level of education or kind of profession before retirement. PMID:27445734

CX3CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment

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Laura eMaggi

2011-10-01

Full Text Available In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning and memory performances are deeply modulated by social, motor and sensorial experiences. Fractalkine/CX3CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX3CR1 expressed by microglia. In this paper we investigated the role of CX3CL1/CX3CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX3CR1GFP/GFP mice were exposed to long-lasting-enriched environment (EE and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation (LTP of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG.We found that CX3CR1 deficiency increases hippocampal plasticity and spatial memory blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX3CR1GFP/GFP mice. These data indicate that CX3CL1/CX3CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs.

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Pernille Tveden-Nyborg

Full Text Available While having the highest vitamin C (VitC concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg or Low (100 mg VitC per kg diet. Newborn pups (n = 157 were randomized into a total of four postnatal feeding regimens: High/High (Control; High/Low (Depleted, Low/Low (Deficient; and Low/High (Repleted. Proliferation and migration of newborn cells in the dentate gyrus was assessed by BrdU labeling and hippocampal volumes were determined by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P<0.001 which was not reversed by postnatal repletion. There was no difference in postnatal cellular proliferation and survival rates in the hippocampus between dietary groups, however, migration of newborn cells into the granular layer of the hippocampus dentate gyrus was significantly reduced in prenatally deficient animals (P<0.01. We conclude that a prenatal VitC deficiency in guinea pigs leads to persistent impairment of postnatal hippocampal development which is not alleviated by postnatal repletion. Our findings place attention on a yet unrecognized consequence of marginal VitC deficiency during pregnancy.

Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood.

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Daugherty, Ana M; Flinn, Robert; Ofen, Noa

2017-06-01

Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution images in a sample of healthy participants (age 8-25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. Copyright © 2017 Elsevier Inc. All rights reserved.

Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood

Science.gov (United States)

Daugherty, Ana M.; Flinn, Robert; Ofen, Noa

2017-01-01

Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution proton density-weighted images in a sample of healthy participants (age 8–25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. PMID:28342999

Visuospatial and Verbal Short-Term Memory Correlates of Vocabulary Ability in Preschool Children

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Stokes, Stephanie F.; Klee, Thomas; Kornisch, Myriam; Furlong, Lisa

2017-01-01

Background: Recent studies indicate that school-age children's patterns of performance on measures of verbal and visuospatial short-term memory (STM) and working memory (WM) differ across types of neurodevelopmental disorders. Because these disorders are often characterized by early language delay, administering STM and WM tests to toddlers could…

The effects of hormones and physical exercise on hippocampal structural plasticity.

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Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

2016-04-01

The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Definition of a visuospatial dimension as a step forward in the diagnostic puzzle of nonverbal learning disability.

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Poletti, Michele

2017-01-01

Although clinically recognized for almost 50 years, the categorical distinction of specific learning disabilities due to an impairment of the nonverbal domain (nonverbal learning disability [NLD]) is still debated and controversial. Unsolved issues involve theoretical models, diagnostic criteria, rehabilitative interventions, and moderator factors. These issues are briefly overviewed to sustain the need for a shift toward dimensional approaches, as suggested by research domain criteria, as a step forward in the diagnostic puzzle of NLD. With this aim, a visuospatial dimension, or spectrum, is proposed, and then clinical conditions that may fit with its impaired side are systemized, while specifying in which conditions a visuospatial impairment may be considered an NLD.

The role of short-term memory and visuo-spatial skills in numerical magnitude processing: Evidence from Turner syndrome.

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Lucie Attout

Full Text Available Most studies on magnitude representation have focused on the visual modality with no possibility of disentangling the influence of visuo-spatial skills and short-term memory (STM abilities on quantification processes. This study examines this issue in patients with Turner syndrome (TS, a genetic condition characterized by a specific cognitive profile frequently associating poor mathematical achievement, low spatial skills and reduced STM abilities. In order to identify the influence of visuo-spatial and STM processing on numerical magnitude abilities, twenty female participants with TS and twenty control female participants matched for verbal IQ and education level were administered a series of magnitude comparison tasks. The tasks differed on the nature of the magnitude to be processed (continuous, discrete and symbolic magnitude, on visuo-spatial processing requirement (no/high and on STM demands (low in simultaneous presentation vs. high in sequential presentation. Our results showed a lower acuity when participants with TS compared the numerical magnitudes of stimuli presented sequentially (low visuo-spatial processing and high STM load: Dot sequence and Sound sequence while no difference was observed in the numerical comparison of sets presented simultaneously. In addition, the group difference in sequential tasks disappeared when controlling for STM abilities. Finally, both groups demonstrated similar performance when comparing continuous or symbolic magnitude stimuli and they exhibited comparable subitizing abilities. These results highlight the importance of STM abilities in extracting numerosity through a sequential presentation and underline the importance of considering the impact of format presentation on magnitude judgments.

A new neural framework for visuospatial processing.

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Kravitz, Dwight J; Saleem, Kadharbatcha S; Baker, Chris I; Mishkin, Mortimer

2011-04-01

The division of cortical visual processing into distinct dorsal and ventral streams is a key framework that has guided visual neuroscience. The characterization of the ventral stream as a 'What' pathway is relatively uncontroversial, but the nature of dorsal stream processing is less clear. Originally proposed as mediating spatial perception ('Where'), more recent accounts suggest it primarily serves non-conscious visually guided action ('How'). Here, we identify three pathways emerging from the dorsal stream that consist of projections to the prefrontal and premotor cortices, and a major projection to the medial temporal lobe that courses both directly and indirectly through the posterior cingulate and retrosplenial cortices. These three pathways support both conscious and non-conscious visuospatial processing, including spatial working memory, visually guided action and navigation, respectively.

Parkia biglobosa Improves Mitochondrial Functioning and Protects against Neurotoxic Agents in Rat Brain Hippocampal Slices

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Kayode Komolafe

2014-01-01

Full Text Available Objective. Methanolic leaf extracts of Parkia biglobosa, PBE, and one of its major polyphenolic constituents, catechin, were investigated for their protective effects against neurotoxicity induced by different agents on rat brain hippocampal slices and isolated mitochondria. Methods. Hippocampal slices were preincubated with PBE (25, 50, 100, or 200 µg/mL or catechin (1, 5, or 10 µg/mL for 30 min followed by further incubation with 300 µM H2O2, 300 µM SNP, or 200 µM PbCl2 for 1 h. Effects of PBE and catechin on SNP- or CaCl2-induced brain mitochondrial ROS formation and mitochondrial membrane potential (ΔΨm were also determined. Results. PBE and catechin decreased basal ROS generation in slices and blunted the prooxidant effects of neurotoxicants on membrane lipid peroxidation and nonprotein thiol contents. PBE rescued hippocampal cellular viability from SNP damage and caused a significant boost in hippocampus Na+, K+-ATPase activity but with no effect on the acetylcholinesterase activity. Both PBE and catechin also mitigated SNP- or CaCl2-dependent mitochondrial ROS generation. Measurement by safranine fluorescence however showed that the mild depolarization of the ΔΨm by PBE was independent of catechin. Conclusion. The results suggest that the neuroprotective effect of PBE is dependent on its constituent antioxidants and mild mitochondrial depolarization propensity.

Hippocampal place cells construct reward related sequences through unexplored space.

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Ólafsdóttir, H Freyja; Barry, Caswell; Saleem, Aman B; Hassabis, Demis; Spiers, Hugo J

2015-06-26

Dominant theories of hippocampal function propose that place cell representations are formed during an animal's first encounter with a novel environment and are subsequently replayed during off-line states to support consolidation and future behaviour. Here we report that viewing the delivery of food to an unvisited portion of an environment leads to off-line pre-activation of place cells sequences corresponding to that space. Such 'preplay' was not observed for an unrewarded but otherwise similar portion of the environment. These results suggest that a hippocampal representation of a visible, yet unexplored environment can be formed if the environment is of motivational relevance to the animal. We hypothesise such goal-biased preplay may support preparation for future experiences in novel environments.

Decoding the cognitive map: ensemble hippocampal sequences and decision making.

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Wikenheiser, Andrew M; Redish, A David

2015-06-01

Tolman proposed that complex animal behavior is mediated by the cognitive map, an integrative learning system that allows animals to reconfigure previous experience in order to compute predictions about the future. The discovery of place cells in the rodent hippocampus immediately suggested a plausible neural mechanism to fulfill the 'map' component of Tolman's theory. Recent work examining hippocampal representations occurring at fast time scales suggests that these sequences might be important for supporting the inferential mental operations associated with the cognitive map function. New findings that hippocampal sequences play an important causal role in mediating adaptive behavior on a moment-by-moment basis suggest specific neural processes that may underlie Tolman's cognitive map framework. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intrahippocampal Administration of Amyloid-β1–42 Oligomers Acutely Impairs Spatial Working Memory, Insulin Signaling, and Hippocampal Metabolism

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Pearson-Leary, Jiah; McNay, Ewan C.

2017-01-01

Increasing evidence suggests that abnormal brain accumulation of amyloid-β1–42 (Aβ1–42) oligomers plays a causal role in Alzheimer’s disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ1–42 oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ1–42 oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ1–42 oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ1–42 oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ1–42 oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ1–42 leads to cognitive impairment via interference with hippocampal insulin signaling. PMID:22430529

Positional priming of pop-out is nested in visuospatial context.

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Gokce, Ahu; Müller, Hermann J; Geyer, Thomas

2013-11-26

The present study investigated facilitatory and inhibitory positional priming using a variant of Maljkovic and Nakayama's (1996) priming of pop-out task. Here, the singleton target and the distractors could be presented in different visuospatial contexts-but identical screen locations-across trials, permitting positional priming based on individual locations to be disentangled from priming based on interitem configural relations. The results revealed both significant facilitatory priming, i.e., faster reaction times (RTs) to target presented at previous target relative to previously empty locations, and inhibitory priming, i.e., slower RTs to target at previous distractor relative to previously empty locations. However, both effects were contingent on repetitions versus changes of stimulus arrangement: While facilitation of target locations was dependent on the repetition of the exact item configuration (e.g., T-type followed by T-type stimulus arrangement), the inhibitory effect was more "tolerant," being influenced by repetitions versus changes of the item's visuospatial category (T-type followed by Z-type pattern; cf. Garner & Clement, 1963). The results suggest that facilitatory and inhibitory priming are distinct phenomena (Finke et al., 2009) and that both effects are sensitive to subtle information about the arrangement of the display items (Geyer, Zehetleitner, & Müller, 2010). The results are discussed with respect to the stage(s) of visual pop-out search that are influenced by positional priming.

Exploratory study of the relationship between the musical, visuospatial, bodily-kinesthetic intelligence and drive creativity in the process of learning

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Paula MARCHENA CRUZ

2017-12-01

Full Text Available Currently, the Spanish educational system focuses its attention on the development of priority subjects such as language and mathematics versus other secondary such as music (Palacios, 2006, without considering numerous neuropsychological research that provides new theories of mind and learning that can positively influence the transformation of current educational models (Martin-Lobo, 2015. This research aims to determine the relation between musical intelligence, bodily-kinesthetic intelligence, intelligence visuospatial and motor creativity in a sample among 5 years old students from the last year of Early Childhood Education. The instrument used to assess the three intelligences, based on Gardner’s theory, was the Multiple Intelligences questionnaire for children of pre-school age (Prieto and Ballester, 2003; for the evaluation of motor creativity was used Test of Creative Thinking in Action and Movement (Torrance, Reisman and Floyd, 1981. A descriptive and correlational statistical analysis (using the Pearson correlation index applying the Microsoft Excel program along with the supplement known as Ezanalyze. The results indicated no significant relationship between musical intelligence and motor creativity (p = 0.988; the visuospatial intelligence and motor creativity (p = 0.992; and the bodily-kinesthetic intelligence and motor creativity (p = 0.636. Although there was significant relation between the musical and visuospatial intelligence (p = 0.000; the musical and bodily-kinesthetic intelligence (p = 0.000; and the bodily-kinesthetic and visuospatial intelligence (p = 0.025.

Hippocampal insulin microinjection and in vivo microdialysis during spatial memory testing.

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McNay, Ewan C; Sandusky, Leslie A; Pearson-Leary, Jiah

2013-01-11

Glucose metabolism is a useful marker for local neural activity, forming the basis of methods such as 2-deoxyglucose and functional magnetic resonance imaging. However, use of such methods in animal models requires anesthesia and hence both alters the brain state and prevents behavioral measures. An alternative method is the use of in vivo microdialysis to take continuous measurement of brain extracellular fluid concentrations of glucose, lactate, and related metabolites in awake, unrestrained animals. This technique is especially useful when combined with tasks designed to rely on specific brain regions and/or acute pharmacological manipulation; for example, hippocampal measurements during a spatial working memory task (spontaneous alternation) show a dip in extracellular glucose and rise in lactate that are suggestive of enhanced glycolysis, and intrahippocampal insulin administration both improves memory and increases hippocampal glycolysis. Substances such as insulin can be delivered to the hippocampus via the same microdialysis probe used to measure metabolites. The use of spontaneous alternation as a measure of hippocampal function is designed to avoid any confound from stressful motivators (e.g. footshock), restraint, or rewards (e.g. food), all of which can alter both task performance and metabolism; this task also provides a measure of motor activity that permits control for nonspecific effects of treatment. Combined, these methods permit direct measurement of the neurochemical and metabolic variables regulating behavior.

A Familiar Pattern? Semantic Memory Contributes to the Enhancement of Visuo-Spatial Memories

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Riby, Leigh M.; Orme, Elizabeth

2013-01-01

In this study we quantify for the first time electrophysiological components associated with incorporating long-term semantic knowledge with visuo-spatial information using two variants of a traditional matrix patterns task. Results indicated that the matrix task with greater semantic content was associated with enhanced accuracy and RTs in a…

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

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Booth, Clair A; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W; Randall, Andrew D; Brown, Jonathan T

2016-01-13

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. Copyright © 2016 Booth, Witton et al.

Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

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Mattson, M P; Lee, R E; Adams, M E; Guthrie, P B; Kater, S B

1988-11-01

A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

Novel genetic loci associated with hippocampal volume

NARCIS (Netherlands)

D.P. Hibar (Derrek); H.H.H. Adams (Hieab); N. Jahanshad (Neda); G. Chauhan (Ganesh); J.L. Stein; E. Hofer (Edith); M.E. Rentería (Miguel); J.C. Bis (Joshua); A. Arias-Vásquez (Alejandro); Ikram, M.K. (M. Kamran); S. Desrivières (Sylvane); M.W. Vernooij (Meike); L. Abramovic (Lucija); S. Alhusaini (Saud); N. Amin (Najaf); M. Andersson (Micael); K. Arfanakis (Konstantinos); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); L. Athanasiu (Lavinia); T. Axelsson (Tomas); A.H. Beecham (Ashley); A. Beiser (Alexa); M. Bernard (Manon); S.H. Blanton (Susan H.); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.M. Brickman (Adam M.); Carmichael, O. (Owen); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); V. Chouraki (Vincent); G. Cuellar-Partida (Gabriel); F. Crivello (Fabrice); A. den Braber (Anouk); Doan, N.T. (Nhat Trung); S.M. Ehrlich (Stefan); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); R.F. Gottesman (Rebecca); O. Grimm (Oliver); M.D. Griswold (Michael); T. Guadalupe (Tulio); Gutman, B.A. (Boris A.); J. Hass (Johanna); U.K. Haukvik (Unn); D. Hoehn (David); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); Jørgensen, K.N. (Kjetil N.); N. Karbalai (Nazanin); D. Kasperaviciute (Dalia); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil); D.C. Liewald (David C.); L.M. Lopez (Lorna); M. Luciano (Michelle); C. MacAre (Christine); Marquand, A.F. (Andre F.); M. Matarin (Mar); R. Mather; M. Mattheisen (Manuel); McKay, D.R. (David R.); Milaneschi, Y. (Yuri); S. Muñoz Maniega (Susana); K. Nho (Kwangsik); A.C. Nugent (Allison); P. Nyquist (Paul); Loohuis, L.M.O. (Loes M. Olde); J. Oosterlaan (Jaap); M. Papmeyer (Martina); Pirpamer, L. (Lukas); B. Pütz (Benno); A. Ramasamy (Adaikalavan); Richards, J.S. (Jennifer S.); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); N. Rommelse (Nanda); S. Ropele (Stefan); E.J. Rose (Emma); N.A. Royle (Natalie); T. Rundek (Tatjana); P.G. Sämann (Philipp); Saremi, A. (Arvin); C.L. Satizabal (Claudia L.); L. Schmaal (Lianne); N.J. Schork (Nicholas); Shen, L. (Li); J. Shin (Jean); Shumskaya, E. (Elena); A.V. Smith (Albert Vernon); R. Sprooten (Roy); L.T. Strike (Lachlan); A. Teumer (Alexander); D. Tordesillas-Gutierrez (Diana); R. Toro (Roberto); D. Trabzuni (Danyah); S. Trompet (Stella); D. Vaidya (Dhananjay); J. van der Grond (Jeroen); S.J. van der Lee (Sven); Van Der Meer, D. (Dennis); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); T.G.M. van Erp (Theo G.); Van Rooij, D. (Daan); E. Walton (Esther); L.T. Westlye (Lars); C.D. Whelan (Christopher); B.G. Windham (B Gwen); A.M. Winkler (Anderson); K. Wittfeld (Katharina); G. Woldehawariat (Girma); A. Björnsson (Asgeir); Wolfers, T. (Thomas); L.R. Yanek (Lisa); Yang, J. (Jingyun); A.P. Zijdenbos; M.P. Zwiers (Marcel); I. Agartz (Ingrid); L. Almasy (Laura); D.J. Ames (David); Amouyel, P. (Philippe); O.A. Andreassen (Ole); S. Arepalli (Sampath); A.A. Assareh; S. Barral (Sandra); M.E. Bastin (Mark); Becker, D.M. (Diane M.); J.T. Becker (James); D.A. Bennett (David A.); J. Blangero (John); H. van Bokhoven (Hans); D.I. Boomsma (Dorret); H. Brodaty (Henry); R.M. Brouwer (Rachel); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan); K. Bulayeva (Kazima); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); D.M. Cannon (Dara); G. Cavalleri (Gianpiero); Cheng, C.-Y. (Ching-Yu); S. Cichon (Sven); M.R. Cookson (Mark); A. Corvin (Aiden); B. Crespo-Facorro (Benedicto); J.E. Curran (Joanne); M. Czisch (Michael); A.M. Dale (Anders); G.E. Davies (Gareth); A.J. de Craen (Anton); E.J.C. de Geus (Eco); P.L. de Jager (Philip); G.I. de Zubicaray (Greig); I.J. Deary (Ian J.); S. Debette (Stéphanie); C. DeCarli (Charles); N. Delanty; C. Depondt (Chantal); A.L. DeStefano (Anita); A. Dillman (Allissa); S. Djurovic (Srdjan); D.J. Donohoe (Dennis); D.A. Drevets (Douglas); Duggirala, R. (Ravi); M.D. Dyer (Matthew); C. Enzinger (Christian); S. Erk; T. Espeseth (Thomas); Fedko, I.O. (Iryna O.); Fernández, G. (Guillén); L. Ferrucci (Luigi); S.E. Fisher (Simon); D. Fleischman (Debra); I. Ford (Ian); M. Fornage (Myriam); T. Foroud (Tatiana); P.T. Fox (Peter); C. Francks (Clyde); Fukunaga, M. (Masaki); Gibbs, J.R. (J. Raphael); D.C. Glahn (David); R.L. Gollub (Randy); H.H.H. Göring (Harald H.); R.C. Green (Robert C.); O. Gruber (Oliver); V. Gudnason (Vilmundur); S. Guelfi (Sebastian); Håberg, A.K. (Asta K.); N.K. Hansell (Narelle); J. Hardy (John); C.A. Hartman (C.); Hashimoto, R. (Ryota); K. Hegenscheid (Katrin); J. Heinz (Judith); S. Le Hellard (Stephanie); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); Ho, B.-C. (Beng-Choon); P.J. Hoekstra (Pieter); W. Hoffmann (Wolfgang); A. Hofman (Albert); F. Holsboer (Florian); G. Homuth (Georg); N. Hosten (Norbert); J.J. Hottenga (Jouke Jan); M.J. Huentelman (Matthew); H.H. Pol; Ikeda, M. (Masashi); Jack, C.R. (Clifford R.); S. Jenkinson (Sarah); R. Johnson (Robert); Jönsson, E.G. (Erik G.); J.W. Jukema; R. Kahn (René); Kanai, R. (Ryota); I. Kloszewska (Iwona); Knopman, D.S. (David S.); P. Kochunov (Peter); Kwok, J.B. (John B.); S. Lawrie (Stephen); H. Lemaître (Herve); X. Liu (Xinmin); D.L. Longo (Dan L.); O.L. Lopez (Oscar L.); S. Lovestone (Simon); Martinez, O. (Oliver); J.-L. Martinot (Jean-Luc); V.S. Mattay (Venkata S.); McDonald, C. (Colm); A.M. McIntosh (Andrew); McMahon, F.J. (Francis J.); McMahon, K.L. (Katie L.); P. Mecocci (Patrizia); I. Melle (Ingrid); Meyer-Lindenberg, A. (Andreas); S. Mohnke (Sebastian); Montgomery, G.W. (Grant W.); D.W. Morris (Derek W); T.H. Mosley (Thomas H.); T.W. Mühleisen (Thomas); B. Müller-Myhsok (B.); M.A. Nalls (Michael); M. Nauck (Matthias); T.E. Nichols (Thomas); W.J. Niessen (Wiro); M.M. Nöthen (Markus); L. Nyberg (Lars); Ohi, K. (Kazutaka); R.L. Olvera (Rene); R.A. Ophoff (Roel); M. Pandolfo (Massimo); T. Paus (Tomas); Z. Pausova (Zdenka); B.W.J.H. Penninx (Brenda); Pike, G.B. (G. Bruce); S.G. Potkin (Steven); B.M. Psaty (Bruce); S. Reppermund; M. Rietschel (Marcella); J.L. Roffman (Joshua); N. Seiferth (Nina); J.I. Rotter (Jerome I.); M. Ryten (Mina); Sacco, R.L. (Ralph L.); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); R. Schmidt (Reinhold); Schmidt, H. (Helena); C.J. Schofield (Christopher); Sigursson, S. (Sigurdur); Simmons, A. (Andrew); A. Singleton (Andrew); S.M. Sisodiya (Sanjay); Smith, C. (Colin); J.W. Smoller; H. Soininen (H.); V.M. Steen (Vidar); D.J. Stott (David J.); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); M. Tsolaki (Magda); C. Tzourio (Christophe); A.G. Uitterlinden (André); Hernández, M.C.V. (Maria C. Valdés); M.P. van der Brug (Marcel); A. van der Lugt (Aad); N.J. van der Wee (Nic); N.E.M. van Haren (Neeltje E.); D. van 't Ent (Dennis); M.J.D. van Tol (Marie-José); B.N. Vardarajan (Badri); B. Vellas (Bruno); D.J. Veltman (Dick); H. Völzke (Henry); H.J. Walter (Henrik); J. Wardlaw (Joanna); A.M.J. Wassink (Annemarie); M.E. Weale (Michael); Weinberger, D.R. (Daniel R.); Weiner, M.W. (Michael W.); Wen, W. (Wei); E. Westman (Eric); T.J.H. White (Tonya); Wong, T.Y. (Tien Y.); Wright, C.B. (Clinton B.); R.H. Zielke (Ronald H.); A.B. Zonderman; N.G. Martin (Nicholas); C.M. van Duijn (Cornelia); M.J. Wright (Margaret); W.T. Longstreth Jr; G. Schumann (Gunter); H.J. Grabe (Hans Jörgen); B. Franke (Barbara); L.J. Launer (Lenore); S.E. Medland (Sarah Elizabeth); S. Seshadri (Sudha); P.M. Thompson (Paul); M.K. Ikram (Kamran)

2017-01-01

textabstractThe hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic

NeuroD2 regulates the development of hippocampal mossy fiber synapses

Directory of Open Access Journals (Sweden)

Wilke Scott A

2012-02-01

Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Novel genetic loci associated with hippocampal volume

NARCIS (Netherlands)

Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; van der Grond, Jeroen; van der Lee, Sven J.; van der Meer, Dennis; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; van Erp, Theo G. M.; van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; de Craen, Anton J. M.; de Geus, Eco J. C.; de Jager, Philip L.; de Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; Decarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; van Haren, Neeltje E. M.; van 't Ent, Dennis; van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

2017-01-01

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of

Spatial memory and hippocampal plasticity are differentially sensitive to the availability of choline in adulthood as a function of choline supply in utero

OpenAIRE

Wong-Goodrich, Sarah J.E.; Glenn, Melissa J.; Mellott, Tiffany J.; Blusztajn, Jan K.; Meck, Warren H.; Williams, Christina L.

2008-01-01

Altered dietary choline availability early in life leads to persistent changes in spatial memory and hippocampal plasticity in adulthood. Developmental programming by early choline nutrition may determine the range of adult choline intake that is optimal for the types of neural plasticity involved in cognitive function. To test this, male Sprague-Dawley rats were exposed to a choline chloride deficient (DEF), sufficient (CON), or supplemented (SUP) diet during embryonic days 12-17 and then re...

Visual performance of pigeons following hippocampal lesions.

Science.gov (United States)

Bingman, V P; Hodos, W

1992-11-15

The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.

Visuospatial asymmetry and non-spatial attention in subacute stroke patients with and without neglect

NARCIS (Netherlands)

Van Kessel, M.E.; Van Nes, I.J.W.; Brouwer, W.H.; Geurts, A.C.H.; Fasotti, L

Asymmetry in performance and an association with non-lateralized attention are often mentioned as two important aspects of the clinical manifestation of visuospatial neglect. Both these aspects were investigated in 21 left (LH) and 24 right hemisphere (RH) stroke patients and in 20 healthy subjects.

Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls

NARCIS (Netherlands)

van Ewijk, Hanneke; Weeda, Wouter D.; Heslenfeld, Dirk J.; Luman, Marjolein; Hartman, Catharina A.; Hoekstra, Pieter J.; Faraone, Stephen V.; Franke, Barbara; Buitelaar, Jan K.; Oosterlaan, Jaap

2015-01-01

Impaired visuospatial working memory (VSWM) is suggested to be a core neurocognitive deficit in attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural activation patterns are poorly understood. Furthermore, it is unclear to what extent age and gender effects may play a role in

Hippocampal “Time Cells”: Time versus Path Integration

Science.gov (United States)

Kraus, Benjamin J.; Robinson, Robert J.; White, John A.; Eichenbaum, Howard; Hasselmo, Michael E.

2014-01-01

SUMMARY Recent studies have reported the existence of hippocampal “time cells,” neurons that fire at particular moments during periods when behavior and location are relatively constant. However, an alternative explanation of apparent time coding is that hippocampal neurons “path integrate” to encode the distance an animal has traveled. Here, we examined hippocampal neuronal firing patterns as rats ran in place on a treadmill, thus “clamping” behavior and location, while we varied the treadmill speed to distinguish time elapsed from distance traveled. Hippocampal neurons were strongly influenced by time and distance, and less so by minor variations in location. Furthermore, the activity of different neurons reflected integration over time and distance to varying extents, with most neurons strongly influenced by both factors and some significantly influenced by only time or distance. Thus, hippocampal neuronal networks captured both the organization of time and distance in a situation where these dimensions dominated an ongoing experience. PMID:23707613

Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats.

Science.gov (United States)

Hsu, Ted M; Konanur, Vaibhav R; Taing, Lilly; Usui, Ryan; Kayser, Brandon D; Goran, Michael I; Kanoski, Scott E

2015-02-01

Excessive consumption of added sugars negatively impacts metabolic systems; however, effects on cognitive function are poorly understood. Also unknown is whether negative outcomes associated with consumption of different sugars are exacerbated during critical periods of development (e.g., adolescence). Here we examined the effects of sucrose and high fructose corn syrup-55 (HFCS-55) intake during adolescence or adulthood on cognitive and metabolic outcomes. Adolescent or adult male rats were given 30-day access to chow, water, and either (1) 11% sucrose solution, (2) 11% HFCS-55 solution, or (3) an extra bottle of water (control). In adolescent rats, HFCS-55 intake impaired hippocampal-dependent spatial learning and memory in a Barne's maze, with moderate learning impairment also observed for the sucrose group. The learning and memory impairment is unlikely based on nonspecific behavioral effects as adolescent HFCS-55 consumption did not impact anxiety in the zero maze or performance in a non-spatial response learning task using the same mildly aversive stimuli as the Barne's maze. Protein expression of pro-inflammatory cytokines (interleukin 6, interleukin 1β) was increased in the dorsal hippocampus for the adolescent HFCS-55 group relative to controls with no significant effect in the sucrose group, whereas liver interleukin 1β and plasma insulin levels were elevated for both adolescent-exposed sugar groups. In contrast, intake of HFCS-55 or sucrose in adults did not impact spatial learning, glucose tolerance, anxiety, or neuroinflammatory markers. These data show that consumption of added sugars, particularly HFCS-55, negatively impacts hippocampal function, metabolic outcomes, and neuroinflammation when consumed in excess during the adolescent period of development. © 2014 Wiley Periodicals, Inc.

Mild prenatal protein malnutrition increases alpha2C-adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long-term potentiation and visuo-spatial performance in rats.

Science.gov (United States)

Soto-Moyano, Rubén; Valladares, Luis; Sierralta, Walter; Pérez, Hernán; Mondaca, Mauricio; Fernández, Victor; Burgos, Héctor; Hernández, Alejandro

2005-06-01

Mild reduction in the protein content of the mother's diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long-term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the alpha2C-adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo-spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical alpha2C-adrenoceptor density. At 60 days-of-age, alpha2C-adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo-spatial memory performance. Results suggest that overexpression of neocortical alpha2C-adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo-spatial memory formation.

Impaired neuronal maturation of hippocampal neural progenitor cells in mice lacking CRAF.

Science.gov (United States)

Pfeiffer, Verena; Götz, Rudolf; Camarero, Guadelupe; Heinsen, Helmut; Blum, Robert; Rapp, Ulf Rüdiger

2018-01-01

RAF kinases are major constituents of the mitogen activated signaling pathway, regulating cell proliferation, differentiation and cell survival of many cell types, including neurons. In mammals, the family of RAF proteins consists of three members, ARAF, BRAF, and CRAF. Ablation of CRAF kinase in inbred mouse strains causes major developmental defects during fetal growth and embryonic or perinatal lethality. Heterozygous germline mutations in CRAF result in Noonan syndrome, which is characterized by neurocognitive impairment that may involve hippocampal physiology. The role of CRAF signaling during hippocampal development and generation of new postnatal hippocampal granule neurons has not been examined and may provide novel insight into the cause of hippocampal dysfunction in Noonan syndrome. In this study, by crossing CRAF-deficiency to CD-1 outbred mice, a CRAF mouse model was established which enabled us to investigate the interplay of neural progenitor proliferation and postmitotic differentiation during adult neurogenesis in the hippocampus. Albeit the general morphology of the hippocampus was unchanged, CRAF-deficient mice displayed smaller granule cell layer (GCL) volume at postnatal day 30 (P30). In CRAF-deficient mice a substantial number of abnormal, chromophilic, fast dividing cells were found in the subgranular zone (SGZ) and hilus of the dentate gyrus (DG), indicating that CRAF signaling contributes to hippocampal neural progenitor proliferation. CRAF-deficient neural progenitor cells showed an increased cell death rate and reduced neuronal maturation. These results indicate that CRAF function affects postmitotic neural cell differentiation and points to a critical role of CRAF-dependent growth factor signaling pathway in the postmitotic development of adult-born neurons.

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development.

Science.gov (United States)

Nguyen, Tuong-Vi; Wu, Mia; Lew, Jimin; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, D Louis; Campbell, Benjamin C; Booij, Linda; Herba, Catherine; Monnier, Patricia; Ducharme, Simon; McCracken, James T

2017-12-01

Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6-22 years old, mean age: 13.6 +/-3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatial representation in the hippocampal formation: a history.

Science.gov (United States)

Moser, Edvard I; Moser, May-Britt; McNaughton, Bruce L

2017-10-26

Since the first place cell was recorded and the cognitive-map theory was subsequently formulated, investigation of spatial representation in the hippocampal formation has evolved in stages. Early studies sought to verify the spatial nature of place cell activity and determine its sensory origin. A new epoch started with the discovery of head direction cells and the realization of the importance of angular and linear movement-integration in generating spatial maps. A third epoch began when investigators turned their attention to the entorhinal cortex, which led to the discovery of grid cells and border cells. This review will show how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal-entorhinal systems from the 1970s until today. It is now possible to investigate how specialized cell types of these systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.

Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration

Science.gov (United States)

Suzzi, Stefano; Vargas-Caballero, Mariana; Fransen, Nina L.; Al-Malki, Hussain; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose Manuel; Riecken, Kristoffer; Fehse, Boris; Perry, V. Hugh

2014-01-01

The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer’s disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases. PMID:24941947

Hippocampal lesions, contextual retrieval, and autoshaping in pigeons.

Science.gov (United States)

Richmond, Jenny; Colombo, Michael

2002-02-22

Both pigeons and rats with damage to the hippocampus are slow to acquire an autoshaped response and emit fewer overall responses than control animals. Experiment 1 explored the possibility that the autoshaping deficit was due to an impairment in contextual retrieval. Pigeons were trained for 14 days on an autoshaping task in which a red stimulus was followed by reinforcement in context A, and a green stimulus was followed by reinforcement in context B. On day 15, the subjects were given a context test in which the red and green stimuli were presented simultaneously in context A and then later in context B. Both control and hippocampal animals showed context specificity, that is, they responded more to the red stimulus in context A and to the green stimulus in context B. In Experiment 2 we video-recorded the control and hippocampal animals performing the autoshaping task. Hippocampal animals tended to miss-peck the key more often than control animals. In addition, the number of missed pecks increased across days for hippocampal animals but not for control animals, suggesting that while the control animals increased their pecking accuracy, the hippocampal animals actually decreased their pecking accuracy. Our findings suggest that impairments in moving through space may underlie the hippocampal autoshaping deficit.

Declarative memory formation in hippocampal sclerosis: an intracranial event-related potentials study.

NARCIS (Netherlands)

Mormann, F.; Fernandez, G.S.E.; Klaver, P.; Weber, B.; Elger, C.E.; Fell, J.

2007-01-01

The functional deficits associated with hippocampal sclerosis during declarative memory formation are largely unknown. In this study, we analyzed intracranial event-related potentials recorded from the medial temporal lobes of nine epilepsy patients performing a word memorization task. We used

Visuospatial Aptitude Testing Differentially Predicts Simulated Surgical Skill.

Science.gov (United States)

Hinchcliff, Emily; Green, Isabel; Destephano, Christopher; Cox, Mary; Smink, Douglas; Kumar, Amanika; Hokenstad, Erik; Bengtson, Joan; Cohen, Sarah

2018-02-05

To determine if visuospatial perception (VSP) testing is correlated to simulated or intraoperative surgical performance as rated by the American College of Graduate Medical Education (ACGME) milestones. Classification II-2 SETTING: Two academic training institutions PARTICIPANTS: 41 residents, including 19 Brigham and Women's Hospital and 22 Mayo Clinic residents from three different specialties (OBGYN, general surgery, urology). Participants underwent three different tests: visuospatial perception testing (VSP), Fundamentals of Laparoscopic Surgery (FLS®) peg transfer, and DaVinci robotic simulation peg transfer. Surgical grading from the ACGME milestones tool was obtained for each participant. Demographic and subject background information was also collected including specialty, year of training, prior experience with simulated skills, and surgical interest. Standard statistical analysis using Student's t test were performed, and correlations were determined using adjusted linear regression models. In univariate analysis, BWH and Mayo training programs differed in both times and overall scores for both FLS® peg transfer and DaVinci robotic simulation peg transfer (p<0.05 for all). Additionally, type of residency training impacted time and overall score on robotic peg transfer. Familiarity with tasks correlated with higher score and faster task completion (p= 0.05 for all except VSP score). There was no difference in VSP scores by program, specialty, or year of training. In adjusted linear regression modeling, VSP testing was correlated only to robotic peg transfer skills (average time p=0.006, overall score p=0.001). Milestones did not correlate to either VSP or surgical simulation testing. VSP score was correlated with robotic simulation skills but not with FLS skills or ACGME milestones. This suggests that the ability of VSP score to predict competence differs between tasks. Therefore, further investigation is required into aptitude testing, especially prior

Hippocampal Damage Increases Deontological Responses during Moral Decision Making.

Science.gov (United States)

McCormick, Cornelia; Rosenthal, Clive R; Miller, Thomas D; Maguire, Eleanor A

2016-11-30

Complex moral decision making is associated with the ventromedial prefrontal cortex (vmPFC) in humans, and damage to this region significantly increases the frequency of utilitarian judgments. Since the vmPFC has strong anatomical and functional links with the hippocampus, here we asked how patients with selective bilateral hippocampal damage would derive moral decisions on a classic moral dilemmas paradigm. We found that the patients approved of the utilitarian options significantly less often than control participants, favoring instead deontological responses-rejecting actions that harm even one person. Thus, patients with hippocampal damage have a strikingly opposite approach to moral decision making than vmPFC-lesioned patients. Skin-conductance data collected during the task showed increased emotional arousal in the hippocampal-damaged patients and they stated that their moral decisions were based on emotional instinct. By contrast, control participants made moral decisions based on the integration of an adverse emotional response to harming others, visualization of the consequences of one's action, and the rational re-evaluation of future benefits. This integration may be disturbed in patients with either hippocampal or vmPFC damage. Hippocampal lesions decreased the ability to visualize a scenario and its future consequences, which seemed to render the adverse emotional response overwhelmingly dominant. In patients with vmPFC damage, visualization might also be reduced alongside an inability to detect the adverse emotional response, leaving only the utilitarian option open. Overall, these results provide insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions. The ventromedial prefrontal cortex (vmPFC) is closely associated with the ability to make complex moral judgements. When this area is damaged, patients become more utilitarian (the ends justify the means) and have

An association between human hippocampal volume and topographical memory in healthy young adults.

Directory of Open Access Journals (Sweden)

Tom eHartley

2012-12-01

Full Text Available The association between human hippocampal structure and topographical memory was investigated in healthy adults (N=30. Structural MR images were acquired, and voxel-based morphometry (VBM was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

Low-frequency transcranial magnetic stimulation over left dorsal premotor cortex improves the dynamic control of visuospatially cued actions

DEFF Research Database (Denmark)

Ward, Nick S; Bestmann, Sven; Hartwigsen, Gesa

2010-01-01

Left rostral dorsal premotor cortex (rPMd) and supramarginal gyrus (SMG) have been implicated in the dynamic control of actions. In 12 right-handed healthy individuals, we applied 30 min of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) over left rPMd to investigate...... the involvement of left rPMd and SMG in the rapid adjustment of actions guided by visuospatial cues. After rTMS, subjects underwent functional magnetic resonance imaging while making spatially congruent button presses with the right or left index finger in response to a left- or right-sided target. Subjects were...... that left rPMd and SMG-AIP contribute toward dynamic control of actions and demonstrate that low-frequency rTMS can enhance functional coupling between task-relevant brain regions and improve some aspects of motor performance....

Role of adult hippocampal neurogenesis in stress resilience

Directory of Open Access Journals (Sweden)

Brunno R. Levone

2015-01-01

Full Text Available There is a growing appreciation that adult hippocampal neurogenesis plays a role in emotional and cognitive processes related to psychiatric disorders. Although many studies have investigated the effects of stress on adult hippocampal neurogenesis, most have not focused on whether stress-induced changes in neurogenesis occur specifically in animals that are more resilient or more susceptible to the behavioural and neuroendocrine effects of stress. Thus, in the present review we explore whether there is a clear relationship between stress-induced changes in adult hippocampal neurogenesis, stress resilience and antidepressant-induced recovery from stress-induced changes in behaviour. Exposure to different stressors is known to reduce adult hippocampal neurogenesis, but some stressors have also been shown to exert opposite effects. Ablation of neurogenesis does not lead to a depressive phenotype, but it can enhance responsiveness to stress and affect stress susceptibility. Monoaminergic-targeted antidepressants, environmental enrichment and adrenalectomy are beneficial for reversing stress-induced changes in behaviour and have been shown to do so in a neurogenesis-dependant manner. In addition, stress and antidepressants can affect hippocampal neurogenesis, preferentially in the ventral hippocampus. Together, these data show that adult hippocampal neurogenesis may play a role in the neuroendocrine and behavioural responses to stress, although it is not yet fully clear under which circumstances neurogenesis promotes resilience or susceptibility to stress. It will be important that future studies carefully examine how adult hippocampal neurogenesis can contribute to stress resilience/susceptibility so that it may be appropriately exploited for the development of new and more effective treatments for stress-related psychiatric disorders.

Distinguishing Depressive Pseudodementia from Alzheimer Disease: A Comparative Study of Hippocampal Volumetry and Cognitive Tests

Directory of Open Access Journals (Sweden)

Sevki Sahin

2017-07-01

Full Text Available Background and Aim: Depressive pseudodementia (DPD is a condition which may develop secondary to depression. The aim of this study was to contribute to the differential diagnosis between Alzheimer disease (AD and DPD by comparing the neurocognitive tests and hippocampal volume. Materials and Methods: Patients who met criteria of AD/DPD were enrolled in the study. All patients were assessed using the Wechsler Memory Scale (WMS, clock-drawing test, Stroop test, Benton Facial Recognition Test (BFRT, Boston Naming Test, Mini-Mental State Examination (MMSE, and Geriatric Depression Scale (GDS. Hippocampal volume was measured by importing the coronal T1-weighted magnetic resonance images to the Vitrea 2 workstation. Results: A significant difference was found between the AD and DPD groups on the WMS test, clock-drawing test, Stroop test, Boston Naming Test, MMSE, GDS, and left hippocampal volume. A significant correlation between BFRT and bilateral hippocampal volumes was found in the AD group. No correlation was found among parameters in DPD patients. Conclusions: Our results suggest that evaluation of facial recognition and left hippocampal volume may provide more reliable evidence for distinguishing DPD from AD. Further investigations combined with functional imaging techniques including more patients are needed.

Noncredible cognitive performance at clinical evaluation of adult ADHD: An embedded validity indicator in a visuospatial working memory test.

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Fuermaier, Anselm B M; Tucha, Oliver; Koerts, Janneke; Lange, Klaus W; Weisbrod, Matthias; Aschenbrenner, Steffen; Tucha, Lara

2017-12-01

The assessment of performance validity is an essential part of the neuropsychological evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). Most available tools, however, are inaccurate regarding the identification of noncredible performance. This study describes the development of a visuospatial working memory test, including a validity indicator for noncredible cognitive performance of adults with ADHD. Visuospatial working memory of adults with ADHD (n = 48) was first compared to the test performance of healthy individuals (n = 48). Furthermore, a simulation design was performed including 252 individuals who were randomly assigned to either a control group (n = 48) or to 1 of 3 simulation groups who were requested to feign ADHD (n = 204). Additional samples of 27 adults with ADHD and 69 instructed simulators were included to cross-validate findings from the first samples. Adults with ADHD showed impaired visuospatial working memory performance of medium size as compared to healthy individuals. Simulation groups committed significantly more errors and had shorter response times as compared to patients with ADHD. Moreover, binary logistic regression analysis was carried out to derive a validity index that optimally differentiates between true and feigned ADHD. ROC analysis demonstrated high classification rates of the validity index, as shown in excellent specificity (95.8%) and adequate sensitivity (60.3%). The visuospatial working memory test as presented in this study therefore appears sensitive in indicating cognitive impairment of adults with ADHD. Furthermore, the embedded validity index revealed promising results concerning the detection of noncredible cognitive performance of adults with ADHD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Functional asymmetries in early learning during right, left, and bimanual performance in right-handed subjects.

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Aznárez-Sanado, Maite; Fernández-Seara, Maria A; Loayza, Francis R; Pastor, Maria A

2013-03-01

To elucidate differences in activity and connectivity during early learning due to the performing hand. Twenty right-handed subjects were recruited. The neural correlates of explicit visuospatial learning executed with the right, the left hand, and bimanually were investigated using functional magnetic resonance imaging. Connectivity analyses were carried out using the psychophysiological interactions model, considering right and left anterior putamen as index regions. A common neural network was found for the three tasks during learning. Main activity increases were located in posterior cingulate cortex, supplementary motor area, parietal cortex, anterior putamen, and cerebellum (IV-V), whereas activity decrements were observed in prefrontal regions. However, the left hand task showed a greater recruitment of left hippocampal areas when compared with the other tasks. In addition, enhanced connectivity between the right anterior putamen and motor cortical and cerebellar regions was found for the left hand when compared with the right hand task. An additional recruitment of brain regions and increased striato-cortical and striato-cerebellar functional connections is needed when early learning is performed with the nondominant hand. In addition, access to brain resources during learning may be directed by the dominant hand in the bimanual task. Copyright © 2012 Wiley Periodicals, Inc.

A metacognitive visuospatial working memory training for children

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Sara Caviola

2009-10-01

Full Text Available The paper studies whether visuospatial working memory (VSWM and, specifically, recall of sequential-spatial information, can be improved by metacognitive training. Twenty-two fourth-grade children were involved in seven sessions of sequential-spatial memory training, while twenty-four children attended lessons given by their teacher. The posttraining evaluation demonstrated a specific improvement of performances in the Corsi blocks task, considered a sequential-spatial working memory task. However, no benefits of training were observed in either a verbal working memory task or a simultaneous-spatial working memory task. The results have important theoretical implications, in the study of VSWM components, and educational implications, in catering for children with specific VSWM impairments.

Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development.

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Schachtschneider, Kyle M; Liu, Yingkai; Rund, Laurie A; Madsen, Ole; Johnson, Rodney W; Groenen, Martien A M; Schook, Lawrence B

2016-11-03

Iron deficiency is a common childhood micronutrient deficiency that results in altered hippocampal function and cognitive disorders. However, little is known about the mechanisms through which neonatal iron deficiency results in long lasting alterations in hippocampal gene expression and function. DNA methylation is an epigenetic mark involved in gene regulation and altered by environmental factors. In this study, hippocampal DNA methylation and gene expression were assessed via reduced representation bisulfite sequencing and RNA-seq on samples from a previous study reporting reduced hippocampal-based learning and memory in a porcine biomedical model of neonatal iron deficiency. In total 192 differentially expressed genes (DEGs) were identified between the iron deficient and control groups. GO term and pathway enrichment analysis identified DEGs associated with hypoxia, angiogenesis, increased blood brain barrier (BBB) permeability, and altered neurodevelopment and function. Of particular interest are genes previously implicated in cognitive deficits and behavioral disorders in humans and mice, including HTR2A, HTR2C, PAK3, PRSS12, and NETO1. Altered genome-wide DNA methylation was observed across 0.5 million CpG and 2.4 million non-CpG sites. In total 853 differentially methylated (DM) CpG and 99 DM non-CpG sites were identified between groups. Samples clustered by group when comparing DM non-CpG sites, suggesting high conservation of non-CpG methylation in response to neonatal environment. In total 12 DM sites were associated with 9 DEGs, including genes involved in angiogenesis, neurodevelopment, and neuronal function. Neonatal iron deficiency leads to altered hippocampal DNA methylation and gene regulation involved in hypoxia, angiogenesis, increased BBB permeability, and altered neurodevelopment and function. Together, these results provide new insights into the mechanisms through which neonatal iron deficiency results in long lasting reductions in cognitive

Suggested use of sensitive measures of memory to detect functional effects of maternal iodine supplementation on hippocampal development.

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Bauer, Patricia J; Dugan, Jessica A

2016-09-01

Maternal hypothyroxinemia secondary to iodine deficiency may have neurodevelopmental effects on the specific neurocognitive domain of memory. Associated disruption of thyroid hormone-dependent protein synthesis in the hippocampus has the potential to result in compromised development of the structure with consequential impairments in memory function. Despite links between maternal iodine deficiency during gestation and lactation and abnormal hippocampal development in rat fetuses and pups, there has been little research on the specific function of memory in human infants and young children born to iodine-deficient mothers. Several candidate measures have proven to be sensitive to the effects of gestational iron deficiency on memory function in infants and young children, including habituation and dishabituation, imitation-based tasks, and event-related potentials. Such measures could be used to test the effects of maternal iodine supplementation on the specific neurocognitive domain of memory in infants and young children. Furthermore, progress in understanding the effects of maternal iodine supplementation on neurocognitive development could be accelerated by the development of a nonhuman primate model to complement the rodent model. © 2016 American Society for Nutrition.

Visuospatial performance on an internet line judgment task and potential hormonal markers: sex, sexual orientation, and 2D:4D.

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Collaer, Marcia L; Reimers, Stian; Manning, John T

2007-04-01

We investigated whether performance on a visuospatial line judgment task, the Judgment of Line Angle and Position-15 test (JLAP-15), showed evidence of sensitivity to early sex steroid exposure by examining how it related to sex, as well as to sexual orientation and 2D:4D digit ratios. Participants were drawn from a large Internet study with over 250,000 participants. In the main sample (ages 12-58 years), males outperformed females on the JLAP-15, showing a moderate effect size for sex. In agreement with a prenatal sex hormone hypothesis, line judgment accuracy in adults related to 2D:4D and sexual orientation, both of which are postulated to be influenced by early steroids. In both sexes, better visuospatial performance was associated with lower (more male-typical) digit ratios. For men, heterosexual participants outperformed homosexual/bisexual participants on the JLAP-15 and, for women, homosexual/bisexual participants outperformed heterosexual participants. In children aged 8-10 years, presumed to be a largely prepubertal group, boys also outperformed girls. These findings are consistent with the hypothesis that visuospatial ability is influenced by early sex steroids, although they do not rule out alternative explanations or additional influences. More broadly, such results support a prenatal sex hormone hypothesis that degree of androgen exposure may influence the neural circuitry underlying cognition (visuospatial ability) and sexual orientation as well as aspects of somatic (digit ratio) development.

Optimizing hippocampal segmentation in infants utilizing MRI post-acquisition processing.

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Thompson, Deanne K; Ahmadzai, Zohra M; Wood, Stephen J; Inder, Terrie E; Warfield, Simon K; Doyle, Lex W; Egan, Gary F

2012-04-01

This study aims to determine the most reliable method for infant hippocampal segmentation by comparing magnetic resonance (MR) imaging post-acquisition processing techniques: contrast to noise ratio (CNR) enhancement, or reformatting to standard orientation. MR scans were performed with a 1.5 T GE scanner to obtain dual echo T2 and proton density (PD) images at term equivalent (38-42 weeks' gestational age). 15 hippocampi were manually traced four times on ten infant images by 2 independent raters on the original T2 image, as well as images processed by: a) combining T2 and PD images (T2-PD) to enhance CNR; then b) reformatting T2-PD images perpendicular to the long axis of the left hippocampus. CNRs and intraclass correlation coefficients (ICC) were calculated. T2-PD images had 17% higher CNR (15.2) than T2 images (12.6). Original T2 volumes' ICC was 0.87 for rater 1 and 0.84 for rater 2, whereas T2-PD images' ICC was 0.95 for rater 1 and 0.87 for rater 2. Reliability of hippocampal segmentation on T2-PD images was not improved by reformatting images (rater 1 ICC = 0.88, rater 2 ICC = 0.66). Post-acquisition processing can improve CNR and hence reliability of hippocampal segmentation in neonate MR scans when tissue contrast is poor. These findings may be applied to enhance boundary definition in infant segmentation for various brain structures or in any volumetric study where image contrast is sub-optimal, enabling hippocampal structure-function relationships to be explored.

Exogenous and endogenous spatial attention effects on visuospatial working memory.

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Botta, Fabiano; Santangelo, Valerio; Raffone, Antonino; Lupiáñez, Juan; Belardinelli, Marta Olivetti

2010-08-01

In this study, we investigate how exogenous and endogenous orienting of spatial attention affect visuospatial working memory (VSWM). Specifically, we focused on two attentional effects and their consequences on storage in VSWM, when exogenous (Experiment 1) or endogenous (Experiment 2) orienting cues were used. The first effect, known as the meridian effect, is given by a decrement in behavioural performance when spatial cues and targets are presented in locations separated by vertical and/or horizontal meridians. The second effect, known as the distance effect, is given by a decrement in the orienting effects as a function of the spatial distance between cues and targets. Our results revealed a dissociation between exogenous and endogenous orienting mechanisms in terms of both meridian and distance effects. We found that meridian crossing affects performance only when endogenous cues were used. Specifically, VSWM performance with endogenous cueing depended more on the number of meridian crossings than on distance between cue and target. By contrast, a U-shaped distance dependency was observed using exogenous cues. Our findings therefore suggest that exogenous and endogenous orienting mechanisms lead to different forms of attentional bias for storage in VSWM.

Schizophrenia: Evidence Implicating Hippocampal GluN2B protein and REST Epigenetics in Psychosis Pathophysiology

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Tamminga, Carol A.; Zukin, R. Suzanne

2017-01-01

The hippocampus is strongly implicated in the psychotic symptoms of schizophrenia. Functionally, basal hippocampal activity (perfusion) is elevated in schizophrenic psychosis, as measured with positron emission tomography (PET) and with magnetic resonance (MR) perfusion techniques, while hippocampal activation to memory tasks is reduced. Subfield-specific hippocampal molecular pathology exists in human psychosis tissue which could underlie this neuronal hyperactivity, including increased GluN2B-containing NMDA receptors in hippocampal CA3, along with increased postsynaptic density protein-95 (PSD-95) along with augmented dendritic spines on the pyramidal neuron apical dendrites. We interpret these observations to implicate a reduction in the influence of a ubiquitous gene repressor, repressor element-1 silencing transcription factor (REST) in psychosis; REST is involved in the age-related maturation of the NMDA receptor from GluN2B- to GluN2A-containing NMDA receptors through epigenetic remodeling. These CA3 changes in psychosis leave the hippocampus liable to pathological increases in neuronal activity, feedforward excitation and false memory formation, sometimes with psychotic content. PMID:26211447

Effect of Musical Expertise on Visuospatial Abilities: Evidence from Reaction Times and Mental Imagery

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Brochard, Renaud; Dufour, Andre; Despres, Olivier

2004-01-01

Recently, the relationship between music and nonmusical cognitive abilities has been highly debated. It has been documented that formal music training would improve verbal, mathematical or visuospatial performance in children. In the experiments described here, we tested if visual perception and imagery abilities were enhanced in adult musicians…

Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder

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Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J.; Bremner, J. Douglas

2011-01-01

Objective Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects. PMID:16585437