[Coactivators in energy metabolism: peroxisome proliferator-activated receptor-gamma coactivator 1 family].

PubMed

Wang, Rui; Chang, Yong-sheng; Fang, Fu-de

2009-12-01

Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.

Co-activation patterns in resting-state fMRI signals.

PubMed

Liu, Xiao; Zhang, Nanyin; Chang, Catie; Duyn, Jeff H

2018-02-08

The brain is a complex system that integrates and processes information across multiple time scales by dynamically coordinating activities over brain regions and circuits. Correlations in resting-state functional magnetic resonance imaging (rsfMRI) signals have been widely used to infer functional connectivity of the brain, providing a metric of functional associations that reflects a temporal average over an entire scan (typically several minutes or longer). Not until recently was the study of dynamic brain interactions at much shorter time scales (seconds to minutes) considered for inference of functional connectivity. One method proposed for this objective seeks to identify and extract recurring co-activation patterns (CAPs) that represent instantaneous brain configurations at single time points. Here, we review the development and recent advancement of CAP methodology and other closely related approaches, as well as their applications and associated findings. We also discuss the potential neural origins and behavioral relevance of CAPs, along with methodological issues and future research directions in the analysis of fMRI co-activation patterns. Copyright © 2018 Elsevier Inc. All rights reserved.

A neuronal model of a global workspace in effortful cognitive tasks.

PubMed

Dehaene, S; Kerszberg, M; Changeux, J P

1998-11-24

A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.

CREB binding protein is required for both short-term and long-term memory formation.

PubMed

Chen, Guiquan; Zou, Xiaoyan; Watanabe, Hirotaka; van Deursen, Jan M; Shen, Jie

2010-09-29

CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated conditional knock-out (cKO) mice in which CBP is completely inactivated in excitatory neurons of the postnatal forebrain. Histological analysis revealed normal neuronal morphology and absence of age-dependent neuronal degeneration in the CBP cKO cerebral cortex. CBP cKO mice exhibited robust impairment in the formation of spatial, associative, and object-recognition memory. In addition to impaired long-term memory, CBP cKO mice also displayed deficits in short-term associative and object-recognition memory. Administration of a histone deacetylase inhibitor, trichostatin A, rescued the reduction of acetylated histones in the CBP cKO cortex but failed to rescue either short- or long-term memory deficits, suggesting that the memory impairment may not be caused by general reduction of histone acetyltransferase activity in CBP cKO mice. Further microarray and Western analysis showed decreased expression of calcium-calmodulin-dependent kinase isoforms and NMDA and AMPA receptor subunits in the cerebral cortex of CBP cKO mice. Collectively, these findings suggest a crucial role for CBP in the formation of both short- and long-term memory.

Location-Unbound Color-Shape Binding Representations in Visual Working Memory.

PubMed

Saiki, Jun

2016-02-01

The mechanism by which nonspatial features, such as color and shape, are bound in visual working memory, and the role of those features' location in their binding, remains unknown. In the current study, I modified a redundancy-gain paradigm to investigate these issues. A set of features was presented in a two-object memory display, followed by a single object probe. Participants judged whether the probe contained any features of the memory display, regardless of its location. Response time distributions revealed feature coactivation only when both features of a single object in the memory display appeared together in the probe, regardless of the response time benefit from the probe and memory objects sharing the same location. This finding suggests that a shared location is necessary in the formation of bound representations but unnecessary in their maintenance. Electroencephalography data showed that amplitude modulations reflecting location-unbound feature coactivation were different from those reflecting the location-sharing benefit, consistent with the behavioral finding that feature-location binding is unnecessary in the maintenance of color-shape binding. © The Author(s) 2015.

ICA model order selection of task co-activation networks.

PubMed

Ray, Kimberly L; McKay, D Reese; Fox, Peter M; Riedel, Michael C; Uecker, Angela M; Beckmann, Christian F; Smith, Stephen M; Fox, Peter T; Laird, Angela R

2013-01-01

Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders.

ICA model order selection of task co-activation networks

PubMed Central

Ray, Kimberly L.; McKay, D. Reese; Fox, Peter M.; Riedel, Michael C.; Uecker, Angela M.; Beckmann, Christian F.; Smith, Stephen M.; Fox, Peter T.; Laird, Angela R.

2013-01-01

Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders. PMID:24339802

The Exercising Brain: Changes in Functional Connectivity Induced by an Integrated Multimodal Cognitive and Whole-Body Coordination Training

PubMed Central

Demirakca, Traute; Cardinale, Vita; Dehn, Sven; Ruf, Matthias; Ende, Gabriele

2016-01-01

This study investigated the impact of “life kinetik” training on brain plasticity in terms of an increased functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI). The training is an integrated multimodal training that combines motor and cognitive aspects and challenges the brain by introducing new and unfamiliar coordinative tasks. Twenty-one subjects completed at least 11 one-hour-per-week “life kinetik” training sessions in 13 weeks as well as before and after rs-fMRI scans. Additionally, 11 control subjects with 2 rs-fMRI scans were included. The CONN toolbox was used to conduct several seed-to-voxel analyses. We searched for functional connectivity increases between brain regions expected to be involved in the exercises. Connections to brain regions representing parts of the default mode network, such as medial frontal cortex and posterior cingulate cortex, did not change. Significant connectivity alterations occurred between the visual cortex and parts of the superior parietal area (BA7). Premotor area and cingulate gyrus were also affected. We can conclude that the constant challenge of unfamiliar combinations of coordination tasks, combined with visual perception and working memory demands, seems to induce brain plasticity expressed in enhanced connectivity strength of brain regions due to coactivation. PMID:26819776

Structural covariance mapping delineates medial and medio-lateral temporal networks in déjà vu.

PubMed

Shaw, Daniel Joel; Mareček, Radek; Brázdil, Milan

2016-12-01

Déjà vu (DV) is an eerie phenomenon experienced frequently as an aura of temporal lobe epilepsy, but also reported commonly by healthy individuals. The former pathological manifestation appears to result from aberrant neural activity among brain structures within the medial temporal lobes. Recent studies also implicate medial temporal brain structures in the non-pathological experience of DV, but as one element of a diffuse neuroanatomical correlate; it remains to be seen if neural activity among the medial temporal lobes also underlies this benign manifestation. The present study set out to investigate this. Due to its unpredictable and infrequent occurrence, however, non-pathological DV does not lend itself easily to functional neuroimaging. Instead, we draw on research showing that brain structure covaries among regions that interact frequently as nodes of functional networks. Specifically, we assessed whether grey-matter covariance among structures implicated in non-pathological DV differs according to the frequency with which the phenomenon is experienced. This revealed two diverging patterns of structural covariation: Among the first, comprised primarily of medial temporal structures and the caudate, grey-matter volume becomes more positively correlated with higher frequency of DV experience. The second pattern encompasses medial and lateral temporal structures, among which greater DV frequency is associated with more negatively correlated grey matter. Using a meta-analytic method of co-activation mapping, we demonstrate a higher probability of functional interactions among brain structures constituting the former pattern, particularly during memory-related processes. Our findings suggest that altered neural signalling within memory-related medial temporal brain structures underlies both pathological and non-pathological DV.

Prefrontal Consolidation Supports the Attainment of Fear Memory Accuracy

ERIC Educational Resources Information Center

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.; Korzus, Edward

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required…

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

Financial literacy is associated with medial brain region functional connectivity in old age.

PubMed

Han, S Duke; Boyle, Patricia A; Yu, Lei; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A

2014-01-01

Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Financial Literacy is Associated with Medial Brain Region Functional Connectivity in Old Age

PubMed Central

Han, S. Duke; Boyle, Patricia A.; Yu, Lei; Fleischman, Debra A.; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A.

2014-01-01

Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post-hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. PMID:24893911

Functional neuroimaging studies of prospective memory: what have we learnt so far?

PubMed

Burgess, Paul W; Gonen-Yaacovi, Gil; Volle, Emmanuelle

2011-07-01

The complexity of the behaviour described by the term "prospective memory" meant that it was not at all clear, when the earliest studies were conducted, that this would prove a fruitful area for neuroimaging study. However, a consistent relation rapidly emerged between activation in rostral prefrontal cortex (approximating Brodmann Area 10) and performance of prospective memory paradigms. This consistency has greatly increased the accumulation of findings, since each study has offered perspectives on the previous ones. Considerable help too has come from broad agreement between functional neuroimaging findings and those from other methods (e.g. human lesion studies, electrophysiology). The result has been a quite startling degree of advance given the relatively few studies that have been conducted. These findings are summarised, along with those from other brain regions, and new directions suggested. Key points are that there is a medial-lateral dissociation within rostral PFC. Some (but not all) regions of medial rostral PFC are typically more active during performance of the ongoing task only, and lateral aspects are relatively more active during conditions involving delayed intentions. Some of these rostral PFC activations seem remarkably insensitive to the form of stimulus material presented, the nature of the ongoing task, the specifics of the intention, how easy or hard the PM cue is to detect, or the intended action is to recall. However there are other regions within rostral PFC where haemodynamic changes vary with alterations in these, and other, aspects of prospective memory paradigms. It is concluded that rostral PFC most likely plays a super-ordinate role during many stages of creating, maintaining and enacting delayed intentions, which in some cases may be linked to recent evidence showing that this brain region is involved in the control of stimulus-oriented vs. stimulus-independent attending. Other key brain regions activated during prospective memory paradigms appear to be the parietal lobe, especially Brodmann Area (BA) 40 and precuneus (BA 7), and the anterior cingulate (BA 32). These regions are often co-activated with lateral rostral PFC across a wide range of tasks, not just those involving prospective memory. Copyright © 2011. Published by Elsevier Ltd.

Sigma 1 receptor activation regulates brain-derived neurotrophic factor through NR2A-CaMKIV-TORC1 pathway to rescue the impairment of learning and memory induced by brain ischaemia/reperfusion.

PubMed

Xu, Qian; Ji, Xue-Fei; Chi, Tian-Yan; Liu, Peng; Jin, Ge; Gu, Shao-Li; Zou, Li-Bo

2015-05-01

Sigma-1 receptor (Sig-1R) agonists showed anti-amnesic properties in Alzheimer's disease models and anti-inflammatory properties in cerebrum ischaemia models. The agonist of Sig-1R was reported to up-regulate brain-derived neurotrophic factor (BDNF) levels in the hippocampus of mice. Here, we investigate whether the activation of Sig-1R attenuates the learning and memory impairment induced by ischaemia/reperfusion and how it affects the expression of BDNF. Bilateral common carotid artery occlusion (BCCAO) was induced for 20 min in C57BL/6 mice. Sig-1R agonist, PRE084, sigma 1/2 non-selective agonist, DTG, Sig-1R antagonist and BD1047 were injected once daily throughout the experiment. Behavioural tests were performed from day 8. On day 22 after BCCAO, mice were sacrificed for biochemical analysis. PRE084 and DTG ameliorated learning and memory impairments in the Y maze, novel object recognition, and water maze tasks and prevented the decline of synaptic proteins and BDNF expression in the hippocampus of BCCAO mice. Furthermore, PRE084 and DTG up-regulated the level of NMDA receptor 2A (NR2A), calcium/calmodulin-dependent protein kinase type IV (CaMKIV) and CREB-specific co-activator transducer of regulated CREB activity 1 (TORC1). Additionally, the effects of PRE084 and DTG were antagonised by the co-administration of BD1047. Sig-1R activation showed an attenuation in the ischaemia/reperfusion model and the activation of Sig-1R increased the expression of BDNF, possibly through the NR2A-CaMKIV-TORC1 pathway, and Sig-1R agonists might function as neuroprotectant agents in vascular dementia.

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions

PubMed Central

Cohen, Michael S.; Rissman, Jesse; Suthana, Nanthia A.; Castel, Alan D.; Knowlton, Barbara J.

2014-01-01

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system co-activates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to examine how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants’ selectivity index, a measure of how close participants were to their optimal point total given the number of items recalled. Greater selectivity scores were associated with greater differences in activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items. PMID:24683066

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions.

PubMed

Cohen, Michael S; Rissman, Jesse; Suthana, Nanthia A; Castel, Alan D; Knowlton, Barbara J

2014-06-01

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system coactivates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to assess how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants' selectivity index, which measures how close participants were to their optimal point total, given the number of items recalled. Greater selectivity scores were associated with greater differences in the activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during the encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items.

Modulation of Frontoparietal Neurovascular Dynamics in Working Memory

PubMed Central

Ardestani, Allen; Shen, Wei; Darvas, Felix; Toga, Arthur W.; Fuster, Joaquin M.

2016-01-01

Our perception of the world is represented in widespread, overlapping, and interactive neuronal networks of the cerebral cortex. A majority of physiological studies on the subject have focused on oscillatory synchrony as the binding mechanism for representation and transmission of neural information. Little is known, however, about the stability of that synchrony during prolonged cognitive operations that span more than just a few seconds. The present research, in primates, investigated the dynamic patterns of oscillatory synchrony by two complementary recording methods, surface field potentials (SFPs) and near-infrared spectroscopy (NIRS). The signals were first recorded during the resting state to examine intrinsic functional connectivity. The temporal modulation of coactivation was then examined on both signals during performance of working memory ( WM) tasks with long delays (memory retention epochs). In both signals, the peristimulus period exhibited characteristic features in frontal and parietal regions. Examination of SFP signals over delays lasting tens of seconds, however, revealed alternations of synchronization and desynchronization. These alternations occurred within the same frequency bands observed in the peristimulus epoch, without a specific correspondence between any definite cognitive process (e.g., WM) and synchrony within a given frequency band. What emerged instead was a correlation between the degree of SFP signal fragmentation (in time, frequency, and brain space) and the complexity and efficiency of the task being performed. In other words, the incidence and extent of SFP transitions between synchronization and desynchronization—rather than the absolute degree of synchrony—augmented in correct task performance compared with incorrect performance or in a control task without WM demand. An opposite relationship was found in NIRS: increasing task complexity induced more uniform, rather than fragmented, NIRS coactivations. These findings indicate that the particular features of neural oscillations cannot be linearly mapped to cognitive functions. Rather, information and the cognitive operations performed on it are primarily reflected in their modulations over time. The increased complexity and fragmentation of electrical frequencies in WM may reflect the activation of hierarchically diverse cognits (cognitive networks) in that condition. Conversely, the homogeneity in coherence of NIRS responses may reflect the cumulative vascular reactions that accompany that neuroelectrical proliferation of frequencies and the longer time constant of the NIRS signal. These findings are directly relevant to the mechanisms mediating cognitive processes and to physiologically based interpretations of functional brain imaging. PMID:26679214

A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction

PubMed Central

Fusco, Salvatore; Ripoli, Cristian; Podda, Maria Vittoria; Ranieri, Sofia Chiatamone; Leone, Lucia; Toietta, Gabriele; McBurney, Michael W.; Schütz, Günther; Riccio, Antonella; Grassi, Claudio; Galeotti, Tommaso; Pani, Giovambattista

2012-01-01

Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD+-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1α and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes. PMID:22190495

Correspondent Functional Topography of the Human Left Inferior Parietal Lobule at Rest and Under Task Revealed Using Resting-State fMRI and Coactivation Based Parcellation.

PubMed

Wang, Jiaojian; Xie, Sangma; Guo, Xin; Becker, Benjamin; Fox, Peter T; Eickhoff, Simon B; Jiang, Tianzi

2017-03-01

The human left inferior parietal lobule (LIPL) plays a pivotal role in many cognitive functions and is an important node in the default mode network (DMN). Although many previous studies have proposed different parcellation schemes for the LIPL, the detailed functional organization of the LIPL and the exact correspondence between the DMN and LIPL subregions remain unclear. Mounting evidence indicates that spontaneous fluctuations in the brain are strongly associated with cognitive performance at the behavioral level. However, whether a consistent functional topographic organization of the LIPL during rest and under task can be revealed remains unknown. Here, they used resting-state functional connectivity (RSFC) and task-related coactivation patterns separately to parcellate the LIPL and identified seven subregions. Four subregions were located in the supramarginal gyrus (SMG) and three subregions were located in the angular gyrus (AG). The subregion-specific networks and functional characterization revealed that the four anterior subregions were found to be primarily involved in sensorimotor processing, movement imagination and inhibitory control, audition perception and speech processing, and social cognition, whereas the three posterior subregions were mainly involved in episodic memory, semantic processing, and spatial cognition. The results revealed a detailed functional organization of the LIPL and suggested that the LIPL is a functionally heterogeneous area. In addition, the present study demonstrated that the functional architecture of the LIPL during rest corresponds with that found in task processing. Hum Brain Mapp 38:1659-1675, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Convergent functional architecture of the superior parietal lobule unraveled with multimodal neuroimaging approaches.

PubMed

Wang, Jiaojian; Yang, Yong; Fan, Lingzhong; Xu, Jinping; Li, Changhai; Liu, Yong; Fox, Peter T; Eickhoff, Simon B; Yu, Chunshui; Jiang, Tianzi

2015-01-01

The superior parietal lobule (SPL) plays a pivotal role in many cognitive, perceptive, and motor-related processes. This implies that a mosaic of distinct functional and structural subregions may exist in this area. Recent studies have demonstrated that the ongoing spontaneous fluctuations in the brain at rest are highly structured and, like coactivation patterns, reflect the integration of cortical locations into long-distance networks. This suggests that the internal differentiation of a complex brain region may be revealed by interaction patterns that are reflected in different neuroimaging modalities. On the basis of this perspective, we aimed to identify a convergent functional organization of the SPL using multimodal neuroimaging approaches. The SPL was first parcellated based on its structural connections as well as on its resting-state connectivity and coactivation patterns. Then, post hoc functional characterizations and connectivity analyses were performed for each subregion. The three types of connectivity-based parcellations consistently identified five subregions in the SPL of each hemisphere. The two anterior subregions were found to be primarily involved in action processes and in visually guided visuomotor functions, whereas the three posterior subregions were primarily associated with visual perception, spatial cognition, reasoning, working memory, and attention. This parcellation scheme for the SPL was further supported by revealing distinct connectivity patterns for each subregion in all the used modalities. These results thus indicate a convergent functional architecture of the SPL that can be revealed based on different types of connectivity and is reflected by different functions and interactions. © 2014 Wiley Periodicals, Inc.

Fasting launches CRTC to facilitate long-term memory formation in Drosophila.

PubMed

Hirano, Yukinori; Masuda, Tomoko; Naganos, Shintaro; Matsuno, Motomi; Ueno, Kohei; Miyashita, Tomoyuki; Horiuchi, Junjiro; Saitoe, Minoru

2013-01-25

Canonical aversive long-term memory (LTM) formation in Drosophila requires multiple spaced trainings, whereas appetitive LTM can be formed after a single training. Appetitive LTM requires fasting prior to training, which increases motivation for food intake. However, we found that fasting facilitated LTM formation in general; aversive LTM formation also occurred after single-cycle training when mild fasting was applied before training. Both fasting-dependent LTM (fLTM) and spaced training-dependent LTM (spLTM) required protein synthesis and cyclic adenosine monophosphate response element-binding protein (CREB) activity. However, spLTM required CREB activity in two neural populations--mushroom body and DAL neurons--whereas fLTM required CREB activity only in mushroom body neurons. fLTM uses the CREB coactivator CRTC, whereas spLTM uses the coactivator CBP. Thus, flies use distinct LTM machinery depending on their hunger state.

The Cerebellum and Premenstrual Dysphoric Disorder

PubMed Central

Rapkin, Andrea J.; Berman, Steven M.; London, Edythe D.

2017-01-01

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed. PMID:28275721

The Cerebellum and Premenstrual Dysphoric Disorder.

PubMed

Rapkin, Andrea J; Berman, Steven M; London, Edythe D

2014-01-01

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

[Neurological and psychiatric aspects of some endocrine diseases. The role of neurosteroids and neuroactive steroids].

PubMed

Aszalós, Zsuzsa

2007-10-14

Regardless of their origin, neuroactive steroids are capable of modifying neural activities by modulating different types of membrane receptors. Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic enzymes are found in the central nervous system. Classical steroid receptors are localized in the cytoplasm, they exert regulatory actions on the genome, and their activation causes medium- and long-term effects. Non-classical receptors are located within the membrane and act as mediators of short-term effects. Other important players are co-repressors and co-activators that can interfere with or enhance the activity of steroid receptors. Beyond their function in stress, corticosteroids play a very important role in fear, anxiety, and memory functions. Patients with Cushing's syndrome frequently develop mood disorder, reversible brain atrophy with transient memory loss, rarely delirium or psychosis. Well-known peripheral symptom is steroidal myopathy. In patients with Addison's disease the main signs are weakness of muscles, lack of energy, decreased mental functions and reduced quality of life. Estrogen and progesterone have their own respective hormone receptors, whereas allopregnanolone acts via the GABA receptors. These hormones have significant role in the development of brain, the architecture of neural circuits and dendrites, density of axonal connections, and the number of neurons. They influence maturation, neuroprotection, seizures, cognitive functions, mood, anxiety, pain, and restitution of peripheral nerves. Androgens also affect cognitive functions, pain, anxiety, mood, and additionally aggression.

Heterogeneous fractionation profiles of meta-analytic coactivation networks.

PubMed

Laird, Angela R; Riedel, Michael C; Okoe, Mershack; Jianu, Radu; Ray, Kimberly L; Eickhoff, Simon B; Smith, Stephen M; Fox, Peter T; Sutherland, Matthew T

2017-04-01

Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d=20-300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how "parent" functional brain systems decompose into constituent "child" sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication. Copyright © 2017 Elsevier Inc. All rights reserved.

Heterogeneous fractionation profiles of meta-analytic coactivation networks

PubMed Central

Laird, Angela R.; Riedel, Michael C.; Okoe, Mershack; Jianu, Radu; Ray, Kimberly L.; Eickhoff, Simon B.; Smith, Stephen M.; Fox, Peter T.; Sutherland, Matthew T.

2017-01-01

Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d = 20 to 300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how “parent” functional brain systems decompose into constituent “child” sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication. PMID:28222386

Functional organization of human subgenual cortical areas: Relationship between architectonical segregation and connectional heterogeneity.

PubMed

Palomero-Gallagher, Nicola; Eickhoff, Simon B; Hoffstaedter, Felix; Schleicher, Axel; Mohlberg, Hartmut; Vogt, Brent A; Amunts, Katrin; Zilles, Karl

2015-07-15

Human subgenual anterior cingulate cortex (sACC) is involved in affective experiences and fear processing. Functional neuroimaging studies view it as a homogeneous cortical entity. However, sACC comprises several distinct cyto- and receptorarchitectonical areas: 25, s24, s32, and the ventral portion of area 33. Thus, we hypothesized that the areas may also be connectionally and functionally distinct. We performed structural post mortem and functional in vivo analyses. We computed probabilistic maps of each area based on cytoarchitectonical analysis of ten post mortem brains. Maps, publicly available via the JuBrain atlas and the Anatomy Toolbox, were used to define seed regions of task-dependent functional connectivity profiles and quantitative functional decoding. sACC areas presented distinct co-activation patterns within widespread networks encompassing cortical and subcortical regions. They shared common functional domains related to emotion, perception and cognition. A more specific analysis of these domains revealed an association of s24 with sadness, and of s32 with fear processing. Both areas were activated during taste evaluation, and co-activated with the amygdala, a key node of the affective network. s32 co-activated with areas of the executive control network, and was associated with tasks probing cognition in which stimuli did not have an emotional component. Area 33 was activated by painful stimuli, and co-activated with areas of the sensorimotor network. These results support the concept of a connectional and functional specificity of the cyto- and receptorarchitectonically defined areas within the sACC, which can no longer be seen as a structurally and functionally homogeneous brain region. Copyright © 2015 Elsevier Inc. All rights reserved.

Nuclear receptor coactivators function in estrogen receptor- and progestin receptor-dependent aspects of sexual behavior in female rats

PubMed Central

Molenda-Figueira, Heather A.; Williams, Casey A.; Griffin, Andreana L.; Rutledge, Eric M.; Blaustein, Jeffrey D.; Tetel, Marc J.

2008-01-01

The ovarian hormones, estradiol (E) and progesterone (P) facilitate the expression of sexual behavior in female rats. E and P mediate many of these behavioral effects by binding to their respective intracellular receptors in specific brain regions. Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro. Previously, our lab has shown that SRC-1 and CBP modulate estrogen receptor (ER)-mediated induction of progestin receptor (PR) gene expression in the ventromedial nucleus of the hypothalamus (VMN) and hormone-dependent sexual receptivity in female rats. Female sexual behaviors can be activated by high doses of E alone in ovariectomized rats, and thus are believed to be ER-dependent. However, the full repertoire of female sexual behavior, in particular, proceptive behaviors such as hopping, darting and ear wiggling, are considered to be PR-dependent. In the present experiments, the function of SRC-1 and CBP in distinct ER- (Exp. 1) and PR- (Exp. 2) dependent aspects of female sexual behavior was investigated. In Exp. 1, infusion of antisense oligodeoxynucleotides to SRC-1 and CBP mRNA into the VMN decreased lordosis intensity in rats treated with E alone, suggesting that these coactivators modulate ER-mediated female sexual behavior. In Exp. 2, antisense to SRC-1 and CBP mRNA around the time of P administration reduced PR-dependent ear wiggling and hopping and darting. Taken together, these data suggest that SRC-1 and CBP modulate ER and PR action in brain and influence distinct aspects of hormone-dependent sexual behaviors. These findings support our previous studies and provide further evidence that SRC-1 and CBP function together to regulate ovarian hormone action in behaviorally-relevant brain regions. PMID:16769066

Coactivation of cognitive control networks during task switching.

PubMed

Yin, Shouhang; Deák, Gedeon; Chen, Antao

2018-01-01

The ability to flexibly switch between tasks is considered an important component of cognitive control that involves frontal and parietal cortical areas. The present study was designed to characterize network dynamics across multiple brain regions during task switching. Functional magnetic resonance images (fMRI) were captured during a standard rule-switching task to identify switching-related brain regions. Multiregional psychophysiological interaction (PPI) analysis was used to examine effective connectivity between these regions. During switching trials, behavioral performance declined and activation of a generic cognitive control network increased. Concurrently, task-related connectivity increased within and between cingulo-opercular and fronto-parietal cognitive control networks. Notably, the left inferior frontal junction (IFJ) was most consistently coactivated with the 2 cognitive control networks. Furthermore, switching-dependent effective connectivity was negatively correlated with behavioral switch costs. The strength of effective connectivity between left IFJ and other regions in the networks predicted individual differences in switch costs. Task switching was supported by coactivated connections within cognitive control networks, with left IFJ potentially acting as a key hub between the fronto-parietal and cingulo-opercular networks. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Same as it ever was: vividness modulates the similarities and differences between the neural networks that support retrieving remote and recent autobiographical memories.

PubMed

Sheldon, Signy; Levine, Brian

2013-12-01

The comparison of recent and remote autobiographical memories is often confounded by qualitative disparities across memories of different ages, such as vividness. In this study, ten individuals prospectively collected audio recordings that were used to cue memories of recent (~1 month old) and remote (~1.5 year old) everyday events. Because the retrieval cues were recorded at the time of event, they were highly potent. Although remote events did not differ in novelty, importance, or emotional change at the time at the time of encoding, half of the cues for these events induced retrieval comparable in vividness to recent events (all of which were vividly re-experienced). Recent and remote vivid memories were associated with a neural pattern that included right frontal, left parietal and limbic regions that were active early in the retrieval period. Non-vivid remote memories were associated with a later onset of a bilateral distributed pattern that included regions in the frontal, parietal, and temporal lobes. Functional connectivity analysis indicated that the left anterior hippocampus was co-activated with bilateral frontal, parahippocampal, and parietal regions for vivid memories (irrespective of memory age) early in the retrieval period, whereas non-vivid memories, alongside recent memories, showed later and broader co-activation with frontal, parietal, occipital, and temporal regions. The absence of a significant difference between the recent and remote vivid memories may be due to insufficient power to detect potential subtle differences between these conditions. Nonetheless, there was evidence for different patterns of hippocampal-neocortical connectivity for remote memories and recent memories, irrespective of vividness. These findings suggest that while there is a functional shift in hippocampal connectivity that is associated with memory age when very recent events are used, vividness is strongly associated with both activation and functional connectivity patterns irrespective of memory age. © 2013.

Reduction in Responding for Sucrose and Cocaine Reinforcement by Disruption of Memory Reconsolidation1,2,3

PubMed Central

2015-01-01

Abstract Stored memories are dynamic and, when reactivated, can undergo a process of destabilization and reconsolidation to update them with new information. Reconsolidation has been shown for a variety of experimental settings; most recently for well-learned instrumental memories, a class of memory previously thought not to undergo reconsolidation. Here we tested, in rats, whether a weakly-trained lever-pressing memory destabilized following a shift in reinforcement contingency. We show that lever-pressing memory for both sucrose and cocaine reinforcement destabilized under appropriate conditions, and that the reconsolidation of this memory was impaired by systemic administration of the NMDA receptor (NMDAR) antagonist [5R,10S]-[+]-5-methyl-10,1-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801). We went on to investigate the potential role of the nucleus accumbens (NAc) in the reconsolidation of sucrose-reinforced instrumental memories, showing that co-infusion of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and the dopamine-1 receptor (D1R) antagonist 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH23390) into the NAc prior to memory reactivation impaired reconsolidation; however, there was no effect when these drugs were infused alone. Further investigation of this effect suggests the combined infusion disrupted the reconsolidation of pavlovian components of memory, and we hypothesize that coactivation of accumbal D1Rs and NMDARs may contribute to both the destabilization and reconsolidation of appetitive memory. Our work demonstrates that weakly-trained instrumental memories undergo reconsolidation under similar parameters to well-trained ones, and also suggests that receptor coactivation in the NAc may contribute to memory destabilization. Furthermore, it provides an important demonstration of the therapeutic potential of reconsolidation-based treatments that target the instrumental components of memory in maladaptive drug seeking. PMID:26464973

CRTC1 Function During Memory Encoding Is Disrupted in Neurodegeneration.

PubMed

Parra-Damas, Arnaldo; Chen, Meng; Enriquez-Barreto, Lilian; Ortega, Laura; Acosta, Sara; Perna, Judith Camats; Fullana, M Neus; Aguilera, José; Rodríguez-Alvarez, José; Saura, Carlos A

2017-01-15

Associative memory impairment is an early clinical feature of dementia patients, but the molecular and cellular mechanisms underlying these deficits are largely unknown. In this study, we investigated the functional regulation of the cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) by associative learning in physiological and neurodegenerative conditions. We evaluated the activation of CRTC1 in the hippocampus of control mice and mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after one-trial contextual fear conditioning by using biochemical, immunohistochemical, and gene expression analyses. PS cDKO mice display classical features of neurodegeneration occurring in Alzheimer's disease including age-dependent cortical atrophy, neuron loss, dendritic degeneration, and memory deficits. Context-associative learning, but not single context or unconditioned stimuli, induces rapid dephosphorylation (Ser151) and translocation of CRTC1 from the cytosol/dendrites to the nucleus of hippocampal neurons in the mouse brain. Accordingly, context-associative learning induces differential CRTC1-dependent transcription of c-fos and the nuclear receptor subfamily 4 (Nr4a) genes Nr4a1-3 in the hippocampus through a mechanism that involves CRTC1 recruitment to CRE promoters. Deregulation of CRTC1 dephosphorylation, nuclear translocation, and transcriptional function are associated with long-term contextual memory deficits in PS cDKO mice. Importantly, CRTC1 gene therapy in the hippocampus ameliorates context memory and transcriptional deficits and dendritic degeneration despite ongoing cortical degeneration in this neurodegeneration mouse model. These findings reveal a critical role of CRTC1 in the hippocampus during associative memory, and provide evidence that CRTC1 deregulation underlies memory deficits during neurodegeneration. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The integrated role of ACh, ERK and mTOR in the mechanisms of hippocampal inhibitory avoidance memory.

PubMed

Giovannini, Maria Grazia; Lana, Daniele; Pepeu, Giancarlo

2015-03-01

The purpose of this review is to summarize the present knowledge on the interplay among the cholinergic system, Extracellular signal-Regulated Kinase (ERK) and Mammalian Target of Rapamycin (mTOR) pathways in the development of short and long term memories during the acquisition and recall of the step-down inhibitory avoidance in the hippocampus. The step-down inhibitory avoidance is a form of associative learning that is acquired in a relatively simple one-trial test through several sensorial inputs. Inhibitory avoidance depends on the integrated activity of hippocampal CA1 and other brain areas. Recall can be performed at different times after acquisition, thus allowing for the study of both short and long term memory. Among the many neurotransmitter systems involved, the cholinergic neurons that originate in the basal forebrain and project to the hippocampus are of crucial importance in inhibitory avoidance processes. Acetylcholine released from cholinergic fibers during acquisition and/or recall of behavioural tasks activates muscarinic and nicotinic acetylcholine receptors and brings about a long-lasting potentiation of the postsynaptic membrane followed by downstream activation of intracellular pathway (ERK, among others) that create conditions favourable for neuronal plasticity. ERK appears to be salient not only in long term memory, but also in the molecular mechanisms underlying short term memory formation in the hippocampus. Since ERK can function as a biochemical coincidence detector in response to extracellular signals in neurons, the activation of ERK-dependent downstream effectors is determined, in part, by the duration of ERK phosphorylation itself. Long term memories require protein synthesis, that in the synapto-dendritic compartment represents a direct mechanism that can produce rapid changes in protein content in response to synaptic activity. mTOR in the brain regulates protein translation in response to neuronal activity, thereby modulating synaptic plasticity and long term memory formation. Some studies demonstrate a complex interplay among the cholinergic system, ERK and mTOR. It has been shown that co-activation of muscarinic acetylcholine receptors and β-adrenergic receptors facilitates the conversion of short term to long term synaptic plasticity through an ERK- and mTOR-dependent mechanism which requires translation initiation. It seems therefore that the complex interplay among the cholinergic system, ERK and mTOR is crucial in the development of new inhibitory avoidance memories in the hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

Hormonal regulation of steroid receptor coactivator-1 mRNA in the male and female green anole brain.

PubMed

Kerver, H N; Wade, J

2015-03-01

Green anole lizards are seasonal breeders, with male sexual behaviour primarily regulated by an annual increase in testosterone. Morphological, biochemical and behavioural changes associated with reproduction are activated by testosterone, generally with a greater effect in the breeding season (BS) than in the nonbreeding season (NBS). The present study investigates the possibility that differences in a steroid receptor coactivator may regulate this seasonal difference in responsiveness to testosterone. In situ hybridisation was used to examine the expression of steroid receptor coactivator-1 (SRC-1) in the brains of gonadally intact male and female green anoles across breeding states. A second experiment examined gonadectomised animals with and without testosterone treatment. Gonadally intact males had more SRC-1 expressing cells in the preoptic area and larger volumes of this region as defined by these cells than females. Main effects of both sex and season (males > females and BS > NBS) were present in cell number and volume of the ventromedial hypothalamus. An interaction between sex and season suggested that high expression in BS males was driving these effects. In hormone-manipulated animals, testosterone treatment increased both the number of SRC-1 expressing cells in and volumes of the preoptic area and amygdala. These results suggest that testosterone selectively regulates SRC-1, and that this coactivator may play a role in facilitating reproductive behaviours across both sexes. However, changes in SRC-1 expression are not likely responsible for the seasonal change in responsiveness to testosterone. © 2014 British Society for Neuroendocrinology.

A brain-region-based meta-analysis method utilizing the Apriori algorithm.

PubMed

Niu, Zhendong; Nie, Yaoxin; Zhou, Qian; Zhu, Linlin; Wei, Jieyao

2016-05-18

Brain network connectivity modeling is a crucial method for studying the brain's cognitive functions. Meta-analyses can unearth reliable results from individual studies. Meta-analytic connectivity modeling is a connectivity analysis method based on regions of interest (ROIs) which showed that meta-analyses could be used to discover brain network connectivity. In this paper, we propose a new meta-analysis method that can be used to find network connectivity models based on the Apriori algorithm, which has the potential to derive brain network connectivity models from activation information in the literature, without requiring ROIs. This method first extracts activation information from experimental studies that use cognitive tasks of the same category, and then maps the activation information to corresponding brain areas by using the automatic anatomical label atlas, after which the activation rate of these brain areas is calculated. Finally, using these brain areas, a potential brain network connectivity model is calculated based on the Apriori algorithm. The present study used this method to conduct a mining analysis on the citations in a language review article by Price (Neuroimage 62(2):816-847, 2012). The results showed that the obtained network connectivity model was consistent with that reported by Price. The proposed method is helpful to find brain network connectivity by mining the co-activation relationships among brain regions. Furthermore, results of the co-activation relationship analysis can be used as a priori knowledge for the corresponding dynamic causal modeling analysis, possibly achieving a significant dimension-reducing effect, thus increasing the efficiency of the dynamic causal modeling analysis.

The Mechanosensory Lateral Line System Mediates Activation of Socially-Relevant Brain Regions during Territorial Interactions.

PubMed

Butler, Julie M; Maruska, Karen P

2016-01-01

Animals use multiple senses during social interactions and must integrate this information in the brain to make context-dependent behavioral decisions. For fishes, the largest group of vertebrates, the mechanosensory lateral line system provides crucial hydrodynamic information for survival behaviors, but little is known about its function in social communication. Our previous work using the African cichlid fish, Astatotilapia burtoni, provided the first empirical evidence that fish use their lateral line system to detect water movements from conspecifics for mutual assessment and behavioral choices. It is unknown, however, where this socially-relevant mechanosensory information is processed in the brain to elicit adaptive behavioral responses. To examine for the first time in any fish species which brain regions receive contextual mechanosensory information, we quantified expression of the immediate early gene cfos as a proxy for neural activation in sensory and socially-relevant brain nuclei from lateral line-intact and -ablated fish following territorial interactions. Our in situ hybridization results indicate that in addition to known lateral line processing regions, socially-relevant mechanosensory information is processed in the ATn (ventromedial hypothalamus homolog), Dl (putative hippocampus homolog), and Vs (putative medial extended amygdala homolog). In addition, we identified a functional network within the conserved social decision-making network (SDMN) whose co-activity corresponds with mutual assessment and behavioral choice. Lateral line-intact and -ablated fight winners had different patterns of co-activity of these function networks and group identity could be determined solely by activation patterns, indicating the importance of mechanoreception to co-activity of the SDMN. These data show for the first time that the mechanosensory lateral line system provides relevant information to conserved decision-making centers of the brain during territorial interactions to mediate crucial behavioral choices such as whether or not to engage in a territorial fight. To our knowledge, this is also the first evidence of a subpallial nucleus receiving mechanosensory input, providing important information for elucidating homologies of decision-making circuits across vertebrates. These novel results highlight the importance of considering multimodal sensory input in mediating context-appropriate behaviors that will provide broad insights on the evolution of decision-making networks across all taxa.

Object activation in semantic memory from visual multimodal feature input.

PubMed

Kraut, Michael A; Kremen, Sarah; Moo, Lauren R; Segal, Jessica B; Calhoun, Vincent; Hart, John

2002-01-01

The human brain's representation of objects has been proposed to exist as a network of coactivated neural regions present in multiple cognitive systems. However, it is not known if there is a region specific to the process of activating an integrated object representation in semantic memory from multimodal feature stimuli (e.g., picture-word). A previous study using word-word feature pairs as stimulus input showed that the left thalamus is integrally involved in object activation (Kraut, Kremen, Segal, et al., this issue). In the present study, participants were presented picture-word pairs that are features of objects, with the task being to decide if together they "activated" an object not explicitly presented (e.g., picture of a candle and the word "icing" activate the internal representation of a "cake"). For picture-word pairs that combine to elicit an object, signal change was detected in the ventral temporo-occipital regions, pre-SMA, left primary somatomotor cortex, both caudate nuclei, and the dorsal thalami bilaterally. These findings suggest that the left thalamus is engaged for either picture or word stimuli, but the right thalamus appears to be involved when picture stimuli are also presented with words in semantic object activation tasks. The somatomotor signal changes are likely secondary to activation of the semantic object representations from multimodal visual stimuli.

Activity-dependent synaptic plasticity of a chalcogenide electronic synapse for neuromorphic systems.

PubMed

Li, Yi; Zhong, Yingpeng; Zhang, Jinjian; Xu, Lei; Wang, Qing; Sun, Huajun; Tong, Hao; Cheng, Xiaoming; Miao, Xiangshui

2014-05-09

Nanoscale inorganic electronic synapses or synaptic devices, which are capable of emulating the functions of biological synapses of brain neuronal systems, are regarded as the basic building blocks for beyond-Von Neumann computing architecture, combining information storage and processing. Here, we demonstrate a Ag/AgInSbTe/Ag structure for chalcogenide memristor-based electronic synapses. The memristive characteristics with reproducible gradual resistance tuning are utilised to mimic the activity-dependent synaptic plasticity that serves as the basis of memory and learning. Bidirectional long-term Hebbian plasticity modulation is implemented by the coactivity of pre- and postsynaptic spikes, and the sign and degree are affected by assorted factors including the temporal difference, spike rate and voltage. Moreover, synaptic saturation is observed to be an adjustment of Hebbian rules to stabilise the growth of synaptic weights. Our results may contribute to the development of highly functional plastic electronic synapses and the further construction of next-generation parallel neuromorphic computing architecture.

MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

PubMed Central

Kubík, Štěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

2014-01-01

Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated neurons. PMID:24659959

Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis.

PubMed

Wilkins, Heather M; Harris, Janna L; Carl, Steven M; E, Lezi; Lu, Jianghua; Eva Selfridge, J; Roy, Nairita; Hutfles, Lewis; Koppel, Scott; Morris, Jill; Burns, Jeffrey M; Michaelis, Mary L; Michaelis, Elias K; Brooks, William M; Swerdlow, Russell H

2014-12-15

Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions or post-translational modifications of mRNA and proteins (proliferator-activated receptor-gamma coactivator 1α, PGC1 related co-activator, nuclear respiratory factor 1, transcription factor A of the mitochondria, cytochrome oxidase subunit 4 isoform 1, cAMP-response element binding, p38 MAPK and adenosine monophosphate-activated protein kinase) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mammalian target of rapamycin and P70S6K phosphorylation. OAA lowered nuclear factor κB nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal vascular endothelial growth factor mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts and neurite length increased in OAA-treated mice. (1)H-MRS showed OAA increased brain lactate, GABA and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation and activates hippocampal neurogenesis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Top-down cortical input during NREM sleep consolidates perceptual memory.

PubMed

Miyamoto, D; Hirai, D; Fung, C C A; Inutsuka, A; Odagawa, M; Suzuki, T; Boehringer, R; Adaikkan, C; Matsubara, C; Matsuki, N; Fukai, T; McHugh, T J; Yamanaka, A; Murayama, M

2016-06-10

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation. Copyright © 2016, American Association for the Advancement of Science.

Exploring variations in functional connectivity of the resting state default mode network in mild traumatic brain injury.

PubMed

Nathan, Dominic E; Oakes, Terrence R; Yeh, Ping Hong; French, Louis M; Harper, Jamie F; Liu, Wei; Wolfowitz, Rachel D; Wang, Bin Quan; Graner, John L; Riedy, Gerard

2015-03-01

A definitive diagnosis of mild traumatic brain injury (mTBI) is difficult due to the absence of biomarkers in standard clinical imaging. The brain is a complex network of interconnected neurons and subtle changes can modulate key networks of cognitive function. The resting state default mode network (DMN) has been shown to be sensitive to changes induced by pathology. This study seeks to determine whether quantitative measures of the DMN are sensitive in distinguishing mTBI subjects. Resting state functional magnetic resonance imaging data were obtained for healthy (n=12) and mTBI subjects (n=15). DMN maps were computed using dual-regression Independent Component Analysis (ICA). A goodness-of-fit (GOF) index was calculated to assess the degree of spatial specificity and sensitivity between healthy controls and mTBI subjects. DMN regions and neuropsychological assessments were examined to identify potential relationships. The resting state DMN maps indicate an increase in spatial coactivity in mTBI subjects within key regions of the DMN. Significant coactivity within the cerebellum and supplementary motor areas of mTBI subjects were also observed. This has not been previously reported in seed-based resting state network analysis. The GOF suggested the presence of high variability within the mTBI subject group, with poor sensitivity and specificity. The neuropsychological data showed correlations between areas of coactivity within the resting state network in the brain with a number of measures of emotion and cognitive functioning. The poor performance of the GOF highlights the key challenge associated with mTBI injury: the high variability in injury mechanisms and subsequent recovery. However, the quantification of the DMN using dual-regression ICA has potential to distinguish mTBI from healthy subjects, and provide information on the relationship of aspects of cognitive and emotional functioning with their potential neural correlates.

Not so Fast: Co-Requirements for Sonic Hedgehog Induced Brain Tumorigenesis.

PubMed

Ward, Stacey A; Rubin, Joshua B

2015-08-06

The Sonic hedgehog (Shh) pathway plays an integral role in cellular proliferation during normal brain development and also drives growth in a variety of cancers including brain cancer. Clinical trials of Shh pathway inhibitors for brain tumors have yielded disappointing results, indicating a more nuanced role for Shh signaling. We postulate that Shh signaling does not work alone but requires co-activation of other signaling pathways for tumorigenesis and stem cell maintenance. This review will focus on the interplay between the Shh pathway and these pathways to promote tumor growth in brain tumors, presenting opportunities for the study of combinatorial therapies.

Ablation of Steroid Receptor Coactivator-3 resembles the human CACT metabolic myopathy

PubMed Central

York, Brian; Reineke, Erin L.; Sagen, Jørn V.; Nikolai, Bryan C.; Zhou, Suoling; Louet, Jean-Francois; Chopra, Atul R.; Chen, Xian; Reed, Graham; Noebels, Jeffrey; Adesina, Adekunle M.; Yu, Hui; Wong, Lee-Jun C.; Tsimelzon, Anna; Hilsenbeck, Susan; Stevens, Robert D.; Wenner, Brett R.; Ilkayeva, Olga; Xu, Jianming; Newgard, Christopher B.; O’Malley, Bert W.

2012-01-01

Summary Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression. Consistent with human cases of CACT deficiency, dietary rescue with short chain fatty acids drastically attenuates the clinical hallmarks of the disease in mice devoid of SRC-3. Collectively, our results position SRC-3 as a key regulator of β-oxidation. Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic. PMID:22560224

Touch activates human auditory cortex.

PubMed

Schürmann, Martin; Caetano, Gina; Hlushchuk, Yevhen; Jousmäki, Veikko; Hari, Riitta

2006-05-01

Vibrotactile stimuli can facilitate hearing, both in hearing-impaired and in normally hearing people. Accordingly, the sounds of hands exploring a surface contribute to the explorer's haptic percepts. As a possible brain basis of such phenomena, functional brain imaging has identified activations specific to audiotactile interaction in secondary somatosensory cortex, auditory belt area, and posterior parietal cortex, depending on the quality and relative salience of the stimuli. We studied 13 subjects with non-invasive functional magnetic resonance imaging (fMRI) to search for auditory brain areas that would be activated by touch. Vibration bursts of 200 Hz were delivered to the subjects' fingers and palm and tactile pressure pulses to their fingertips. Noise bursts served to identify auditory cortex. Vibrotactile-auditory co-activation, addressed with minimal smoothing to obtain a conservative estimate, was found in an 85-mm3 region in the posterior auditory belt area. This co-activation could be related to facilitated hearing at the behavioral level, reflecting the analysis of sound-like temporal patterns in vibration. However, even tactile pulses (without any vibration) activated parts of the posterior auditory belt area, which therefore might subserve processing of audiotactile events that arise during dynamic contact between hands and environment.

A History of Spike-Timing-Dependent Plasticity

PubMed Central

Markram, Henry; Gerstner, Wulfram; Sjöström, Per Jesper

2011-01-01

How learning and memory is achieved in the brain is a central question in neuroscience. Key to today’s research into information storage in the brain is the concept of synaptic plasticity, a notion that has been heavily influenced by Hebb's (1949) postulate. Hebb conjectured that repeatedly and persistently co-active cells should increase connective strength among populations of interconnected neurons as a means of storing a memory trace, also known as an engram. Hebb certainly was not the first to make such a conjecture, as we show in this history. Nevertheless, literally thousands of studies into the classical frequency-dependent paradigm of cellular learning rules were directly inspired by the Hebbian postulate. But in more recent years, a novel concept in cellular learning has emerged, where temporal order instead of frequency is emphasized. This new learning paradigm – known as spike-timing-dependent plasticity (STDP) – has rapidly gained tremendous interest, perhaps because of its combination of elegant simplicity, biological plausibility, and computational power. But what are the roots of today’s STDP concept? Here, we discuss several centuries of diverse thinking, beginning with philosophers such as Aristotle, Locke, and Ribot, traversing, e.g., Lugaro’s plasticità and Rosenblatt’s perceptron, and culminating with the discovery of STDP. We highlight interactions between theoretical and experimental fields, showing how discoveries sometimes occurred in parallel, seemingly without much knowledge of the other field, and sometimes via concrete back-and-forth communication. We point out where the future directions may lie, which includes interneuron STDP, the functional impact of STDP, its mechanisms and its neuromodulatory regulation, and the linking of STDP to the developmental formation and continuous plasticity of neuronal networks. PMID:22007168

The role of sleep in changing our minds: A psychologist's discussion of papers on memory reactivation and consolidation in sleep

PubMed Central

Cartwright, Rosalind D.

2004-01-01

The group of papers on memory reactivation and consolidation during sleep included in this volume represents cutting edge work in both animals and humans. They support that the two types of sleep serve different necessary functions. The role of slow wave sleep (SWS) is reactivation of the hippocampal-neocortical circuits activated during a waking learning period, while REM sleep is responsible for the consolidation of this new learning into long-term memory. These studies provide further insights into mechanisms involved in brain plasticity. Robeiro has demonstrated the upregulation of an immediate-early gene (IEG zif 268) to waking levels, which occurs only in REM and only in connection with new learning. McNaughton and his group have identified electrical indicators that the hippocampus and neocortex are talking to each other by testing the coactivation of hippocampal sharp wave bursts in SWS and shifts from down to up states of activation in the neocortex. In human studies Smith's group reports work on individual differences such as intelligence and presleep alcohol that affect postsleep performance, and Stickgold and collaborators report that a short nap will improve performance if it contains REM sleep. Payne and Nadel suggest that the recall benefit associated with REM sleep may be due to its association with increased cortisol levels. These papers are important not only in their individual contributions but also in revitalizing the work coordinating waking and sleep. This promises to further the understanding of how our unique capacity to learn from experience and modify our behavior takes place. PMID:15576882

A "theory of relativity" for cognitive elasticity of time and modality dimensions supporting constant working memory capacity: involvement of harmonics among ultradian clocks?

PubMed

Glassman, R B

2000-02-01

1. The capacity of working memory (WM) for about 7+/-2 ("the magical number") serially organized simple verbal items may represent a fundamental constant of cognition. Indeed, there is the same capacity for sense of familiarity of a number of recently encountered places, observed in radial maze performance both of lab rats and of humans. 2. Moreover, both species show a peculiar capacity for retaining WM of place over delays. The literature also describes paradoxes of extended time duration in certain human verbal recall tasks. Certain bird species have comparable capacity for delayed recall of about 4 to 8 food caches in a laboratory room. 3. In addition to these paradoxes of the time dimension with WM (still sometimes called "short-term" memory) there are another set of paradoxes of dimensionality for human judgment of magnitudes, noted by Miller in his classic 1956 paper on "the magical number." We are able to reliably refer magnitudes to a rating scale of up to about seven divisions. Remarkably, that finding is largely independent of perceptual modality or even of the extent of a linear interval selected within any given modality. 4. These paradoxes suggest that "the magical number 7+/2" depends on fundamental properties of mammalian brains. 5. This paper theorizes that WM numerosity is conserved as a fundamental constant, by means of elasticity of cognitive dimensionality, including the temporal pace of arrival of significant items of cognitive information. 6. A conjectural neural code for WM item-capacity is proposed here, which extends the hypothetical principle of binding-by-synchrony. The hypothesis is that several coactive frequencies of brain electrical rhythms each mark a WM item. 7. If, indeed, WM does involve a brain wave frequency code (perhaps within the gamma frequency range that has often been suggested with the binding hypothesis) mathematical considerations suggest additional relevance of harmonic relationships. That is, if copresent sinusoids bear harmony-like ratios and are confined within a single octave, then they have fast temporal properties, while avoiding spurious difference rhythms. Therefore, if the present hypothesis is valid, it implies a natural limit on parallel processing of separate items in organismic brains. 8. Similar logic of periodic signals may hold for slower ultradian rhythms, including hypothetical ones that contribute to time-tagging and fresh sense of familiarity of a day's event memories. Similar logic may also hold for spatial periodic functions across brain tissue that, hypothetically, represent cognitive information. Thus, harmonic transitions among temporal and spatial periodic functions are a possible vehicle for the cognitive dimensional elasticity that conserves WM capacity. 9. Supporting roles are proposed of (a) basal ganglia, as a high-capacity cache for traces of recent experience temporarily suspended from active task-relevant processing and (b) of hippocampus as a phase and interval comparator for oscillating signals, whose spatiotemporal dynamics are topologically equivalent to a toroidal grid.

Functional Characterization and Differential Coactivation Patterns of Two Cytoarchitectonic Visual Areas on the Human Posterior Fusiform Gyrus

PubMed Central

Caspers, Julian; Zilles, Karl; Amunts, Katrin; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

2016-01-01

The ventral stream of the human extrastriate visual cortex shows a considerable functional heterogeneity from early visual processing (posterior) to higher, domain-specific processing (anterior). The fusiform gyrus hosts several of those “high-level” functional areas. We recently found a subdivision of the posterior fusiform gyrus on the microstructural level, that is, two distinct cytoarchitectonic areas, FG1 and FG2 (Caspers et al., Brain Structure & Function, 2013). To gain a first insight in the function of these two areas, here we studied their behavioral involvement and coactivation patterns by means of meta-analytic connectivity modeling based on the BrainMap database (www.brainmap.org), using probabilistic maps of these areas as seed regions. The coactivation patterns of the areas support the concept of a common involvement in a core network subserving different cognitive tasks, that is, object recognition, visual language perception, or visual attention. In addition, the analysis supports the previous cytoarchitectonic parcellation, indicating that FG1 appears as a transitional area between early and higher visual cortex and FG2 as a higher-order one. The latter area is furthermore lateralized, as it shows strong relations to the visual language processing system in the left hemisphere, while its right side is stronger associated with face selective regions. These findings indicate that functional lateralization of area FG2 relies on a different pattern of connectivity rather than side-specific cytoarchitectonic features. PMID:24038902

Co-activated yet disconnected-Neural correlates of eye closures when trying to stay awake.

PubMed

Ong, Ju Lynn; Kong, Danyang; Chia, Tiffany T Y; Tandi, Jesisca; Thomas Yeo, B T; Chee, Michael W L

2015-09-01

Spontaneous eye-closures that herald sleep onset become more frequent when we are sleep deprived. Although these are typically associated with decreased responsiveness to external stimuli, it is less clear what occurs in the brain at these transitions to drowsiness and light sleep. To investigate this, task-free fMRI of sleep-deprived participants was acquired. BOLD activity associated with periods of spontaneously occurring eye closures were marked and analyzed. We observed concurrent and extensive hypnagogic co-activation of the extrastriate visual, auditory, and somatosensory cortices as well as the default mode network, consistent with internal sensory activity without external stimulation. Co-activation of fronto-parietal areas known to mediate attentional control could correspond with participants resisting sleep or additional engagement of mental imagery. This constellation of signal changes differed from those elicited by cued eye closures of similar duration and distribution in the same, rested participants. They also differ from signal changes associated with mind-wandering and consolidated light sleep. Concurrent with the observed event-related changes, eye closures elicited additional reduction in functional connectivity within nodes of the DMN and DAN, superposed on already reduced connectivity associated with sleep deprivation. There was concurrent deactivation of the thalamus during eye-closure during the sleep-deprived state but almost similar changes occurred in the well-rested state that may also be relevant. These findings highlight the dynamic shifts in brain activity and connectivity at border between wakefulness and sleep. Copyright © 2015. Published by Elsevier Inc.

Ca2+ -stimulated adenylyl cyclases regulate ERK-dependent activation of MSK1 during fear conditioning.

PubMed

Sindreu, Carlos Balet; Scheiner, Zachary S; Storm, Daniel R

2007-01-04

The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory, a process that depends on CREB-mediated transcription. However, the extent of crosstalk between these pathways and the downstream CREB kinase activated during memory formation has not been elucidated. Here we report that PKA, MAPK, and MSK1, a CREB kinase, are coactivated in a subset of hippocampal CA1 pyramidal neurons following contextual fear conditioning. Activation of PKA, MAPK, MSK1, and CREB is absolutely dependent on Ca(2+)-stimulated adenylyl cyclase activity. We conclude that adenylyl cyclase activity supports the activation of MAPK, and that MSK1 is the major CREB kinase activated during training for contextual memory.

Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 During Fear Conditioning

PubMed Central

Sindreu, Carlos Balet; Scheiner, Zachary S.; Storm, Daniel R.

2007-01-01

The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for hippocampus-dependent memory, a process that depends on CREB-mediated transcription. However, the extent of crosstalk between these pathways and the downstream CREB kinase activated during memory formation have not been elucidated. Here we report that PKA, MAPK, and MSK1, a CREB kinase, are co-activated in a subset of hippocampal CA1 pyramidal neurons following contextual fear conditioning. Activation of PKA, MAPK, MSK1, and CREB is absolutely dependent on Ca2+-stimulated adenylyl cyclase activity. We conclude that adenylyl cyclase activity supports the activation of MAPK, and that MSK1 is the major CREB kinase activated during training for contextual memory. PMID:17196532

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice.

PubMed

Veniaminova, Ekaterina; Cespuglio, Raymond; Cheung, Chi Wai; Umriukhin, Alexei; Markova, Nataliia; Shevtsova, Elena; Lesch, Klaus-Peter; Anthony, Daniel C; Strekalova, Tatyana

2017-01-01

Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.

Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

PubMed Central

Cespuglio, Raymond; Umriukhin, Alexei

2017-01-01

Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder. PMID:28685102

TORCing up metabolic control in the brain.

PubMed

Hietakangas, Ville; Cohen, Stephen M

2008-05-01

Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.

A Neural Mechanism of Social Categorization.

PubMed

Stolier, Ryan M; Freeman, Jonathan B

2017-06-07

Humans readily sort one another into multiple social categories from mere facial features. However, the facial features used to do so are not always clear-cut because they can be associated with opponent categories (e.g., feminine male face). Recently, computational models and behavioral studies have provided indirect evidence that categorizing such faces is accomplished through dynamic competition between parallel, coactivated social categories that resolve into a stable categorical percept. Using a novel paradigm combining fMRI with real-time hand tracking, the present study examined how the brain translates diverse social cues into categorical percepts. Participants (male and female) categorized faces varying in gender and racial typicality. When categorizing atypical faces, participants' hand movements were simultaneously attracted toward the unselected category response, indexing the degree to which such faces activated the opposite category in parallel. Multivoxel pattern analyses (MVPAs) provided evidence that such social category coactivation manifested in neural patterns of the right fusiform cortex. The extent to which the hand was simultaneously attracted to the opposite gender or race category response option corresponded to increased neural pattern similarity with the average pattern associated with that category, which in turn associated with stronger engagement of the dorsal anterior cingulate cortex. The findings point to a model of social categorization in which occasionally conflicting facial features are resolved through competition between coactivated ventral-temporal cortical representations with the assistance of conflict-monitoring regions. More broadly, the results offer a promising multimodal paradigm to investigate the neural basis of "hidden", temporarily active representations in the service of a broad range of cognitive processes. SIGNIFICANCE STATEMENT Individuals readily sort one another into social categories (e.g., sex, race), which have important consequences for a variety of interpersonal behaviors. However, individuals routinely encounter faces that contain diverse features associated with multiple categories (e.g., feminine male face). Using a novel paradigm combining neuroimaging with hand tracking, the present research sought to address how the brain comes to arrive at stable social categorizations from multiple social cues. The results provide evidence that opponent social categories coactivate in face-processing regions, which compete and may resolve into an eventual stable categorization with the assistance of conflict-monitoring regions. Therefore, the findings provide a neural mechanism through which the brain may translate inherently diverse social cues into coherent categorizations of other people. Copyright © 2017 the authors 0270-6474/17/375711-11$15.00/0.

Left inferior parietal lobe engagement in social cognition and language

PubMed Central

Bzdok, Danilo; Hartwigsen, Gesa; Reid, Andrew; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

2017-01-01

Social cognition and language are two core features of the human species. Despite distributed recruitment of brain regions in each mental capacity, the left parietal lobe (LPL) represents a zone of topographical convergence. The present study quantitatively summarizes hundreds of neuroimaging studies on social cognition and language. Using connectivity-based parcellation on a meta-analytically defined volume of interest (VOI), regional coactivation patterns within this VOI allowed identifying distinct subregions. Across parcellation solutions, two clusters emerged consistently in rostro-ventral and caudo-ventral aspects of the parietal VOI. Both clusters were functionally significantly associated with social-cognitive and language processing. In particular, the rostro-ventral cluster was associated with lower-level processing facets, while the caudo-ventral cluster was associated with higher-level processing facets in both mental capacities. Contrarily, in the (less stable) dorsal parietal VOI, all clusters reflected computation of general-purpose processes, such as working memory and matching tasks, that are frequently co-recruited by social or language processes. Our results hence favour a rostro-caudal distinction of lower-versus higher-level processes underlying social cognition and language in the left inferior parietal lobe. PMID:27241201

Eating habits modulate short term memory and epigenetical regulation of brain derived neurotrophic factor in hippocampus of low- and high running capacity rats.

PubMed

Torma, Ferenc; Bori, Zoltan; Koltai, Erika; Felszeghy, Klara; Vacz, Gabriella; Koch, Lauren; Britton, Steven; Boldogh, Istvan; Radak, Zsolt

2014-08-01

Exercise capacity and dietary restriction (DR) are linked to improved quality of life, including enhanced brain function and neuro-protection. Brain derived neurotrophic factor (BDNF) is one of the key proteins involved in the beneficial effects of exercise on brain. Low capacity runner (LCR) and high capacity runner (HCR) rats were subjected to DR in order to investigate the regulation of BDNF. HCR-DR rats out-performed other groups in a passive avoidance test. BDNF content increased significantly in the hippocampus of HCR-DR groups compared to control groups (p<0.05). The acetylation of H3 increased significantly only in the LCR-DR group. However, chip-assay revealed that the specific binding between acetylated histone H3 and BNDF promoter was increased in both LCR-DR and HCR-DR groups. In spite of these increases in binding, at the transcriptional level only, the LCR-DR group showed an increase in BDNF mRNA content. Additionally, DR also induced the activity of cAMP response element-binding protein (CREB), while the content of SIRT1 was not altered. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) was elevated in HCR-DR groups. But, based on the levels of nuclear respiratory factor-1 and cytocrome c oxidase, it appears that DR did not cause mitochondrial biogenesis. The data suggest that DR-mediated induction of BDNF levels includes chromatin remodeling. Moreover, DR does not induce mitochondrial biogenesis in the hippocampus of LCR/HCR rats. DR results in different responses to a passive avoidance test, and BDNF regulation in LCR and HCR rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional Network Dynamics of the Language System.

PubMed

Chai, Lucy R; Mattar, Marcelo G; Blank, Idan Asher; Fedorenko, Evelina; Bassett, Danielle S

2016-10-17

During linguistic processing, a set of brain regions on the lateral surfaces of the left frontal, temporal, and parietal cortices exhibit robust responses. These areas display highly correlated activity while a subject rests or performs a naturalistic language comprehension task, suggesting that they form an integrated functional system. Evidence suggests that this system is spatially and functionally distinct from other systems that support high-level cognition in humans. Yet, how different regions within this system might be recruited dynamically during task performance is not well understood. Here we use network methods, applied to fMRI data collected from 22 human subjects performing a language comprehension task, to reveal the dynamic nature of the language system. We observe the presence of a stable core of brain regions, predominantly located in the left hemisphere, that consistently coactivate with one another. We also observe the presence of a more flexible periphery of brain regions, predominantly located in the right hemisphere, that coactivate with different regions at different times. However, the language functional ROIs in the angular gyrus and the anterior temporal lobe were notable exceptions to this trend. By highlighting the temporal dimension of language processing, these results suggest a trade-off between a region's specialization and its capacity for flexible network reconfiguration. © The Author 2016. Published by Oxford University Press.

Functional Network Dynamics of the Language System

PubMed Central

Chai, Lucy R.; Mattar, Marcelo G.; Blank, Idan Asher; Fedorenko, Evelina; Bassett, Danielle S.

2016-01-01

During linguistic processing, a set of brain regions on the lateral surfaces of the left frontal, temporal, and parietal cortices exhibit robust responses. These areas display highly correlated activity while a subject rests or performs a naturalistic language comprehension task, suggesting that they form an integrated functional system. Evidence suggests that this system is spatially and functionally distinct from other systems that support high-level cognition in humans. Yet, how different regions within this system might be recruited dynamically during task performance is not well understood. Here we use network methods, applied to fMRI data collected from 22 human subjects performing a language comprehension task, to reveal the dynamic nature of the language system. We observe the presence of a stable core of brain regions, predominantly located in the left hemisphere, that consistently coactivate with one another. We also observe the presence of a more flexible periphery of brain regions, predominantly located in the right hemisphere, that coactivate with different regions at different times. However, the language functional ROIs in the angular gyrus and the anterior temporal lobe were notable exceptions to this trend. By highlighting the temporal dimension of language processing, these results suggest a trade-off between a region's specialization and its capacity for flexible network reconfiguration. PMID:27550868

Conversion of Short-Term Potentiation to Long-Term Potentiation in Mouse CA1 by Coactivation of [beta]-Adrenergic and Muscarinic Receptors

ERIC Educational Resources Information Center

Connor, Steven A.; Maity, Sabyasachi; Roy, Birbickram; Ali, Declan W.; Nguyen, Peter V.

2012-01-01

Encoding new information requires dynamic changes in synaptic strength. The brain can boost synaptic plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how neuromodulatory substances alter synaptic properties. However, determination of the…

Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha as a Novel Target for Bipolar Disorder and Other Neuropsychiatric Disorders.

PubMed

Nierenberg, Andrew A; Ghaznavi, Sharmin A; Sande Mathias, Isadora; Ellard, Kristen K; Janos, Jessica A; Sylvia, Louisa G

2018-05-01

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti-triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials. Copyright © 2018. Published by Elsevier Inc.

Online evaluation of novel choices by simultaneous representation of multiple memories

PubMed Central

Barron, Helen C; Dolan, Raymond J; Behrens, Timothy E J

2014-01-01

Prior experience plays a critical role in decision making. It enables explicit representation of potential outcomes and provides training to valuation mechanisms. However, we can also make choices in the absence of prior experience, by merely imagining the consequences of a new experience. Here, using fMRI repetition suppression in humans, we show how neuronal representations of novel rewards can be constructed and evaluated. A likely novel experience is constructed by invoking multiple independent memories within hippocampus and medial prefrontal cortex. This construction persists for only a short time period, during which new associations are observed between the memories for component items. Together these findings suggest that in the absence of direct experience, co-activation of multiple relevant memories can provide a training signal to the valuation system which allows the consequences of new experiences to be imagined and acted upon. PMID:24013592

Staying Cool when Things Get Hot: Emotion Regulation Modulates Neural Mechanisms of Memory Encoding

PubMed Central

Hayes, Jasmeet Pannu; Morey, Rajendra A.; Petty, Christopher M.; Seth, Srishti; Smoski, Moria J.; McCarthy, Gregory; LaBar, Kevin S.

2010-01-01

During times of emotional stress, individuals often engage in emotion regulation to reduce the experiential and physiological impact of negative emotions. Interestingly, emotion regulation strategies also influence memory encoding of the event. Cognitive reappraisal is associated with enhanced memory while expressive suppression is associated with impaired explicit memory of the emotional event. However, the mechanism by which these emotion regulation strategies affect memory is unclear. We used event-related fMRI to investigate the neural mechanisms that give rise to memory formation during emotion regulation. Twenty-five participants viewed negative pictures while alternately engaging in cognitive reappraisal, expressive suppression, or passive viewing. As part of the subsequent memory design, participants returned to the laboratory two weeks later for a surprise memory test. Behavioral results showed a reduction in negative affect and a retention advantage for reappraised stimuli relative to the other conditions. Imaging results showed that successful encoding during reappraisal was uniquely associated with greater co-activation of the left inferior frontal gyrus, amygdala, and hippocampus, suggesting a possible role for elaborative encoding of negative memories. This study provides neurobehavioral evidence that engaging in cognitive reappraisal is advantageous to both affective and mnemonic processes. PMID:21212840

Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-01-01

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

PubMed

Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

2017-12-15

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

New therapeutic options for the metabolic syndrome: what's next?

PubMed

Flordellis, Christodoulos S; Ilias, Ioannis; Papavassiliou, Athanasios G

2005-08-01

The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.

Identification and Biological Evaluation of Coactivator Binding Inhibitors for the Estrogen Receptor

ERIC Educational Resources Information Center

Gunther, Jillian Rebecca

2009-01-01

The physiologic effects of estrogen action through the estrogen receptor (ER) are widespread, as this hormone exerts actions in both reproductive (e.g., uterus) and non-reproductive (e.g., bone, brain) tissues in both men and women. As such, the regulation of the activity of this ligand-activated transcription factor is highly relevant to the…

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

Mapping perception to action in piano practice: a longitudinal DC-EEG study

PubMed Central

Bangert, Marc; Altenmüller, Eckart O

2003-01-01

Background Performing music requires fast auditory and motor processing. Regarding professional musicians, recent brain imaging studies have demonstrated that auditory stimulation produces a co-activation of motor areas, whereas silent tapping of musical phrases evokes a co-activation in auditory regions. Whether this is obtained via a specific cerebral relay station is unclear. Furthermore, the time course of plasticity has not yet been addressed. Results Changes in cortical activation patterns (DC-EEG potentials) induced by short (20 minute) and long term (5 week) piano learning were investigated during auditory and motoric tasks. Two beginner groups were trained. The 'map' group was allowed to learn the standard piano key-to-pitch map. For the 'no-map' group, random assignment of keys to tones prevented such a map. Auditory-sensorimotor EEG co-activity occurred within only 20 minutes. The effect was enhanced after 5-week training, contributing elements of both perception and action to the mental representation of the instrument. The 'map' group demonstrated significant additional activity of right anterior regions. Conclusion We conclude that musical training triggers instant plasticity in the cortex, and that right-hemispheric anterior areas provide an audio-motor interface for the mental representation of the keyboard. PMID:14575529

The Source for Learning & Memory Strategies.

ERIC Educational Resources Information Center

Richards, Regina G.

This book is a comprehensive guide to learning and memory strategies for all students and especially those with learning problems. Chapter 1, on memory and the brain, explains brain cells, the cortex, function of the cerebral lobes, and other brain structures. Chapter 2 examines the memory process and discusses sensory memory, short-term memory,…

Memory as the "whole brain work": a large-scale model based on "oscillations in super-synergy".

PubMed

Başar, Erol

2005-01-01

According to recent trends, memory depends on several brain structures working in concert across many levels of neural organization; "memory is a constant work-in progress." The proposition of a brain theory based on super-synergy in neural populations is most pertinent for the understanding of this constant work in progress. This report introduces a new model on memory basing on the processes of EEG oscillations and Brain Dynamics. This model is shaped by the following conceptual and experimental steps: 1. The machineries of super-synergy in the whole brain are responsible for formation of sensory-cognitive percepts. 2. The expression "dynamic memory" is used for memory processes that evoke relevant changes in alpha, gamma, theta and delta activities. The concerted action of distributed multiple oscillatory processes provides a major key for understanding of distributed memory. It comprehends also the phyletic memory and reflexes. 3. The evolving memory, which incorporates reciprocal actions or reverberations in the APLR alliance and during working memory processes, is especially emphasized. 4. A new model related to "hierarchy of memories as a continuum" is introduced. 5. The notions of "longer activated memory" and "persistent memory" are proposed instead of long-term memory. 6. The new analysis to recognize faces emphasizes the importance of EEG oscillations in neurophysiology and Gestalt analysis. 7. The proposed basic framework called "Memory in the Whole Brain Work" emphasizes that memory and all brain functions are inseparable and are acting as a "whole" in the whole brain. 8. The role of genetic factors is fundamental in living system settings and oscillations and accordingly in memory, according to recent publications. 9. A link from the "whole brain" to "whole body," and incorporation of vegetative and neurological system, is proposed, EEG oscillations and ultraslow oscillations being a control parameter.

How structure sculpts function: Unveiling the contribution of anatomical connectivity to the brain's spontaneous correlation structure

NASA Astrophysics Data System (ADS)

Bettinardi, R. G.; Deco, G.; Karlaftis, V. M.; Van Hartevelt, T. J.; Fernandes, H. M.; Kourtzi, Z.; Kringelbach, M. L.; Zamora-López, G.

2017-04-01

Intrinsic brain activity is characterized by highly organized co-activations between different regions, forming clustered spatial patterns referred to as resting-state networks. The observed co-activation patterns are sustained by the intricate fabric of millions of interconnected neurons constituting the brain's wiring diagram. However, as for other real networks, the relationship between the connectional structure and the emergent collective dynamics still evades complete understanding. Here, we show that it is possible to estimate the expected pair-wise correlations that a network tends to generate thanks to the underlying path structure. We start from the assumption that in order for two nodes to exhibit correlated activity, they must be exposed to similar input patterns from the entire network. We then acknowledge that information rarely spreads only along a unique route but rather travels along all possible paths. In real networks, the strength of local perturbations tends to decay as they propagate away from the sources, leading to a progressive attenuation of the original information content and, thus, of their influence. Accordingly, we define a novel graph measure, topological similarity, which quantifies the propensity of two nodes to dynamically correlate as a function of the resemblance of the overall influences they are expected to receive due to the underlying structure of the network. Applied to the human brain, we find that the similarity of whole-network inputs, estimated from the topology of the anatomical connectome, plays an important role in sculpting the backbone pattern of time-average correlations observed at rest.

Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

PubMed

Censor, Nitzan; Dimyan, Michael A; Cohen, Leonardo G

2010-09-14

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

The contributions of cerebro-cerebellar circuitry to executive verbal working memory.

PubMed

Marvel, Cherie L; Desmond, John E

2010-01-01

Contributions of cerebro-cerebellar function to executive verbal working memory were examined using event-related functional magnetic resonance imaging (fMRI) while 16 subjects completed two versions of the Sternberg task. In both versions subjects were presented with two or six target letters during the encoding phase, which were held in memory during the maintenance phase. A single probe letter was presented during the retrieval phase. In the "match condition", subjects decided whether the probe matched the target letters. In the "executive condition", subjects created a new probe by counting two alphabetical letters forward (e.g., f-->h) and decided whether the new probe matched the target letters. Neural activity during the match and executive conditions was compared during each phase of the task. There were four main findings. First, cerebro-cerebellar activity increased as a function of executive load. Second, the dorsal cerebellar dentate co-activated with the supplementary motor area (SMA) during encoding. This likely represented the formation of an articulatory (motor) trajectory. Third, the ventral cerebellar dentate co-activated with anterior prefrontal regions Brodmann Area (BA) 9/46 and the pre-SMA during retrieval. This likely represented the manipulation of information and formation of a response. A functional dissociation between the dorsal "motor" dentate and "cognitive" ventral dentate agrees with neuroanatomical tract tracing studies that have demonstrated separate neural pathways involving each region of the dentate: the dorsal dentate projects to frontal motor areas (including the SMA), and the ventral dentate projects to frontal cognitive areas (including BA 9/46 and the pre-SMA). Finally, activity during the maintenance phase in BA 9, anterior insula, pre-SMA and ventral dentate predicted subsequent accuracy of response to the probe during the retrieval phase. This finding underscored the significant contribution of the pre-SMA/ventral dentate pathway--observed several seconds prior to any motor response to the probe--to executive verbal working memory. Copyright (c) 2009 Elsevier Srl. All rights reserved.

The Contributions of Cerebro-Cerebellar Circuitry to Executive Verbal Working Memory

PubMed Central

Marvel, Cherie L.; Desmond, John E.

2009-01-01

Contributions of cerebro-cerebellar function to executive verbal working memory were examined using event-related functional magnetic resonance imaging (fMRI) while 16 subjects completed two versions of the Sternberg task. In both versions subjects were presented with two or six target letters during the encoding phase, which were held in memory during the maintenance phase. A single probe letter was presented during the retrieval phase. In the “match condition”, subjects decided whether the probe matched the target letters. In the “executive condition”, subjects created a new probe by counting two alphabetical letters forward (e.g., f → h) and decided whether the new probe matched the target letters. Neural activity during the match and executive conditions was compared during each phase of the task. There were four main findings. First, cerebro-cerebellar activity increased as a function of executive load. Second, the dorsal cerebellar dentate co-activated with the supplementary motor area (SMA) during encoding. This likely represented the formation of an articulatory (motor) trajectory. Third, the ventral cerebellar dentate co-activated with anterior prefrontal regions BA 9/46 and the pre-SMA during retrieval. This likely represented the manipulation of information and formation of a response. A functional dissociation between the dorsal “motor” dentate and “cognitive” ventral dentate agrees with neuroanatomical tract tracing studies that have demonstrated separate neural pathways involving each region of the dentate: the dorsal dentate projects to frontal motor areas (including the SMA), and the ventral dentate projects to frontal cognitive areas (including BA 9/46 and the pre-SMA). Finally, activity during the maintenance phase in BA 9, anterior insula, pre-SMA and ventral dentate predicted subsequent accuracy of response to the probe during the retrieval phase. This finding underscored the significant contribution of the pre-SMA/ventral dentate pathway – observed several seconds prior to any motor response to the probe -- to executive verbal working memory. PMID:19811779

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2016-10-01

onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s

Chromaticity of color perception and object color knowledge.

PubMed

Hsu, Nina S; Frankland, Steven M; Thompson-Schill, Sharon L

2012-01-01

Sensorimotor theories of semantic memory require overlap between conceptual and perceptual representations. One source of evidence for such overlap comes from neuroimaging reports of co-activation during memory retrieval and perception; for example, regions involved in color perception (i.e., regions that respond more to colored than grayscale stimuli) are activated by retrieval of object color. One unanswered question from these studies is whether distinctions that are observed during perception are likewise observed during memory retrieval. That is, are regions defined by a chromaticity effect in perception similarly modulated by the chromaticity of remembered objects (e.g., lemons more than coal)? Subjects performed color perception and color retrieval tasks while undergoing fMRI. We observed increased activation during both perception and memory retrieval of chromatic compared to achromatic stimuli in overlapping areas of the left lingual gyrus, but not in dorsal or anterior regions activated during color perception. These results support sensorimotor theories but suggest important distinctions within the conceptual system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Left inferior parietal lobe engagement in social cognition and language.

PubMed

Bzdok, Danilo; Hartwigsen, Gesa; Reid, Andrew; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

2016-09-01

Social cognition and language are two core features of the human species. Despite distributed recruitment of brain regions in each mental capacity, the left parietal lobe (LPL) represents a zone of topographical convergence. The present study quantitatively summarizes hundreds of neuroimaging studies on social cognition and language. Using connectivity-based parcellation on a meta-analytically defined volume of interest (VOI), regional coactivation patterns within this VOI allowed identifying distinct subregions. Across parcellation solutions, two clusters emerged consistently in rostro-ventral and caudo-ventral aspects of the parietal VOI. Both clusters were functionally significantly associated with social-cognitive and language processing. In particular, the rostro-ventral cluster was associated with lower-level processing facets, while the caudo-ventral cluster was associated with higher-level processing facets in both mental capacities. Contrarily, in the (less stable) dorsal parietal VOI, all clusters reflected computation of general-purpose processes, such as working memory and matching tasks, that are frequently co-recruited by social or language processes. Our results hence favour a rostro-caudal distinction of lower- versus higher-level processes underlying social cognition and language in the left inferior parietal lobe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrinology and Pediatric Exercise Science-2016.

PubMed

Eliakim, Alon

2017-02-01

The Pediatric Exercise Science Year That Was section aims to highlight the most important (to the author's opinion) manuscripts that were published in 2016 in the field of endocrinology and pediatric exercise science. This year's selection includes studies showing that 1) Induction of T4 to T3 conversion by type 2 deiodinase following aerobic exercise in skeletal muscles was associated with concomitant increase in peroxisome proliferatoractivated receptor-γ coactivator-1α, and mitochondrial oxidative capacity and therefore plays an important mechanistic role in the muscle adaptation to exercise training. 2) Hypothyroidism in fetal and early postnatal life was associated with impaired spatial learning and memory and with reduced hippocampal brain-derived neurotrophic factor in male and female rat pups. Forced (treadmill) and voluntary (wheel) exercise alleviated all these biochemical and neuro-cognitive deficits. 3) The relationship between different exercise intensities and carbohydrate requirements to maintain euglycemia at basal insulin levels among adolescent and young adults with Type 1 diabetes are nonlinear but rather inverted- U with no exogenous glucose required to maintain stable glucose level at high-intensity exercise (80%). The implication of these studies to the pediatric population, their importance and the new research avenues that were opened by these studies is emphasized.

Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance.

PubMed

Keerativittayayut, Ruedeerat; Aoki, Ryuta; Sarabi, Mitra Taghizadeh; Jimura, Koji; Nakahara, Kiyoshi

2018-06-18

Although activation/deactivation of specific brain regions have been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here we investigated time-varying functional connectivity patterns across the human brain in periods of 30-40 s, which have recently been implicated in various cognitive functions. During functional magnetic resonance imaging, participants performed a memory encoding task, and their performance was assessed with a subsequent surprise memory test. A graph analysis of functional connectivity patterns revealed that increased integration of the subcortical, default-mode, salience, and visual subnetworks with other subnetworks is a hallmark of successful memory encoding. Moreover, multivariate analysis using the graph metrics of integration reliably classified the brain network states into the period of high (vs. low) memory encoding performance. Our findings suggest that a diverse set of brain systems dynamically interact to support successful memory encoding. © 2018, Keerativittayayut et al.

A convergent functional architecture of the insula emerges across imaging modalities.

PubMed

Kelly, Clare; Toro, Roberto; Di Martino, Adriana; Cox, Christine L; Bellec, Pierre; Castellanos, F Xavier; Milham, Michael P

2012-07-16

Empirical evidence increasingly supports the hypothesis that patterns of intrinsic functional connectivity (iFC) are sculpted by a history of evoked coactivation within distinct neuronal networks. This, together with evidence of strong correspondence among the networks defined by iFC and those delineated using a variety of other neuroimaging techniques, suggests a fundamental brain architecture detectable across multiple functional and structural imaging modalities. Here, we leverage this insight to examine the functional organization of the human insula. We parcellated the insula on the basis of three distinct neuroimaging modalities - task-evoked coactivation, intrinsic (i.e., task-independent) functional connectivity, and gray matter structural covariance. Clustering of these three different covariance-based measures revealed a convergent elemental organization of the insula that likely reflects a fundamental brain architecture governing both brain structure and function at multiple spatial scales. While not constrained to be hierarchical, our parcellation revealed a pseudo-hierarchical, multiscale organization that was consistent with previous clustering and meta-analytic studies of the insula. Finally, meta-analytic examination of the cognitive and behavioral domains associated with each of the insular clusters obtained elucidated the broad functional dissociations likely underlying the topography observed. To facilitate future investigations of insula function across healthy and pathological states, the insular parcels have been made freely available for download via http://fcon_1000.projects.nitrc.org, along with the analytic scripts used to perform the parcellations. Copyright © 2012 Elsevier Inc. All rights reserved.

Following the crowd: Brain Substrates of Long-Term Memory Conformity

PubMed Central

Edelson, Micah; Sharot, Tali; Dolan, Raymond J; Dudai, Yadin

2012-01-01

Human memory is strikingly susceptible to social influences, yet we know little about the underlying mechanisms. We examined how socially induced memory errors are generated in the brain by studying the memory of individuals exposed to recollections of others. Participants exhibited a strong tendency to conform to erroneous recollections of the group, producing both long-lasting and temporary errors, even when their initial memory was strong and accurate. Functional brain imaging revealed that social influence modified the neuronal representation of memory. Specifically, a particular brain signature of enhanced amygdala activity and enhanced amygdala-hippocampus connectivity predicted long-lasting, but not temporary memory alterations. Our findings reveal how social manipulation can alter memory and extend the known functions of the amygdala to encompass socially-mediated memory distortions. PMID:21719681

Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling.

PubMed

Zhou, Yulian; Nathans, Jeremy

2014-10-27

Canonical Wnt signaling in endothelial cells (ECs) is required for vascularization of the central nervous system (CNS) and for formation and maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan member of the adhesion G protein-coupled receptor family that is expressed in ECs and is essential for CNS angiogenesis and barrier formation via an unknown mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss- and gain-of-function experiments in mice, we show that Gpr124 functions as a coactivator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in concert with Norrin/Frizzled4 signaling to control CNS vascular development. These experiments identify Gpr124 as a ligand-specific coactivator of canonical Wnt signaling.

Is functional integration of resting state brain networks an unspecific biomarker for working memory performance?

PubMed

Alavash, Mohsen; Doebler, Philipp; Holling, Heinz; Thiel, Christiane M; Gießing, Carsten

2015-03-01

Is there one optimal topology of functional brain networks at rest from which our cognitive performance would profit? Previous studies suggest that functional integration of resting state brain networks is an important biomarker for cognitive performance. However, it is still unknown whether higher network integration is an unspecific predictor for good cognitive performance or, alternatively, whether specific network organization during rest predicts only specific cognitive abilities. Here, we investigated the relationship between network integration at rest and cognitive performance using two tasks that measured different aspects of working memory; one task assessed visual-spatial and the other numerical working memory. Network clustering, modularity and efficiency were computed to capture network integration on different levels of network organization, and to statistically compare their correlations with the performance in each working memory test. The results revealed that each working memory aspect profits from a different resting state topology, and the tests showed significantly different correlations with each of the measures of network integration. While higher global network integration and modularity predicted significantly better performance in visual-spatial working memory, both measures showed no significant correlation with numerical working memory performance. In contrast, numerical working memory was superior in subjects with highly clustered brain networks, predominantly in the intraparietal sulcus, a core brain region of the working memory network. Our findings suggest that a specific balance between local and global functional integration of resting state brain networks facilitates special aspects of cognitive performance. In the context of working memory, while visual-spatial performance is facilitated by globally integrated functional resting state brain networks, numerical working memory profits from increased capacities for local processing, especially in brain regions involved in working memory performance. Copyright © 2014 Elsevier Inc. All rights reserved.

Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

PubMed

Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

Identification and Manipulation of Memory Engram Cells.

PubMed

Liu, Xu; Ramirez, Steve; Redondo, Roger L; Tonegawa, Susumu

2014-01-01

How memories are formed and stored in the brain remains a fascinating question in neuroscience. Here we discuss the memory engram theory, our recent attempt to identify and manipulate memory engram cells in the brain with optogenetics, and how these methods are used to address questions such as how false memory is formed and how the valence of a memory can be changed in the brain. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

The iconic memory skills of brain injury survivors and non-brain injured controls after visual scanning training.

PubMed

McClure, J T; Browning, R T; Vantrease, C M; Bittle, S T

1994-01-01

Previous research suggests that traumatic brain injury (TBI) results in impairment of iconic memory abilities.We would like to acknowledge the contribution of Jeffrey D. Vantrease, who wrote the software program for the Iconic Memory procedure and measurement. This raises serious implications for brain injury rehabilitation. Most cognitive rehabilitation programs do not include iconic memory training. Instead it is common for cognitive rehabilitation programs to focus on attention and concentration skills, memory skills, and visual scanning skills.This study compared the iconic memory skills of brain-injury survivors and control subjects who all reached criterion levels of visual scanning skills. This involved previous training for the brain-injury survivors using popular visual scanning programs that allowed them to visually scan with response time and accuracy within normal limits. Control subjects required only minimal training to reach normal limits criteria. This comparison allows for the dissociation of visual scanning skills and iconic memory skills.The results are discussed in terms of their implications for cognitive rehabilitation and the relationship between visual scanning training and iconic memory skills.

Premotor cortex is sensitive to auditory-visual congruence for biological motion.

PubMed

Wuerger, Sophie M; Parkes, Laura; Lewis, Penelope A; Crocker-Buque, Alex; Rutschmann, Roland; Meyer, Georg F

2012-03-01

The auditory and visual perception systems have developed special processing strategies for ecologically valid motion stimuli, utilizing some of the statistical properties of the real world. A well-known example is the perception of biological motion, for example, the perception of a human walker. The aim of the current study was to identify the cortical network involved in the integration of auditory and visual biological motion signals. We first determined the cortical regions of auditory and visual coactivation (Experiment 1); a conjunction analysis based on unimodal brain activations identified four regions: middle temporal area, inferior parietal lobule, ventral premotor cortex, and cerebellum. The brain activations arising from bimodal motion stimuli (Experiment 2) were then analyzed within these regions of coactivation. Auditory footsteps were presented concurrently with either an intact visual point-light walker (biological motion) or a scrambled point-light walker; auditory and visual motion in depth (walking direction) could either be congruent or incongruent. Our main finding is that motion incongruency (across modalities) increases the activity in the ventral premotor cortex, but only if the visual point-light walker is intact. Our results extend our current knowledge by providing new evidence consistent with the idea that the premotor area assimilates information across the auditory and visual modalities by comparing the incoming sensory input with an internal representation.

Computational Cognitive Neuroscience of Early Memory Development

ERIC Educational Resources Information Center

Munakata, Yuko

2004-01-01

Numerous brain areas work in concert to subserve memory, with distinct memory functions relying differentially on distinct brain areas. For example, semantic memory relies heavily on posterior cortical regions, episodic memory on hippocampal regions, and working memory on prefrontal cortical regions. This article reviews relevant findings from…

Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear.

PubMed

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-09-19

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or retrieval. To investigate this possibility, we systematically imaged the brain activity patterns in the lateral amygdala, MGm/PIN, and AuV/TeA using activity-dependent induction of immediate early gene zif268 after recent and remote memory retrieval of auditory conditioned fear. Consistent with the critical role of the amygdala in fear memory, the zif268 activity in the lateral amygdala was significantly increased after both recent and remote memory retrieval. Interesting, however, the density of zif268 (+) neurons in both MGm/PIN and AuV/TeA, particularly in layers IV and VI, was increased only after remote but not recent fear memory retrieval compared to control groups. Further analysis of zif268 signals in AuV/TeA revealed that conditioned tone induced stronger zif268 induction compared to familiar tone in each individual zif268 (+) neuron after recent memory retrieval. Taken together, our results support that the lateral amygdala is a key brain site for permanent fear memory storage and suggest that MGm/PIN and AuV/TeA might play a role for remote memory storage or retrieval of auditory conditioned fear, or, alternatively, that these auditory brain regions might have a different way of processing for familiar or conditioned tone information at recent and remote time phases.

Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

PubMed

Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

2018-02-01

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

PubMed Central

Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

2014-01-01

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigating the Intersession Reliability of Dynamic Brain-State Properties.

PubMed

Smith, Derek M; Zhao, Yrian; Keilholz, Shella D; Schumacher, Eric H

2018-06-01

Dynamic functional connectivity metrics have much to offer to the neuroscience of individual differences of cognition. Yet, despite the recent expansion in dynamic connectivity research, limited resources have been devoted to the study of the reliability of these connectivity measures. To address this, resting-state functional magnetic resonance imaging data from 100 Human Connectome Project subjects were compared across 2 scan days. Brain states (i.e., patterns of coactivity across regions) were identified by classifying each time frame using k means clustering. This was done with and without global signal regression (GSR). Multiple gauges of reliability indicated consistency in the brain-state properties across days and GSR attenuated the reliability of the brain states. Changes in the brain-state properties across the course of the scan were investigated as well. The results demonstrate that summary metrics describing the clustering of individual time frames have adequate test/retest reliability, and thus, these patterns of brain activation may hold promise for individual-difference research.

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory.

PubMed

Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin

2016-10-01

Electrical stimulation of the brain is a unique tool to perturb endogenous neural signals, allowing us to evaluate the necessity of given neural processes to cognitive processing. An important issue, gaining increasing interest in the literature, is whether and how stimulation can be employed to selectively improve or disrupt declarative memory processes. Here, we provide a comprehensive review of both invasive and non-invasive stimulation studies aimed at modulating memory performance. The majority of past studies suggest that invasive stimulation of the hippocampus impairs memory performance; similarly, most non-invasive studies show that disrupting frontal or parietal regions also impairs memory performance, suggesting that these regions also play necessary roles in declarative memory. On the other hand, a handful of both invasive and non-invasive studies have also suggested modest improvements in memory performance following stimulation. These studies typically target brain regions connected to the hippocampus or other memory "hubs," which may affect endogenous activity in connected areas like the hippocampus, suggesting that to augment declarative memory, altering the broader endogenous memory network activity is critical. Together, studies reporting memory improvements/impairments are consistent with the idea that a network of distinct brain "hubs" may be crucial for successful memory encoding and retrieval rather than a single primary hub such as the hippocampus. Thus, it is important to consider neurostimulation from the network perspective, rather than from a purely localizationalist viewpoint. We conclude by proposing a novel approach to neurostimulation for declarative memory modulation that aims to facilitate interactions between multiple brain "nodes" underlying memory rather than considering individual brain regions in isolation. Copyright © 2016. Published by Elsevier Inc.

The Reduction of Ventrolateral Prefrontal Cortex Gray Matter Volume Correlates with Loss of Economic Rationality in Aging.

PubMed

Chung, Hui-Kuan; Tymula, Agnieszka; Glimcher, Paul

2017-12-06

The population of people above 65 years old continues to grow, and there is mounting evidence that as humans age they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole-brain voxel-based morphometry analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 years correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference. All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared with younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong coactivation patterns with nearly all of the value-associated regions identified in previous studies. These findings point toward a neuroanatomic locus for economic rationality in the aging brain and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making. SIGNIFICANCE STATEMENT Age is a crucial factor in decision-making, with older individuals making more errors in choices. Using whole-brain voxel-based morphometry analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference. Furthermore, this brain area strongly coactivates with other reward-associated regions identified with Neurosynth. These findings point toward a role for neuroscientific discoveries in shaping long-standing economic views of decision-making. Copyright © 2017 the authors 0270-6474/17/3712068-10$15.00/0.

The Reduction of Ventrolateral Prefrontal Cortex Gray Matter Volume Correlates with Loss of Economic Rationality in Aging

PubMed Central

Tymula, Agnieszka

2017-01-01

The population of people above 65 years old continues to grow, and there is mounting evidence that as humans age they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole-brain voxel-based morphometry analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 years correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference. All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared with younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong coactivation patterns with nearly all of the value-associated regions identified in previous studies. These findings point toward a neuroanatomic locus for economic rationality in the aging brain and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making. SIGNIFICANCE STATEMENT Age is a crucial factor in decision-making, with older individuals making more errors in choices. Using whole-brain voxel-based morphometry analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference. Furthermore, this brain area strongly coactivates with other reward-associated regions identified with Neurosynth. These findings point toward a role for neuroscientific discoveries in shaping long-standing economic views of decision-making. PMID:28982708

Episodic Memory Impairments in Primary Brain Tumor Patients.

PubMed

Durand, Thomas; Berzero, Giulia; Bompaire, Flavie; Hoffmann, Sabine; Léger, Isabelle; Jego, Virginie; Baruteau, Marie; Delgadillo, Daniel; Taillia, Hervé; Psimaras, Dimitri; Ricard, Damien

2018-01-04

Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacologic inhibition of phospholipase C in the brain attenuates early memory formation in the honeybee (Apis mellifera L.)

PubMed Central

Iino, Shiori; Kubo, Takeo

2018-01-01

ABSTRACT Although the molecular mechanisms involved in learning and memory in insects have been studied intensively, the intracellular signaling mechanisms involved in early memory formation are not fully understood. We previously demonstrated that phospholipase C epsilon (PLCe), whose product is involved in calcium signaling, is almost selectively expressed in the mushroom bodies, a brain structure important for learning and memory in the honeybee. Here, we pharmacologically examined the role of phospholipase C (PLC) in learning and memory in the honeybee. First, we identified four genes for PLC subtypes in the honeybee genome database. Quantitative reverse transcription-polymerase chain reaction revealed that, among these four genes, three, including PLCe, were expressed higher in the brain than in sensory organs in worker honeybees, suggesting their main roles in the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased PLC activities in homogenates of the brain tissues. These drugs injected into the head of foragers significantly attenuated memory acquisition in comparison with the control groups, whereas memory retention was not affected. These findings suggest that PLC in the brain is involved in early memory formation in the honeybee. To our knowledge, this is the first report of a role for PLC in learning and memory in an insect. PMID:29330349

Neuroanatomical and Cognitive Mediators of Age-Related Differences in Episodic Memory

PubMed Central

Head, Denise; Rodrigue, Karen M.; Kennedy, Kristen M.; Raz, Naftali

2009-01-01

Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging. PMID:18590361

Differences in Brain Activity during a Verbal Associative Memory Encoding Task in High- and Low-fit Adolescents

PubMed Central

Herting, Megan M.; Nagel, Bonnie J.

2013-01-01

Aerobic fitness is associated with better memory performance as well as larger volumes in memory-related brain regions in children, adolescents, and elderly. It is unclear if aerobic exercise also influences learning and memory functional neural circuitry. Here, we examine brain activity in 17 high-fit (HF) and 17 low-fit (LF) adolescents during a subsequent memory encoding paradigm using fMRI. Despite similar memory performance, HF and LF youth displayed a number of differences in memory-related and default mode (DMN) brain regions during encoding later remembered versus forgotten word pairs. Specifically, HF youth displayed robust deactivation in DMN areas, including the ventral medial PFC and posterior cingulate cortex, whereas LF youth did not show this pattern. Furthermore, LF youth showed greater bilateral hippocampal and right superior frontal gyrus activation during encoding of later remembered versus forgotten word pairs. Follow-up task-dependent functional correlational analyses showed differences in hippocampus and DMN activity coupling during successful encoding between the groups, suggesting aerobic fitness during adolescents may impact functional connectivity of the hippocampus and DMN during memory encoding. To our knowledge, this study is the first to examine the influence of aerobic fitness on hippocampal function and memory-related neural circuitry using fMRI. Taken together with previous research, these findings suggest aerobic fitness can influence not only memory-related brain structure, but also brain function. PMID:23249350

Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis.

PubMed

Sumowski, James F; Wylie, Glenn R; Chiaravalloti, Nancy; DeLuca, John

2010-06-15

Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis.

The MNESIS model: Memory systems and processes, identity and future thinking.

PubMed

Eustache, Francis; Viard, Armelle; Desgranges, Béatrice

2016-07-01

The Memory NEo-Structural Inter-Systemic model (MNESIS; Eustache and Desgranges, Neuropsychology Review, 2008) is a macromodel based on neuropsychological data which presents an interactive construction of memory systems and processes. Largely inspired by Tulving's SPI model, MNESIS puts the emphasis on the existence of different memory systems in humans and their reciprocal relations, adding new aspects, such as the episodic buffer proposed by Baddeley. The more integrative comprehension of brain dynamics offered by neuroimaging has contributed to rethinking the existence of memory systems. In the present article, we will argue that understanding the concept of memory by dividing it into systems at the functional level is still valid, but needs to be considered in the light of brain imaging. Here, we reinstate the importance of this division in different memory systems and illustrate, with neuroimaging findings, the links that operate between memory systems in response to task demands that constrain the brain dynamics. During a cognitive task, these memory systems interact transiently to rapidly assemble representations and mobilize functions to propose a flexible and adaptative response. We will concentrate on two memory systems, episodic and semantic memory, and their links with autobiographical memory. More precisely, we will focus on interactions between episodic and semantic memory systems in support of 1) self-identity in healthy aging and in brain pathologies and 2) the concept of the prospective brain during future projection. In conclusion, this MNESIS global framework may help to get a general representation of human memory and its brain implementation with its specific components which are in constant interaction during cognitive processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tough times call for bigger brains

PubMed Central

Pravosudov, Vladimir V

2009-01-01

Memory is crucial for survival in many animals. Spatial memory in particular is important for food-caching species and may be influenced by selective pressures such as climate. The influence of climate on memory may be facilitated through the hippocampus (Hp), the part of the brain responsible in part for spatial memory. In a recent paper, we conducted the first large-scale test of the relationship between memory, the climate and the brain in a single food-caching species, the black-capped chickadee (Poecile atricapillus). We found that birds from more harsh northern climates had significantly larger hippocampal volumes and more neurons than those from more mild southern latitudes. This work suggests that environmental pressures are capable of influencing specific brain regions, which may result in enhanced memory, and hence survival, in harsh climates. This work gives us a better understanding of how the brain responds to different environments and how animals can adapt to their environment in general. PMID:19641741

Human Genomic Signatures of Brain Oscillations During Memory Encoding.

PubMed

Berto, Stefano; Wang, Guang-Zhong; Germi, James; Lega, Bradley C; Konopka, Genevieve

2018-05-01

Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.

Episodic memory in aspects of large-scale brain networks

PubMed Central

Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

2015-01-01

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

MEMORY MODULATION

PubMed Central

Roozendaal, Benno; McGaugh, James L.

2011-01-01

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

[Memory and brain--neurobiological correlates of memory disturbances].

PubMed

Calabrese, P; Markowitsch, H J

2003-04-01

A differentiation of memory is possible on the basis of chronological and contents-related aspects. Furthermore, it is possible to make process-specific subdivisions (encoding, transfer, consolidation, retrieval). The time-related division on the one hand refers to the general differentiation into short-term and long-term memory, and, on the other, to that between anterograde and retrograde memory ("new" and "old memory"; measured from a given time point, usually that when brain damage occurred). Anterograde memory means the successful encoding and storing of new information; retrograde the ability to retrieve successfully acquired and/or stored information. On the contents-based level, memory can be divided into five basic long-term systems--episodic memory, the knowledge system, perceptual, procedural and the priming form of memory. Neural correlates for these divisions are discussed with special emphasis of the episodic and the knowledge systems, based both on normal individuals and brain-damaged subjects. It is argued that structures of the limbic system are important for encoding of information and for its transfer into long-term memory. For this, two independent, but interacting memory circuits are proposed--one of them controlling and integrating primarily the emotional, and the other primarily the cognitive components of newly incoming information. For information storage principally neocortical structures are regarded as important and for the recall of information from the episodic and semantic memory systems the combined action of portions of prefrontal and anterior temporal regions is regarded as essential. Within this fronto-temporal agglomerate, a moderate hemispheric-specificity is assumed to exist with the right-hemispheric combination being mainly engaged in episodic memory retrieval and the left-hemispheric in that of semantic information. Evidence for this specialization comes from the results from focally brain-damaged patients as well as from that functional brain imaging in normal human subjects. Comparing results from imaging studies in memory disturbed patients with brain damage and from patients with a psychiatric diagnosis (e. g., psychogenic amnesia) revealed that both patient groups demonstrate comparable metabolic changes on the brain level. It can therefore be concluded that in neurological patients distinct, identifiable tissue damage is existent, while in psychiatric patients changes in the brain's biochemistry (release of stress hormones, and transmitters) constitute the physiological bases for the memory disturbances.

Declarative and nondeclarative memory: multiple brain systems supporting learning and memory.

PubMed

Squire, L R

1992-01-01

Abstract The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).

Memory and functional brain differences in a national sample of U.S. veterans with Gulf War Illness.

PubMed

Cooper, Crystal M; Briggs, Richard W; Farris, Emily A; Bartlett, James; Haley, Robert W; Odegard, Timothy N

2016-04-30

Roughly 26-32% of U. S. veterans who served in the 1991 Persian Gulf War report suffering from chronic health problems. Memory complaints are regularly reported by ill Gulf War veterans (GWV), but limited data verify their complaints. This study investigated episodic memory and brain function in a nationally representative sample of GWV, using a face-name memory task and functional magnetic resonance imaging during encoding. A syndrome classification system was used to subdivide ill GWV into the three major Gulf War Illness syndrome types, "impaired cognition" (GWV-1), "confusion ataxia" (GWV-2), and "central pain" (GWV-3). Memory and brain function of ill GWV were contrasted to deployed and nondeployed well GWV controls (GWV-C). Ill GWV exhibited impaired memory function relative to GWV-C but the patterns of functional brain differences varied. Brain activation differentiated the GWV-C from the ill GWV. The different syndrome types also differed from one another in several brain regions. Additionally, the current study was the first to observe differences in brain function between deployed and nondeployed GWV-C. These results provide (1) evidence of memory impairment in ill GWV and differentiate the syndrome types at a functional neurobiological level, and (2) the role of deployment in the war on brain function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study.

PubMed

Kanayama, Gen; Rogowska, Jadwiga; Pope, Harrison G; Gruber, Staci A; Yurgelun-Todd, Deborah A

2004-11-01

Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users. However, little is known about the effects of cannabis on brain activity. We assessed brain function among recent heavy cannabis users while they performed a working memory task. Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users, 6-36 h after last use, and in 10 control subjects while they performed a spatial working memory task. Regional brain activation was analyzed and compared using statistical parametric mapping techniques. Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex and anterior cingulate). Users also recruited additional regions not typically used for spatial working memory (such as regions in the basal ganglia). These findings remained essentially unchanged when re-analyzed using subjects' ages as a covariate. Brain activation showed little or no significant correlation with subjects' years of education, verbal IQ, lifetime episodes of cannabis use, or urinary cannabinoid levels at the time of scanning. Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by "working harder"-calling upon additional brain regions to meet the demands of the task.

Hippocampal SWR Activity Predicts Correct Decisions during the Initial Learning of an Alternation Task

PubMed Central

Singer, Annabelle C.; Carr, Margaret F.; Karlsson, Mattias P.; Frank, Loren M.

2013-01-01

SUMMARY The hippocampus frequently replays memories of past experiences during sharp-wave ripple (SWR) events. These events can represent spatial trajectories extending from the animal’s current location to distant locations, suggesting a role in the evaluation of upcoming choices. While SWRs have been linked to learning and memory, the specific role of awake replay remains unclear. Here we show that there is greater coordinated neural activity during SWRs preceding correct, as compared to incorrect, trials in a spatial alternation task. As a result, the proportion of cell pairs coactive during SWRs was predictive of subsequent correct or incorrect responses on a trial-by-trial basis. This effect was seen specifically during early learning, when the hippocampus is essential for task performance. SWR activity preceding correct trials represented multiple trajectories that included both correct and incorrect options. These results suggest that reactivation during awake SWRs contributes to the evaluation of possible choices during memory-guided decision making. PMID:23522050

Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism.

PubMed

Brand, Matthias; Eggers, Carsten; Reinhold, Nadine; Fujiwara, Esther; Kessler, Josef; Heiss, Wolf-Dieter; Markowitsch, Hans J

2009-10-30

Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.

A biased competition account of attention and memory in Alzheimer's disease

PubMed Central

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-01-01

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD. PMID:24018724

A biased competition account of attention and memory in Alzheimer's disease.

PubMed

Finke, Kathrin; Myers, Nicholas; Bublak, Peter; Sorg, Christian

2013-10-19

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application.

PubMed

Zahodne, Laura B; Manly, Jennifer J; Brickman, Adam M; Narkhede, Atul; Griffith, Erica Y; Guzman, Vanessa A; Schupf, Nicole; Stern, Yaakov

2015-10-01

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point. Copyright © 2015. Published by Elsevier Ltd.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application

PubMed Central

Zahodne, Laura B.; Manly, Jennifer J.; Brickman, Adam M.; Narkhede, Atul; Griffith, Erica Y.; Guzman, Vanessa A.; Schupf, Nicole; Stern, Yaakov

2016-01-01

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point. PMID:26348002

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis

PubMed Central

Sumowski, James F.; Wylie, Glenn R.; Chiaravalloti, Nancy; DeLuca, John

2010-01-01

Objective: Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Methods: Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Results: Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. Conclusion: These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis. GLOSSARY AD = Alzheimer disease; ANOVA = analysis of variance; MPRAGE = magnetization-prepared rapid gradient echo; MS = multiple sclerosis; SRT = Selective Reminding Test; TVW = third ventricle width; WASI = Wechsler Abbreviated Scale of Intelligence. PMID:20548040

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study

PubMed Central

Karolis, Vyacheslav; Caldinelli, Chiara; Brittain, Philip J.; Kroll, Jasmin; Rodríguez-Toscano, Elisa; Tesse, Marcello; Colquhoun, Matthew; Howes, Oliver; Dell'Acqua, Flavio; Thiebaut de Schotten, Michel; Murray, Robin M.; Williams, Steven C.R.; Nosarti, Chiara

2015-01-01

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI. SIGNIFICANCE STATEMENT Here we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brain's ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this “extra” activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI. PMID:26631462

Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

PubMed

Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

2013-08-01

This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action.

Dopaminergic contributions to working memory-related brain activation in postmenopausal women.

PubMed

Dumas, Julie A; Filippi, Christopher G; Newhouse, Paul A; Naylor, Magdalena R

2017-02-01

The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed a functional magnetic resonance imaging visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared with dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Patterns of increased blood-oxygen-level dependent signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women to determine the effects of the increased brain activation on cognition and behavior.

Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

PubMed

Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

2017-09-07

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

PubMed Central

Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

2017-01-01

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

Episodic Memory in Detoxified Alcoholics: Contribution of Grey Matter Microstructure Alteration

PubMed Central

Chanraud, Sandra; Leroy, Claire; Martelli, Catherine; Kostogianni, Nikoleta; Delain, Françoise; Aubin, Henri-Jean; Reynaud, Michel; Martinot, Jean-Luc

2009-01-01

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics. Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software. In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant. These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence. PMID:19707568

Impact of the Educational Boost Your Brain and Memory Program Among Senior Living Residents.

PubMed

Nicholson, Roscoe; O'Brien, Catherine

2017-12-01

This random assignment waitlist control intervention study examined an implementation of the educational Boost Your Brain and Memory cognitive fitness intervention in 12 senior living organizations. Older adult participants ( n = 166) completed measures of brain health knowledge, use of memory techniques, physical and intellectual activity, and mindfulness, at baseline and after the intervention group's completion of the course. Changes in knowledge scores and in self-reported physical and intellectual activity increased significantly more for intervention participants than for waitlist controls at the conclusion of the course. There were no significant changes between the groups in mindfulness or use of memory techniques. This suggests that in senior living settings Boost Your Brain and Memory is effective in educating participants about brain healthy behaviors and in motivating behavioral change in the areas of physical and intellectual activity.

From Hippocampus to Whole-Brain: The Role of Integrative Processing in Episodic Memory Retrieval

PubMed Central

Geib, Benjamin R.; Stanley, Matthew L.; Dennis, Nancy A.; Woldorff, Marty G.; Cabeza, Roberto

2017-01-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. PMID:28112460

Brain Information Sharing During Visual Short-Term Memory Binding Yields a Memory Biomarker for Familial Alzheimer's Disease.

PubMed

Parra, Mario A; Mikulan, Ezequiel; Trujillo, Natalia; Sala, Sergio Della; Lopera, Francisco; Manes, Facundo; Starr, John; Ibanez, Agustin

2017-01-01

Alzheimer's disease (AD) as a disconnection syndrome which disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions share pathophysiological mechanisms remains unknown. To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the Visual Short-Term Memory binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evidence-Based Practice for the Use of Internal Strategies as a Memory Compensation Technique After Brain Injury: A Systematic Review.

PubMed

OʼNeil-Pirozzi, Therese M; Kennedy, Mary R T; Sohlberg, McKay M

2016-01-01

To complete a systematic review of internal memory strategy use with people who have brain injury and provide practitioners with information that will impact their clinical work. A systematic literature search to identify published intervention studies that evaluated an internal memory strategy or technique to improve memory function of individuals with brain injury. Relevant data from reviewed articles were coded using 4 clinical questions targeting participants, interventions, research methods, and outcomes. A comprehensive search identified 130 study citations and abstracts. Forty-six met inclusion/exclusion criteria and were systematically reviewed. Visual imagery was most frequently studied, in isolation or in combination with other internal strategies. Despite significant variability in research methods and outcomes across studies, the evidence provides impetus for use of internal memory strategies with individuals following brain injury. Individuals with traumatic brain injury may benefit from internal memory strategy use, and clinicians should consider internal memory strategy instruction as part of intervention plans. Further research needs to better delineate influences on intervention candidacy and outcomes.

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

From hippocampus to whole-brain: The role of integrative processing in episodic memory retrieval.

PubMed

Geib, Benjamin R; Stanley, Matthew L; Dennis, Nancy A; Woldorff, Marty G; Cabeza, Roberto

2017-04-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242-2259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

PubMed

Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

2015-01-01

Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms.

Tracking the fear engram: the lateral amygdala is an essential locus of fear memory storage.

PubMed

Schafe, Glenn E; Doyère, Valérie; LeDoux, Joseph E

2005-10-26

Although it is believed that different types of memories are localized in discreet regions of the brain, concrete experimental evidence of the existence of such engrams is often elusive. Despite being one of the best characterized memory systems of the brain, the question of where fear memories are localized in the brain remains a hotly debated issue. Here, we combine site-specific behavioral pharmacology with multisite electrophysiological recording techniques to show that the lateral nucleus of the amygdala, long thought to be critical for the acquisition of fear memories, is also an essential locus of fear memory storage.

Ligand and coactivator identity determines the requirement of the charge clamp for coactivation of the peroxisome proliferator-activated receptor gamma.

PubMed

Wu, Yifei; Chin, William W; Wang, Yong; Burris, Thomas P

2003-03-07

The activation function 2 (AF-2)-dependent recruitment of coactivator is essential for gene activation by nuclear receptors. We show that the peroxisome proliferator-activated receptor gamma (PPARgamma) (NR1C3) coactivator-1 (PGC-1) requires both the intact AF-2 domain of PPARgamma and the LXXLL domain of PGC-1 for ligand-dependent and ligand-independent interaction and coactivation. Although the AF-2 domain of PPARgamma is absolutely required for PGC-1-mediated coactivation, this coactivator displayed a unique lack of requirement for the charge clamp of the ligand-binding domain of the receptor that is thought to be essential for LXXLL motif recognition. The mutation of a single serine residue adjacent to the core LXXLL motif of PGC-1 led to restoration of the typical charge clamp requirement. Thus, the unique structural features of the PGC-1 LXXLL motif appear to mediate an atypical mode of interaction with PPARgamma. Unexpectedly, we discovered that various ligands display variability in terms of their requirement for the charge clamp of PPARgamma for coactivation by PGC-1. This ligand-selective variable requirement for the charge clamp was coactivator-specific. Thus, distinct structural determinants, which may be unique for a particular ligand, are utilized by the receptor to recognize the coactivator. Our data suggest that even subtle differences in ligand structure are perceived by the receptor and translated into a unique display of the coactivator-binding surface of the ligand-binding domain, allowing for differential recognition of coactivators that may underlie distinct pharmacological profiles observed for ligands of a particular nuclear receptor.

Explaining how brain stimulation can evoke memories.

PubMed

Jacobs, Joshua; Lega, Bradley; Anderson, Christopher

2012-03-01

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

Epigenetic memory: the Lamarckian brain

PubMed Central

Fischer, Andre

2014-01-01

Recent data support the view that epigenetic processes play a role in memory consolidation and help to transmit acquired memories even across generations in a Lamarckian manner. Drugs that target the epigenetic machinery were found to enhance memory function in rodents and ameliorate disease phenotypes in models for brain diseases such as Alzheimer's disease, Chorea Huntington, Depression or Schizophrenia. In this review, I will give an overview on the current knowledge of epigenetic processes in memory function and brain disease with a focus on Morbus Alzheimer as the most common neurodegenerative disease. I will address the question whether an epigenetic therapy could indeed be a suitable therapeutic avenue to treat brain diseases and discuss the necessary steps that should help to take neuroepigenetic research to the next level. PMID:24719207

Slow-Wave Sleep-Imposed Replay Modulates Both Strength and Precision of Memory

PubMed Central

2014-01-01

Odor perception is hypothesized to be an experience-dependent process involving the encoding of odor objects by distributed olfactory cortical ensembles. Olfactory cortical neurons coactivated by a specific pattern of odorant evoked input become linked through association fiber synaptic plasticity, creating a template of the familiar odor. In this way, experience and memory play an important role in odor perception and discrimination. In other systems, memory consolidation occurs partially via slow-wave sleep (SWS)-dependent replay of activity patterns originally evoked during waking. SWS is ideal for replay given hyporesponsive sensory systems, and thus reduced interference. Here, using artificial patterns of olfactory bulb stimulation in a fear conditioning procedure in the rat, we tested the effects of imposed post-training replay during SWS and waking on strength and precision of pattern memory. The results show that imposed replay during post-training SWS enhanced the subsequent strength of memory, whereas the identical replay during waking induced extinction. The magnitude of this enhancement was dependent on the timing of imposed replay relative to cortical sharp-waves. Imposed SWS replay of stimuli, which differed from the conditioned stimulus, did not affect conditioned stimulus memory strength but induced generalization of the fear memory to novel artificial patterns. Finally, post-training disruption of piriform cortex intracortical association fiber synapses, hypothesized to be critical for experience-dependent odor coding, also impaired subsequent memory precision but not strength. These results suggest that SWS replay in the olfactory cortex enhances memory consolidation, and that memory precision is dependent on the fidelity of that replay. PMID:24719093

[Memory engram of brain circuit].

PubMed

Kojima, Hiroto; Sakaguchi, Tetsuya; Ikegaya, Yuji

2015-05-01

How are memories stored in the brain and retrieved on demand? This is a frequently asked question. Indeed, we acquire new memories daily and remember old ones. However, how we can memorize one-time experiences is yet to be investigated. Here, we review possible mechanisms by which memories are maintained in neural networks.

A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.

PubMed

Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John; Chiaravalloti, Nancy D

2014-09-01

Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.

Enhancing an appointment diary on a pocket computer for use by people after brain injury.

PubMed

Wright, P; Rogers, N; Hall, C; Wilson, B; Evans, J; Emslie, H

2001-12-01

People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury.

Memory Impairment in Multiple Sclerosis is Due to a Core Deficit in Initial Learning

PubMed Central

DeLuca, John; Leavitt, Victoria M.; Chiaravalloti, Nancy; Wylie, Glenn

2013-01-01

Persons with multiple sclerosis (MS) suffer memory impairment, but research on the nature of MS-related memory problems is mixed. Some have argued for a core deficit in retrieval, while others have identified deficient initial learning as the core deficit. We used a selective reminding paradigm to determine whether deficient initial learning or delayed retrieval represents the primary memory deficit in 44 persons with MS. Brain atrophy was measured from high-resolution MRIs. Regression analyses examined the impact of brain atrophy on (a) initial learning and delayed retrieval separately, and then (b) delayed retrieval controlling for initial learning. Brain atrophy was negatively associated with both initial learning and delayed retrieval (ps < .01), but brain atrophy was unrelated to retrieval when controlling for initial learning (p > .05). In addition, brain atrophy was associated with inefficient learning across initial acquisition trials, and brain atrophy was unrelated to delayed recall among MS subjects who successfully acquired the word list (although such learning frequently required many exposures). Taken together, memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS. PMID:23832311

Compound mechanism hypothesis on +Gz induced brain injury and dysfunction of learning and memory

NASA Astrophysics Data System (ADS)

Sun, Xi-Qing; Li, Jin-Sheng; Cao, Xin-Sheng; Wu, Xing-Yu

2005-08-01

We systematically studied the effect of high- sustained +Gz on the brain and its mechanism in past ten years by animal centrifuge experiments. On the basis of the facts we observed and the more recent advances in acceleration physiology, we put forward a compound mechanism hypothesis to offer a possible explanation for +Gz-induced brain injury and dysfunction of learning and memory. It states that, ischemia during high G exposure might be the main factor accounting for +Gz-induced brain injury and dysfunction of learning and memory, including transient depression of brain energy metabolism, disturbance of ion homeostasis, increased blood-brain barrier permeability, increased brain nitric oxide synthase expression, and the protective effect of heat shock protein 70. In addition, the large rapid change of intracranial pressure and increased stress during +Gz exposure, and the hemorrheologic change after +Gz exposure might be one of the important factors accounting for +Gz-induced brain injury and dysfunction of learning and memory.

Computing the Social Brain Connectome Across Systems and States.

PubMed

Alcalá-López, Daniel; Smallwood, Jonathan; Jefferies, Elizabeth; Van Overwalle, Frank; Vogeley, Kai; Mars, Rogier B; Turetsky, Bruce I; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B; Bzdok, Danilo

2017-05-18

Social skills probably emerge from the interaction between different neural processing levels. However, social neuroscience is fragmented into highly specialized, rarely cross-referenced topics. The present study attempts a systematic reconciliation by deriving a social brain definition from neural activity meta-analyses on social-cognitive capacities. The social brain was characterized by meta-analytic connectivity modeling evaluating coactivation in task-focused brain states and physiological fluctuations evaluating correlations in task-free brain states. Network clustering proposed a functional segregation into (1) lower sensory, (2) limbic, (3) intermediate, and (4) high associative neural circuits that together mediate various social phenomena. Functional profiling suggested that no brain region or network is exclusively devoted to social processes. Finally, nodes of the putative mirror-neuron system were coherently cross-connected during tasks and more tightly coupled to embodied simulation systems rather than abstract emulation systems. These first steps may help reintegrate the specialized research agendas in the social and affective sciences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Increased lower limb muscle coactivation reduces gait performance and increases metabolic cost in patients with hereditary spastic paraparesis.

PubMed

Rinaldi, Martina; Ranavolo, Alberto; Conforto, Silvia; Martino, Giovanni; Draicchio, Francesco; Conte, Carmela; Varrecchia, Tiwana; Bini, Fabiano; Casali, Carlo; Pierelli, Francesco; Serrao, Mariano

2017-10-01

The aim of this study was to investigate the lower limb muscle coactivation and its relationship with muscles spasticity, gait performance, and metabolic cost in patients with hereditary spastic paraparesis. Kinematic, kinetic, electromyographic and energetic parameters of 23 patients and 23 controls were evaluated by computerized gait analysis system. We computed ankle and knee antagonist muscle coactivation indexes throughout the gait cycle and during the subphases of gait. Energy consumption and energy recovery were measured as well. In addition to the correlation analysis between coactivation indexes and clinical variables, correlations between coactivation indexes and time-distance, kinematic, kinetic, and energetic parameters were estimated. Increased coactivity indexes of both knee and ankle muscles throughout the gait cycle and during the subphases of gait were observed in patients compared with controls. Energetic parameters were significantly higher in patients than in controls. Both knee and ankle muscle coactivation indexes were positively correlated with knee and ankle spasticity (Ashworth score), respectively. Knee and ankle muscle coactivation indexes were both positively correlated with energy consumption and both negatively correlated with energy recovery. Positive correlations between the Ashworth score and lower limb muscle coactivation suggest that abnormal lower limb muscle coactivation in patients with hereditary spastic paraparesis reflects a primary deficit linked to lower limb spasticity. Furthermore, these abnormalities influence the energetic mechanisms during walking. Identifying excessive muscle coactivation may be helpful in individuating the rehabilitative treatments and designing specific orthosis to restrain spasticity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dopaminergic contributions to working memory-related brain activation in postmenopausal women

PubMed Central

Dumas, Julie A.; Filippi, Christopher G.; Newhouse, Paul A.; Naylor, Magdalena R.

2016-01-01

Objective The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. Method Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed an fMRI visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. Results We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared to dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. Conclusions Patterns of increased BOLD signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women in order to determine the effects of the increased brain activation on cognition and behavior. PMID:27676634

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

Emotion regulation modulates anticipatory brain activity that predicts emotional memory encoding in women.

PubMed

Galli, Giulia; Griffiths, Victoria A; Otten, Leun J

2014-03-01

It has been shown that the effectiveness with which unpleasant events are encoded into memory is related to brain activity set in train before the events. Here, we assessed whether encoding-related activity before an aversive event can be modulated by emotion regulation. Electrical brain activity was recorded from the scalps of healthy women while they performed an incidental encoding task on randomly intermixed unpleasant and neutral visual scenes. A cue presented 1.5 s before each picture indicated the upcoming valence. In half of the blocks of trials, the instructions emphasized to let emotions arise in a natural way. In the other half, participants were asked to decrease their emotional response by adopting the perspective of a detached observer. Memory for the scenes was probed 1 day later with a recognition memory test. Brain activity before unpleasant scenes predicted later memory of the scenes, but only when participants felt their emotions and did not detach from them. The findings indicate that emotion regulation can eliminate the influence of anticipatory brain activity on memory encoding. This may be relevant for the understanding and treatment of psychiatric diseases with a memory component.

Functional brain microstate predicts the outcome in a visuospatial working memory task.

PubMed

Muthukrishnan, Suriya-Prakash; Ahuja, Navdeep; Mehta, Nalin; Sharma, Ratna

2016-11-01

Humans have limited capacity of processing just up to 4 integrated items of information in the working memory. Thus, it is inevitable to commit more errors when challenged with high memory loads. However, the neural mechanisms that determine the accuracy of response at high memory loads still remain unclear. High temporal resolution of Electroencephalography (EEG) technique makes it the best tool to resolve the temporal dynamics of brain networks. EEG-defined microstate is the quasi-stable scalp electrical potential topography that represents the momentary functional state of brain. Thus, it has been possible to assess the information processing currently performed by the brain using EEG microstate analysis. We hypothesize that the EEG microstate preceding the trial could determine its outcome in a visuospatial working memory (VSWM) task. Twenty-four healthy participants performed a high memory load VSWM task, while their brain activity was recorded using EEG. Four microstate maps were found to represent the functional brain state prior to the trials in the VSWM task. One pre-trial microstate map was found to determine the accuracy of subsequent behavioural response. The intracranial generators of the pre-trial microstate map that determined the response accuracy were localized to the visuospatial processing areas at bilateral occipital, right temporal and limbic cortices. Our results imply that the behavioural outcome in a VSWM task could be determined by the intensity of activation of memory representations in the visuospatial processing brain regions prior to the trial. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Ephs and Ephrins in Memory Formation

PubMed Central

Dines, Monica

2016-01-01

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer’s disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. PMID:26371183

Optimization of immunolabeling and clearing techniques for indelibly-labeled memory traces.

PubMed

Pavlova, Ina P; Shipley, Shannon C; Lanio, Marcos; Hen, René; Denny, Christine A

2018-04-16

Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e. engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clearing solutions, such as tert-Butanol, circumvented these harmful effects, but still did not permit whole-brain immunolabeling. CUBIC and CUBIC with Reagent 1A produced improved antibody penetration and preserved EYFP fluorescence, but also did not allow for whole-brain memory trace visualization. Modification of CUBIC with Reagent-1A resulted in EYFP fluorescence preservation and immunolabeling of the immediate early gene (IEG) Arc in deep brain areas; however, optimized memory trace labeling still required tissue slicing into mm-thick tissue sections. In summary, our data show that CUBIC with Reagent-1A* is the ideal method for reproducible clearing and immunolabeling for the visualization of memory traces in mm-thick tissue sections from ArcCreER T2 mice. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging.

PubMed

Sun, Felicia W; Stepanovic, Michael R; Andreano, Joseph; Barrett, Lisa Feldman; Touroutoglou, Alexandra; Dickerson, Bradford C

2016-09-14

Decline in cognitive skills, especially in memory, is often viewed as part of "normal" aging. Yet some individuals "age better" than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20-30 years younger (i.e., "superagers"), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60-80 years old) based on their performance compared to young adults (18-32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults. Copyright © 2016 Sun, Stepanovic et al.

Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

PubMed

Raffa, R B

2013-08-01

Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation. © 2013 John Wiley & Sons Ltd.

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma.

PubMed

Liu, Rui; Zhang, Haiyang; Zhang, Yan; Li, Shuang; Wang, Xinyi; Wang, Xia; Wang, Cheng; Liu, Bin; Zen, Ke; Zhang, Chen-Yu; Zhang, Chunni; Ba, Yi

2017-04-01

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in the formation and development of hepatocellular carcinoma and that peroxisome proliferator-activated receptor gamma coactivator-1 alpha may be a potential therapeutic target for hepatocellular carcinoma.

Brain Networks Shaping Religious Belief

PubMed Central

Deshpande, Gopikrishna; Krueger, Frank; Thornburg, Matthew P.; Grafman, Jordan Henry

2014-01-01

Abstract We previously demonstrated with functional magnetic resonance imaging (fMRI) that religious belief depends upon three cognitive dimensions, which can be mapped to specific brain regions. In the present study, we considered these co-activated regions as nodes of three networks each one corresponding to a particular dimension, corresponding to each dimension and examined the causal flow within and between these networks to address two important hypotheses that remained untested in our previous work. First, we hypothesized that regions involved in theory of mind (ToM) are located upstream the causal flow and drive non-ToM regions, in line with theories attributing religion to the evolution of ToM. Second, we hypothesized that differences in directional connectivity are associated with differences in religiosity. To test these hypotheses, we performed a multivariate Granger causality-based directional connectivity analysis of fMRI data to demonstrate the causal flow within religious belief-related networks. Our results supported both hypotheses. Religious subjects preferentially activated a pathway from inferolateral to dorsomedial frontal cortex to monitor the intent and involvement of supernatural agents (SAs; intent-related ToM). Perception of SAs engaged pathways involved in fear regulation and affective ToM. Religious beliefs are founded both on propositional statements for doctrine, but also on episodic memory and imagery. Beliefs based on doctrine engaged a pathway from Broca's to Wernicke's language areas. Beliefs related to everyday life experiences engaged pathways involved in imagery. Beliefs implying less involved SAs and evoking imagery activated a pathway from right lateral temporal to occipital regions. This pathway was more active in non-religious compared to religious subjects, suggesting greater difficulty and procedural demands for imagining and processing the intent of SAs. Insights gained by Granger connectivity analysis inform us about the causal binding of individual regions activated during religious belief processing. PMID:24279687

Brain networks shaping religious belief.

PubMed

Kapogiannis, Dimitrios; Deshpande, Gopikrishna; Krueger, Frank; Thornburg, Matthew P; Grafman, Jordan Henry

2014-02-01

We previously demonstrated with functional magnetic resonance imaging (fMRI) that religious belief depends upon three cognitive dimensions, which can be mapped to specific brain regions. In the present study, we considered these co-activated regions as nodes of three networks each one corresponding to a particular dimension, corresponding to each dimension and examined the causal flow within and between these networks to address two important hypotheses that remained untested in our previous work. First, we hypothesized that regions involved in theory of mind (ToM) are located upstream the causal flow and drive non-ToM regions, in line with theories attributing religion to the evolution of ToM. Second, we hypothesized that differences in directional connectivity are associated with differences in religiosity. To test these hypotheses, we performed a multivariate Granger causality-based directional connectivity analysis of fMRI data to demonstrate the causal flow within religious belief-related networks. Our results supported both hypotheses. Religious subjects preferentially activated a pathway from inferolateral to dorsomedial frontal cortex to monitor the intent and involvement of supernatural agents (SAs; intent-related ToM). Perception of SAs engaged pathways involved in fear regulation and affective ToM. Religious beliefs are founded both on propositional statements for doctrine, but also on episodic memory and imagery. Beliefs based on doctrine engaged a pathway from Broca's to Wernicke's language areas. Beliefs related to everyday life experiences engaged pathways involved in imagery. Beliefs implying less involved SAs and evoking imagery activated a pathway from right lateral temporal to occipital regions. This pathway was more active in non-religious compared to religious subjects, suggesting greater difficulty and procedural demands for imagining and processing the intent of SAs. Insights gained by Granger connectivity analysis inform us about the causal binding of individual regions activated during religious belief processing.

On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus.

PubMed

Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-10-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

On Initial Brain Activity Mapping of Associative Memory Code in the Hippocampus

PubMed Central

Tsien, Joe Z.; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Lei Wang, Phillip; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-01-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. PMID:23838072

The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Zhu, Jingfen; Shi, Rong; Chen, Su; Dai, Lihua; Shen, Tian; Feng, Yi; Gu, Pingping; Shariff, Mina; Nguyen, Tuong; Ye, Yeats; Rao, Jianyu; Xing, Guoqiang

2016-01-01

Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47-88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs.

How Does the Sparse Memory “Engram” Neurons Encode the Memory of a Spatial–Temporal Event?

PubMed Central

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns. PMID:27601979

How Does the Sparse Memory "Engram" Neurons Encode the Memory of a Spatial-Temporal Event?

PubMed

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns.

Brain-behavior relationships in source memory: Effects of age and memory ability.

PubMed

Meusel, Liesel-Ann; Grady, Cheryl L; Ebert, Patricia E; Anderson, Nicole D

2017-06-01

There is considerable evidence for age-related decrements in source memory retrieval, but the literature on the neural correlates of these impairments is mixed. In this study, we used functional magnetic resonance imaging to examine source memory retrieval-related brain activity, and the monotonic relationship between retrieval-related brain activity and source memory accuracy, as a function of both healthy aging (younger vs older) and memory ability within the older adult group (Hi-Old vs Lo-Old). Participants studied lists of word pairs, half visually, half aurally; these were re-presented visually in a scanned test phase and participants indicated if the pair was 'seen' or 'heard' in the study phase. The Lo-Old, but not the Hi-Old, showed source memory performance decrements compared to the Young. During retrieval of source memories, younger and older adults engaged lateral and medial prefrontal cortex (PFC) and medial posterior parietal (and occipital) cortices. The groups differed in how brain activity related to source memory accuracy in dorsal anterior cingulate cortex, precuneus/cuneus, and the inferior parietal cortex; in each of these areas, greater activity was associated with poorer accuracy in the Young, but with higher accuracy in the Hi-Old (anterior cingulate and precuneus/cuneus) and Lo-Old (inferior parietal lobe). Follow-up pairwise group interaction analyses revealed that greater activity in right parahippocampal gyrus was associated with better source memory in the Hi-Old, but not in the Lo-Old. We conclude that older adults recruit additional brain regions to compensate for age-related decline in source memory, but the specific regions involved differ depending on their episodic memory ability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Memory-related brain lateralisation in birds and humans.

PubMed

Moorman, Sanne; Nicol, Alister U

2015-03-01

Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

[The pharmacology of memory (results and prospects)].

PubMed

Borodkin, Iu S; Zaĭtsev, Iu V

1984-07-01

Principal possibilities and limits of using the pharmacological approach for control of memory in studies of neurophysiological and neurochemical mechanisms of learning and memory in humans and animals are reviewed as well as its place in experimental and clinical therapy of memory disorders. Using an unspecific connector aethimizol as a pharmacological probe aided to assess changes accompanying the formation and consolidation of memory traces. The significance of fast and slow bioelectrical brain activity in the memory processing, the role of enzymes involved in transcription and template chromatine activity of the neurons under the effect of drugs on memory and learning, the correlation between time-depending learning and the pattern of RNA synthesis in brain cells, as well as possibilities and pathways of utilization of drugs in the correction of the long-term memory matrix formed by a stable pathological state of the brain, are discussed.

Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

PubMed

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

Variability in memory performance in aged healthy individuals: an fMRI study.

PubMed

Grön, Georg; Bittner, Daniel; Schmitz, Bernd; Wunderlich, Arthur P; Tomczak, Reinhard; Riepe, Matthias W

2003-01-01

Episodic memory performance varies in older subjects but underlying biological correlates remain as yet ambiguous. We investigated episodic memory in healthy older individuals (n=24; mean age: 64.4+/-6.7 years) without subjective memory complaints or objective cognitive impairment. Episodic memory was assessed with repetitive learning and recall of abstract geometric patterns during fMRI. Group analysis of brain activity during initial learning and maximum recall revealed hippocampal activation. Correlation analysis of brain activation and task performance demonstrated significant hippocampal activity during initial learning and maximum recall in a success-dependent manner. Neither age nor gray matter densities correlated with hippocampal activation. Functional imaging of episodic memory thus permits to detect objectively variability in hippocampal recruitment in healthy aged individuals without subjective memory complaints. Correlation analysis of brain activation and performance during an episodic memory task may be used to determine and follow-up hippocampal malfunction in a very sensitive manner.

Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welzel, Grit; Fleckenstein, Katharina; Department of Radiation Oncology, Duke University Medical Center, Durham, NC

2008-12-01

Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy,more » prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.« less

Aging-related changes in the default mode network and its anti-correlated networks: a resting-state fMRI study.

PubMed

Wu, Jing-Tao; Wu, Hui-Zhen; Yan, Chao-Gan; Chen, Wen-Xin; Zhang, Hong-Ying; He, Yong; Yang, Hai-Shan

2011-10-17

Intrinsic brain activity in a resting state incorporates components of the task negative network called default mode network (DMN) and task-positive networks called attentional networks. In the present study, the reciprocal neuronal networks in the elder group were compared with the young group to investigate the differences of the intrinsic brain activity using a method of temporal correlation analysis based on seed regions of posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC). We found significant decreased positive correlations and negative correlations with the seeds of PCC and vmPFC in the old group. The decreased coactivations in the DMN network components and their negative networks in the old group may reflect age-related alterations in various brain functions such as attention, motor control and inhibition modulation in cognitive processing. These alterations in the resting state anti-correlative networks could provide neuronal substrates for the aging brain. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

PubMed

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

PubMed Central

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

Objective It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. PMID:26139105

Committing to Memory: Memory Prosthetics Show Promise in Helping Those with Neurodegenerative Disorders.

PubMed

Solis, Michele

2017-01-01

Cell phone chimes, sticky notes, even the proverbial string around a finger-these timehonored external cues help guard against our inevitable memory lapses. But some internal help to the brain itself may be on the way in the form of what's being called memory prosthetics. Once considered to be on the fringes of neuroscience, the idea of adding hardware to the brain to help with memory has gathered steam. In 2014, the U.S. Defense Advanced Research Projects Agency (DARPA) made a US$30 million investment in memory prosthetic research as part of the Obama administration's Brain Research through Advancing Innovative Neurotechnologies initiative. In August 2016, Kernel, a startup based in Los Angeles, California, announced its goal to develop a clinical memory device for those debilitated by neurodegenerative disorders such as Alzheimer's disease.

Abnormal interactions of verbal- and spatial-memory networks in young people at familial high-risk for schizophrenia.

PubMed

Li, Xiaobo; Thermenos, Heidi W; Wu, Ziyan; Momura, Yoko; Wu, Kai; Keshavan, Matcheri; Seidman, Lawrence; DeLisi, Lynn E

2016-10-01

Working memory impairment (especially in verbal and spatial domains) is the core neurocognitive impairment in schizophrenia and the familial high-risk (FHR) population. Inconsistent results have been reported in clinical and neuroimaging studies examining the verbal- and spatial-memory deficits in the FHR subjects, due to sample differences and lack of understanding on interactions of the brain regions for processing verbal- and spatial-working memory. Functional MRI data acquired during a verbal- vs. spatial-memory task were included from 51 young adults [26 FHR and 25 controls]. Group comparisons were conducted in brain activation patterns responding to 1) verbal-memory condition (A), 2) spatial-memory condition (B), 3) verbal higher than spatial (A-B), 4) spatial higher than verbal (B-A), 5) conjunction of brain regions that were activated during both A and B (A∧B). Group difference of the laterality index (LI) in inferior frontal lobe for condition A was also assessed. Compared to controls, the FHR group exhibited significantly decreased brain activity in left inferior frontal during A, and significantly stronger involvement of ACC, PCC, paracentral gyrus for the contrast of A-B. The LI showed a trend of reduced left-higher-than-right pattern for verbal-memory processing in the HR group. Our findings suggest that in the entire functional brain network for working-memory processing, verbal information processing associated brain pathways are significantly altered in people at familial high risk for developing schizophrenia. Future studies will need to examine whether these alterations may indicate vulnerability for predicting the onset of Schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain regions involved in subprocesses of small-space episodic object-location memory: a systematic review of lesion and functional neuroimaging studies.

PubMed

Zimmermann, Kathrin; Eschen, Anne

2017-04-01

Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143-160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339-1345. doi: 10.1016/j.neubiorev.2008.05.001 ) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimaging studies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimaging studies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps.

Professionals' views on the use of smartphone technology to support children and adolescents with memory impairment due to acquired brain injury.

PubMed

Plackett, Ruth; Thomas, Sophie; Thomas, Shirley

2017-04-01

Purpose To identify from a health-care professionals' perspective whether smartphones are used by children and adolescents with acquired brain injury as memory aids; what factors predict smartphone use and what barriers prevent the use of smartphones as memory aids by children and adolescents. Method A cross-sectional online survey was undertaken with 88 health-care professionals working with children and adolescents with brain injury. Results Children and adolescents with brain injury were reported to use smartphones as memory aids by 75% of professionals. However, only 42% of professionals helped their clients to use smartphones. The only factor that significantly predicted reported smartphone use was the professionals' positive attitudes toward assistive technology. Several barriers to using smartphones as memory aids were identified, including the poor accessibility of devices and cost of devices. Conclusion Many children and adolescents with brain injury are already using smartphones as memory aids but this is often not facilitated by professionals. Improving the attitudes of professionals toward using smartphones as assistive technology could help to increase smartphone use in rehabilitation. Implications for Rehabilitation Smartphones could be incorporated into rehabilitation programs for young people with brain injury as socially acceptable compensatory aids. Further training and support for professionals on smartphones as compensatory aids could increase professionals' confidence and attitudes in facilitating the use of smartphones as memory aids. Accessibility could be enhanced by the development of a smartphone application specifically designed to be used by young people with brain injury.

Age-related impairments in active learning and strategic visual exploration.

PubMed

Brandstatt, Kelly L; Voss, Joel L

2014-01-01

Old age could impair memory by disrupting learning strategies used by younger individuals. We tested this possibility by manipulating the ability to use visual-exploration strategies during learning. Subjects controlled visual exploration during active learning, thus permitting the use of strategies, whereas strategies were limited during passive learning via predetermined exploration patterns. Performance on tests of object recognition and object-location recall was matched for younger and older subjects for objects studied passively, when learning strategies were restricted. Active learning improved object recognition similarly for younger and older subjects. However, active learning improved object-location recall for younger subjects, but not older subjects. Exploration patterns were used to identify a learning strategy involving repeat viewing. Older subjects used this strategy less frequently and it provided less memory benefit compared to younger subjects. In previous experiments, we linked hippocampal-prefrontal co-activation to improvements in object-location recall from active learning and to the exploration strategy. Collectively, these findings suggest that age-related memory problems result partly from impaired strategies during learning, potentially due to reduced hippocampal-prefrontal co-engagement.

Through the Immune Looking Glass: A Model for Brain Memory Strategies

PubMed Central

Sánchez-Ramón, Silvia; Faure, Florence

2016-01-01

The immune system (IS) and the central nervous system (CNS) are complex cognitive networks involved in defining the identity (self) of the individual through recognition and memory processes that enable one to anticipate responses to stimuli. Brain memory has traditionally been classified as either implicit or explicit on psychological and anatomical grounds, with reminiscences of the evolutionarily-based innate-adaptive IS responses. Beyond the multineuronal networks of the CNS, we propose a theoretical model of brain memory integrating the CNS as a whole. This is achieved by analogical reasoning between the operational rules of recognition and memory processes in both systems, coupled to an evolutionary analysis. In this new model, the hippocampus is no longer specifically ascribed to explicit memory but rather it both becomes part of the innate (implicit) memory system and tightly controls the explicit memory system. Alike the antigen presenting cells for the IS, the hippocampus would integrate transient and pseudo-specific (i.e., danger-fear) memories and would drive the formation of long-term and highly specific or explicit memories (i.e., the taste of the Proust’s madeleine cake) by the more complex and recent, evolutionarily speaking, neocortex. Experimental and clinical evidence is provided to support the model. We believe that the singularity of this model’s approximation could help to gain a better understanding of the mechanisms operating in brain memory strategies from a large-scale network perspective. PMID:26869886

Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

PubMed

Fjell, Anders M; Sneve, Markus H; Storsve, Andreas B; Grydeland, Håkon; Yendiki, Anastasia; Walhovd, Kristine B

2016-03-01

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Brain plasticity, memory, and aging: a discussion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, E.L.; Rosenzweig, M.R.

1977-12-01

It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing formore » the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.« less

Associations Between White Matter Microstructure and Infants’ Working Memory

PubMed Central

Short, Sarah J.; Elison, Jed T.; Goldman, Barbara Davis; Styner, Martin; Gu, Hongbin; Connelly, Mark; Maltbie, Eric; Woolson, Sandra; Lin, Weili; Gerig, Guido; Reznick, J. Steven; Gilmore, John H.

2013-01-01

Working memory emerges in infancy and plays a privileged role in subsequent adaptive cognitive development. The neural networks important for the development of working memory during infancy remain unknown. We used diffusion tensor imaging (DTI) and deterministic fiber tracking to characterize the microstructure of white matter fiber bundles hypothesized to support working memory in 12-month-old infants (n=73). Here we show robust associations between infants’ visuospatial working memory performance and microstructural characteristics of widespread white matter. Significant associations were found for white matter tracts that connect brain regions known to support working memory in older children and adults (genu, anterior and superior thalamic radiations, anterior cingulum, arcuate fasciculus, and the temporal-parietal segment). Better working memory scores were associated with higher FA and lower RD values in these selected white matter tracts. These tract-specific brain-behavior relationships accounted for a significant amount of individual variation above and beyond infants’ gestational age and developmental level, as measured with the Mullen Scales of Early Learning. Working memory was not associated with global measures of brain volume, as expected, and few associations were found between working memory and control white matter tracts. To our knowledge, this study is among the first demonstrations of brain-behavior associations in infants using quantitative tractography. The ability to characterize subtle individual differences in infant brain development associated with complex cognitive functions holds promise for improving our understanding of normative development, biomarkers of risk, experience-dependent learning and neuro-cognitive periods of developmental plasticity. PMID:22989623

Competition between thyroid hormone receptor-associated protein (TRAP) 220 and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors. Implications for the recruitment of TRAP and p160 coactivator complexes.

PubMed

Treuter, E; Johansson, L; Thomsen, J S; Wärnmark, A; Leers, J; Pelto-Huikko, M; Sjöberg, M; Wright, A P; Spyrou, G; Gustafsson, J A

1999-03-05

Transcriptional activation by nuclear receptors (NRs) involves the concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging complex to the basal transcription machinery. TRAP220, the 220-kDa NR-binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.

The Role of Ephs and Ephrins in Memory Formation.

PubMed

Dines, Monica; Lamprecht, Raphael

2016-04-01

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer's disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

PubMed

Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

2018-05-09

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

A History and Overview of the Behavioral Neuroscience of Learning and Memory.

PubMed

Clark, Robert E

2018-01-01

Here, I provide a basic history of important milestones in the development of theories for how the brain accomplishes the phenomenon of learning and memory. Included are the ideas of Plato, René Descartes, Théodule Ribot, William James, Ivan Pavlov, John Watson, Karl Lashley, and others. The modern era of learning and memory research begins with the description of H.M. by Brenda Milner and the gradual discovery that the brain contains multiple learning and memory systems that are supported by anatomically discrete brain structures. Finally, a brief overview is provided for the chapters that are included in current topics in Behavioral Neuroscience-Learning and Memory.

A History and Overview of the Behavioral Neuroscience of Learning and Memory.

PubMed

Clark, Robert E

2018-01-05

Here, I provide a basic history of important milestones in the development of theories for how the brain accomplishes the phenomenon of learning and memory. Included are the ideas of Plato, René Descartes, Théodule Ribot, William James, Ivan Pavlov, John Watson, Karl Lashley, and others. The modern era of learning and memory research begins with the description of H.M. by Brenda Milner and the gradual discovery that the brain contains multiple learning and memory systems that are supported by anatomically discrete brain structures. Finally, a brief overview is provided for the chapters that are included in current topics in Behavioral Neuroscience-Learning and Memory.

Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

PubMed Central

Wahl, Devin; Coogan, Sean CP; Solon-Biet, Samantha M; de Cabo, Rafael; Haran, James B; Raubenheimer, David; Cogger, Victoria C; Mattson, Mark P; Simpson, Stephen J; Le Couteur, David G

2017-01-01

Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients. Dietary interventions have been shown to influence various cognitive and behavioral tests in rodents indicating that nutrition can influence brain aging and possibly neurodegeneration. PMID:28932108

Mitochondrial impairments contribute to spatial learning and memory dysfunction induced by chronic tramadol administration in rat: Protective effect of physical exercise.

PubMed

Mehdizadeh, Hajar; Pourahmad, Jalal; Taghizadeh, Ghorban; Vousooghi, Nasim; Yoonessi, Ali; Naserzadeh, Parvaneh; Behzadfar, Ladan; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2017-10-03

Despite the worldwide use of tramadol, few studies have been conducted about its effects on memory and mitochondrial function, and controversial results have been reported. Recently, there has been an increasing interest in physical exercise as a protective approach to neuronal and cognitive impairments. Therefore, the aim of this study was to investigate the effects of physical exercise on spatial learning and memory and brain mitochondrial function in tramadol-treated rats. After completion of 2-week (short-term) and 4-week (long-term) treadmill exercise regimens, male Wistar rats received tramadol (20, 40, 80mg/kg/day) intraperitoneally for 30days. Then spatial learning and memory was assessed by Morris water maze test (MWM). Moreover, brain mitochondrial function was evaluated by determination of mitochondrial reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release from mitochondria. Chronic administration of tramadol impaired spatial learning and memory as well as brain mitochondrial function as indicated by increased ROS level, MMP collapse, increased mitochondrial swelling and cytochrome c release from mitochondria. Conversely, treadmill exercise significantly attenuated the impairments of spatial learning and memory and brain mitochondrial dysfunction induced by tramadol. The results revealed that chronic tramadol treatment caused memory impairments through induction of brain mitochondrial dysfunction. Furthermore, pre-exposure to physical exercise markedly mitigated these impairments through its positive effects on brain mitochondrial function. Copyright © 2017. Published by Elsevier Inc.

Co-activation: its association with weakness and specific neurological pathology

PubMed Central

Busse, Monica E; Wiles, Charles M; van Deursen, Robert WM

2006-01-01

Background Net agonist muscle strength is in part determined by the degree of antagonist co-activation. The level of co-activation might vary in different neurological disorders causing weakness or might vary with agonist strength. Aim This study investigated whether antagonist co-activation changed a) with the degree of muscle weakness and b) with the nature of the neurological lesion causing weakness. Methods Measures of isometric quadriceps and hamstrings strength were obtained. Antagonist (hamstring) co-activation during knee extension was calculated as a ratio of hamstrings over quadriceps activity both during an isometric and during a functional sit to stand (STS) task (using kinematics) in groups of patients with extrapyramidal (n = 15), upper motor neuron (UMN) (n = 12), lower motor neuron (LMN) with (n = 18) or without (n = 12) sensory loss, primary muscle or neuromuscular junction disorder (n = 17) and in healthy matched controls (n = 32). Independent t-tests or Mann Witney U tests were used to compare between the groups. Correlations between variables were also investigated. Results In healthy subjects mean (SD) co-activation of hamstrings during isometric knee extension was 11.8 (6.2)% and during STS was 20.5 (12.9)%. In patients, co-activation ranged from 7 to 17% during isometric knee extension and 15 to 25% during STS. Only the extrapyramidal group had lower co-activation levels than healthy matched controls (p < 0.05). Agonist isometric muscle strength and co-activation correlated only in muscle disease (r = -0.6, p < 0.05) and during STS in UMN disorders (r = -0.7, p < 0.5). Conclusion It is concluded that antagonist co-activation does not systematically vary with the site of neurological pathology when compared to healthy matched controls or, in most patient groups, with strength. The lower co-activation levels found in the extrapyramidal group require confirmation and further investigation. Co-activation may be relevant to individuals with muscle weakness. Within patient serial studies in the presence of changing muscle strength may help to understand these relationships more clearly. PMID:17116259

Brain STAT5 signaling modulates learning and memory formation.

PubMed

Furigo, Isadora C; Melo, Helen M; Lyra E Silva, Natalia M; Ramos-Lobo, Angela M; Teixeira, Pryscila D S; Buonfiglio, Daniella C; Wasinski, Frederick; Lima, Eliana R; Higuti, Eliza; Peroni, Cibele N; Bartolini, Paolo; Soares, Carlos R J; Metzger, Martin; de Felice, Fernanda G; Donato, Jose

2018-06-01

The signal transducer and activator of transcription 5 (STAT5) is a transcription factor recruited by numerous cytokines. STAT5 is important for several physiological functions, including body and tissue growth, mammary gland development, immune system and lipid metabolism. However, the role of STAT5 signaling for brain functions is still poorly investigated, especially regarding cognitive aspects. Therefore, the objective of the present study was to investigate whether brain STAT5 signaling modulates learning and memory formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were studied in well-established memory tests. Initially, we confirmed a robust reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5 KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth, somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific STAT5 ablation impaired learning and memory formation in the novel object recognition, Barnes maze and contextual fear conditioning tests. To unravel possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we assessed neurogenesis in the hippocampus, but no significant differences were observed between groups. On the other hand, reduced insulin-like growth factor-1 (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO mice. These findings collectively indicate that brain STAT5 signaling is required to attain normal learning and memory. Therefore, STAT5 is an important downstream cellular mechanism shared by several cytokines to regulate cognitive functions.

Identification of novel targets for PGC-1{alpha} and histone deacetylase inhibitors in neuroblastoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowell, Rita M.; Department of Neurology, University of Michigan, Ann Arbor, MI 48109; Talati, Pratik

2009-02-06

Recent evidence suggests that the transcriptional coactivator peroxisome proliferator activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) is involved in the pathology of Huntington's Disease (HD). While animals lacking PGC-1{alpha} express lower levels of genes involved in antioxidant defense and oxidative phosphorylation in the brain, little is known about other targets for PGC-1{alpha} in neuronal cells and whether there are ways to pharmacologically target PGC-1{alpha} in neurons. Here, PGC-1{alpha} overexpression in SH-SY5Y neuroblastoma cells upregulated expression of genes involved in mitochondrial function, glucose transport, fatty acid metabolism, and synaptic function. Overexpression also decreased vulnerability to hydrogen peroxide-induced cell death and caspase 3more » activation. Treatment of cells with the histone deacetylase inhibitors (HDACi's) trichostatin A and valproic acid upregulated PGC-1{alpha} and glucose transporter 4 (GLUT4). These results suggest that PGC-1{alpha} regulates multiple pathways in neurons and that HDACi's may be good candidates to target PGC-1{alpha} and GLUT4 in HD and other neurological disorders.« less

Mitochondrial thermogenesis and obesity.

PubMed

Gambert, Ségolène; Ricquier, Daniel

2007-11-01

Thermogenesis is activated at the expense of carbon molecules. Mitochondria play a dominant role in oxidation and parallel heat production since the recovery of oxidation energy is less than perfect. Recent data of mitochondriogenesis and mitochondrial thermogenesis may boost research into certain aspects of obesity. Recent studies have outlined the unexpected decreased thermogenesis that limits fat loss during prolonged food restriction. Activation of fat oxidation in skeletal muscle remains a strategy against fat accumulation, however. Certain adipose depots have the potential to promote thermogenesis, either using mitochondrial uncoupling protein or independently. Peroxisome proliferator-activated receptor gamma coactivators alpha and ss are important regulators of mitochondria thermogenesis. Brain mitochondria are involved in the control of refeeding after starvation. This dual action of mitochondria inform their role in thermogenesis and energy partitioning. The importance of thyroid hormones in mitochondria thermogenesis is also confirmed. The clinical and research implications of these findings are that the mechanisms inhibiting adaptive thermogenesis during diet restriction should be investigated. An important field of research is the contribution of transcriptional coactivators to adipocyte plasticity since adipocytes have an underestimated ability to oxidise fatty acids in addition to their role in triglyceride storage.

Brain Oscillations during Semantic Evaluation of Speech

ERIC Educational Resources Information Center

Shahin, Antoine J.; Picton, Terence W.; Miller, Lee M.

2009-01-01

Changes in oscillatory brain activity have been related to perceptual and cognitive processes such as selective attention and memory matching. Here we examined brain oscillations, measured with electroencephalography (EEG), during a semantic speech processing task that required both lexically mediated memory matching and selective attention.…

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

PubMed

Choi, Mi-Ran; Lee, Min Young; Hong, Ji Eun; Kim, Jeong Eun; Lee, Jae-Yong; Kim, Tae Hwan; Chun, Jang Woo; Shin, Hyun Kyung; Kim, Eun Ji

2014-10-01

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

Dual Gamma Rhythm Generators Control Interlaminar Synchrony in Auditory Cortex

PubMed Central

Ainsworth, Matthew; Lee, Shane; Cunningham, Mark O.; Roopun, Anita K.; Traub, Roger D.; Kopell, Nancy J.; Whittington, Miles A.

2013-01-01

Rhythmic activity in populations of cortical neurons accompanies, and may underlie, many aspects of primary sensory processing and short-term memory. Activity in the gamma band (30 Hz up to > 100 Hz) is associated with such cognitive tasks and is thought to provide a substrate for temporal coupling of spatially separate regions of the brain. However, such coupling requires close matching of frequencies in co-active areas, and because the nominal gamma band is so spectrally broad, it may not constitute a single underlying process. Here we show that, for inhibition-based gamma rhythms in vitro in rat neocortical slices, mechanistically distinct local circuit generators exist in different laminae of rat primary auditory cortex. A persistent, 30 – 45 Hz, gap-junction-dependent gamma rhythm dominates rhythmic activity in supragranular layers 2/3, whereas a tonic depolarization-dependent, 50 – 80 Hz, pyramidal/interneuron gamma rhythm is expressed in granular layer 4 with strong glutamatergic excitation. As a consequence, altering the degree of excitation of the auditory cortex causes bifurcation in the gamma frequency spectrum and can effectively switch temporal control of layer 5 from supragranular to granular layers. Computational modeling predicts the pattern of interlaminar connections may help to stabilize this bifurcation. The data suggest that different strategies are used by primary auditory cortex to represent weak and strong inputs, with principal cell firing rate becoming increasingly important as excitation strength increases. PMID:22114273

The association between antagonist hamstring coactivation and episodes of knee joint shifting and buckling

PubMed Central

Segal, N.A.; Nevitt, M.C.; Welborn, R.D.; Nguyen, U.-S.D.T.; Niu, J.; Lewis, C.E.; Felson, D.T.; Frey-Law, L.

2016-01-01

SUMMARY Objective Hamstring coactivation during quadriceps activation is necessary to counteract the quadriceps pull on the tibia, but coactivation can be elevated with symptomatic knee osteoarthritis (OA). To guide rehabilitation to attenuate risk for mobility limitations and falls, this study evaluated whether higher antagonistic open kinetic chain hamstring coactivation is associated with knee joint buckling (sudden loss of support) and shifting (a sensation that the knee might give way). Design At baseline, median hamstring coactivation was assessed during maximal isokinetic knee extensor strength testing and at baseline and 24-month follow-up, knee buckling and shifting was self-reported. Associations between tertiles of co-activation and knee (1) buckling, (2) shifting and (3) either buckling or shifting were assessed using logistic regression, adjusted for age, sex, knee OA and pain. Results 1826 participants (1089 women) were included. Mean ± SD age was 61.7 ± 7.7 years, BMI was 30.3 ± 5.5 kg/m2 and 38.2% of knees had OA. There were no consistent statistically significant associations between hamstring coactivation and ipsilateral prevalent or incident buckling or the combination of buckling and shifting. The odds ratios for incident shifting in the highest in comparison with the lowest tertile of coactivation had similar magnitudes in the combined and medial hamstrings, but only reached statistical significance for lateral hamstring coactivation, OR(95%CI) 1.53 (0.99, 2.36). Conclusions Hamstring coactivation during an open kinetic chain quadriceps exercise was not consistently associated with prevalent or incident self-reported knee buckling or shifting in older adults with or at risk for knee OA. PMID:25765501

Behavioral and Functional Neuroanatomical Correlates of Anterograde Autobiographical Memory in Isolated Retrograde Amnesic Patient M. L.

ERIC Educational Resources Information Center

Levine, Brian; Svoboda, Eva; Turner, Gary R.; Mandic, Marina; Mackey, Allison

2009-01-01

Patient M. L. [Levine, B., Black, S. E., Cabeza, R., Sinden, M., Mcintosh, A. R., Toth, J. P., et al. (1998). "Episodic memory and the self in a case of isolated retrograde amnesia." "Brain", "121", 1951-1973], lost memory for events occurring before his severe traumatic brain injury, yet his anterograde (post-injury) learning and memory appeared…

Contralateral Cortical Organisation of Information in Visual Short-Term Memory: Evidence from Lateralized Brain Activity during Retrieval

ERIC Educational Resources Information Center

Fortier-Gauthier, Ulysse; Moffat, Nicolas; Dell'Acqua, Robert; McDonald, John J.; Jolicoeur, Pierre

2012-01-01

We studied brain activity during retention and retrieval phases of two visual short-term memory (VSTM) experiments. Experiment 1 used a balanced memory array, with one color stimulus in each hemifield, followed by a retention interval and a central probe, at the fixation point that designated the target stimulus in memory about which to make a…

Effect of higher muscle coactivation on standing postural response to perturbation in older adults.

PubMed

Nagai, Koutatsu; Okita, Yusuke; Ogaya, Shinya; Tsuboyama, Tadao

2017-04-01

Although several studies have reported that muscle coactivation during postural control increases with age, the effect of higher muscle coactivation on standing postural response to perturbation is unknown. To investigate whether higher muscle coactivation affects standing postural response to perturbation in older adults. Thirty-four community-dwelling older participants were randomly assigned either to the coactivation group (CG), where muscle coactivation was increased intentionally, or to the non-coactivation group (NCG). The participants were instructed to stand on a force plate that moved forward or backward. Electromyography data were collected from the lower leg muscles. We requested the participants in the CG to increase the activity of their tibialis anterior, and to maintain this posture during the tasks. We moved the force plate with a constant amplitude and velocity, and measured kinematic data with a camera during the tasks. During forward transfer, the knee extension and hip flexion decreased in the CG after perturbation compared to NCG, and the trunk extension angle increased. The center of pressure (COP) displacement decreased around the peak of the movement in the CG compared to NCG. During backward transfer, ankle dorsal and knee flexion changed after perturbation in the CG compared to NCG. Our study found that higher muscle coactivation inhibits lower limb and COP movement as well as increases trunk tilt and the risk for falls during forward perturbations. Postural control with higher coactivation appears to be inefficient for maintaining balance during the backward sway of posture.

Preterm Infant Hippocampal Volumes Correlate with Later Working Memory Deficits

ERIC Educational Resources Information Center

Beauchamp, Miriam H.; Thompson, Deanne K.; Howard, Kelly; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.; Anderson, Peter J.

2008-01-01

Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal…

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Brain training game boosts executive functions, working memory and processing speed in the young adults: a randomized controlled trial.

PubMed

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. UMIN Clinical Trial Registry 000005618.

Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

PubMed Central

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

2013-01-01

Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial Registration UMIN Clinical Trial Registry 000005618. PMID:23405164

First steps in using machine learning on fMRI data to predict intrusive memories of traumatic film footage

PubMed Central

Clark, Ian A.; Niehaus, Katherine E.; Duff, Eugene P.; Di Simplicio, Martina C.; Clifford, Gari D.; Smith, Stephen M.; Mackay, Clare E.; Woolrich, Mark W.; Holmes, Emily A.

2014-01-01

After psychological trauma, why do some only some parts of the traumatic event return as intrusive memories while others do not? Intrusive memories are key to cognitive behavioural treatment for post-traumatic stress disorder, and an aetiological understanding is warranted. We present here analyses using multivariate pattern analysis (MVPA) and a machine learning classifier to investigate whether peri-traumatic brain activation was able to predict later intrusive memories (i.e. before they had happened). To provide a methodological basis for understanding the context of the current results, we first show how functional magnetic resonance imaging (fMRI) during an experimental analogue of trauma (a trauma film) via a prospective event-related design was able to capture an individual's later intrusive memories. Results showed widespread increases in brain activation at encoding when viewing a scene in the scanner that would later return as an intrusive memory in the real world. These fMRI results were replicated in a second study. While traditional mass univariate regression analysis highlighted an association between brain processing and symptomatology, this is not the same as prediction. Using MVPA and a machine learning classifier, it was possible to predict later intrusive memories across participants with 68% accuracy, and within a participant with 97% accuracy; i.e. the classifier could identify out of multiple scenes those that would later return as an intrusive memory. We also report here brain networks key in intrusive memory prediction. MVPA opens the possibility of decoding brain activity to reconstruct idiosyncratic cognitive events with relevance to understanding and predicting mental health symptoms. PMID:25151915

Differential associations between types of verbal memory and prefrontal brain structure in healthy aging and late life depression.

PubMed

Lamar, Melissa; Charlton, Rebecca; Zhang, Aifeng; Kumar, Anand

2012-07-01

Verbal memory deficits attributed to late life depression (LLD) may result from executive dysfunction that is more detrimental to list-learning than story-based recall when compared to healthy aging. Despite these behavioral dissociations, little work has been done investigating related neuroanatomical dissociations across types of verbal memory performance in LLD. We compared list-learning to story-based memory performance in 24 non-demented individuals with LLD (age ~ 66.1 ± 7.8) and 41 non-demented/non-depressed healthy controls (HC; age ~ 67.6 ± 5.3). We correlated significant results of between-group analyses across memory performance variables with brain volumes of frontal, temporal and parietal regions known to be involved with verbal learning and memory. When compared to the HC group, the LLD group showed significantly lower verbal memory performance for spontaneous recall after repeated exposure and after a long-delay but only for the list-learning task; groups did not differ on story-based memory performance. Despite equivalent brain volumes across regions, only the LLD group showed brain associations with verbal memory performance and only for the list-learning task. Specifically, frontal volumes important for subjective organization and response monitoring correlated with list-learning performance in the LLD group. This study is the first to demonstrate neuroanatomical dissociations across types of verbal memory performance in individuals with LLD. Results provide structural evidence for the behavioral dissociations between list-learning and story-based recall in LLD when compared to healthy aging. More specifically, it points toward a network of predominantly anterior brain regions that may underlie the executive contribution to list-learning in older adults with depression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Long-term effects of frequent cannabis use on working memory and attention: an fMRI study.

PubMed

Jager, Gerry; Kahn, Rene S; Van Den Brink, Wim; Van Ree, Jan M; Ramsey, Nick F

2006-04-01

Excessive use of cannabis may have long-term effects on cognitive abilities. Mild impairments have been found in several cognitive domains, particularly in memory and attention. It is not clear, however, whether these effects also occur with moderate, recreational use of cannabis. Furthermore, little is known about underlying brain correlates. The aim of this study is to assess brain function in frequent but relatively moderate cannabis users in the domains of working memory and selective attention. Functional magnetic resonance imaging was used to examine verbal working memory and visuo-auditory selective attention in ten frequent cannabis users (after 1 week of abstinence) and ten non-using healthy controls. Groups were similar in age, gender and estimated IQ. Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. However, for working memory, a more specific region-of-interest analysis showed that, in comparison to the controls, cannabis users displayed a significant alteration in brain activity in the left superior parietal cortex. No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence. Nonetheless, frequent cannabis use may affect brain function, as indicated by altered neurophysiological dynamics in the left superior parietal cortex during working memory processing.

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

PubMed

Tabassum, Saiqa; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Shahzad, Sidrah; Batool, Zehra; Haider, Saida

2017-05-01

Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

Galantamine

MedlinePlus

... AD; a brain disease that slowly destroys the memory and the ability to think, learn, communicate and ... substance in the brain that is needed for memory and thought. Galantamine may improve the ability to ...

Individual Differences in Working Memory, Nonverbal IQ, and Mathematics Achievement and Brain Mechanisms Associated with Symbolic and Nonsymbolic Number Processing

ERIC Educational Resources Information Center

Gullick, Margaret M.; Sprute, Lisa A.; Temple, Elise

2011-01-01

Individual differences in mathematics performance may stem from domain-general factors like working memory and intelligence. Parietal and frontal brain areas have been implicated in number processing, but the influence of such cognitive factors on brain activity during mathematics processing is not known. The relationship between brain mechanisms…

Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal

PubMed Central

Namazi, Hamidreza; Kulish, Vladimir V.

2016-01-01

One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory. PMID:27528219

Memory and Self–Neuroscientific Landscapes

PubMed Central

Markowitsch, Hans J.

2013-01-01

Relations between memory and the self are framed from a number of perspectives—developmental aspects, forms of memory, interrelations between memory and the brain, and interactions between the environment and memory. The self is seen as dividable into more rudimentary and more advanced aspects. Special emphasis is laid on memory systems and within them on episodic autobiographical memory which is seen as a pure human form of memory that is dependent on a proper ontogenetic development and shaped by the social environment, including culture. Self and episodic autobiographical memory are seen as interlocked in their development and later manifestation. Aside from content-based aspects of memory, time-based aspects are seen along two lines—the division between short-term and long-term memory and anterograde—future-oriented—and retrograde—past-oriented memory. The state dependency of episodic autobiographical is stressed and implications of it—for example, with respect to the occurrence of false memories and forensic aspects—are outlined. For the brain level, structural networks for encoding, consolidation, storage, and retrieval are discussed both by referring to patient data and to data obtained in normal participants with functional brain imaging methods. It is elaborated why descriptions from patients with functional or dissociative amnesia are particularly apt to demonstrate the facets in which memory, self, and personal temporality are interwoven. PMID:24967303

Analysis of the influence of memory content of auditory stimuli on the memory content of EEG signal.

PubMed

Namazi, Hamidreza; Khosrowabadi, Reza; Hussaini, Jamal; Habibi, Shaghayegh; Farid, Ali Akhavan; Kulish, Vladimir V

2016-08-30

One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that may exist between the memory content of stimulus and the memory content of EEG signal. For this purpose we consider the Hurst exponent as the measure of memory. This study reveals the plasticity of human EEG signals in relation to the auditory stimuli. For the first time we demonstrated that the memory content of an EEG signal shifts towards the memory content of the auditory stimulus used. The results of this analysis showed that an auditory stimulus with higher memory content causes a larger increment in the memory content of an EEG signal. For the verification of this result, we benefit from approximate entropy as indicator of time series randomness. The capability, observed in this research, can be further investigated in relation to human memory.

Retrieval Search and Strength Evoke Dissociable Brain Activity during Episodic Memory Recall

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Neuroimaging studies of episodic memory retrieval have revealed activations in the human frontal, parietal, and medial-temporal lobes that are associated with memory strength. However, it remains unclear whether these brain responses are veritable signals of memory strength or are instead regulated by concomitant subcomponents of retrieval such as retrieval effort or mental search. This study used event-related fMRI during cued recall of previously memorized word-pair associates to dissociate brain responses modulated by memory search from those modulated by the strength of a recalled memory. Search-related deactivations, dissociated from activity due to memory strength, were observed in regions of the default network, whereas distinctly strength-dependent activations were present in superior and inferior parietal and dorsolateral PFC. Both search and strength regulated activity in dorsal anterior cingulate and anterior insula. These findings suggest that, although highly correlated and partially subserved by overlapping cognitive control mechanisms, search and memory strength engage dissociable regions of frontoparietal attention and default networks. PMID:23190328

Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

PubMed Central

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

Mnemonic training reshapes brain networks to support superior memory

PubMed Central

Dresler, Martin; Shirer, William R.; Konrad, Boris N.; Müller, Nils C.J.; Wagner, Isabella C.; Fernández, Guillén; Czisch, Michael; Greicius, Michael D.

2017-01-01

Summary Memory skills strongly differ across the general population, however little is known about the brain characteristics supporting superior memory performance. Here, we assess functional brain network organization of 23 of the world’s most successful memory athletes and matched controls by fMRI during both task-free resting state baseline and active memory encoding. We demonstrate that in a group of naïve controls, functional connectivity changes induced by six weeks of mnemonic training were correlated with the network organization that distinguishes athletes from controls. During rest, this effect was mainly driven by connections between rather than within the visual, medial temporal lobe and default mode networks, whereas during task it was driven by connectivity within these networks. Similarity with memory athlete connectivity patterns predicted memory improvements up to 4 months after training. In conclusion, mnemonic training drives distributed rather than regional changes, reorganizing the brain’s functional network organization to enable superior memory performance. PMID:28279356

Mechanisms of interactive specialization and emergence of functional brain circuits supporting cognitive development in children

NASA Astrophysics Data System (ADS)

Battista, Christian; Evans, Tanya M.; Ngoon, Tricia J.; Chen, Tianwen; Chen, Lang; Kochalka, John; Menon, Vinod

2018-01-01

Cognitive development is thought to depend on the refinement and specialization of functional circuits over time, yet little is known about how this process unfolds over the course of childhood. Here we investigated growth trajectories of functional brain circuits and tested an interactive specialization model of neurocognitive development which posits that the refinement of task-related functional networks is driven by a shared history of co-activation between cortical regions. We tested this model in a longitudinal cohort of 30 children with behavioral and task-related functional brain imaging data at multiple time points spanning childhood and adolescence, focusing on the maturation of parietal circuits associated with numerical problem solving and learning. Hierarchical linear modeling revealed selective strengthening as well as weakening of functional brain circuits. Connectivity between parietal and prefrontal cortex decreased over time, while connectivity within posterior brain regions, including intra-hemispheric and inter-hemispheric parietal connectivity, as well as parietal connectivity with ventral temporal occipital cortex regions implicated in quantity manipulation and numerical symbol recognition, increased over time. Our study provides insights into the longitudinal maturation of functional circuits in the human brain and the mechanisms by which interactive specialization shapes children's cognitive development and learning.

Muscle Co-activation: Definitions, Mechanisms, and Functions.

PubMed

Latash, Mark L

2018-03-28

The phenomenon of agonist-antagonist muscle co-activation is discussed with respect to its consequences for movement mechanics (such as increasing joint apparent stiffness, facilitating faster movements, and effects on action stability), implication for movement optimization, and involvement of different neurophysiological structures. Effects of co-activation on movement stability are ambiguous and depend on the effector representing a kinematic chain with a fixed origin or free origin. Further, co-activation is discussed within the framework of the equilibrium-point hypothesis and the idea of hierarchical control with spatial referent coordinates. Relations of muscle co-activation to changes in one of the basic commands, the c-command, are discussed and illustrated. A hypothesis is suggested that agonist-antagonist co-activation reflects a deliberate neural control strategy to preserve effector-level control and avoid making it degenerate and facing the necessity to control at the level of signals to individual muscles. This strategy, in particular, allows stabilizing motor actions by co-varied adjustments in spaces of control variables. This hypothesis is able to account for higher levels of co-activation in young healthy persons performing challenging tasks and across various populations with movement impairments.

Iconic memory and parietofrontal network: fMRI study using temporal integration.

PubMed

Saneyoshi, Ayako; Niimi, Ryosuke; Suetsugu, Tomoko; Kaminaga, Tatsuro; Yokosawa, Kazuhiko

2011-08-03

We investigated the neural basis of iconic memory using functional magnetic resonance imaging. The parietofrontal network of selective attention is reportedly relevant to readout from iconic memory. We adopted a temporal integration task that requires iconic memory but not selective attention. The results showed that the task activated the parietofrontal network, confirming that the network is involved in readout from iconic memory. We further tested a condition in which temporal integration was performed by visual short-term memory but not by iconic memory. However, no brain region revealed higher activation for temporal integration by iconic memory than for temporal integration by visual short-term memory. This result suggested that there is no localized brain region specialized for iconic memory per se.

Mental Imagery and Post-Traumatic Stress Disorder: A Neuroimaging and Experimental Psychopathology Approach to Intrusive Memories of Trauma

PubMed Central

Clark, Ian A.; Mackay, Clare E.

2015-01-01

This hypothesis and theory paper presents a pragmatic framework to help bridge the clinical presentation and neuroscience of intrusive memories following psychological trauma. Intrusive memories are a hallmark symptom of post-traumatic stress disorder (PTSD). However, key questions, including those involving etiology, remain. In particular, we know little about the brain mechanisms involved in why only some moments of the trauma return as intrusive memories while others do not. We first present an overview of the patient experience of intrusive memories and the neuroimaging studies that have investigated intrusive memories in PTSD patients. Next, one mechanism of how to model intrusive memories in the laboratory, the trauma film paradigm, is examined. In particular, we focus on studies combining the trauma film paradigm with neuroimaging. Stemming from the clinical presentation and our current understanding of the processes involved in intrusive memories, we propose a framework in which an intrusive memory comprises five component parts; autobiographical (trauma) memory, involuntary recall, negative emotions, attention hijacking, and mental imagery. Each component part is considered in turn, both behaviorally and from a brain imaging perspective. A mapping of these five components onto our understanding of the brain is described. Unanswered questions that exist in our understanding of intrusive memories are considered using the proposed framework. Overall, we suggest that mental imagery is key to bridging the experience, memory, and intrusive recollection of the traumatic event. Further, we suggest that by considering the brain mechanisms involved in the component parts of an intrusive memory, in particular mental imagery, we may be able to aid the development of a firmer bridge between patients’ experiences of intrusive memories and the clinical neuroscience behind them. PMID:26257660

Electrical engram: how deep brain stimulation affects memory.

PubMed

Lee, Hweeling; Fell, Jürgen; Axmacher, Nikolai

2013-11-01

Deep brain stimulation (DBS) is a surgical procedure involving implantation of a pacemaker that sends electric impulses to specific brain regions. DBS has been applied in patients with Parkinson's disease, depression, and obsessive-compulsive disorder (among others), and more recently in patients with Alzheimer's disease to improve memory functions. Current DBS approaches are based on the concept that high-frequency stimulation inhibits or excites specific brain regions. However, because DBS entails the application of repetitive electrical stimuli, it primarily exerts an effect on extracellular field-potential oscillations similar to those recorded with electroencephalography. Here, we suggest a new perspective on how DBS may ameliorate memory dysfunction: it may enhance normal electrophysiological patterns underlying long-term memory processes within the medial temporal lobe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spatial distribution of the messenger ribonucleic acid and protein of the nuclear receptor coactivator, amplified in breast cancer-3, in mice.

PubMed

Zhang, Hao; Liao, Lan; Kuang, Shao-Qing; Xu, Jianming

2003-04-01

Transcriptional activities of nuclear receptors are modulated by coactivators and corepressors. The amplified in breast cancer-3 protein (AIB3, also known as ASC-2, RAP250, PRIP, TRBP, and NCR) is a newly identified nuclear receptor coactivator that is amplified and overexpressed in breast cancers. This study aims to investigate the spatial expression of AIB3 mRNA and protein in various murine tissues. Quantitative measurements revealed that the concentrations of AIB3 mRNA differ substantially in different tissues in a descending order from the following: testis, brain, thymus, white fat, pituitary, ovary, adrenal gland, lung, uterus, kidney, heart, skeletal muscle, liver, and virgin mammary gland. The AIB3 mRNA level in the testis is 165-fold higher than that in the virgin mammary gland. Specific antiserum was generated and used to map the distribution of AIB3 protein by immunohistochemistry. Although AIB3 protein was detected in many tissues, the AIB3 immunoreactivities varied significantly from cell type to cell type. High levels of AIB3 immunoreactivity were observed in hormone target cells including the testicular Sertoli cells, follicular granulosa cells, and epithelial cells of the prostate, uterus, mammary gland, and kidney tubules. Medium and low levels of AIB3 immunoreactivities were also detected in a variety of other cell types. These results demonstrate that AIB3 mRNA and protein are preferentially expressed in specific cell types, suggesting that AIB3 may support the function of nuclear receptors in a cell type-specific manner.

Learning & Memory: The Brain in Action.

ERIC Educational Resources Information Center

Sprenger, Marilee

Based on the assumption that the more teachers know about brain science, the better prepared they will be to make instructional decisions, this book presents information on current research regarding learning and memory, and applies the research to situations that educators face daily. Chapter 1 examines the structure of the brain and its…

Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

ERIC Educational Resources Information Center

Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

2010-01-01

Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

Assessment of Syntax after Adolescent Brain Injury: Effects of Memory on Test Performance.

ERIC Educational Resources Information Center

Turkstra, Lyn S.; Holland, Audrey L.

1998-01-01

This study of six adolescents with brain injuries, and six controls, investigated the influence of working memory load on performance of a task designed to measure receptive syntax ability. The performance of the adolescents with brain injuries was significantly worse than that of controls. (Author/CR)

Fast associative memory + slow neural circuitry = the computational model of the brain.

NASA Astrophysics Data System (ADS)

Berkovich, Simon; Berkovich, Efraim; Lapir, Gennady

1997-08-01

We propose a computational model of the brain based on a fast associative memory and relatively slow neural processors. In this model, processing time is expensive but memory access is not, and therefore most algorithmic tasks would be accomplished by using large look-up tables as opposed to calculating. The essential feature of an associative memory in this context (characteristic for a holographic type memory) is that it works without an explicit mechanism for resolution of multiple responses. As a result, the slow neuronal processing elements, overwhelmed by the flow of information, operate as a set of templates for ranking of the retrieved information. This structure addresses the primary controversy in the brain architecture: distributed organization of memory vs. localization of processing centers. This computational model offers an intriguing explanation of many of the paradoxical features in the brain architecture, such as integration of sensors (through DMA mechanism), subliminal perception, universality of software, interrupts, fault-tolerance, certain bizarre possibilities for rapid arithmetics etc. In conventional computer science the presented type of a computational model did not attract attention as it goes against the technological grain by using a working memory faster than processing elements.

Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

PubMed Central

2016-01-01

Traumatic brain injuries (TBIs) are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub), left hippocampus (the personal experience binding hub), and left parahippocampal gyrus (the contextual association hub) were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory) and the right medial frontal gyrus (MeFG) in the anterior prefrontal cortex (PFC). We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging. PMID:28074162

The Use of Melodic and Rhythmic Mnemonics to Improve Memory and Recall in Elementary Students in the Content Areas

ERIC Educational Resources Information Center

Hayes, Orla C.

2009-01-01

Mnemonic strategies that use imagery and visual cues to facilitate memory recall are commonly used in the classroom. A familiar tune, song or jingle, used as a mnemonic device is another popular memory aid. Studies of the brain and memory reveal that exposure to music not only alters but increases brain function in students. The purpose of this…

Making lasting memories: Remembering the significant

PubMed Central

McGaugh, James L.

2013-01-01

Although forgetting is the common fate of most of our experiences, much evidence indicates that emotional arousal enhances the storage of memories, thus serving to create, selectively, lasting memories of our more important experiences. The neurobiological systems mediating emotional arousal and memory are very closely linked. The adrenal stress hormones epinephrine and corticosterone released by emotional arousal regulate the consolidation of long-term memory. The amygdala plays a critical role in mediating these stress hormone influences. The release of norepinephrine in the amygdala and the activation of noradrenergic receptors are essential for stress hormone-induced memory enhancement. The findings of both animal and human studies provide compelling evidence that stress-induced activation of the amygdala and its interactions with other brain regions involved in processing memory play a critical role in ensuring that emotionally significant experiences are well-remembered. Recent research has determined that some human subjects have highly superior autobiographic memory of their daily experiences and that there are structural differences in the brains of these subjects compared with the brains of subjects who do not have such memory. Understanding of neurobiological bases of such exceptional memory may provide additional insights into the processes underlying the selectivity of memory. PMID:23754441

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

PubMed

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-04-07

Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

Neural Basis of Working Memory Enhancement after Acute Aerobic Exercise: fMRI Study of Preadolescent Children.

PubMed

Chen, Ai-Guo; Zhu, Li-Na; Yan, Jun; Yin, Heng-Chan

2016-01-01

Working memory lies at the core of cognitive function and plays a crucial role in children's learning, reasoning, problem solving, and intellectual activity. Behavioral findings have suggested that acute aerobic exercise improves children's working memory; however, there is still very little knowledge about whether a single session of aerobic exercise can alter working memory's brain activation patterns, as assessed by functional magnetic resonance imaging (fMRI). Therefore, we investigated the effect of acute moderate-intensity aerobic exercise on working memory and its brain activation patterns in preadolescent children, and further explored the neural basis of acute aerobic exercise on working memory in these children. We used a within-subjects design with a counterbalanced order. Nine healthy, right-handed children were scanned with a Siemens MAGNETOM Trio 3.0 Tesla magnetic resonance imaging scanner while they performed a working memory task (N-back task), following a baseline session and a 30-min, moderate-intensity exercise session. Compared with the baseline session, acute moderate-intensity aerobic exercise benefitted performance in the N-back task, increasing brain activities of bilateral parietal cortices, left hippocampus, and the bilateral cerebellum. These data extend the current knowledge by indicating that acute aerobic exercise enhances children's working memory, and the neural basis may be related to changes in the working memory's brain activation patterns elicited by acute aerobic exercise.

The effects of cholesterol on learning and memory.

PubMed

Schreurs, Bernard G

2010-07-01

Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, pro-inflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.

Using chaotic artificial neural networks to model memory in the brain

NASA Astrophysics Data System (ADS)

Aram, Zainab; Jafari, Sajad; Ma, Jun; Sprott, Julien C.; Zendehrouh, Sareh; Pham, Viet-Thanh

2017-03-01

In the current study, a novel model for human memory is proposed based on the chaotic dynamics of artificial neural networks. This new model explains a biological fact about memory which is not yet explained by any other model: There are theories that the brain normally works in a chaotic mode, while during attention it shows ordered behavior. This model uses the periodic windows observed in a previously proposed model for the brain to store and then recollect the information.

Neuropeptide-Y both Improves and Impairs Delayed Matching-to-Sample Performance in Rats

DTIC Science & Technology

1991-01-01

Neuropeptide Y distribution in the 422 THOMAS AND AHLERS rat brain. Science 221:877-879; 1983. of animal learning. In: Roitblat , H. L.; Bever, T. G.; Terrace, H...Sources of proactive interference in memory. Hillsdale, NJ: Erlbaum; 1976. animal memory. J. Exp. Psychol. (Anim. Behav.) 1456-70; 1988. 32. Roitblat , H...memory processing by neuropeptide Y varies with brain 33. Roitblat , H. L., Scopatz, R. A. Sequential effects in pigeons de- injection site. Brain Res

Relationship between metabolic cost and muscular coactivation across running speeds.

PubMed

Moore, Isabel S; Jones, Andrew M; Dixon, Sharon J

2014-11-01

Muscular coactivation can help stabilise a joint, but contrasting results in previous gait studies highlight that it is not clear whether this is metabolically beneficial. The aim was to assess the relationship between the metabolic cost of running and muscular coactivation across different running speeds, in addition to assessing the reliability and precision of lower limb muscular coactivation. Eleven female recreational runners visited the laboratory on two separate occasions. On both occasions subjects ran at three speeds (9.1, 11 and 12 km h(-1)) for six minutes each. Oxygen consumption and electromyographic data were simultaneously recorded during the final two minutes of each speed. Temporal coactivations of lower limb muscles during the stance phase were calculated. Five muscles were assessed: rectus femoris, vastus lateralis, biceps femoris, tibialis anterior and gastrocnemius lateralis. Nonparametric correlations revealed at least one significant, positive association between lower limb muscular coactivation and the metabolic cost of running for each speed. The length of tibialis anterior activation and muscular coactivation of the biceps femoris-tibialis anterior and gastrocnemius lateralis-tibialis anterior decreased with speed. These results show that longer coactivations of the proximal (rectus femoris-biceps femoris and vastus lateralis-biceps femoris) and leg extensor (rectus femoris-gastrocnemius lateralis) muscles were related to a greater metabolic cost of running, which could be detrimental to performance. The decrease in coactivation in the flexor and distal muscles at faster speeds occurs due to the shorter duration of tibialis anterior activation as speed increases, yet stability may be maintained. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

PubMed

Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas

2018-06-01

Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.

Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory.

PubMed

Censor, Nitzan; Cohen, Leonardo G

2011-01-01

In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications.

Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice.

PubMed

Broussard, John I; Acion, Laura; De Jesús-Cortés, Héctor; Yin, Terry; Britt, Jeremiah K; Salas, Ramiro; Costa-Mattioli, Mauro; Robertson, Claudia; Pieper, Andrew A; Arciniegas, David B; Jorge, Ricardo

2018-01-01

Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour. We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group. We assessed the effects of smTBI and rmTBI using measures of motor performance (Rotarod Test [RT]), anxiety-like behaviour (Elevated Plus Maze [EPM] and Open Field [OF] tests), and spatial memory (Morris Water Maze [MWM]) within 12 days of the final injury. In separate groups of mice, astrocytosis and microglial activation were assessed 24 hours after the final injury using GFAP and IBA-1 immunohistochemistry. RmTBI impaired spatial memory in the MWM and increased anxiety-like behaviour in the EPM and OFT. In addition, rmTBI elevated GFAP and IBA-1 immunohistochemistry throughout the mouse brain. RmTBI produced astrocytosis and microglial activation, and elicited impaired spatial memory and anxiety-like behaviour. rmTBI produces acute cognitive and anxiety-like disturbances associated with inflammatory changes in brain regions involved in spatial memory and anxiety.

fMRI brain activation in patients with insomnia disorder during a working memory task.

PubMed

Son, Young-Don; Kang, Jae Myeong; Cho, Seong-Jin; Lee, Jung-Sun; Hwang, Hee Young; Kang, Seung-Gul

2018-05-01

This study used functional magnetic resonance imaging (fMRI) to investigate differences in the functional brain activation of patients with insomnia disorder (n = 21, mean age = 36.6) and of good sleepers (n = 26, mean age = 33.2) without other comorbidities or structural brain abnormalities during a working memory task. All participants completed a clinical questionnaire, were subjected to portable polysomnography (PSG), and performed the working memory task during an fMRI scan. The subjects who were suspected of major sleep disorder and comorbid psychiatric disorders except insomnia disorder were excluded. To compare the brain activation on working memory from the insomnia group with those from the good-sleeper group, a two-sample t test was performed. Statistical significance was determined using 3DClustSim with the updated algorithm to obtain a reasonable cluster size and p value for each analysis. We observed higher levels of brain activation in the right lateral inferior frontal cortex and the right superior temporal pole in the insomnia group compared to good sleepers (cluster-based multiple comparison correction, p < 0.001, k = 34 @ α = 0.01). Thus, patients with insomnia disorder showed increased brain activation during working memory relative to good sleepers, and this may be indicative of compensatory brain activation to maintain cognitive performance in patients with insomnia disorder without other comorbidities.

Memory: Organization and Control

PubMed Central

Eichenbaum, Howard

2017-01-01

A major goal of memory research is to understand how cognitive processes in memory are supported at the level of brain systems and network representations. Especially promising in this direction are new findings in humans and animals that converge in indicating a key role for the hippocampus in the systematic organization of memories. New findings also indicate that the prefrontal cortex may play an equally important role in the active control of memory organization during both encoding and retrieval. Observations about the dialog between the hippocampus and prefrontal cortex provide new insights into the operation of the larger brain system that serves memory. PMID:27687117

Test-Retest Reliability of fMRI Brain Activity during Memory Encoding

PubMed Central

Brandt, David J.; Sommer, Jens; Krach, Sören; Bedenbender, Johannes; Kircher, Tilo; Paulus, Frieder M.; Jansen, Andreas

2013-01-01

The mechanisms underlying hemispheric specialization of memory are not completely understood. Functional magnetic resonance imaging (fMRI) can be used to develop and test models of hemispheric specialization. In particular for memory tasks however, the interpretation of fMRI results is often hampered by the low reliability of the data. In the present study we therefore analyzed the test-retest reliability of fMRI brain activation related to an implicit memory encoding task, with a particular focus on brain activity of the medial temporal lobe (MTL). Fifteen healthy subjects were scanned with fMRI on two sessions (average retest interval 35 days) using a commonly applied novelty encoding paradigm contrasting known and unknown stimuli. To assess brain lateralization, we used three different stimuli classes that differed in their verbalizability (words, scenes, fractals). Test-retest reliability of fMRI brain activation was assessed by an intraclass-correlation coefficient (ICC), describing the stability of inter-individual differences in the brain activation magnitude over time. We found as expected a left-lateralized brain activation network for the words paradigm, a bilateral network for the scenes paradigm, and predominantly right-hemispheric brain activation for the fractals paradigm. Although these networks were consistently activated in both sessions on the group level, across-subject reliabilities were only poor to fair (ICCs ≤ 0.45). Overall, the highest ICC values were obtained for the scenes paradigm, but only in strongly activated brain regions. In particular the reliability of brain activity of the MTL was poor for all paradigms. In conclusion, for novelty encoding paradigms the interpretation of fMRI results on a single subject level is hampered by its low reliability. More studies are needed to optimize the retest reliability of fMRI activation for memory tasks. PMID:24367338

Is there pre-attentive memory-based comparison of pitch?

PubMed

Jacobsen, T; Schröger, E

2001-07-01

The brain's responsiveness to changes in sound frequency has been demonstrated by an overwhelming number of studies. Change detection occurs unintentionally and automatically. It is generally assumed that this brain response, the so-called mismatch negativity (MMN) of the event-related brain potential or evoked magnetic field, is based on the outcome of a memory-comparison mechanism rather than being due to a differential state of refractoriness of tonotopically organized cortical neurons. To the authors' knowledge, however, there is no entirely compelling evidence for this belief. An experimental protocol controlling for refractoriness effects was developed and a true memory-comparison-based brain response to pitch change was demonstrated.

Making Memories Matter

PubMed Central

Gold, Paul E.; Korol, Donna L.

2012-01-01

This article reviews some of the neuroendocrine bases by which emotional events regulate brain mechanisms of learning and memory. In laboratory rodents, there is extensive evidence that epinephrine influences memory processing through an inverted-U relationship, at which moderate levels enhance and high levels impair memory. These effects are, in large part, mediated by increases in blood glucose levels subsequent to epinephrine release, which then provide support for the brain processes engaged by learning and memory. These brain processes include augmentation of neurotransmitter release and of energy metabolism, the latter apparently including a key role for astrocytic glycogen. In addition to up- and down-regulation of learning and memory in general, physiological concomitants of emotion and arousal can also switch the neural system that controls learning at a particular time, at once improving some attributes of learning and impairing others in a manner that results in a change in the strategy used to solve a problem. PMID:23264764

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

PubMed

Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

2011-04-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neural correlates of free recall of "famous events" in a "hypermnestic" individual as compared to an age- and education-matched reference group.

PubMed

Fehr, Thorsten; Staniloiu, Angelica; Markowitsch, Hans J; Erhard, Peter; Herrmann, Manfred

2018-06-19

Memory performance of an individual (within the age range: 50-55 years old) showing superior memory abilities (protagonist PR) was compared to an age- and education-matched reference group in a historical facts ("famous events") retrieval task. Contrasting task versus baseline performance both PR and the reference group showed fMRI activation patterns in parietal and occipital brain regions. The reference group additionally demonstrated activation patterns in cingulate gyrus, whereas PR showed additional widespread activation patterns comprising frontal and cerebellar brain regions. The direct comparison between PR and the reference group revealed larger fMRI contrasts for PR in right frontal, superior temporal and cerebellar brain regions. It was concluded that PR generally recruits brain regions as normal memory performers do, but in a more elaborate way, and furthermore, that he applied a memory-strategy that potentially includes executively driven multi-modal transcoding of information and recruitment of implicit memory resources.

Intentional retrieval suppression can conceal guilty knowledge in ERP memory detection tests☆

PubMed Central

Bergström, Zara M.; Anderson, Michael C.; Buda, Marie; Simons, Jon S.; Richardson-Klavehn, Alan

2013-01-01

Brain-activity markers of guilty knowledge have been promoted as accurate and reliable measures for establishing criminal culpability. Tests based on these markers interpret the presence or absence of memory-related neural activity as diagnostic of whether or not incriminating information is stored in a suspect's brain. This conclusion critically relies on the untested assumption that reminders of a crime uncontrollably elicit memory-related brain activity. However, recent research indicates that, in some circumstances, humans can control whether they remember a previous experience by intentionally suppressing retrieval. We examined whether people could use retrieval suppression to conceal neural evidence of incriminating memories as indexed by Event-Related Potentials (ERPs). When people were motivated to suppress crime retrieval, their memory-related ERP effects were significantly decreased, allowing guilty individuals to evade detection. Our findings indicate that brain measures of guilty knowledge may be under criminals’ intentional control and place limits on their use in legal settings. PMID:23664804

[Effects of nano-selenium on the capability of learning memory and the activity of Se-protein of mice].

PubMed

Qin, Fenju; Ye, Yaxin; Yao, Xuemei

2008-07-01

To investigate the effects of Nano-Selenium on learning memory capability and activity of two kinds of Se-protein in brain and liver of mice, Na, SeO3 as the controls. The mice were administred two kinds of origin (doses of 1 microgSe/d, 2 microgSe/d, 4 microgSe/d) Se by intra-gastric injection respectively. The learning memory ability of the mice was measured by Y-type maze test. Activities of glutathione peroxidase (GSH-Px) and iodothyronine deiodinase (ID) in brain and liver were also measured. In comparison with the control groups of Na2 Se03, learning memory abilities were improved and activities of ID and GSH-Px (P < 0.01 or P < 0.05) of brain and liver were increased in Nano-Se treatment groups. Nano-Se could improve learning memory ability of mice, and enhance ID and GSH-Px activities of brain and liver in mice.

Recollecting, recognizing, and other acts of remembering: an overview of human memory.

PubMed

LaVoie, Donna J; Cobia, Derin J

2007-09-01

The question of whether memory is important to human existence is simple to answer: life without memory would be devoid of any meaning. The question of what memory is, however, is much more difficult to answer. The main purpose of this article is to provide an overview of memory function, by drawing distinctions between different memory systems, specifically declarative (ie, conscious) versus nondeclarative (ie, nonconscious) memory systems. To distinguish between these larger systems and their various components, we include discussion of deficits in memory that occur as a consequence of brain injury and normative aging processes. Included in these descriptions is discussion of the neuroanatomical correlates of each memory component described to illustrate the importance of particular brain regions to different aspects of memory function.

Emerging Directions in Emotional Episodic Memory.

PubMed

Dolcos, Florin; Katsumi, Yuta; Weymar, Mathias; Moore, Matthew; Tsukiura, Takashi; Dolcos, Sanda

2017-01-01

Building upon the existing literature on emotional memory, the present review examines emerging evidence from brain imaging investigations regarding four research directions: (1) Social Emotional Memory , (2) The Role of Emotion Regulation in the Impact of Emotion on Memory , (3) The Impact of Emotion on Associative or Relational Memory , and (4) The Role of Individual Differences in Emotional Memory . Across these four domains, available evidence demonstrates that emotion- and memory-related medial temporal lobe brain regions (amygdala and hippocampus, respectively), together with prefrontal cortical regions, play a pivotal role during both encoding and retrieval of emotional episodic memories. This evidence sheds light on the neural mechanisms of emotional memories in healthy functioning, and has important implications for understanding clinical conditions that are associated with negative affective biases in encoding and retrieving emotional memories.

Emerging Directions in Emotional Episodic Memory

PubMed Central

Dolcos, Florin; Katsumi, Yuta; Weymar, Mathias; Moore, Matthew; Tsukiura, Takashi; Dolcos, Sanda

2017-01-01

Building upon the existing literature on emotional memory, the present review examines emerging evidence from brain imaging investigations regarding four research directions: (1) Social Emotional Memory, (2) The Role of Emotion Regulation in the Impact of Emotion on Memory, (3) The Impact of Emotion on Associative or Relational Memory, and (4) The Role of Individual Differences in Emotional Memory. Across these four domains, available evidence demonstrates that emotion- and memory-related medial temporal lobe brain regions (amygdala and hippocampus, respectively), together with prefrontal cortical regions, play a pivotal role during both encoding and retrieval of emotional episodic memories. This evidence sheds light on the neural mechanisms of emotional memories in healthy functioning, and has important implications for understanding clinical conditions that are associated with negative affective biases in encoding and retrieving emotional memories. PMID:29255432

Memory engram storage and retrieval.

PubMed

Tonegawa, Susumu; Pignatelli, Michele; Roy, Dheeraj S; Ryan, Tomás J

2015-12-01

A great deal of experimental investment is directed towards questions regarding the mechanisms of memory storage. Such studies have traditionally been restricted to investigation of the anatomical structures, physiological processes, and molecular pathways necessary for the capacity of memory storage, and have avoided the question of how individual memories are stored in the brain. Memory engram technology allows the labeling and subsequent manipulation of components of specific memory engrams in particular brain regions, and it has been established that cell ensembles labeled by this method are both sufficient and necessary for memory recall. Recent research has employed this technology to probe fundamental questions of memory consolidation, differentiating between mechanisms of memory retrieval from the true neurobiology of memory storage. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pharmacological Findings on the Biochemical Bases of Memory Processes: A General View

PubMed Central

Izquierdo, Iván; Cammarota, Martín; Medina, Jorge H.; Bevilaqua, Lia R. M.

2004-01-01

We have advanced considerably in the past 2 to 3 years in understanding the molecular mechanisms of consolidation, retrieval, and extinction of memories, particularly of fear memory. This advance was mainly due to pharmacological studies in many laboratories using localized brain injections of molecularly specific substances. One area in which significant advances have been made is in understanding that many different brain structures are involved in different memories, and that often several brain regions are involved in processing the same memory. These regions can cooperate or compete with each other, depending on circumstances that are beginning to be identified quite clearly. Another aspect in which major advances were made was retrieval and post-retrieval events, especially extinction, pointing to new therapeutic approaches to fearmotivated mental disorders. PMID:15656267

Decoding the Traumatic Memory among Women with PTSD: Implications for Neurocircuitry Models of PTSD and Real-Time fMRI Neurofeedback

PubMed Central

Cisler, Josh M.; Bush, Keith; James, G. Andrew; Smitherman, Sonet; Kilts, Clinton D.

2015-01-01

Posttraumatic Stress Disorder (PTSD) is characterized by intrusive recall of the traumatic memory. While numerous studies have investigated the neural processing mechanisms engaged during trauma memory recall in PTSD, these analyses have only focused on group-level contrasts that reveal little about the predictive validity of the identified brain regions. By contrast, a multivariate pattern analysis (MVPA) approach towards identifying the neural mechanisms engaged during trauma memory recall would entail testing whether a multivariate set of brain regions is reliably predictive of (i.e., discriminates) whether an individual is engaging in trauma or non-trauma memory recall. Here, we use a MVPA approach to test 1) whether trauma memory vs neutral memory recall can be predicted reliably using a multivariate set of brain regions among women with PTSD related to assaultive violence exposure (N=16), 2) the methodological parameters (e.g., spatial smoothing, number of memory recall repetitions, etc.) that optimize classification accuracy and reproducibility of the feature weight spatial maps, and 3) the correspondence between brain regions that discriminate trauma memory recall and the brain regions predicted by neurocircuitry models of PTSD. Cross-validation classification accuracy was significantly above chance for all methodological permutations tested; mean accuracy across participants was 76% for the methodological parameters selected as optimal for both efficiency and accuracy. Classification accuracy was significantly better for a voxel-wise approach relative to voxels within restricted regions-of-interest (ROIs); classification accuracy did not differ when using PTSD-related ROIs compared to randomly generated ROIs. ROI-based analyses suggested the reliable involvement of the left hippocampus in discriminating memory recall across participants and that the contribution of the left amygdala to the decision function was dependent upon PTSD symptom severity. These results have methodological implications for real-time fMRI neurofeedback of the trauma memory in PTSD and conceptual implications for neurocircuitry models of PTSD that attempt to explain core neural processing mechanisms mediating PTSD. PMID:26241958

Decoding the Traumatic Memory among Women with PTSD: Implications for Neurocircuitry Models of PTSD and Real-Time fMRI Neurofeedback.

PubMed

Cisler, Josh M; Bush, Keith; James, G Andrew; Smitherman, Sonet; Kilts, Clinton D

2015-01-01

Posttraumatic Stress Disorder (PTSD) is characterized by intrusive recall of the traumatic memory. While numerous studies have investigated the neural processing mechanisms engaged during trauma memory recall in PTSD, these analyses have only focused on group-level contrasts that reveal little about the predictive validity of the identified brain regions. By contrast, a multivariate pattern analysis (MVPA) approach towards identifying the neural mechanisms engaged during trauma memory recall would entail testing whether a multivariate set of brain regions is reliably predictive of (i.e., discriminates) whether an individual is engaging in trauma or non-trauma memory recall. Here, we use a MVPA approach to test 1) whether trauma memory vs neutral memory recall can be predicted reliably using a multivariate set of brain regions among women with PTSD related to assaultive violence exposure (N=16), 2) the methodological parameters (e.g., spatial smoothing, number of memory recall repetitions, etc.) that optimize classification accuracy and reproducibility of the feature weight spatial maps, and 3) the correspondence between brain regions that discriminate trauma memory recall and the brain regions predicted by neurocircuitry models of PTSD. Cross-validation classification accuracy was significantly above chance for all methodological permutations tested; mean accuracy across participants was 76% for the methodological parameters selected as optimal for both efficiency and accuracy. Classification accuracy was significantly better for a voxel-wise approach relative to voxels within restricted regions-of-interest (ROIs); classification accuracy did not differ when using PTSD-related ROIs compared to randomly generated ROIs. ROI-based analyses suggested the reliable involvement of the left hippocampus in discriminating memory recall across participants and that the contribution of the left amygdala to the decision function was dependent upon PTSD symptom severity. These results have methodological implications for real-time fMRI neurofeedback of the trauma memory in PTSD and conceptual implications for neurocircuitry models of PTSD that attempt to explain core neural processing mechanisms mediating PTSD.

Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

ERIC Educational Resources Information Center

Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

2011-01-01

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

Finding influential nodes for integration in brain networks using optimal percolation theory.

PubMed

Del Ferraro, Gino; Moreno, Andrea; Min, Byungjoon; Morone, Flaviano; Pérez-Ramírez, Úrsula; Pérez-Cervera, Laura; Parra, Lucas C; Holodny, Andrei; Canals, Santiago; Makse, Hernán A

2018-06-11

Global integration of information in the brain results from complex interactions of segregated brain networks. Identifying the most influential neuronal populations that efficiently bind these networks is a fundamental problem of systems neuroscience. Here, we apply optimal percolation theory and pharmacogenetic interventions in vivo to predict and subsequently target nodes that are essential for global integration of a memory network in rodents. The theory predicts that integration in the memory network is mediated by a set of low-degree nodes located in the nucleus accumbens. This result is confirmed with pharmacogenetic inactivation of the nucleus accumbens, which eliminates the formation of the memory network, while inactivations of other brain areas leave the network intact. Thus, optimal percolation theory predicts essential nodes in brain networks. This could be used to identify targets of interventions to modulate brain function.

Driving working memory with frequency-tuned noninvasive brain stimulation.

PubMed

Albouy, Philippe; Baillet, Sylvain; Zatorre, Robert J

2018-04-29

Frequency-tuned noninvasive brain stimulation is a recent approach in cognitive neuroscience that involves matching the frequency of transcranially applied electromagnetic fields to that of specific oscillatory components of the underlying neurophysiology. The objective of this method is to modulate ongoing/intrinsic brain oscillations, which correspond to rhythmic fluctuations of neural excitability, to causally change behavior. We review the impact of frequency-tuned noninvasive brain stimulation on the research field of human working memory. We argue that this is a powerful method to probe and understand the mechanisms of memory functions, targeting specifically task-related oscillatory dynamics, neuronal representations, and brain networks. We report the main behavioral and neurophysiological outcomes published to date, in particular, how functionally relevant oscillatory signatures in signal power and interregional connectivity yield causal changes of working memory abilities. We also present recent developments of the technique that aim to modulate cross-frequency coupling in polyrhythmic neural activity. Overall, the method has led to significant advances in our understanding of the mechanisms of systems neuroscience, and the role of brain oscillations in cognition and behavior. We also emphasize the translational impact of noninvasive brain stimulation techniques in the development of therapeutic approaches. © 2018 New York Academy of Sciences.

Innate immune memory in the brain shapes neurological disease hallmarks.

PubMed

Wendeln, Ann-Christin; Degenhardt, Karoline; Kaurani, Lalit; Gertig, Michael; Ulas, Thomas; Jain, Gaurav; Wagner, Jessica; Häsler, Lisa M; Wild, Katleen; Skodras, Angelos; Blank, Thomas; Staszewski, Ori; Datta, Moumita; Centeno, Tonatiuh Pena; Capece, Vincenzo; Islam, Md Rezaul; Kerimoglu, Cemil; Staufenbiel, Matthias; Schultze, Joachim L; Beyer, Marc; Prinz, Marco; Jucker, Mathias; Fischer, André; Neher, Jonas J

2018-04-01

Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.

Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian two-hybrid assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Shu; Rowlands, Craig; Safe, Stephen

2008-03-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a high affinity ligand for the aryl hydrocarbon receptor (AhR). In this study, we investigated structure-dependent differences in activation of the AhR by a series of halogenated aromatic hydrocarbons. TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 3,3',4,4',5-pentachlorobiphenyl (PCB126) induced CYP1A1-dependent activities in HEK293 human embryonic kidney, Panc1 pancreatic cancer, and Hepa1c1c7 mouse hepatoma cell lines. There was a structure-dependent difference in the efficacy of TCDF and PCB126 in HEK293 and Panc1 cells since induced CYP1A1 mRNA levels were lower than observed for the other congeners. A mammalian two-hybrid assay in cells transfected with GAL4-coactivator and AhR-VP16more » chimeras was used to investigate structure-dependent interactions of these chimeras in Panc1, HEK293, and Hepa1c1c7 cells. The reporter construct pGAL4-luc contains five tandem GAL4 response elements linked to the luciferase gene and the GAL4-coactivator chimeras express several coactivators including steroid receptor coactivator 1 (SRC-1), SRC-2 and SRC-3, the mediator coactivator TRAP220, coactivator associated arginine methyl transferase 1 (CARM-1), and peroxisome proliferator-activated receptor {gamma} coactivator 1 (PGC-1). Results of the mammalian two-hybrid studies clearly demonstrate that activation of pGAL4-luc in cells transfected with VP-AhR and GAL4-coactivator chimeras is dependent on the structure of the HAH congener, cell context, and coactivator, suggesting that the prototypical HAH congeners used in this study exhibit selective AhR modulator activity.« less

Psychogenic amnesia--a malady of the constricted self.

PubMed

Staniloiu, Angelica; Markowitsch, Hans J; Brand, Matthias

2010-09-01

Autobiographical-episodic memory is the conjunction of subjective time, autonoetic consciousness and the experiencing self. Understanding the neural correlates of autobiographical-episodic memory might therefore be essential for shedding light on the neurobiology underlying the experience of being an autonoetic self. In this contribution we illustrate the intimate relationship between autobiographical-episodic memory and self by reviewing the clinical and neuropsychological features and brain functional imaging correlates of psychogenic amnesia - a condition that is usually characterized by severely impaired retrograde memory functioning, in absence of structural brain damage as detected by standard imaging. We demonstrate that in this disorder the autobiographical-episodic memory deficits do not exist in isolation, but occur with impairments of the autonoetic self-consciousness, emotional processing, and theory of mind or executive functions. Furthermore functional and metabolic brain alterations involving regions that are agreed upon to exert crucial roles in memory processes were frequently found to accompany the psychogenic memory "loss". Copyright © 2010 Elsevier Inc. All rights reserved.

Interacting Brain Systems Modulate Memory Consolidation

PubMed Central

McIntyre, Christa K.; McGaugh, James L.; Williams, Cedric L.

2011-01-01

Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID:22085800

Long-Term Memory Shapes the Primary Olfactory Center of an Insect Brain

ERIC Educational Resources Information Center

Hourcade, Benoit; Perisse, Emmanuel; Devaud, Jean-Marc; Sandoz, Jean-Christophe

2009-01-01

The storage of stable memories is generally considered to rely on changes in the functional properties and/or the synaptic connectivity of neural networks. However, these changes are not easily tractable given the complexity of the learning procedures and brain circuits studied. Such a search can be narrowed down by studying memories of specific…

Memory Strategies to Use With Students Following Traumatic Brain Injury

ERIC Educational Resources Information Center

Pershelli, Andi

2007-01-01

Following a traumatic brain injury, including a mild concussion, most students will have some degree of memory impairment. It can take 1-3 years for a child's memory to improve to its maximum capability following injury. Children cannot wait that long before returning to school. Teachers need to know how to diversify their instruction in order to…

Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

ERIC Educational Resources Information Center

Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

2011-01-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

Endogenous BDNF Is Required for Long-Term Memory Formation in the Rat Parietal Cortex

ERIC Educational Resources Information Center

Alonso, Mariana; Bekinschtein, Pedro, Cammarota, Martin; Vianna, Monica R. M.; Izquierdo, Ivan; Medina, Jorge H.

2005-01-01

Information storage in the brain is a temporally graded process involving different memory phases as well as different structures in the mammalian brain. Cortical plasticity seems to be essential to store stable long-term memories, although little information is available at the moment regarding molecular and cellular events supporting memory…

Implicit Memory Influences on Metamemory during Verbal Learning after Traumatic Brain Injury

ERIC Educational Resources Information Center

Ramanathan, Pradeep; Kennedy, Mary R. T.; Marsolek, Chad J.

2014-01-01

Purpose: Prior research has shown that individuals with traumatic brain injury (TBI) may be overconfident in their judgments of learning (JOLs; online measures of self-monitoring of learning and memory). JOLs had been presumed to be driven by explicit processes, but recent research has also revealed implicit memory involvement. Given that implicit…

Time, Memory, and Consciousness a View from the Brain

NASA Astrophysics Data System (ADS)

Markowitsch, Hans J.

2005-10-01

Memory can be defined as mental time traveling. Seen in this way, memory provides the glue which combines different time episodes and leads to a coherent view of one's own person. The importance of time becomes apparent in a neuroscientific comparison of animals and human beings. All kinds of animals have biorhythms -- times when they sleep, prefer or avoid sex, or move to warmer places. Mammalian brains have a number of time sensitive structures damage to which alters a subject's behavior to his or her environment. For human beings, damage to certain brain regions may alter the sense of time and consciousness of time in quite different ways. Furthermore, brain damage, drugs, or psychiatric disturbances may lead to an impaired perception of time, sometimes leading to major positive or negative accelerations in time perception. An impaired time perception alters consciousness and awareness of oneself. A proper synchronized action of time perception, brain activation, memory processing, and autonoetic (self-aware) consciousness provides the bases of an integrated personality.

Astrocyte glycogen and lactate: New insights into learning and memory mechanisms.

PubMed

Alberini, Cristina M; Cruz, Emmanuel; Descalzi, Giannina; Bessières, Benjamin; Gao, Virginia

2018-06-01

Memory, the ability to retain learned information, is necessary for survival. Thus far, molecular and cellular investigations of memory formation and storage have mainly focused on neuronal mechanisms. In addition to neurons, however, the brain comprises other types of cells and systems, including glia and vasculature. Accordingly, recent experimental work has begun to ask questions about the roles of non-neuronal cells in memory formation. These studies provide evidence that all types of glial cells (astrocytes, oligodendrocytes, and microglia) make important contributions to the processing of encoded information and storing memories. In this review, we summarize and discuss recent findings on the critical role of astrocytes as providers of energy for the long-lasting neuronal changes that are necessary for long-term memory formation. We focus on three main findings: first, the role of glucose metabolism and the learning- and activity-dependent metabolic coupling between astrocytes and neurons in the service of long-term memory formation; second, the role of astrocytic glucose metabolism in arousal, a state that contributes to the formation of very long-lasting and detailed memories; and finally, in light of the high energy demands of the brain during early development, we will discuss the possible role of astrocytic and neuronal glucose metabolisms in the formation of early-life memories. We conclude by proposing future directions and discussing the implications of these findings for brain health and disease. Astrocyte glycogenolysis and lactate play a critical role in memory formation. Emotionally salient experiences form strong memories by recruiting astrocytic β2 adrenergic receptors and astrocyte-generated lactate. Glycogenolysis and astrocyte-neuron metabolic coupling may also play critical roles in memory formation during development, when the energy requirements of brain metabolism are at their peak. © 2017 Wiley Periodicals, Inc.

Dynamic Connectivity between Brain Networks Supports Working Memory: Relationships to Dopamine Release and Schizophrenia.

PubMed

Cassidy, Clifford M; Van Snellenberg, Jared X; Benavides, Caridad; Slifstein, Mark; Wang, Zhishun; Moore, Holly; Abi-Dargham, Anissa; Horga, Guillermo

2016-04-13

Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unknown. We addressed these questions in healthy humans using functional magnetic resonance imaging (during ann-back working-memory task) and positron emission tomography using the radiotracer [(11)C]FLB457 before and after amphetamine to measure the capacity for dopamine release in extrastriatal brain regions. Brain networks were defined by spatial independent component analysis (ICA) and working-memory-load-dependent connectivity between task-relevant pairs of networks was determined via a modified psychophysiological interaction analysis. For most pairs of task-relevant networks, connectivity significantly changed as a function of working-memory load. Moreover, load-dependent changes in connectivity between left and right frontoparietal networks (Δ connectivity lFPN-rFPN) predicted interindividual differences in task performance more accurately than other fMRI and PET imaging measures. Δ Connectivity lFPN-rFPN was not related to cortical dopamine release capacity. A second study in unmedicated patients with schizophrenia showed no abnormalities in load-dependent connectivity but showed a weaker relationship between Δ connectivity lFPN-rFPN and working memory performance in patients compared with matched healthy individuals. Poor working memory performance in patients was, in contrast, related to deficient cortical dopamine release. Our findings indicate that interactions between brain networks dynamically adapt to fluctuating environmental demands. These dynamic adaptations underlie successful working memory performance in healthy individuals and are not well predicted by amphetamine-induced dopamine release capacity. It is unclear how communication between brain networks responds to changing environmental demands during complex cognitive processes. Also, unknown in regard to these network dynamics is the role of neuromodulators, such as dopamine, and whether their dysregulation could underlie cognitive deficits in neuropsychiatric illness. We found that connectivity between brain networks changes with working-memory load and greater increases predict better working memory performance; however, it was not related to capacity for dopamine release in the cortex. Patients with schizophrenia did show dynamic internetwork connectivity; however, this was more weakly associated with successful performance in patients compared with healthy individuals. Our findings indicate that dynamic interactions between brain networks may support the type of flexible adaptations essential to goal-directed behavior. Copyright © 2016 the authors 0270-6474/16/364378-12$15.00/0.

Dynamic Connectivity between Brain Networks Supports Working Memory: Relationships to Dopamine Release and Schizophrenia

PubMed Central

Van Snellenberg, Jared X.; Benavides, Caridad; Slifstein, Mark; Wang, Zhishun; Moore, Holly; Abi-Dargham, Anissa

2016-01-01

Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unknown. We addressed these questions in healthy humans using functional magnetic resonance imaging (during an n-back working-memory task) and positron emission tomography using the radiotracer [11C]FLB457 before and after amphetamine to measure the capacity for dopamine release in extrastriatal brain regions. Brain networks were defined by spatial independent component analysis (ICA) and working-memory-load-dependent connectivity between task-relevant pairs of networks was determined via a modified psychophysiological interaction analysis. For most pairs of task-relevant networks, connectivity significantly changed as a function of working-memory load. Moreover, load-dependent changes in connectivity between left and right frontoparietal networks (Δ connectivity lFPN-rFPN) predicted interindividual differences in task performance more accurately than other fMRI and PET imaging measures. Δ Connectivity lFPN-rFPN was not related to cortical dopamine release capacity. A second study in unmedicated patients with schizophrenia showed no abnormalities in load-dependent connectivity but showed a weaker relationship between Δ connectivity lFPN-rFPN and working memory performance in patients compared with matched healthy individuals. Poor working memory performance in patients was, in contrast, related to deficient cortical dopamine release. Our findings indicate that interactions between brain networks dynamically adapt to fluctuating environmental demands. These dynamic adaptations underlie successful working memory performance in healthy individuals and are not well predicted by amphetamine-induced dopamine release capacity. SIGNIFICANCE STATEMENT It is unclear how communication between brain networks responds to changing environmental demands during complex cognitive processes. Also, unknown in regard to these network dynamics is the role of neuromodulators, such as dopamine, and whether their dysregulation could underlie cognitive deficits in neuropsychiatric illness. We found that connectivity between brain networks changes with working-memory load and greater increases predict better working memory performance; however, it was not related to capacity for dopamine release in the cortex. Patients with schizophrenia did show dynamic internetwork connectivity; however, this was more weakly associated with successful performance in patients compared with healthy individuals. Our findings indicate that dynamic interactions between brain networks may support the type of flexible adaptations essential to goal-directed behavior. PMID:27076432

Distributed Patterns of Reactivation Predict Vividness of Recollection.

PubMed

St-Laurent, Marie; Abdi, Hervé; Buchsbaum, Bradley R

2015-10-01

According to the principle of reactivation, memory retrieval evokes patterns of brain activity that resemble those instantiated when an event was first experienced. Intuitively, one would expect neural reactivation to contribute to recollection (i.e., the vivid impression of reliving past events), but evidence of a direct relationship between the subjective quality of recollection and multiregional reactivation of item-specific neural patterns is lacking. The current study assessed this relationship using fMRI to measure brain activity as participants viewed and mentally replayed a set of short videos. We used multivoxel pattern analysis to train a classifier to identify individual videos based on brain activity evoked during perception and tested how accurately the classifier could distinguish among videos during mental replay. Classification accuracy correlated positively with memory vividness, indicating that the specificity of multivariate brain patterns observed during memory retrieval was related to the subjective quality of a memory. In addition, we identified a set of brain regions whose univariate activity during retrieval predicted both memory vividness and the strength of the classifier's prediction irrespective of the particular video that was retrieved. Our results establish distributed patterns of neural reactivation as a valid and objective marker of the quality of recollection.

Brain activity associated with memory and cognitive function during jaw-tapping movement in healthy subjects using functional magnetic resonance imaging.

PubMed

Cho, Seung-Yeon; Shin, Ae-Sook; Na, Byung-Jo; Jahng, Geon-Ho; Park, Seong-Uk; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi

2013-06-01

To determine whether jaw-tapping movement, a classically described as an indication of personal well-being and mental health, stimulates the memory and the cognitive regions of the brain and is associated with improved brain performance. Twelve healthy right-handed female subjects completed the study. Each patient performed a jaw-tapping task and an n-back task during functional magnetic resonance imaging (fMRI). The subjects were trained to carry out the jaw-tapping movement at home twice a day for 4 weeks. The fMRI was repeated when they returned. During the first and second jaw-tapping session, both sides of precentral gyrus and the right middle frontal gyrus (BA 6) were activated. And during the second session of the jaw-tapping task, parts of frontal lobe and temporal lobe related to memory function were more activated. In addition, the total percent task accuracy in n-back task significantly increased after 4 weeks of jawtapping movement. After jaw-tapping training for 4 weeks, brain areas related to memory showed significantly increased blood oxygen level dependent signals. Jaw-tapping movement might be a useful exercise for stimulating the memory and cognitive regions of the brain.

Fluorescence anisotropy microplate assay to investigate the interaction of full-length steroid receptor coactivator-1a with steroid receptors

PubMed Central

Zhang, Chen; Nordeen, Steven K.; Shapiro, David J.

2013-01-01

Estrogens, acting via estrogen receptor (ER) play key roles in growth, differentiation and gene regulation in the reproductive, central nervous and skeletal systems. ER-mediated gene transcription contributes to the development and spread of breast, uterine, and liver cancer. Steroid receptor coactivator-1a (SRC1a) belongs to the P160 family of coactivators, which is the best known of the many coactivators implicated in ER-mediated transactivation. Binding of full-length P160 coactivators to steroid receptors has been difficult to investigate in vitro. This chapter details how to investigate the interaction of SRC1a with ER using the fluorescence anisotropy/polarization microplate assay (FAMA). PMID:23436375

The Royal Road to Time: How Understanding of the Evolution of Time in the Brain Addresses Memory, Dreaming, Flow, and Other Psychological Phenomena.

PubMed

Hancock, Peter A

2015-01-01

It has been claimed that dreams are the royal road to the unconscious mind. The present work argues that dreams and associated brain states such as memory, attention, flow, and perhaps even consciousness itself arise from diverse conflicts over control of time in the brain. Dreams are the brain's offline efforts to distill projections of the future, while memory represents the vestiges of the past successes and survived failures of those and other conscious projections. Memory thus acts to inform and improve the prediction of possible future states through the use of conscious prospects (planning) and unconscious prospective memory (dreams). When successful, these prospects result in states of flow for conscious planning and déjà vu for its unconscious comparator. In consequence, and contrary to normal expectation, memory is overwhelmingly oriented to deal with the future. Consciousness is the comparable process operating in the present moment. Thus past, present, and future are homeomorphic with the parts of memory (episodic and autobiographical) that recall a personal past, consciousness, and the differing dimensions of prospective memory to plan for future circumstances, respectively. Dreaming (i.e., unconscious prospective memory), has the luxury to run multiple "what if" simulations of many possible futures, essentially offline. I explicate these propositions and their relations to allied constructs such as déjà vu and flow. More generally, I propose that what appear to us as a range of normal psychological experiences are actually manifestations of an ongoing pathological battle for control within the brain. The landscape of this conflict is time. I suggest that there are at least 3 general systems bidding for this control, and in the process of evolution, each system has individually conferred a sequentially increasing survival advantage, but only at the expense of a still incomplete functional integration. Through juxtaposition of these respective brain systems, I endeavor to resolve some fundamental paradoxes and conundrums expressed in the basic psychological and behavioral processes of sleep, consciousness, and memory. The implication of this conceptual framework for the overall conception of time is then briefly adumbrated.

Stability of whole brain and regional network topology within and between resting and cognitive states.

PubMed

Rzucidlo, Justyna K; Roseman, Paige L; Laurienti, Paul J; Dagenbach, Dale

2013-01-01

Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI) data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression After Whole-Brain Irradiation

PubMed Central

Wong-Goodrich, Sarah J.E.; Pfau, Madeline L.; Flores, Catherine T.; Fraser, Jennifer A.; Williams, Christina L.; Jones, Lee W.

2010-01-01

Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention, and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to four months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting one month after sham- or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdU) immunolabeling and ELISA indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdU+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor, and occurred despite irradiation-induced elevations in hippocampal pro-inflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention. PMID:20884629

Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance.

PubMed

Su, Hui-Min

2010-05-01

Docosahexaenoic acid (DHA, 22:6n-3) is specifically enriched in the brain and mainly anchored in the neuronal membrane, where it is involved in the maintenance of normal neurological function. Most DHA accumulation in the brain takes place during brain development in the perinatal period. However, hippocampal DHA levels decrease with age and in the brain disorder Alzheimer's disease (AD), and this decrease is associated with reduced hippocampal-dependent spatial learning memory ability. A potential mechanism is proposed by which the n-3 fatty acids DHA and eicosapentaenoic acid (20:5n-3) aid the development and maintenance of spatial learning memory performance. The developing brain or hippocampal neurons can synthesize and take up DHA and incorporate it into membrane phospholipids, especially phosphatidylethanolamine, resulting in enhanced neurite outgrowth, synaptogenesis and neurogenesis. Exposure to n-3 fatty acids enhances synaptic plasticity by increasing long-term potentiation and synaptic protein expression to increase the dendritic spine density, number of c-Fos-positive neurons and neurogenesis in the hippocampus for learning memory processing. In aged rats, n-3 fatty acid supplementation reverses age-related changes and maintains learning memory performance. n-3 fatty acids have anti-oxidative stress, anti-inflammation, and anti-apoptosis effects, leading to neuron protection in the aged, damaged, and AD brain. Retinoid signaling may be involved in the effects of DHA on learning memory performance. Estrogen has similar effects to n-3 fatty acids on hippocampal function. It would be interesting to know if there is any interaction between DHA and estrogen so as to provide a better strategy for the development and maintenance of learning memory. Copyright 2010 Elsevier Inc. All rights reserved.

Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats.

PubMed

O'Hagan, Caroline; Li, Jia V; Marchesi, Julian R; Plummer, Sue; Garaiova, Iveta; Good, Mark A

2017-10-01

Ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15-17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. Short-term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. 1 H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory. Copyright © 2017 Elsevier Inc. All rights reserved.

The development of neural correlates for memory formation

PubMed Central

Ofen, Noa

2012-01-01

A growing body of literature considers the development of episodic memory systems in the brain; the majority are neuroimaging studies conducted during memory encoding in order to explore developmental trajectories in memory formation. This review considers evidence from behavioral studies of memory development, neural correlates of memory formation in adults, and structural brain development, all of which form the foundation of a developmental cognitive neuroscience approach to memory development. I then aim to integrate the current evidence from developmental functional neuroimaging studies of memory formation with respect to three hypotheses. First, memory development reflects the development in the use of memory strategies, linked to prefrontal cortex. Second, developmental effects within the medial temporal lobes are more complex, and correspond to current notions about the nature in which the MTL support the formation of memory. Third, neurocognitive changes in content representation influence memory. Open issues and current directions are discussed. PMID:22414608

Upgrading the sleeping brain with targeted memory reactivation.

PubMed

Oudiette, Delphine; Paller, Ken A

2013-03-01

A fundamental feature of human memory is the propensity for beneficial changes in information storage after initial encoding. Recent research findings favor the possibility that memory consolidation during sleep is instrumental for actively maintaining the storehouse of memories that individuals carry through their lives. The information that ultimately remains available for retrieval may tend to be that which is reactivated during sleep. A novel source of support for this idea comes from demonstrations that neurocognitive processing during sleep can benefit memory storage when memories are covertly cued via auditory or olfactory stimulation. Investigations of these subtle manipulations of memory processing during sleep can help elucidate the mechanisms of memory preservation in the human brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Verbal Memory Performance and Reduced Cortical Thickness of Brain Regions Along the Uncinate Fasciculus in Young Adult Cannabis Users

PubMed Central

Levar, Nina; Francis, Alan N.; Smith, Matthew J.; Ho, Wilson C.; Gilman, Jodi M.

2018-01-01

Abstract Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory. This study investigated the impact of cannabis use on UF structures and its association with memory performance in young adult cannabis users (CU) and non-using controls (CON). Materials and Methods: Nineteen CU and 22 CON completed a verbal memory task and a neuroimaging protocol, in which diffusion tensor imaging and structural scans were collected. We compared memory performance, diffusion and tractography measures of the UF, and cortical thickness of regions connected by the UF, between CU and CON. In regions showing a significant group effect, we also examined associations between verbal memory performance, cortical thickness, and age of onset of cannabis use. Results: Compared to non-users, CU had worse memory performance, decreased fiber bundle length in the UF, and decreased cortical thickness of brain regions along the UF such as the entorhinal cortex and fusiform gyrus. Verbal memory performance was significantly associated with age of onset of cannabis use, indicating that those who initiated cannabis use at an earlier age performed worse. Cortical thickness of the entorhinal cortex was significantly correlated with age of first use and memory performance. Conclusion: This study provides evidence that cannabis use, especially when initiated at a young age, may be associated with worse verbal memory and altered neural development along the UF. Reductions in cortical thickness in regions implicated in memory processes may underlie weaknesses in verbal memory performance. PMID:29607411

Changes in Brain Network Efficiency and Working Memory Performance in Aging

PubMed Central

Stanley, Matthew L.; Simpson, Sean L.; Dagenbach, Dale; Lyday, Robert G.; Burdette, Jonathan H.; Laurienti, Paul J.

2015-01-01

Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory. PMID:25875001

Changes in brain network efficiency and working memory performance in aging.

PubMed

Stanley, Matthew L; Simpson, Sean L; Dagenbach, Dale; Lyday, Robert G; Burdette, Jonathan H; Laurienti, Paul J

2015-01-01

Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory.

Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin {alpha}3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeung, Percy Luk; Zhang, Aihua; Chen, J. Don

2006-09-15

The nuclear receptor coactivator RAC3 (also known as SRC-3/ACTR/AIB1/p/CIP/TRAM-1) belongs to the p160 coactivator family, which are involved in several physiological processes and diseases. Here we have investigated how RAC3 is translocated into the nucleus and show that it is mediated through a bipartite NLS and importin {alpha}3. This bipartite NLS is located within the conserved bHLH domain, and its mutation abolished nuclear localization. The NLS is also sufficient to cause nuclear import of EGFP, and the activity requires basic amino acids within the NLS. RAC3 binds strongly to importin {alpha}3, which also depends on the basic amino acids. Functionally,more » RAC3 cytoplasmic mutant loses its ability to enhance transcription, suggesting that nuclear localization is essential for coactivator function. Together, these results reveal a previous unknown mechanism for nuclear translocation of p160 coactivators and a critical function of the conserved bHLH within the coactivator.« less

Nuclear receptor coactivator/coregulator NCoA6(NRC) is a pleiotropic coregulator involved in transcription, cell survival, growth and development.

PubMed

Mahajan, Muktar A; Samuels, Herbert H

2008-02-01

NCoA6 (also referred to as NRC, ASC-2, TRBP, PRIP and RAP250) was originally isolated as a ligand-dependent nuclear receptor interacting protein. However, NCoA6 is a multifunctional coregulator or coactivator necessary for transcriptional activation of a wide spectrum of target genes. The NCoA6 gene is amplified and overexpressed in breast, colon and lung cancers. NCoA6 is a 250 kDa protein which harbors a potent N-terminal activation domain, AD1; and a second, centrally-located activation domain, AD2, which is necessary for nuclear receptor signaling. The intrinsic activation potential of NCoA6 is regulated by its C-terminal STL regulatory domain. Near AD2 is an LxxLL-1 motif which interacts with a wide spectrum of ligand-bound NRs with high-affinity. A second LxxLL motif (LxxLL-2) located towards the C-terminal region is more restricted in its NR specificity. The potential role of NCoA6 as a co-integrator is suggested by its ability to enhance transcriptional activation of a wide variety of transcription factors and from its in vivo association with a number of known cofactors including CBP/p300. NCoA6 has been shown to associate with at least three distinct coactivator complexes containing Set methyltransferases as core polypeptides. The composition of these complexes suggests that NCoA6 may play a fundamental role in transcriptional activation by modulating chromatin structure through histone methylation. Knockout studies in mice suggest that NCoA6 is an essential coactivator. NCoA6-/- embryos die between 8.5-12.5 dpc from general growth retardation coupled with developmental defects in the heart, liver, brain and placenta. NCoA6-/- MEFs grow at a reduced rate compared to WT MEFs and spontaneously undergo apoptosis, indicating the importance of NCoA6 as a prosurvival and anti-apoptotic gene. Studies with NCoA6+/- and conditional knockout mice suggest that NCoA6 is a pleiotropic coregulator involved in growth, development, wound healing and maintenance of energy homeostasis.

Catching the engram: strategies to examine the memory trace.

PubMed

Sakaguchi, Masanori; Hayashi, Yasunori

2012-09-21

Memories are stored within neuronal ensembles in the brain. Modern genetic techniques can be used to not only visualize specific neuronal ensembles that encode memories (e.g., fear, craving) but also to selectively manipulate those neurons. These techniques are now being expanded for the study of various types of memory. In this review, we will summarize the genetic methods used to visualize and manipulate neurons involved in the representation of memory engrams. The methods will help clarify how memory is encoded, stored and processed in the brain. Furthermore, these approaches may contribute to our understanding of the pathological mechanisms associated with human memory disorders and, ultimately, may aid the development of therapeutic strategies to ameliorate these diseases.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus.

PubMed

Canto de Souza, Lucas; Provensi, Gustavo; Vullo, Daniela; Carta, Fabrizio; Scozzafava, Andrea; Costa, Alessia; Schmidt, Scheila Daiane; Passani, Maria Beatrice; Supuran, Claudiu T; Blandina, Patrizio

2017-05-15

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathophysiology and Treatment of Memory Dysfunction after Traumatic Brain Injury

PubMed Central

Paterno, Rosalia; Folweiler, Kaitlin A.; Cohen, Akiva S.

2018-01-01

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury. PMID:28500417

Family history and APOE4 risk for Alzheimer's disease impact the neural correlates of episodic memory by early midlife.

PubMed

Rajah, M N; Wallace, L M K; Ankudowich, E; Yu, E H; Swierkot, A; Patel, R; Chakravarty, M M; Naumova, D; Pruessner, J; Joober, R; Gauthier, S; Pasvanis, S

2017-01-01

Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA + FH ), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA + FH + APOE4 ), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls. We also hypothesized that the two at-risk MA groups will exhibit distinct patterns of correlation between brain activity and memory performance, compared to controls. To test these hypotheses we conducted multivariate task, and behavior, partial least squares analysis of fMRI data obtained during successful context encoding and retrieval. Our results indicate that even though there were no significant group differences in context memory performance, there were significant differences in brain activity and brain-behavior correlations involving the hippocampus, inferior parietal cortex, cingulate, and precuneus cortex in MA with AD risk factors, compared to controls. In addition, we observed that brain activity and brain-behavior correlations in anterior-medial PFC and in ventral visual cortex differentiated the two MA risk groups from each other, and from MA controls . Our results indicate that functional differences in episodic memory-related regions are present by early midlife in adults with + FH and + APOE-4 risk factors for late onset AD, compared to middle-aged controls.

Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

PubMed

Park, Chang-Hyun; Choi, Yun Seo; Jung, A-Reum; Chung, Hwa-Kyoung; Kim, Hyeon Jin; Yoo, Jeong Hyun; Lee, Hyang Woon

2017-01-01

Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover.

PubMed

Dere, Ekrem; De Souza-Silva, Maria A; Topic, Bianca; Spieler, Richard E; Haas, Helmut L; Huston, Joseph P

2003-01-01

The brain's histaminergic system has been implicated in hippocampal synaptic plasticity, learning, and memory, as well as brain reward and reinforcement. Our past pharmacological and lesion studies indicated that the brain's histamine system exerts inhibitory effects on the brain's reinforcement respective reward system reciprocal to mesolimbic dopamine systems, thereby modulating learning and memory performance. Given the close functional relationship between brain reinforcement and memory processes, the total disruption of brain histamine synthesis via genetic disruption of its synthesizing enzyme, histidine decarboxylase (HDC), in the mouse might have differential effects on learning dependent on the task-inherent reinforcement contingencies. Here, we investigated the effects of an HDC gene disruption in the mouse in a nonreinforced object exploration task and a negatively reinforced water-maze task as well as on neo- and ventro-striatal dopamine systems known to be involved in brain reward and reinforcement. Histidine decarboxylase knockout (HDC-KO) mice had higher dihydrophenylacetic acid concentrations and a higher dihydrophenylacetic acid/dopamine ratio in the neostriatum. In the ventral striatum, dihydrophenylacetic acid/dopamine and 3-methoxytyramine/dopamine ratios were higher in HDC-KO mice. Furthermore, the HDC-KO mice showed improved water-maze performance during both hidden and cued platform tasks, but deficient object discrimination based on temporal relationships. Our data imply that disruption of brain histamine synthesis can have both memory promoting and suppressive effects via distinct and independent mechanisms and further indicate that these opposed effects are related to the task-inherent reinforcement contingencies.

Structural Dissociation of Attentional Control and Memory in Adults with and without Mild Traumatic Brain Injury

ERIC Educational Resources Information Center

Niogi, Sumit N.; Mukherjee, Pratik; Ghajar, Jamshid; Johnson, Carl E.; Kolster, Rachel; Lee, Hana; Suh, Minah; Zimmerman, Robert D.; Manley, Geoffrey T.; McCandliss, Bruce D.

2008-01-01

Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether…

Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

PubMed

Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

2016-10-01

Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional brain imaging of episodic memory decline in ageing.

PubMed

Nyberg, L

2017-01-01

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Neural events that underlie remembering something that never happened.

PubMed

Gonsalves, B; Paller, K A

2000-12-01

We induced people to experience a false-memory illusion by first asking them to visualize common objects when cued with the corresponding word; on some trials, a photograph of the object was presented 1800 ms after the cue word. We then tested their memory for the photographs. Posterior brain potentials in response to words at encoding were more positive if the corresponding object was later falsely remembered as a photograph. Similar brain potentials during the memory test were more positive for true than for false memories. These results implicate visual imagery in the generation of false memories and provide neural correlates of processing differences between true and false memories.

Brain oscillatory substrates of visual short-term memory capacity.

PubMed

Sauseng, Paul; Klimesch, Wolfgang; Heise, Kirstin F; Gruber, Walter R; Holz, Elisa; Karim, Ahmed A; Glennon, Mark; Gerloff, Christian; Birbaumer, Niels; Hummel, Friedhelm C

2009-11-17

The amount of information that can be stored in visual short-term memory is strictly limited to about four items. Therefore, memory capacity relies not only on the successful retention of relevant information but also on efficient suppression of distracting information, visual attention, and executive functions. However, completely separable neural signatures for these memory capacity-limiting factors remain to be identified. Because of its functional diversity, oscillatory brain activity may offer a utile solution. In the present study, we show that capacity-determining mechanisms, namely retention of relevant information and suppression of distracting information, are based on neural substrates independent of each other: the successful maintenance of relevant material in short-term memory is associated with cross-frequency phase synchronization between theta (rhythmical neural activity around 5 Hz) and gamma (> 50 Hz) oscillations at posterior parietal recording sites. On the other hand, electroencephalographic alpha activity (around 10 Hz) predicts memory capacity based on efficient suppression of irrelevant information in short-term memory. Moreover, repetitive transcranial magnetic stimulation at alpha frequency can modulate short-term memory capacity by influencing the ability to suppress distracting information. Taken together, the current study provides evidence for a double dissociation of brain oscillatory correlates of visual short-term memory capacity.

Hippocampal size is related to short-term true and false memory, and right fusiform size is related to long-term true and false memory.

PubMed

Zhu, Bi; Chen, Chuansheng; Loftus, Elizabeth F; He, Qinghua; Lei, Xuemei; Dong, Qi; Lin, Chongde

2016-11-01

There is a keen interest in identifying specific brain regions that are related to individual differences in true and false memories. Previous functional neuroimaging studies showed that activities in the hippocampus, right fusiform gyrus, and parahippocampal gyrus were associated with true and false memories, but no study thus far has examined whether the structures of these brain regions are associated with short-term and long-term true and false memories. To address that question, the current study analyzed data from 205 healthy young adults, who had valid data from both structural brain imaging and a misinformation task. In the misinformation task, subjects saw the crime scenarios, received misinformation, and took memory tests about the crimes an hour later and again after 1.5 years. Results showed that bilateral hippocampal volume was associated with short-term true and false memories, whereas right fusiform gyrus volume and surface area were associated with long-term true and false memories. This study provides the first evidence for the structural neural bases of individual differences in short-term and long-term true and false memories.

Rehabilitation of memory following brain injury (ReMemBrIn): study protocol for a randomised controlled trial.

PubMed

das Nair, Roshan; Lincoln, Nadina B; Ftizsimmons, Deborah; Brain, Nicola; Montgomery, Alan; Bradshaw, Lucy; Drummond, Avril; Sackley, Catherine; Newby, Gavin; Thornton, Jim; Stapleton, Sandip; Pink, Anthony

2015-01-06

Impairments of memory are commonly reported by people with traumatic brain injuries (TBI). Such deficits are persistent, debilitating, and can severely impact quality of life. Currently, many do not routinely receive follow-up appointments for residual memory problems following discharge. This is a multi-centre, randomised controlled trial investigating the clinical and cost-effectiveness of a group-based memory rehabilitation programme. Three hundred and twelve people with a traumatic brain injury will be randomised from four centres. Participants will be eligible if they had a traumatic brain injury more than 3 months prior to recruitment, have memory problems, are 18 to 69 years of age, are able to travel to one of our centres and attend group sessions, and are able to give informed consent. Participants will be randomised in clusters of 4 to 6 to the group rehabilitation intervention or to usual care. Intervention groups will receive 10 weekly sessions of a manualised memory rehabilitation programme, which has been developed in previous pilot studies. The intervention will include restitution strategies to retrain impaired memory functions and compensation strategies to enable participants to cope with their memory problems. All participants will receive a follow-up postal questionnaire and an assessment by a research assistant at 6 and 12 months post-randomisation. The primary outcome is the Everyday Memory Questionnaire at 6 months. Secondary outcomes include the Rivermead Behavioural Memory Test-3, General Health Questionnaire-30, health related quality of life, cost-effectiveness analysis determined by the EQ-5D and a service use questionnaire, individual goal attainment, European Brain Injury Questionnaire (patient and relative versions), and the Everyday Memory Questionnaire-relative version. The primary analysis will be based on intention to treat. A mixed-model regression analysis of the Everyday Memory Questionnaire at 6 months will be used to estimate the effect of the group memory rehabilitation programme. The study will hopefully provide robust evidence regarding the clinical and cost-effectiveness of a group-based memory rehabilitation intervention for civilians and military personnel following TBI. We discuss our decision-making regarding choice of outcome measures and control group, and the unique challenges to recruiting people with memory problems to trials. ISRCTN65792154; Date: 18 October 2012.

The Episodic Engram Transformed: Time Reduces Retrieval-Related Brain Activity but Correlates It with Memory Accuracy

ERIC Educational Resources Information Center

Furman, Orit; Mendelsohn, Avi; Dudai, Yadin

2012-01-01

We took snapshots of human brain activity with fMRI during retrieval of realistic episodic memory over several months. Three groups of participants were scanned during a memory test either hours, weeks, or months after viewing a documentary movie. High recognition accuracy after hours decreased after weeks and remained at similar levels after…

Memory Restoration Using Computerized Cognitive Training after Pediatric Traumatic Brain Injury: A Review of the Evidence. EBP Briefs. Volume 12, Issue 3

ERIC Educational Resources Information Center

Lundine, Jennifer P.

2017-01-01

Clinical Question: For children and adolescents with memory impairments after traumatic brain injury (TBI), do computerized cognitive training (CCT) programs used in conjunction with traditional therapy vs. traditional therapy alone lead to memory gains in daily activities? Method: Literature Review. Study Sources: Google Scholar, CINAHL via…

Longitudinal association between hippocampus atrophy and episodic-memory decline.

PubMed

Gorbach, Tetiana; Pudas, Sara; Lundquist, Anders; Orädd, Greger; Josefsson, Maria; Salami, Alireza; de Luna, Xavier; Nyberg, Lars

2017-03-01

There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The role of sleep in human declarative memory consolidation.

PubMed

Alger, Sara E; Chambers, Alexis M; Cunningham, Tony; Payne, Jessica D

2015-01-01

Through a variety of methods, researchers have begun unraveling the mystery of why humans spend one-third of their lives asleep. Though sleep likely serves multiple functions, it has become clear that the sleeping brain offers an ideal environment for solidifying newly learned information in the brain. Sleep , which comprises a complex collection of brain states, supports the consolidation of many different types of information. It not only promotes learning and memory stabilization, but also memory reorganization that can lead to various forms of insightful behavior. As this chapter will describe, research provides ample support for these crucial cognitive functions of sleep . Focusing on the declarative memory system in humans, we review the literature regarding the benefits of sleep for both neutral and emotionally salient declarative memory. Finally, we discuss the literature regarding the impact of sleep on emotion regulation.

Understanding Memory Loss | NIH MedlinePlus the Magazine

MedlinePlus

... urine. She or he also checks your memory, problem solving, counting, and language skills. The doctor also may suggest a brain scan to show the normal and problem areas in the brain. Once the cause of ...

Memory Impairment in Korsakoff's Psychosis: A Correlation with Brain Noradrenergic Activity.

ERIC Educational Resources Information Center

McEntee, William J.; Mair, Robert G.

1978-01-01

The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is correlated with measures of memory impairment. (BB)

Neural correlates of verbal associative memory and mnemonic strategy use following childhood traumatic brain injury

PubMed Central

Kramer, Megan E.; Chiu, C.-Y. Peter; Shear, Paula K.; Wade, Shari L.

2010-01-01

Children with traumatic brain injury (TBI) often experience memory deficits, although the nature, functional implication, and recovery trajectory of such difficulties are poorly understood. The present fMRI study examined the neural activation patterns in a group of young children who sustained moderate TBI in early childhood (n = 7), and a group of healthy control children (n = 13) during a verbal paired associate learning (PAL) task that promoted the use of two mnemonic strategies differing in efficacy. The children with TBI demonstrated intact memory performance and were able to successfully utilize the mnemonic strategies. However, the TBI group also demonstrated altered brain activation patterns during the task compared to the control children. These findings suggest early childhood TBI may alter activation within the network of brain regions supporting associative memory even in children who show good behavioral performance. PMID:21188286

Multiple determinants of lifespan memory differences.

PubMed

Henson, Richard N; Campbell, Karen L; Davis, Simon W; Taylor, Jason R; Emery, Tina; Erzinclioglu, Sharon; Kievit, Rogier A

2016-09-07

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss.

Episodic Memory Retrieval Benefits from a Less Modular Brain Network Organization

PubMed Central

2017-01-01

Most complex cognitive tasks require the coordinated interplay of multiple brain networks, but the act of retrieving an episodic memory may place especially heavy demands for communication between the frontoparietal control network (FPCN) and the default mode network (DMN), two networks that do not strongly interact with one another in many task contexts. We applied graph theoretical analysis to task-related fMRI functional connectivity data from 20 human participants and found that global brain modularity—a measure of network segregation—is markedly reduced during episodic memory retrieval relative to closely matched analogical reasoning and visuospatial perception tasks. Individual differences in modularity were correlated with memory task performance, such that lower modularity levels were associated with a lower false alarm rate. Moreover, the FPCN and DMN showed significantly elevated coupling with each other during the memory task, which correlated with the global reduction in brain modularity. Both networks also strengthened their functional connectivity with the hippocampus during the memory task. Together, these results provide a novel demonstration that reduced modularity is conducive to effective episodic retrieval, which requires close collaboration between goal-directed control processes supported by the FPCN and internally oriented self-referential processing supported by the DMN. SIGNIFICANCE STATEMENT Modularity, an index of the degree to which nodes of a complex system are organized into discrete communities, has emerged as an important construct in the characterization of brain connectivity dynamics. We provide novel evidence that the modularity of the human brain is reduced when individuals engage in episodic memory retrieval, relative to other cognitive tasks, and that this state of lower modularity is associated with improved memory performance. We propose a neural systems mechanism for this finding where the nodes of the frontoparietal control network and default mode network strengthen their interaction with one another during episodic retrieval. Such across-network communication likely facilitates effective access to internally generated representations of past event knowledge. PMID:28242796

Evidence for a double dissociation of articulatory rehearsal and non-articulatory maintenance of phonological information in human verbal working memory.

PubMed

Trost, Sarah; Gruber, Oliver

2012-01-01

Recent functional neuroimaging studies have provided evidence that human verbal working memory is represented by two complementary neural systems, a left lateralized premotor-parietal network implementing articulatory rehearsal and a presumably phylogenetically older bilateral anterior-prefrontal/inferior-parietal network subserving non-articulatory maintenance of phonological information. In order to corroborate these findings from functional neuroimaging, we performed a targeted behavioural study in patients with very selective and circumscribed brain lesions to key regions suggested to support these different subcomponents of human verbal working memory. Within a sample of over 500 neurological patients assessed with high-resolution structural magnetic resonance imaging, we identified 2 patients with corresponding brain lesions, one with an isolated lesion to Broca's area and the other with a selective lesion bilaterally to the anterior middle frontal gyrus. These 2 patients as well as groups of age-matched healthy controls performed two circuit-specific verbal working memory tasks. In this way, we systematically assessed the hypothesized selective behavioural effects of these brain lesions on the different subcomponents of verbal working memory in terms of a double dissociation. Confirming prior findings, the lesion to Broca's area led to reduced performance under articulatory rehearsal, whereas the non-articulatory maintenance of phonological information was unimpaired. Conversely, the bifrontopolar brain lesion was associated with impaired non-articulatory phonological working memory, whereas performance under articulatory rehearsal was unaffected. The present experimental neuropsychological study in patients with specific and circumscribed brain lesions confirms the hypothesized double dissociation of two complementary brain systems underlying verbal working memory in humans. In particular, the results demonstrate the functional relevance of the anterior prefrontal cortex for non-articulatory maintenance of phonological information and, in this way, provide further support for the evolutionary-based functional-neuroanatomical model of human working memory. Copyright © 2012 S. Karger AG, Basel.

Effects of exercise intensity on spatial memory performance and hippocampal synaptic plasticity in transient brain ischemic rats.

PubMed

Shih, Pei-Cheng; Yang, Yea-Ru; Wang, Ray-Yau

2013-01-01

Memory impairment is commonly noted in stroke survivors, and can lead to delay of functional recovery. Exercise has been proved to improve memory in adult healthy subjects. Such beneficial effects are often suggested to relate to hippocampal synaptic plasticity, which is important for memory processing. Previous evidence showed that in normal rats, low intensity exercise can improve synaptic plasticity better than high intensity exercise. However, the effects of exercise intensities on hippocampal synaptic plasticity and spatial memory after brain ischemia remain unclear. In this study, we investigated such effects in brain ischemic rats. The middle cerebral artery occlusion (MCAO) procedure was used to induce brain ischemia. After the MCAO procedure, rats were randomly assigned to sedentary (Sed), low-intensity exercise (Low-Ex), or high-intensity exercise (High-Ex) group. Treadmill training began from the second day post MCAO procedure, 30 min/day for 14 consecutive days for the exercise groups. The Low-Ex group was trained at the speed of 8 m/min, while the High-Ex group at the speed of 20 m/min. The spatial memory, hippocampal brain-derived neurotrophic factor (BDNF), synapsin-I, postsynaptic density protein 95 (PSD-95), and dendritic structures were examined to document the effects. Serum corticosterone level was also quantified as stress marker. Our results showed the Low-Ex group, but not the High-Ex group, demonstrated better spatial memory performance than the Sed group. Dendritic complexity and the levels of BDNF and PSD-95 increased significantly only in the Low-Ex group as compared with the Sed group in bilateral hippocampus. Notably, increased level of corticosterone was found in the High-Ex group, implicating higher stress response. In conclusion, after brain ischemia, low intensity exercise may result in better synaptic plasticity and spatial memory performance than high intensity exercise; therefore, the intensity is suggested to be considered during exercise training.

Episodic Memory Retrieval Benefits from a Less Modular Brain Network Organization.

PubMed

Westphal, Andrew J; Wang, Siliang; Rissman, Jesse

2017-03-29

Most complex cognitive tasks require the coordinated interplay of multiple brain networks, but the act of retrieving an episodic memory may place especially heavy demands for communication between the frontoparietal control network (FPCN) and the default mode network (DMN), two networks that do not strongly interact with one another in many task contexts. We applied graph theoretical analysis to task-related fMRI functional connectivity data from 20 human participants and found that global brain modularity-a measure of network segregation-is markedly reduced during episodic memory retrieval relative to closely matched analogical reasoning and visuospatial perception tasks. Individual differences in modularity were correlated with memory task performance, such that lower modularity levels were associated with a lower false alarm rate. Moreover, the FPCN and DMN showed significantly elevated coupling with each other during the memory task, which correlated with the global reduction in brain modularity. Both networks also strengthened their functional connectivity with the hippocampus during the memory task. Together, these results provide a novel demonstration that reduced modularity is conducive to effective episodic retrieval, which requires close collaboration between goal-directed control processes supported by the FPCN and internally oriented self-referential processing supported by the DMN. SIGNIFICANCE STATEMENT Modularity, an index of the degree to which nodes of a complex system are organized into discrete communities, has emerged as an important construct in the characterization of brain connectivity dynamics. We provide novel evidence that the modularity of the human brain is reduced when individuals engage in episodic memory retrieval, relative to other cognitive tasks, and that this state of lower modularity is associated with improved memory performance. We propose a neural systems mechanism for this finding where the nodes of the frontoparietal control network and default mode network strengthen their interaction with one another during episodic retrieval. Such across-network communication likely facilitates effective access to internally generated representations of past event knowledge. Copyright © 2017 the authors 0270-6474/17/373523-09$15.00/0.

A gene-brain-cognition pathway for the effect of an Alzheimer׳s risk gene on working memory in young adults.

PubMed

Stevens, Benson W; DiBattista, Amanda M; William Rebeck, G; Green, Adam E

2014-08-01

Identifying pathways by which genetic Alzheimer׳s disease (AD) risk factors exert neurocognitive effects in young adults are essential for the effort to develop early interventions to forestall or prevent AD onset. Here, in a brain-imaging cohort of 59 young adults, we investigated effects of a variant within the clusterin (CLU) gene on working memory function and gray matter volume in cortical areas that support working memory. In addition, we investigated the extent to which effects of CLU genotype on working memory were independent of variation in the strongest AD risk factor gene apolipoprotein E (APOE). CLU is among the strongest genetic AD risk factors and, though it appears to share AD pathogenesis-related features with, APOE, it has been far less well studied. CLU genotype was associated with working memory performance in our study cohort. Notably, we found that variation in gray matter volume in a parietal region, previously implicated in maintenance of information for working memory, mediated the effect of CLU on working memory performance. APOE genotype did not affect working memory within our sample, and did not interact with CLU genotype. To our knowledge, this work represents the first evidence of a behavioral effect of CLU genotype in young people. In addition, this work identifies the first gene-brain-cognition mediation effect pathway for the transmission of the effect of an AD risk factor. Relative to conventional pairwise associations in cognitive neurogenetic research, gene-brain-cognition mediation modeling provides a more integrated understanding of how genetic effects transmit from gene to brain to cognitive function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of penetrating traumatic brain injury on event segmentation and memory.

PubMed

Zacks, Jeffrey M; Kurby, Christopher A; Landazabal, Claudia S; Krueger, Frank; Grafman, Jordan

2016-01-01

Penetrating traumatic brain injury (pTBI) is associated with deficits in cognitive tasks including comprehension and memory, and also with impairments in tasks of daily living. In naturalistic settings, one important component of cognitive task performance is event segmentation, the ability to parse the ongoing stream of behavior into meaningful units. Event segmentation ability is associated with memory performance and with action control, but is not well assessed by standard neuropsychological assessments or laboratory tasks. Here, we measured event segmentation and memory in a sample of 123 male military veterans aged 59-81 who had suffered a traumatic brain injury as young men, and 34 demographically similar controls. Participants watched movies of everyday activities and segmented them to identify fine-grained or coarse-grained events, and then completed tests of recognition memory for pictures from the movies and of memory for the temporal order of actions in the movies. Lesion location and volume were assessed with computed tomography (CT) imaging. Patients with traumatic brain injury were impaired on event segmentation. Those with larger lesions had larger impairments for fine segmentation and also impairments for both memory measures. Further, the degree of memory impairment was statistically mediated by the degree of event segmentation impairment. There was some evidence that lesions to the ventromedial prefrontal cortex (vmPFC) selectively impaired coarse segmentation; however, lesions outside of a priori regions of interest also were associated with impaired segmentation. One possibility is that the effect of vmPFC damage reflects the role of prefrontal event knowledge representations in ongoing comprehension. These results suggest that assessment of naturalistic event comprehension can be a valuable component of cognitive assessment in cases of traumatic brain injury, and that interventions aimed at event segmentation could be clinically helpful. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcription co-activator SAYP mediates the action of STAT activator.

PubMed

Panov, Vladislav V; Kuzmina, Julia L; Doronin, Semen A; Kopantseva, Marina R; Nabirochkina, Elena N; Georgieva, Sofia G; Vorobyeva, Nadezhda E; Shidlovskii, Yulii V

2012-03-01

Jak/STAT is an important signaling pathway mediating multiple events in development. We describe participation of metazoan co-activator SAYP/PHF10 in this pathway downstream of STAT. The latter, via its activation domain, interacts with the conserved core of SAYP. STAT is associated with the SAYP-containing co-activator complex BTFly and recruits BTFly onto genes. SAYP is necessary for stimulating STAT-driven transcription of numerous genes. Mutation of SAYP leads to maldevelopments similar to those observed in STAT mutants. Thus, SAYP is a novel co-activator mediating the action of STAT.

An Extension of SIC Predictions to the Wiener Coactive Model

PubMed Central

Houpt, Joseph W.; Townsend, James T.

2011-01-01

The survivor interaction contrasts (SIC) is a powerful measure for distinguishing among candidate models of human information processing. One class of models to which SIC analysis can apply are the coactive, or channel summation, models of human information processing. In general, parametric forms of coactive models assume that responses are made based on the first passage time across a fixed threshold of a sum of stochastic processes. Previous work has shown that that the SIC for a coactive model based on the sum of Poisson processes has a distinctive down-up-down form, with an early negative region that is smaller than the later positive region. In this note, we demonstrate that a coactive process based on the sum of two Wiener processes has the same SIC form. PMID:21822333

An Extension of SIC Predictions to the Wiener Coactive Model.

PubMed

Houpt, Joseph W; Townsend, James T

2011-06-01

The survivor interaction contrasts (SIC) is a powerful measure for distinguishing among candidate models of human information processing. One class of models to which SIC analysis can apply are the coactive, or channel summation, models of human information processing. In general, parametric forms of coactive models assume that responses are made based on the first passage time across a fixed threshold of a sum of stochastic processes. Previous work has shown that that the SIC for a coactive model based on the sum of Poisson processes has a distinctive down-up-down form, with an early negative region that is smaller than the later positive region. In this note, we demonstrate that a coactive process based on the sum of two Wiener processes has the same SIC form.

Gluteus medius coactivation response in field hockey players with and without low back pain.

PubMed

Bussey, Melanie D; Kennedy, James E; Kennedy, Gavin

2016-01-01

To examine the effect of prolonged standing on gluteus medius coactivation and to observe whether the changes in gluteus medius coactivation over time were related to the development of low back pain in elite female field hockey players. Prospective cohort design. Participants were 39 elite female field hockey players (14 with a history of low back pain). Before the prolonged stand, maximal hip abduction strength, side bridge hold endurance and hip abduction range of motion were measured bilaterally. Surface electromyography was collected from the gluteus medius for coactivation analysis during a prolonged stand for 70 min. Low back pain was rated every 10 min on a visual analogue scale. Fourteen of 39 participants developed low back pain. The Time effect was significant for gluteus medius coactivation response (p = 0.003) and visual analogue scale score (p < 0.001). There were no significant group × time interactions. Yet athletes who developed pain had higher coactivation for the majority of the stand task. While female field hockey players have high agonist-antagonist coactivation patterns during prolonged standing, stand task is a useful tool to predict low back pain occurrence in players with and without history of pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Why musical memory can be preserved in advanced Alzheimer's disease.

PubMed

Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

2015-08-01

Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of biomarker development in these regions (amyloid accumulation → hypometabolism → cortical atrophy) and therefore relatively well preserved. Given the observed overlap of musical memory regions with areas that are relatively spared in Alzheimer's disease, the current findings may thus explain the surprising preservation of musical memory in this neurodegenerative disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

PubMed

McNay, E C; Gold, P E

1998-05-15

Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

PubMed

Elzinga, B M; Bremner, J D

2002-06-01

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

PubMed Central

Elzinga, B.M.; Bremner, J.D.

2017-01-01

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed. PMID:12113915

Neural systems and time course of proactive interference in working memory.

PubMed

Du, Yingchun; Zhang, John X; Xiao, Zhuangwei; Wu, Renhua

2007-01-01

The storage of information in working memory suffers as a function of proactive interference. Many works using neuroimaging technique have been done to reveal the brain mechanism of interference resolution. However, less is yet known about the time course of this process. Event-related potential method(ERP) and standardized Low Resolution Brain Electromagnetic Tomography method (sLORETA) were used in this study to discover the time course of interference resolution in working memory. The anterior P2 was thought to reflect interference resolution and if so, this process occurred earlier in working memory than in long-term memory.

Paradoxical false memory for objects after brain damage.

PubMed

McTighe, Stephanie M; Cowell, Rosemary A; Winters, Boyer D; Bussey, Timothy J; Saksida, Lisa M

2010-12-03

Poor memory after brain damage is usually considered to be a result of information being lost or rendered inaccessible. It is assumed that such memory impairment must be due to the incorrect interpretation of previously encountered information as being novel. In object recognition memory experiments with rats, we found that memory impairment can take the opposite form: a tendency to treat novel experiences as familiar. This impairment could be rescued with the use of a visual-restriction procedure that reduces interference. Such a pattern of data can be explained in terms of a recent representational-hierarchical view of cognition.

Memory as a new therapeutic target

PubMed Central

Nader, Karim; Hardt, Oliver; Lanius, Ruth

2013-01-01

This review aims to demonstrate how an understanding of the brain mechanisms involved in memory provides a basis for; (i) reconceptualizing some mental disorders; (ii) refining existing therapeutic tools; and (iii) designing new ones for targeting processes that maintain these disorders. First, some of the stages which a memory undergoes are defined, and the clinical relevance of an understanding of memory processing by the brain is discussed. This is followed by a brief review of some of the clinical studies that have targeted memory processes. Finally, some new insights provided by the field of neuroscience with implications for conceptualizing mental disorders are presented. PMID:24459414

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

PubMed

Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Psychotic Experiences, Working Memory, and the Developing Brain: A Multimodal Neuroimaging Study

PubMed Central

Fonville, Leon; Cohen Kadosh, Kathrin; Drakesmith, Mark; Dutt, Anirban; Zammit, Stanley; Mollon, Josephine; Reichenberg, Abraham; Lewis, Glyn; Jones, Derek K.; David, Anthony S.

2015-01-01

Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs. PMID:26286920

Post-training gamma irradiation-enhanced contextual fear memory associated with reduced neuronal activation of the infralimbic cortex.

PubMed

Kugelman, Tara; Zuloaga, Damian G; Weber, Sydney; Raber, Jacob

2016-02-01

The brain might be exposed to irradiation under a variety of situations, including clinical treatments, nuclear accidents, dirty bomb scenarios, and military and space missions. Correctly recalling tasks learned prior to irradiation is important but little is known about post-learning effects of irradiation. It is not clear whether exposure to X-ray irradiation during memory consolidation, a few hours following training, is associated with altered contextual fear conditioning 24h after irradiation and which brain region(s) might be involved in these effects. Brain immunoreactivity patterns of the immediately early gene c-Fos, a marker of cellular activity was used to determine which brain areas might be altered in post-training irradiation memory retention tasks. In this study, we show that post-training gamma irradiation exposure (1 Gy) enhanced contextual fear memory 24h later and is associated with reduced cellular activation in the infralimbic cortex. Reduced GABA-ergic neurotransmission in parvalbumin-positive cells in the infralimbic cortex might play a role in this post-training radiation-enhanced contextual fear memory. Copyright © 2015 Elsevier B.V. All rights reserved.

Post-training gamma irradiation-enhanced contextual fear memory associated with reduced neuronal activation of the infralimbic cortex

PubMed Central

Kugelman, Tara; Zuloaga, Damian G.; Weber, Sydney; Raber, Jacob

2015-01-01

The brain might be exposed to irradiation under a variety of situations, including clinical treatments, nuclear accidents, dirty bomb scenarios, and military and space missions. Correctly recalling tasks learned prior to irradiation is important but little is known about post-learning effects of irradiation. It is not clear whether exposure to X-ray irradiation during memory consolidation, a few hours following training, is associated with altered contextual fear conditioning 24 hours after irradiation and which brain region(s) might be involved in these effects. Brain immunoreactivity patterns of the immediately early gene c-Fos, a marker of cellular activity was used to determine which brain areas might be altered in post-training irradiation memory retention tasks. In this study, we show that post-training gamma irradiation exposure (1 Gy) enhanced contextual fear memory 24 hours later and is associated with reduced cellular activation in the infralimbic cortex. Reduced GABA-ergic neurotransmission in parvalbumin-positive cells in the infralimbic cortex might play a role in this post-training radiation-enhanced contextual fear memory. PMID:26522840

Posttraining Epinephrine Reverses Memory Deficits Produced by Traumatic Brain Injury in Rats

PubMed Central

Lorón-Sánchez, Alejandro; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David; Portell-Cortés, Isabel

2016-01-01

The aim of this research is to evaluate whether posttraining systemic epinephrine is able to improve object recognition memory in rats with memory deficits produced by traumatic brain injury. Forty-nine two-month-old naïve male Wistar rats were submitted to surgical procedures to induce traumatic brain injury (TBI) or were sham-operated. Rats were trained in an object recognition task and, immediately after training, received an intraperitoneal injection of distilled water (Sham-Veh and TBI-Veh group) or 0.01 mg/kg epinephrine (TBI-Epi group) or no injection (TBI-0 and Sham-0 groups). Retention was tested 3 h and 24 h after acquisition. The results showed that brain injury produced severe memory deficits and that posttraining administration of epinephrine was able to reverse them. Systemic administration of distilled water also had an enhancing effect, but of a lower magnitude. These data indicate that posttraining epinephrine and, to a lesser extent, vehicle injection reduce memory deficits associated with TBI, probably through induction of a low-to-moderate emotional arousal. PMID:27127685

Using imagination to understand the neural basis of episodic memory

PubMed Central

Hassabis, Demis; Kumaran, Dharshan; Maguire, Eleanor A.

2008-01-01

Functional MRI (fMRI) studies investigating the neural basis of episodic memory recall, and the related task of thinking about plausible personal future events, have revealed a consistent network of associated brain regions. Surprisingly little, however, is understood about the contributions individual brain areas make to the overall recollective experience. In order to examine this, we employed a novel fMRI paradigm where subjects had to imagine fictitious experiences. In contrast to future thinking, this results in experiences that are not explicitly temporal in nature or as reliant on self-processing. By using previously imagined fictitious experiences as a comparison for episodic memories, we identified the neural basis of a key process engaged in common, namely scene construction, involving the generation, maintenance and visualisation of complex spatial contexts. This was associated with activations in a distributed network, including hippocampus, parahippocampal gyrus, and retrosplenial cortex. Importantly, we disambiguated these common effects from episodic memory-specific responses in anterior medial prefrontal cortex, posterior cingulate cortex and precuneus. These latter regions may support self-schema and familiarity processes, and contribute to the brain's ability to distinguish real from imaginary memories. We conclude that scene construction constitutes a common process underlying episodic memory and imagination of fictitious experiences, and suggest it may partially account for the similar brain networks implicated in navigation, episodic future thinking, and the default mode. We suggest that further brain regions are co-opted into this core network in a task-specific manner to support functions such as episodic memory that may have additional requirements. PMID:18160644

Altered prefrontal brain activity in persons at risk for Alzheimer's disease: an fMRI study.

PubMed

Elgh, Eva; Larsson, Anne; Eriksson, Sture; Nyberg, Lars

2003-06-01

Early diagnosis of Alzheimer's disease (AD) is critical for adequate treatment and care. Recently it has been shown that functional magnetic resonance imaging (fMRI) can be important in preclinical detection of AD. The purpose of this study was to examine possible differences in memory-related brain activation between persons with high versus low risk for AD. This was achieved by combining a validated neurocognitive screening battery (the 7-minutes test) with memory assessment and fMRI. One hundred two healthy community-living persons with subjective memory complaints were recruited through advertisement and tested with the 7-minutes test. Based on their test performance they were classified as having either high (n = 8) or low risk (n = 94) for AD. Six high-risk individuals and six age-, sex-, and education-matched low-risk individuals were investigated with fMRI while engaged in episodic memory tasks. The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences (p < .05 corrected). During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. Patterns of prefrontal brain activity related to episodic memory differ between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.

Using imagination to understand the neural basis of episodic memory.

PubMed

Hassabis, Demis; Kumaran, Dharshan; Maguire, Eleanor A

2007-12-26

Functional MRI (fMRI) studies investigating the neural basis of episodic memory recall, and the related task of thinking about plausible personal future events, have revealed a consistent network of associated brain regions. Surprisingly little, however, is understood about the contributions individual brain areas make to the overall recollective experience. To examine this, we used a novel fMRI paradigm in which subjects had to imagine fictitious experiences. In contrast to future thinking, this results in experiences that are not explicitly temporal in nature or as reliant on self-processing. By using previously imagined fictitious experiences as a comparison for episodic memories, we identified the neural basis of a key process engaged in common, namely scene construction, involving the generation, maintenance and visualization of complex spatial contexts. This was associated with activations in a distributed network, including hippocampus, parahippocampal gyrus, and retrosplenial cortex. Importantly, we disambiguated these common effects from episodic memory-specific responses in anterior medial prefrontal cortex, posterior cingulate cortex and precuneus. These latter regions may support self-schema and familiarity processes, and contribute to the brain's ability to distinguish real from imaginary memories. We conclude that scene construction constitutes a common process underlying episodic memory and imagination of fictitious experiences, and suggest it may partially account for the similar brain networks implicated in navigation, episodic future thinking, and the default mode. We suggest that additional brain regions are co-opted into this core network in a task-specific manner to support functions such as episodic memory that may have additional requirements.

Regional brain activity that determines successful and unsuccessful working memory formation.

PubMed

Teramoto, Shohei; Inaoka, Tsubasa; Ono, Yumie

2016-08-01

Using EEG source reconstruction with Multiple Sparse Priors (MSP), we investigated the regional brain activity that determines successful memory encoding in two participant groups of high and low accuracy rates. Eighteen healthy young adults performed a sequential fashion of visual Sternberg memory task. The 32-channel EEG was continuously measured during participants performed two 70 trials of memory task. The regional brain activity corresponding to the oscillatory EEG activity in the alpha band (8-13 Hz) during encoding period was analyzed by MSP implemented in SPM8. We divided the data of all participants into 2 groups (low- and highperformance group) and analyzed differences in regional brain activity between trials in which participants answered correctly and incorrectly within each of the group. Participants in low-performance group showed significant activity increase in the visual cortices in their successful trials compared to unsuccessful ones. On the other hand, those in high-performance group showed a significant activity increase in widely distributed cortical regions in the frontal, temporal, and parietal areas including those suggested as Baddeley's working memory model. Further comparison of activated cortical volumes and mean current source intensities within the cortical regions of Baddeley's model during memory encoding demonstrated that participants in high-performance group showed enhanced activity in the right premotor cortex, which plays an important role in maintaining visuospatial attention, compared to those in low performance group. Our results suggest that better ability in memory encoding is associated with distributed and stronger regional brain activities including the premotor cortex, possibly indicating efficient allocation of cognitive load and maintenance of attention.

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

PubMed

Frenkel, L; Freudenthal, R; Romano, A; Nahmod, V E; Maldonado, H; Delorenzi, A

2002-01-01

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

Catching the engram: strategies to examine the memory trace

PubMed Central

2012-01-01

Memories are stored within neuronal ensembles in the brain. Modern genetic techniques can be used to not only visualize specific neuronal ensembles that encode memories (e.g., fear, craving) but also to selectively manipulate those neurons. These techniques are now being expanded for the study of various types of memory. In this review, we will summarize the genetic methods used to visualize and manipulate neurons involved in the representation of memory engrams. The methods will help clarify how memory is encoded, stored and processed in the brain. Furthermore, these approaches may contribute to our understanding of the pathological mechanisms associated with human memory disorders and, ultimately, may aid the development of therapeutic strategies to ameliorate these diseases. PMID:22999350

Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting.

PubMed

Helfrich, Randolph F; Mander, Bryce A; Jagust, William J; Knight, Robert T; Walker, Matthew P

2018-01-03

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation

PubMed Central

Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon; Nadel, Lynn

2016-01-01

The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains. PMID:26726963

Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation.

PubMed

Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon; Nadel, Lynn

2016-01-01

The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains.

Effect of Knee Joint Angle and Contraction Intensity on Hamstrings Coactivation.

PubMed

Wu, Rui; Delahunt, Eamonn; Ditroilo, Massimiliano; Lowery, Madeleine M; DE Vito, Giuseppe

2017-08-01

This study investigated the effect of knee joint angle and contraction intensity on the coactivation of the hamstring muscles (when acting as antagonists to the quadriceps) in young and older individuals of both sexes. A total of 25 young (24 ± 2.6 yr) and 26 older (70 ± 2.5 yr) healthy men and women participated. Maximal voluntary isometric contraction of the knee extensors and flexors was assessed at two knee joint angles (90° and 60°, 0° = full extension). At each angle, participants performed submaximal contractions of the knee extensors (20%, 50%, and 80% maximal voluntary isometric contraction), whereas surface EMG was simultaneously acquired from the vastus lateralis and biceps femoris muscles to assess the level (EMG root-mean-square) of agonist activation and antagonist coactivation. Subcutaneous adipose tissue in the areas corresponding to surface EMG electrode placements was measured via ultrasonography. The contractions performed at 90° knee flexion demonstrated higher levels of antagonist coactivation (all P < 0.01) and agonist activation (all P < 0.01) as a function of contraction intensity compared with the 60° knee flexion. Furthermore, after controlling for subcutaneous adipose tissue, older participants exhibited a higher level of antagonist coactivation at 60° knee flexion compared with young participants (P < 0.05). The results of the present study suggest that 1) the antagonist coactivation is dependent on knee joint angle and contraction intensity and 2) subcutaneous adipose tissue may affect the measured coactivation level likely because of a cross-talk effect. Antagonist coactivation may play a protective role in stabilizing the knee joint and maintaining constant motor output.

Coiled-coil coactivators play a structural role mediating interactions in hypoxia-inducible factor heterodimerization

DOE PAGES

Guo, Yirui; Scheuermann, Thomas H.; Partch, Carrie L.; ...

2015-01-27

The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor,more » we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. Furthermore, these findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.« less

When the future becomes the past: Differences in brain activation patterns for episodic memory and episodic future thinking.

PubMed

Weiler, Julia A; Suchan, Boris; Daum, Irene

2010-10-15

Episodic memory and episodic future thinking activate a network of overlapping brain regions, but little is known about the mechanism with which the brain separates the two processes. It was recently suggested that differential activity for memory and future thinking may be linked to differences in the phenomenal properties (e.g., richness of detail). Using functional magnetic resonance imaging in healthy subjects and a novel experimental design, we investigated the networks involved in the imagery of future and the recall of past events for the same target occasion, i.e. the Christmas and New Year's holidays, thereby keeping temporal distance and content similar across conditions. Although ratings of phenomenal characteristics were comparable for future thoughts and memories, differential activation patterns emerged. The right posterior hippocampus exhibited stronger memory-related activity during early event recall, and stronger future thought-related activity during late event imagination. Other regions, e.g., the precuneus and lateral prefrontal cortex, showed the reverse activation pattern with early future-associated and late past-associated activation. Memories compared to future thoughts were further related to stronger activation in several visual processing regions, which accords with a reactivation of the original perceptual experience. In conclusion, the results showed for the first time unique neural signatures for both memory and future thinking even in the absence of differences in phenomenal properties and suggested different time courses of brain activation for episodic memory and future thinking. Copyright 2010 Elsevier B.V. All rights reserved.

Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task.

PubMed

Méndez-Couz, Marta; Conejo, Nélida M; Vallejo, Guillermo; Arias, Jorge L

2015-01-01

Several studies suggest a prefrontal cortex involvement during the acquisition and consolidation of spatial memory, suggesting an active modulating role at late stages of acquisition processes. Recently, we have reported that the prelimbic and infralimbic areas of the prefrontal cortex, among other structures, are also specifically involved in the late phases of spatial memory extinction. This study aimed to evaluate whether the inactivation of the prelimbic area of the prefrontal cortex impaired spatial memory extinction. For this purpose, male Wistar rats were implanted bilaterally with cannulae into the prelimbic region of the prefrontal cortex. Animals were trained during 5 consecutive days in a hidden platform task and tested for reference spatial memory immediately after the last training session. One day after completing the training task, bilateral infusion of the GABAA receptor agonist Muscimol was performed before the extinction protocol was carried out. Additionally, cytochrome c oxidase histochemistry was applied to map the metabolic brain activity related to the spatial memory extinction under prelimbic cortex inactivation. Results show that animals acquired the reference memory task in the water maze, and the extinction task was successfully completed without significant impairment. However, analysis of the functional brain networks involved by cytochrome oxidase activity interregional correlations showed changes in brain networks between the group treated with Muscimol as compared to the saline-treated group, supporting the involvement of the mammillary bodies at a the late stage in the memory extinction process. Copyright © 2015 Elsevier B.V. All rights reserved.

Hippocampal volume and memory performance in children with perinatal stroke.

PubMed

Gold, Jeffrey J; Trauner, Doris A

2014-01-01

Pediatric neurologists and neonatologists often are asked to predict cognitive outcome after perinatal brain injury (including likely memory and learning outcomes). However, relatively few data exist on how accurate predictions can be made. Furthermore, although the consequences of brain injury on hippocampal volume and memory performance have been studied extensively in adults, little work has been done in children. We measured the volume of the hippocampus in 27 children with perinatal stroke and 19 controls, and measured their performance on standardized verbal and non-verbal memory tests. We discovered the following: (1) As a group, children with perinatal stroke had smaller left and right hippocampi compared with control children. (2) Individually, children with perinatal stroke demonstrated 1 of 3 findings: no hippocampal loss, unilateral hippocampal loss, or bilateral hippocampal volume loss compared with control children. (3) Hippocampal volume inversely correlated with memory test performance in the perinatal stroke group, with smaller left and right hippocampal volumes related to poorer verbal and non-verbal memory test performance, respectively. (4) Seizures played a significant role in determining memory deficit and extent of hippocampal volume reduction in patients with perinatal stroke. These findings support the view that, in the developing brain, the left and right hippocampi preferentially support verbal and nonverbal memory respectively, a consistent finding in the adult literature but a subject of debate in the pediatric literature. This is the first work to report that children with focal brain injury incurred from perinatal stroke have volume reduction in the hippocampus and impairments in certain aspects of declarative memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Measuring Mathematics Teachers' Professional Competence by Using Video Clips (COACTIV Video)

ERIC Educational Resources Information Center

Bruckmaier, G.; Krauss, S.; Blum, W.; Leiss, D.

2016-01-01

The COACTIV video study is part of the COACTIV research program in which secondary mathematics teachers whose students participated in PISA 03/04 were examined, with respect to their professional knowledge, motivational orientations, beliefs, and self-regulation. In the video study, 284 German secondary mathematics teachers were asked to specify…

Hippocampal brain-network coordination during volitional exploratory behavior enhances learning

PubMed Central

Voss, Joel L.; Gonsalves, Brian D.; Federmeier, Kara D.; Tranel, Daniel; Cohen, Neal J.

2010-01-01

Exploratory behaviors during learning determine what is studied and when, helping to optimize subsequent memory performance. We manipulated how much control subjects had over the position of a moving window through which they studied objects and their locations, in order to elucidate the cognitive and neural determinants of exploratory behaviors. Our behavioral, neuropsychological, and neuroimaging data indicate volitional control benefits memory performance, and is linked to a brain network centered on the hippocampus. Increases in correlated activity between the hippocampus and other areas were associated with specific aspects of memory, suggesting that volitional control optimizes interactions among specialized neural systems via the hippocampus. Memory is therefore an active process intrinsically linked to behavior. Furthermore, brain structures typically seen as passive participants in memory encoding (e.g., the hippocampus) are actually part of an active network that controls behavior dynamically as it unfolds. PMID:21102449

Articulatory rehearsal in verbal working memory: a possible neurocognitive endophenotype that differentiates between schizophrenia and schizoaffective disorder.

PubMed

Gruber, Oliver; Gruber, Eva; Falkai, Peter

2006-09-11

Recent fMRI studies have identified brain systems underlying different components of working memory in healthy individuals. The aim of this study was to compare the functional integrity of these neural networks in terms of behavioural performance in patients with schizophrenia, schizoaffective disorder and healthy controls. In order to detect specific working memory deficits based on dysfunctions of underlying brain circuits we used the same verbal and visuospatial Sternberg item-recognition tasks as in previous neuroimaging studies. Clinical and performance data from matched groups consisting of 14 subjects each were statistically analyzed. Schizophrenic patients exhibited pronounced impairments of both verbal and visuospatial working memory, whereas verbal working memory performance was preserved in schizoaffective patients. The findings provide first evidence that dysfunction of a brain system subserving articulatory rehearsal could represent a biological marker which differentiates between schizophrenia and schizoaffective disorder.

Hippocampal brain-network coordination during volitional exploratory behavior enhances learning.

PubMed

Voss, Joel L; Gonsalves, Brian D; Federmeier, Kara D; Tranel, Daniel; Cohen, Neal J

2011-01-01

Exploratory behaviors during learning determine what is studied and when, helping to optimize subsequent memory performance. To elucidate the cognitive and neural determinants of exploratory behaviors, we manipulated the control that human subjects had over the position of a moving window through which they studied objects and their locations. Our behavioral, neuropsychological and neuroimaging data indicate that volitional control benefits memory performance and is linked to a brain network that is centered on the hippocampus. Increases in correlated activity between the hippocampus and other areas were associated with specific aspects of memory, which suggests that volitional control optimizes interactions among specialized neural systems through the hippocampus. Memory is therefore an active process that is intrinsically linked to behavior. Furthermore, brain structures that are typically seen as passive participants in memory encoding (for example, the hippocampus) are actually part of an active network that controls behavior dynamically as it unfolds.

Cocaine, Appetitive Memory and Neural Connectivity

PubMed Central

Ray, Suchismita

2013-01-01

This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested. PMID:25009766

Molecular Dynamics of "Fuzzy" Transcriptional Activator-Coactivator Interactions

PubMed Central

Scholes, Natalie S.; Weinzierl, Robert O. J.

2016-01-01

Transcriptional activation domains (ADs) are generally thought to be intrinsically unstructured, but capable of adopting limited secondary structure upon interaction with a coactivator surface. The indeterminate nature of this interface made it hitherto difficult to study structure/function relationships of such contacts. Here we used atomistic accelerated molecular dynamics (aMD) simulations to study the conformational changes of the GCN4 AD and variants thereof, either free in solution, or bound to the GAL11 coactivator surface. We show that the AD-coactivator interactions are highly dynamic while obeying distinct rules. The data provide insights into the constant and variable aspects of orientation of ADs relative to the coactivator, changes in secondary structure and energetic contributions stabilizing the various conformers at different time points. We also demonstrate that a prediction of α-helical propensity correlates directly with the experimentally measured transactivation potential of a large set of mutagenized ADs. The link between α-helical propensity and the stimulatory activity of ADs has fundamental practical and theoretical implications concerning the recruitment of ADs to coactivators. PMID:27175900

Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls.

PubMed

Kontos, A P; Huppert, T J; Beluk, N H; Elbin, R J; Henry, L C; French, J; Dakan, S M; Collins, M W

2014-12-01

There is no accepted clinical imaging modality for concussion, and current imaging modalities including fMRI, DTI, and PET are expensive and inaccessible to most clinics/patients. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable, and low-cost imaging modality that can measure brain activity. The purpose of this study was to compare brain activity as measured by fNIRS in concussed and age-matched controls during the performance of cognitive tasks from a computerized neurocognitive test battery. Participants included nine currently symptomatic patients aged 18-45 years with a recent (15-45 days) sport-related concussion and five age-matched healthy controls. The participants completed a computerized neurocognitive test battery while wearing the fNIRS unit. Our results demonstrated reduced brain activation in the concussed subject group during word memory, (spatial) design memory, digit-symbol substitution (symbol match), and working memory (X's and O's) tasks. Behavioral performance (percent-correct and reaction time respectively) was lower for concussed participants on the word memory, design memory, and symbol match tasks than controls. The results of this preliminary study suggest that fNIRS could be a useful, portable assessment tool to assess reduced brain activation and augment current approaches to assessment and management of patients following concussion.

Constructing realistic engrams: poststimulus activity of hippocampus and dorsal striatum predicts subsequent episodic memory.

PubMed

Ben-Yakov, Aya; Dudai, Yadin

2011-06-15

Encoding of real-life episodic memory commonly involves integration of information as the episode unfolds. Offline processing immediately following event offset is expected to play a role in encoding the episode into memory. In this study, we examined whether distinct human brain activity time-locked to the offset of short narrative audiovisual episodes could predict subsequent memory for the gist of the episodes. We found that a set of brain regions, most prominently the bilateral hippocampus and the bilateral caudate nucleus, exhibit memory-predictive activity time-locked to the stimulus offset. We propose that offline activity in these regions reflects registration to memory of integrated episodes.

Sleeping brain, learning brain. The role of sleep for memory systems.

PubMed

Peigneux, P; Laureys, S; Delbeuck, X; Maquet, P

2001-12-21

The hypothesis that sleep participates in the consolidation of recent memory traces has been investigated using four main paradigms: (1) effects of post-training sleep deprivation on memory consolidation, (2) effects of learning on post-training sleep, (3) effects of within sleep stimulation on the sleep pattern and on overnight memories, and (4) re-expression of behavior-specific neural patterns during post-training sleep. These studies convincingly support the idea that sleep is deeply involved in memory functions in humans and animals. However, the available data still remain too scarce to confirm or reject unequivocally the recently upheld hypothesis that consolidations of non-declarative and declarative memories are respectively dependent upon REM and NREM sleep processes.

Sleep, Memory & Brain Rhythms

PubMed Central

Watson, Brendon O.; Buzsáki, György

2015-01-01

Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called “sharp-wave ripple” seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep–REM and non-REM, the latter of which has an abundance of ripple electrical activity–might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function. PMID:26097242

Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring.

PubMed

Rudolph, Marc D; Graham, Alice M; Feczko, Eric; Miranda-Dominguez, Oscar; Rasmussen, Jerod M; Nardos, Rahel; Entringer, Sonja; Wadhwa, Pathik D; Buss, Claudia; Fair, Damien A

2018-05-01

Several lines of evidence support the link between maternal inflammation during pregnancy and increased likelihood of neurodevelopmental and psychiatric disorders in offspring. This longitudinal study seeks to advance understanding regarding implications of systemic maternal inflammation during pregnancy, indexed by plasma interleukin-6 (IL-6) concentrations, for large-scale brain system development and emerging executive function skills in offspring. We assessed maternal IL-6 during pregnancy, functional magnetic resonance imaging acquired in neonates, and working memory (an important component of executive function) at 2 years of age. Functional connectivity within and between multiple neonatal brain networks can be modeled to estimate maternal IL-6 concentrations during pregnancy. Brain regions heavily weighted in these models overlap substantially with those supporting working memory in a large meta-analysis. Maternal IL-6 also directly accounts for a portion of the variance of working memory at 2 years of age. Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging executive function.

Sleep, Memory & Brain Rhythms.

PubMed

Watson, Brendon O; Buzsáki, György

2015-01-01

Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called "sharp-wave ripple" seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep-REM and non-REM, the latter of which has an abundance of ripple electrical activity-might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function.

Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

PubMed

Cheke, Lucy G; Bonnici, Heidi M; Clayton, Nicola S; Simons, Jon S

2017-02-01

Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The plateau zokors' learning and memory ability is related to the high expression levels of foxP2 in the brain.

PubMed

Ma, Ben-Yuan; Wei, Lian; Sun, Sheng-Zhen; Wang, Duo-Wei; Wei, Deng-Bang

2014-04-25

Plateau zokor (Myospalax baileyi) is a subterranean mammal. Plateau zokor has high learning and memory ability, and can determine the location of blocking obstacles in their tunnels. Forkhead box p2 (FOXP2) is a transcription factor implicated in the neural control of orofacial coordination and sensory-motor integration, particularly with respect to learning, memory and vocalization. To explore the association of foxP2 with the high learning and memory ability of plateau zokor, the cDNA of foxP2 of plateau zokor was sequenced; by using plateau pika as control, the expression levels of foxP2 mRNA and FOXP2 protein in brain of plateau zokor were determined by real-time PCR and Western blot, respectively; and the location of FOXP2 protein in the brain of plateau zokor was determined by immunohistochemistry. The result showed that the cDNA sequence of plateau zokor foxP2 was similar to that of other mammals and the amino acid sequences showed a relatively high degree of conservation, with the exception of two particular amino acid substitutions [a Gln (Q)-to-His (H) change at position 231 and a Ser (S)-to-Ile (I) change at position 235]. Higher expression levels of foxP2 mRNA (3-fold higher) and FOXP2 protein (>2-fold higher) were detected in plateau zokor brain relative to plateau pika brain. In plateau zokor brain, FOXP2 protein was highly expressed in the cerebral cortex, thalamus and the striatum (a basal ganglia brain region). The results suggest that the high learning and memory ability of plateau zokor is related to the high expression levels of foxP2 in the brain.

The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed.

PubMed

Staffaroni, Adam M; Brown, Jesse A; Casaletto, Kaitlin B; Elahi, Fanny M; Deng, Jersey; Neuhaus, John; Cobigo, Yann; Mumford, Paige S; Walters, Samantha; Saloner, Rowan; Karydas, Anna; Coppola, Giovanni; Rosen, Howie J; Miller, Bruce L; Seeley, William W; Kramer, Joel H

2018-03-14

The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans ( n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50-66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults. SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity. Copyright © 2018 the authors 0270-6474/18/382810-09$15.00/0.

The associative memory deficit in aging is related to reduced selectivity of brain activity during encoding

PubMed Central

Saverino, Cristina; Fatima, Zainab; Sarraf, Saman; Oder, Anita; Strother, Stephen C.; Grady, Cheryl L.

2016-01-01

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity, or dedifferentiation, has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used functional magnetic resonance imaging (fMRI) to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental-encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole brain patterns of activation that predicted item vs. associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared to young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory. PMID:27082043

Encoding-related brain activity and accelerated forgetting in transient epileptic amnesia.

PubMed

Atherton, Kathryn E; Filippini, Nicola; Zeman, Adam Z J; Nobre, Anna C; Butler, Christopher R

2018-05-17

The accelerated forgetting of newly learned information is common amongst patients with epilepsy and, in particular, in the syndrome of transient epileptic amnesia (TEA). However, the neural mechanisms underlying accelerated forgetting are poorly understood. It has been hypothesised that interictal epileptiform activity during longer retention intervals disrupts normally established memory traces. Here, we tested a distinct hypothesis-that accelerated forgetting relates to the abnormal encoding of memories. We studied a group of 15 patients with TEA together with matched, healthy control subjects. Despite normal performance on standard anterograde memory tasks, patients showed accelerated forgetting of a word list over one week. We used a subsequent memory paradigm to compare encoding-related brain activity in patients and controls. Participants studied a series of visually presented scenes whilst undergoing functional MRI scanning. Recognition memory for these scenes was then probed outside the scanner after delays of 45 min and of 4 days. Patients showed poorer memory for the scenes compared with controls. In the patients but not the controls, subsequently forgotten stimuli were associated with reduced hippocampal activation at encoding. Furthermore, patients demonstrated reduced deactivation of posteromedial cortex regions upon viewing subsequently remembered stimuli as compared to subsequently forgotten ones. These data suggest that abnormal encoding-related activity in key memory areas of the brain contributes to accelerated forgetting in TEA. We propose that abnormally encoded memory traces may be particularly vulnerable to interference from subsequently encountered material and hence be forgotten more rapidly. Our results shed light on the mechanisms underlying memory impairment in epilepsy, and offer support to the proposal that accelerated forgetting may be a useful marker of subtle dysfunction in memory-related brain systems. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A System for True and False Memory Prediction Based on 2D and 3D Educational Contents and EEG Brain Signals.

PubMed

Bamatraf, Saeed; Hussain, Muhammad; Aboalsamh, Hatim; Qazi, Emad-Ul-Haq; Malik, Amir Saeed; Amin, Hafeez Ullah; Mathkour, Hassan; Muhammad, Ghulam; Imran, Hafiz Muhammad

2016-01-01

We studied the impact of 2D and 3D educational contents on learning and memory recall using electroencephalography (EEG) brain signals. For this purpose, we adopted a classification approach that predicts true and false memories in case of both short term memory (STM) and long term memory (LTM) and helps to decide whether there is a difference between the impact of 2D and 3D educational contents. In this approach, EEG brain signals are converted into topomaps and then discriminative features are extracted from them and finally support vector machine (SVM) which is employed to predict brain states. For data collection, half of sixty-eight healthy individuals watched the learning material in 2D format whereas the rest watched the same material in 3D format. After learning task, memory recall tasks were performed after 30 minutes (STM) and two months (LTM), and EEG signals were recorded. In case of STM, 97.5% prediction accuracy was achieved for 3D and 96.6% for 2D and, in case of LTM, it was 100% for both 2D and 3D. The statistical analysis of the results suggested that for learning and memory recall both 2D and 3D materials do not have much difference in case of STM and LTM.

A System for True and False Memory Prediction Based on 2D and 3D Educational Contents and EEG Brain Signals

PubMed Central

2016-01-01

We studied the impact of 2D and 3D educational contents on learning and memory recall using electroencephalography (EEG) brain signals. For this purpose, we adopted a classification approach that predicts true and false memories in case of both short term memory (STM) and long term memory (LTM) and helps to decide whether there is a difference between the impact of 2D and 3D educational contents. In this approach, EEG brain signals are converted into topomaps and then discriminative features are extracted from them and finally support vector machine (SVM) which is employed to predict brain states. For data collection, half of sixty-eight healthy individuals watched the learning material in 2D format whereas the rest watched the same material in 3D format. After learning task, memory recall tasks were performed after 30 minutes (STM) and two months (LTM), and EEG signals were recorded. In case of STM, 97.5% prediction accuracy was achieved for 3D and 96.6% for 2D and, in case of LTM, it was 100% for both 2D and 3D. The statistical analysis of the results suggested that for learning and memory recall both 2D and 3D materials do not have much difference in case of STM and LTM. PMID:26819593

On brain activity mapping: insights and lessons from Brain Decoding Project to map memory patterns in the hippocampus.

PubMed

Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longnian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-09-01

The BRAIN project recently announced by the president Obama is the reflection of unrelenting human quest for cracking the brain code, the patterns of neuronal activity that define who we are and what we are. While the Brain Activity Mapping proposal has rightly emphasized on the need to develop new technologies for measuring every spike from every neuron, it might be helpful to consider both the theoretical and experimental aspects that would accelerate our search for the organizing principles of the brain code. Here we share several insights and lessons from the similar proposal, namely, Brain Decoding Project that we initiated since 2007. We provide a specific example in our initial mapping of real-time memory traces from one part of the memory circuit, namely, the CA1 region of the mouse hippocampus. We show how innovative behavioral tasks and appropriate mathematical analyses of large datasets can play equally, if not more, important roles in uncovering the specific-to-general feature-coding cell assembly mechanism by which episodic memory, semantic knowledge, and imagination are generated and organized. Our own experiences suggest that the bottleneck of the Brain Project is not only at merely developing additional new technologies, but also the lack of efficient avenues to disseminate cutting edge platforms and decoding expertise to neuroscience community. Therefore, we propose that in order to harness unique insights and extensive knowledge from various investigators working in diverse neuroscience subfields, ranging from perception and emotion to memory and social behaviors, the BRAIN project should create a set of International and National Brain Decoding Centers at which cutting-edge recording technologies and expertise on analyzing large datasets analyses can be made readily available to the entire community of neuroscientists who can apply and schedule to perform cutting-edge research.

Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

PubMed

Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

2011-04-01

Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

Transcription co-activator SAYP mediates the action of STAT activator

PubMed Central

Panov, Vladislav V.; Kuzmina, Julia L.; Doronin, Semen A.; Kopantseva, Marina R.; Nabirochkina, Elena N.; Georgieva, Sofia G.; Vorobyeva, Nadezhda E.; Shidlovskii, Yulii V.

2012-01-01

Jak/STAT is an important signaling pathway mediating multiple events in development. We describe participation of metazoan co-activator SAYP/PHF10 in this pathway downstream of STAT. The latter, via its activation domain, interacts with the conserved core of SAYP. STAT is associated with the SAYP-containing co-activator complex BTFly and recruits BTFly onto genes. SAYP is necessary for stimulating STAT-driven transcription of numerous genes. Mutation of SAYP leads to maldevelopments similar to those observed in STAT mutants. Thus, SAYP is a novel co-activator mediating the action of STAT. PMID:22123744

Prefrontal consolidation supports the attainment of fear memory accuracy

PubMed Central

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. PMID:25031365

Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions: A preliminary report of a prospective phase II study.

PubMed

Lin, Shinn-Yn; Yang, Chi-Cheng; Wu, Yi-Ming; Tseng, Chen-Kan; Wei, Kuo-Chen; Chu, Yi-Chuan; Hsieh, Hsiang-Yao; Wu, Tung-Ho; Pai, Ping-Ching; Hsu, Peng-Wei; Chuang, Chi-Cheng

2015-01-01

Whole brain radiotherapy (WBRT) is the treatment of choice for patients with brain metastases. However, neurocognitive functions (NCFs) decline due to impaired hippocampal neurogenesis might occur thereafter. It is hypothesized that conformal hippocampal avoidance during the course of WBRT (HA-WBRT) might provide meaningful NCF preservation. Our study aims to demonstrate the impact of delivering HA-WBRT on NCF changes in patients receiving WBRT. Twenty-five patients who were referred for prophylactic cranial irradiation (PCI) or treating oligometastatic brain disease were enrolled in the study. Before the HA-WBRT course, all participants should receive baseline neurocognitive assessment, including memory, executive functions, and psychomotor speed. The primary endpoint was delayed recall, as determined by the change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III)- Word List score] from the baseline assessment to 4 months after the start of HA-WBRT. Only three patients belonged to the clinical setting of PCI; the remaining 22 patients had oligometastatic brain disease. Regarding neurocognitive outcomes, no statistically significant differences were found between various NCF scores obtained at baseline and at post-radiotherapy intervals, in immediate verbal memory and non-verbal memory, except for delayed recall memory on Word List (F = 5.727, p = 0.048). Functional preservation by hippocampal sparing during WBRT could largely be achieved in this study, which also suggests that HA-WBRT should be a feasible technique preserving neurocognitive functions while maintaining intracranial control.

Development of Spatial and Verbal Working Memory Capacity in the Human Brain

ERIC Educational Resources Information Center

Thomason, Moriah E.; Race, Elizabeth; Burrows, Brittany; Whitfield-Gabrieli, Susan; Glover, Gary H.; Gabrieli, John D. E.

2009-01-01

A core aspect of working memory (WM) is the capacity to maintain goal-relevant information in mind, but little is known about how this capacity develops in the human brain. We compared brain activation, via fMRI, between children (ages 7-12 years) and adults (ages 20-29 years) performing tests of verbal and spatial WM with varying amounts (loads)…

New Hippocampal Neurons Are Not Obligatory for Memory Formation; Cyclin D2 Knockout Mice with No Adult Brain Neurogenesis Show Learning

ERIC Educational Resources Information Center

Jaholkowski, Piotr; Kiryk, Anna; Jedynak, Paulina; Abdallah, Nada M. Ben; Knapska, Ewelina; Kowalczyk, Anna; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Figiel, Izabela; Lioudyno, Victoria; Widy-Tyszkiewicz, Ewa; Wilczynski, Grzegorz M.; Lipp, Hans-Peter; Kaczmarek, Leszek; Filipkowski, Robert K.

2009-01-01

The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs…

True and false memories, parietal cortex, and confidence judgments

PubMed Central

Urgolites, Zhisen J.; Smith, Christine N.

2015-01-01

Recent studies have asked whether activity in the medial temporal lobe (MTL) and the neocortex can distinguish true memory from false memory. A frequent complication has been that the confidence associated with correct memory judgments (true memory) is typically higher than the confidence associated with incorrect memory judgments (false memory). Accordingly, it has often been difficult to know whether a finding is related to memory confidence or memory accuracy. In the current study, participants made recognition memory judgments with confidence ratings in response to previously studied scenes and novel scenes. The left hippocampus and 16 other brain regions distinguished true and false memories when confidence ratings were different for the two conditions. Only three regions (all in the parietal cortex) distinguished true and false memories when confidence ratings were equated. These findings illustrate the utility of taking confidence ratings into account when identifying brain regions associated with true and false memories. Neural correlates of true and false memories are most easily interpreted when confidence ratings are similar for the two kinds of memories. PMID:26472645

Aging Brain, Aging Mind.

ERIC Educational Resources Information Center

Selkoe, Dennis J.

1992-01-01

Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

Short-Term Memory: The "Storage" Component of Human Brain Responses Predicts Recall.

ERIC Educational Resources Information Center

Chapman, Robert M.; And Others

1978-01-01

Presents electrophysiological and behavioral evidence for a neural process related to storage in short-term memory. Predicting recall performance on the basis of the storage component of brain responses is presented. A list of references is also included. (HM)

Ghrelin modulates encoding-related brain function without enhancing memory formation in humans.

PubMed

Kunath, N; Müller, N C J; Tonon, M; Konrad, B N; Pawlowski, M; Kopczak, A; Elbau, I; Uhr, M; Kühn, S; Repantis, D; Ohla, K; Müller, T D; Fernández, G; Tschöp, M; Czisch, M; Steiger, A; Dresler, M

2016-11-15

Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Human hippocampus associates information in memory

PubMed Central

Henke, Katharina; Weber, Bruno; Kneifel, Stefan; Wieser, Heinz Gregor; Buck, Alfred

1999-01-01

The hippocampal formation, one of the most complex and vulnerable brain structures, is recognized as a crucial brain area subserving human long-term memory. Yet, its specific functions in memory are controversial. Recent experimental results suggest that the hippocampal contribution to human memory is limited to episodic memory, novelty detection, semantic (deep) processing of information, and spatial memory. We measured the regional cerebral blood flow by positron-emission tomography while healthy volunteers learned pairs of words with different learning strategies. These led to different forms of learning, allowing us to test the degree to which they challenge hippocampal function. Neither novelty detection nor depth of processing activated the hippocampal formation as much as semantically associating the primarily unrelated words in memory. This is compelling evidence for another function of the human hippocampal formation in memory: establishing semantic associations. PMID:10318979

Emotional arousal and multiple memory systems in the mammalian brain

PubMed Central

Packard, Mark G.; Goodman, Jarid

2012-01-01

Emotional arousal induced by stress and/or anxiety can exert complex effects on learning and memory processes in mammals. Recent studies have begun to link study of the influence of emotional arousal on memory with earlier research indicating that memory is organized in multiple systems in the brain that differ in terms of the “type” of memory they mediate. Specifically, these studies have examined whether emotional arousal may have a differential effect on the “cognitive” and stimulus-response “habit” memory processes sub-served by the hippocampus and dorsal striatum, respectively. Evidence indicates that stress or the peripheral injection of anxiogenic drugs can bias animals and humans toward the use of striatal-dependent habit memory in dual-solution tasks in which both hippocampal and striatal-based strategies can provide an adequate solution. A bias toward the use of habit memory can also be produced by intra-basolateral amygdala (BLA) administration of anxiogenic drugs, consistent with the well documented role of efferent projections of this brain region in mediating the modulatory influence of emotional arousal on memory. In some learning situations, the bias toward the use of habit memory produced by emotional arousal appears to result from an impairing effect on hippocampus-dependent cognitive memory. Further research examining the neural mechanisms linking emotion and the relative use of multiple memory systems should prove useful in view of the potential role for maladaptive habitual behaviors in various human psychopathologies. PMID:22470324

Differential learning and memory performance in OEF/OIF veterans for verbal and visual material.

PubMed

Sozda, Christopher N; Muir, James J; Springer, Utaka S; Partovi, Diana; Cole, Michael A

2014-05-01

Memory complaints are particularly salient among veterans who experience combat-related mild traumatic brain injuries and/or trauma exposure, and represent a primary barrier to successful societal reintegration and everyday functioning. Anecdotally within clinical practice, verbal learning and memory performance frequently appears differentially reduced versus visual learning and memory scores. We sought to empirically investigate the robustness of a verbal versus visual learning and memory discrepancy and to explore potential mechanisms for a verbal/visual performance split. Participants consisted of 103 veterans with reported history of mild traumatic brain injuries returning home from U.S. military Operations Enduring Freedom and Iraqi Freedom referred for outpatient neuropsychological evaluation. Findings indicate that visual learning and memory abilities were largely intact while verbal learning and memory performance was significantly reduced in comparison, residing at approximately 1.1 SD below the mean for verbal learning and approximately 1.4 SD below the mean for verbal memory. This difference was not observed in verbal versus visual fluency performance, nor was it associated with estimated premorbid verbal abilities or traumatic brain injury history. In our sample, symptoms of depression, but not posttraumatic stress disorder, were significantly associated with reduced composite verbal learning and memory performance. Verbal learning and memory performance may benefit from targeted treatment of depressive symptomatology. Also, because visual learning and memory functions may remain intact, these might be emphasized when applying neurocognitive rehabilitation interventions to compensate for observed verbal learning and memory difficulties.

Functional neuroanatomy of sustained memory encoding performance in healthy aging and in Alzheimer's disease.

PubMed

Weis, Susanne; Leube, Dirk; Erb, Michael; Heun, Reinhard; Grodd, Wolfgang; Kircher, Tilo

2011-07-01

The aim of our study was to examine brain networks involved with sustaining memory encoding performance in healthy aging and in Alzheimer's disease (AD). Since different brain regions are affected by degradation in these two conditions, it might be conceivable that different compensation mechanisms occur to keep up memory performance in aging and in AD. Using an event-related functional magnetic resonance imaging (FMRI) design and a correlation analysis, 8 patients suffering from AD and 29 elderly control subjects were scanned while they studied a list of words for a subsequent memory test. Individual performance was assessed on the basis of a subsequent recognition test, and brain regions were identified where functional activations during study correlated with memory performance. In both groups, successful memory encoding performance was significantly correlated with the activation of the right frontal cortex. Furthermore, in healthy controls, there was a significant correlation of memory performance and the activation of the left medial and lateral temporal lobe. In contrast, in AD patients, increasing memory performance goes along with increasing activation of the hippocampus and a bilateral brain network including the frontal and temporal cortices. Our data show that in healthy aging and in AD, common and distinct compensatory mechanisms are employed to keep up a certain level of memory performance. Both in healthy aging and in patients with AD, an increased level of monitoring and control processes mediated by the (right) frontal lobe seems to be necessary to maintain a certain level of memory performance. In addition, memory performance in healthy older subjects seems to rely on an increased effort in encoding item-specific semantic and contextual information in lateral areas of the (left) temporal lobe. In AD patients, on the other hand, the maintenance of memory performance is related to an increase of activation of the (left) hippocampus in conjunction with a bilateral network of cortical areas that might be involved with phonological and visual rehearsal of the incoming information.

Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study.

PubMed

Jager, Gerry; Block, Robert I; Luijten, Maartje; Ramsey, Nick F

2010-06-01

Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and executive control. Prefrontal and temporal regions are critically involved in these functions. Maturational processes leave these brain areas prone to the potentially harmful effects of cannabis use. We performed a two-site (United States and The Netherlands; pooled data) functional magnetic resonance imaging (MRI) study with a cross-sectional design, investigating the effects of adolescent cannabis use on working memory (WM) and associative memory (AM) brain function in 21 abstinent but frequent cannabis-using boys (13-19) years of age and compared them with 24 nonusing peers. Brain activity during WM was assessed before and after rule-based learning (automatization). AM was assessed using a pictorial hippocampal-dependent memory task. Cannabis users performed normally on both memory tasks. During WM assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on AM-related brain function was found. In adolescent cannabis users, the WM system was overactive during a novel task, suggesting functional compensation. Inefficient WM recruitment was not related to a failure in automatization but became evident when processing continuously changing information. The results seem to confirm the vulnerability of still developing frontal lobe functioning for early-onset cannabis use. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

PubMed

Roman-Urrestarazu, Andres; Lindholm, Päivi; Moilanen, Irma; Kiviniemi, Vesa; Miettunen, Jouko; Jääskeläinen, Erika; Mäki, Pirjo; Hurtig, Tuula; Ebeling, Hanna; Barnett, Jennifer H; Nikkinen, Juha; Suckling, John; Jones, Peter B; Veijola, Juha; Murray, Graham K

2016-05-01

When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

PubMed Central

Rocca, Maria A.; Leavitt, Victoria M.; Dackovic, Jelena; Mesaros, Sarlota; Drulovic, Jelena; DeLuca, John; Filippi, Massimo

2014-01-01

Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS. PMID:24748670

Material-specific difficulties in episodic memory tasks in mild traumatic brain injury.

PubMed

Tsirka, Vassiliki; Simos, Panagiotis; Vakis, Antonios; Vourkas, Michael; Arzoglou, Vasileios; Syrmos, Nikolaos; Stavropoulos, Stavros; Micheloyannis, Sifis

2010-03-01

The study examines acute, material-specific secondary memory performance in 26 patients with mild traumatic brain injury (MTBI) and 26 healthy controls, matched on demographic variables and indexes of crystallized intelligence. Neuropsychological tests were used to evaluate primary and secondary memory, executive functions, and verbal fluency. Participants were also tested on episodic memory tasks involving words, pseudowords, pictures of common objects, and abstract kaleidoscopic images. Patients showed reduced performance on episodic memory measures, and on tasks associated with visuospatial processing and executive function (Trail Making Test part B, semantic fluency). Significant differences between groups were also noted for correct rejections and response bias on the kaleidoscope task. MTBI patients' reduced performance on memory tasks for complex, abstract stimuli can be attributed to a dysfunction in the strategic component of memory process.

Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment

PubMed Central

Tomadesso, Clémence; Perrotin, Audrey; Mutlu, Justine; Mézenge, Florence; Landeau, Brigitte; Egret, Stéphanie; de la Sayette, Vincent; Jonin, Pierre-Yves; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

2015-01-01

Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD. PMID:26106572

Brain structural, functional, and cognitive correlates of recent versus remote autobiographical memories in amnestic Mild Cognitive Impairment.

PubMed

Tomadesso, Clémence; Perrotin, Audrey; Mutlu, Justine; Mézenge, Florence; Landeau, Brigitte; Egret, Stéphanie; de la Sayette, Vincent; Jonin, Pierre-Yves; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

2015-01-01

Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.

Multiple determinants of lifespan memory differences

PubMed Central

Henson, Richard N.; Campbell, Karen L.; Davis, Simon W.; Taylor, Jason R.; Emery, Tina; Erzinclioglu, Sharon; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Edward T.; Calder, Andrew C.; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Matthews, Fiona E.; Marslen-Wilson, William D.; Rowe, James B.; Shafto, Meredith A.; Cheung, Teresa; Geerligs, Linda; McCarrey, Anna; Mustafa, Abdur; Price, Darren; Samu, David; Treder, Matthias; Tsvetanov, Kamen A.; van Belle, Janna; Williams, Nitin; Bates, Lauren; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Auer, Tibor; Correia, Marta; Gao, Lu; Green, Emma; Henriques, Rafael; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewa, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Kievit, Rogier A.

2016-01-01

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss. PMID:27600595

Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network.

PubMed

Tchistiakova, Ekaterina; Crane, David E; Mikulis, David J; Anderson, Nicole D; Greenwood, Carol E; Black, Sandra E; MacIntosh, Bradley J

2015-11-01

White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH. Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or ≥2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation. VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2  = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r(2)  = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs. In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation. © 2015 Wiley Periodicals, Inc.

A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.

PubMed

Martin, Ola J; Lai, Ling; Soundarapandian, Mangala M; Leone, Teresa C; Zorzano, Antonio; Keller, Mark P; Attie, Alan D; Muoio, Deborah M; Kelly, Daniel P

2014-02-14

Increasing evidence has shown that proper control of mitochondrial dynamics (fusion and fission) is required for high-capacity ATP production in the heart. Transcriptional coactivators, peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) α and PGC-1β, have been shown to regulate mitochondrial biogenesis in the heart at the time of birth. The function of PGC-1 coactivators in the heart after birth has been incompletely understood. Our aim was to assess the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts in mice. Conditional gene targeting was used in mice to explore the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts. Marked mitochondrial structural derangements were observed in hearts of PGC-1α/β-deficient mice during postnatal growth, including fragmentation and elongation, associated with the development of a lethal cardiomyopathy. The expression of genes involved in mitochondrial fusion (Mfn1, Opa1) and fission (Drp1, Fis1) was altered in the hearts of PGC-1α/β-deficient mice. PGC-lα was shown to directly regulate Mfn1 gene transcription by coactivating the estrogen-related receptor α on a conserved DNA element. Surprisingly, PGC-1α/β deficiency in the adult heart did not result in evidence of abnormal mitochondrial dynamics or heart failure. However, transcriptional profiling demonstrated that PGC-1 coactivators are required for high-level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial dynamics and energy transduction in the adult heart. These results reveal distinct developmental stage-specific programs involved in cardiac mitochondrial dynamics.

Temporal activation of β-catenin signaling in the chondrogenic process of mesenchymal stem cells affects the phenotype of the cartilage generated.

PubMed

Yang, Zheng; Zou, Yu; Guo, Xi Min; Tan, Hwee San; Denslin, Vinitha; Yeow, Chen Hua; Ren, Xia Fei; Liu, Tong Ming; Hui, James Hp; Lee, Eng Hin

2012-07-20

Adult mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering. In vitro predifferentiation of MSCs has been explored as a means to enhance MSC-based articular cartilage repair. However, there remain challenges to control and prevent the premature progression of MSC-derived chondrocytes to the hypertrophy. This study investigated the temporal effect of transforming growth factor (TGF)-β and β-catenin signaling co-activation during MSC chondrogenic differentiation and evaluated the influence of these predifferentiation conditions to subsequent phenotypic development of the cartilage. MSCs were differentiated in chondrogenic medium that contained either TGFβ alone, TGFβ with transient β-catenin coactivation, or TGFβ with continuous β-catenin coactivation. After in vitro differentiation, the pellets were transplanted into SCID mice. Both coactivation protocols resulted in the enhancement of chondrogenic differentiation of MSCs. Compared with TGFβ activation, transient coactivation of TGFβ-induction with β-catenin activation resulted in heightened hypertrophy and formed highly ossified tissues with marrow-like hematopoietic tissue in vivo. The continuous coactivation of the 2 signaling pathways, however, resulted in inhibition of progression to hypertrophy, marked by the suppression of type X collagen, Runx2, and alkaline phosphatase expression, and did not result in ossified tissue in vivo. Chondrocytes of the continuous co-activation samples secreted significantly more parathyroid hormone-related protein (PTHrP) and expressed cyclin D1. Our results suggest that temporal co-activation of the TGFβ signaling pathway with β-catenin can yield cartilage of different phenotype, represents a potential MSC predifferentiation protocol before clinical implantation, and has potential applications for the engineering of cartilage tissue.

Subjective memory complaints are associated with brain activation supporting successful memory encoding.

PubMed

Hayes, Jessica M; Tang, Lingfei; Viviano, Raymond P; van Rooden, Sanneke; Ofen, Noa; Damoiseaux, Jessica S

2017-12-01

Subjective memory complaints, the perceived decline in cognitive abilities in the absence of clinical deficits, may precede Alzheimer's disease. Individuals with subjective memory complaints show differential brain activation during memory encoding; however, whether such differences contribute to successful memory formation remains unclear. Here, we investigated how subsequent memory effects, activation which is greater for hits than misses during an encoding task, differed between healthy older adults aged 50 to 85 years with (n = 23) and without (n = 41) memory complaints. Older adults with memory complaints, compared to those without, showed lower subsequent memory effects in the occipital lobe, superior parietal lobe, and posterior cingulate cortex. In addition, older adults with more memory complaints showed a more negative subsequent memory effects in areas of the default mode network, including the posterior cingulate cortex, precuneus, and ventromedial prefrontal cortex. Our findings suggest that for successful memory formation, older adults with subjective memory complaints rely on distinct neural mechanisms which may reflect an overall decreased task-directed attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback.

PubMed

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-05-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback

PubMed Central

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-01-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: evidence for haploinsufficiency.

PubMed

Weiss, Roy E; Gehin, Martine; Xu, Jianming; Sadow, Peter M; O'Malley, Bert W; Chambon, Pierre; Refetoff, Samuel

2002-04-01

Steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF)-2 are homologous nuclear receptor coactivators. We have investigated their possible redundancy as thyroid hormone (TH) coactivators by measuring thyroid function in compound SRC-1 and TIF-2 knock out (KO) mice. Whereas SRC-1 KO (SRC-1(-/-)) mice are resistant to TH and SRC-1(+/-) are not, we now demonstrate that TIF-2 KO (TIF-2(-/-)) mice have normal thyroid function. Yet double heterozygous, SRC-1(+/-)/TIF-2(+/-) mice manifested resistance to TH of a similar degree as that in mice completely deficient in SRC-1. KO of both SRC-1 and TIF-2 resulted in marked increases of serum TH and thyrotropin concentrations. This work demonstrates gene dosage effect in nuclear coactivators manifesting as haploinsufficiency and functional redundancy of SRC-1 and TIF-2.

Efficiency at rest: magnetoencephalographic resting-state connectivity and individual differences in verbal working memory.

PubMed

del Río, David; Cuesta, Pablo; Bajo, Ricardo; García-Pacios, Javier; López-Higes, Ramón; del-Pozo, Francisco; Maestú, Fernando

2012-11-01

Inter-individual differences in cognitive performance are based on an efficient use of task-related brain resources. However, little is known yet on how these differences might be reflected on resting-state brain networks. Here we used Magnetoencephalography resting-state recordings to assess the relationship between a behavioral measurement of verbal working memory and functional connectivity as measured through Mutual Information. We studied theta (4-8 Hz), low alpha (8-10 Hz), high alpha (10-13 Hz), low beta (13-18 Hz) and high beta (18-30 Hz) frequency bands. A higher verbal working memory capacity was associated with a lower mutual information in the low alpha band, prominently among right-anterior and left-lateral sensors. The results suggest that an efficient brain organization in the domain of verbal working memory might be related to a lower resting-state functional connectivity across large-scale brain networks possibly involving right prefrontal and left perisylvian areas. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of sodium benzoate, a commonly used food preservative, on learning, memory, and oxidative stress in brain of mice.

PubMed

Khoshnoud, Mohammad Javad; Siavashpour, Asma; Bakhshizadeh, Mojgan; Rashedinia, Marzieh

2018-02-01

Sodium benzoate (SB) is a widely used preservative and antimicrobial substance in many foods and soft drinks. However, this compound is generally recognized as safe food additives, but evidence has suggested that a high intake of SB may link to attention deficit-hyperactivity disorder in children. Present study investigate the effects of oral administration of different concentrations of SB (0.56, 1.125, and 2.25 mg/mL) for 4 weeks, on the learning and memory performance tests, and also the levels of malondialdehyde (MDA), reduced glutathione (GSH), and acetylcholinesterase activity (AChE) in the mouse brain. The results showed that SB significantly impaired memory and motor coordination. Moreover, SB decreased reduced GSH and increased the MDA level in the brain significantly (P < 0.001). However, nonsignificant alteration was observed in the AChE activity. These findings suggest that short-term consumption of SB can impair memory performance and increased brain oxidative stress in mice. © 2017 Wiley Periodicals, Inc.

Neuroimaging in Posttraumatic Stress Disorder and Other Stress-related Disorders

PubMed Central

Bremner, J. Douglas

2009-01-01

Synopsis Traumatic stress has a broad range of effects on the brain. Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Studies in patients with posttraumatic stress disorder (PTSD) and other psychiatric disorders related to stress have replicated findings in animal studies by finding alterations in these brain areas. Brain regions implicated in PTSD also play an important role in memory function, highlighting the important interplay between memory and the traumatic stress response. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. PMID:17983968

CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG Oncology RTOG 0933.

PubMed

Caine, Chip; Deshmukh, Snehal; Gondi, Vinai; Mehta, Minesh; Tomé, Wolfgang; Corn, Benjamin W; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey Noah; Konski, Andre A; Bauman, Glenn S; Raben, Adam; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa

2016-01-01

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.

Repeated administration of fresh garlic increases memory retention in rats.

PubMed

Haider, Saida; Naz, Nosheen; Khaliq, Saima; Perveen, Tahira; Haleem, Darakhshan J

2008-12-01

Garlic (Allium sativum) is regarded as both a food and a medicinal herb. Increasing attention has focused on the biological functions and health benefits of garlic as a potentially major dietary component. Chronic garlic administration has been shown to enhance memory function. Evidence also shows that garlic administration in rats affects brain serotonin (5-hydroxytryptamine [5-HT]) levels. 5-HT, a neurotransmitter involved in a number of physiological functions, is also known to enhance cognitive performance. The present study was designed to investigate the probable neurochemical mechanism responsible for the enhancement of memory following garlic administration. Sixteen adult locally bred male albino Wistar rats were divided into control (n = 8) and test (n = 8) groups. The test group was orally administered 250 mg/kg fresh garlic homogenate (FGH), while control animals received an equal amount of water daily for 21 days. Estimation of plasma free and total tryptophan (TRP) and whole brain TRP, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) was determined by high-performance liquid chromatography with electrochemical detection. For assessment of memory, a step-through passive avoidance paradigm (electric shock avoidance) was used. The results showed that the levels of plasma free TRP significantly increased (P < .01) and plasma total TRP significantly decreased (P < .01) in garlic-treated rats. Brain TRP, 5-HT, and 5-HIAA levels were also significantly increased following garlic administration. A significant improvement in memory function was exhibited by garlic-treated rats in the passive avoidance test. Increased brain 5-HT levels were associated with improved cognitive performance. The present results, therefore, demonstrate that the memory-enhancing effect of garlic may be associated with increased brain 5-HT metabolism in rats. The results further support the use of garlic as a food supplement for the enhancement of memory.

Strategies To Enhance Memory Based on Brain-Research.

ERIC Educational Resources Information Center

Banikowski, Alison K.; Mehring, Teresa A.

1999-01-01

This article reviews the literature on three aspects of memory: (1) an information processing model of memory (including the sensory register, attention, short-term memory, and long-term memory); (2) instructional strategies designed to enhance memory (which stress gaining students' attention and active involvement); and (3) reasons why…

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults

PubMed Central

Hayes, Scott M.; Hayes, Jasmeet P.; Williams, Victoria J.; Liu, Huiting; Verfaellie, Mieke

2017-01-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO2) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. PMID:28161031

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults.

PubMed

Hayes, Scott M; Hayes, Jasmeet P; Williams, Victoria J; Liu, Huiting; Verfaellie, Mieke

2017-06-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO 2 ) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO 2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO 2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. Published by Elsevier Ltd.

Memory Reactivation Enables Long-Term Prevention of Interference.

PubMed

Herszage, Jasmine; Censor, Nitzan

2017-05-22

The ability of the human brain to successively learn or perform two competing tasks constitutes a major challenge in daily function. Indeed, exposing the brain to two different competing memories within a short temporal offset can induce interference, resulting in deteriorated performance in at least one of the learned memories [1-4]. Although previous studies have investigated online interference and its effects on performance [5-13], whether the human brain can enable long-term prevention of future interference is unknown. To address this question, we utilized the memory reactivation-reconsolidation framework [2, 12] stemming from studies at the synaptic level [14-17], according to which reactivation of a memory enables its update. In a set of experiments, using the motor sequence learning task [18] we report that a unique pairing of reactivating the original memory (right hand) in synchrony with novel memory trials (left hand) prevented future interference between the two memories. Strikingly, these effects were long-term and observed a month following reactivation. Further experiments showed that preventing future interference was not due to practice per se, but rather specifically depended on a limited time window induced by reactivation of the original memory. These results suggest a mechanism according to which memory reactivation enables long-term prevention of interference, possibly by creating an updated memory trace integrating original and novel memories during the reconsolidation time window. The opportunity to induce a long-term preventive effect on memories may enable the utilization of strategies optimizing normal human learning, as well as recovery following neurological insults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parametric fMRI analysis of visual encoding in the human medial temporal lobe.

PubMed

Rombouts, S A; Scheltens, P; Machielson, W C; Barkhof, F; Hoogenraad, F G; Veltman, D J; Valk, J; Witter, M P

1999-01-01

A number of functional brain imaging studies indicate that the medial temporal lobe system is crucially involved in encoding new information into memory. However, most studies were based on differences in brain activity between encoding of familiar vs. novel stimuli. To further study the underlying cognitive processes, we applied a parametric design of encoding. Seven healthy subjects were instructed to encode complex color pictures into memory. Stimuli were presented in a parametric fashion at different rates, thus representing different loads of encoding. Functional magnetic resonance imaging (fMRI) was used to assess changes in brain activation. To determine the number of pictures successfully stored into memory, recognition scores were determined afterwards. During encoding, brain activation occurred in the medial temporal lobe, comparable to the results obtained by others. Increasing the encoding load resulted in an increase in the number of successfully stored items. This was reflected in a significant increase in brain activation in the left lingual gyrus, in the left and right parahippocampal gyrus, and in the right inferior frontal gyrus. This study shows that fMRI can detect changes in brain activation during variation of one aspect of higher cognitive tasks. Further, it strongly supports the notion that the human medial temporal lobe is involved in encoding novel visual information into memory.

Modulating Hippocampal Plasticity with In Vivo Brain Stimulation

DTIC Science & Technology

2015-09-16

persists in the Schaffer collateral–CA1 region of the hippocampus . NMDA-dependent LTP has been shown to be essential for learning and memory ...S114 –S121. CrossRef Medline Neves G, Cooke SF, Bliss TV (2008) Synaptic plasticity, memory and the hippocampus : a neural network approach to causality...and memory . Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects

Cognition and the Brain

DTIC Science & Technology

1992-05-25

by a by the distinctions between short-term and long-term sensory event. As evidence they shom that %khen the ISI memory ’. episodic , semantic and...Patterson. J.V. and Starr. A. I 19S9a) ams .1 function of variations in semantic citaceori,’itions. In: D. Brain potentials in a memory scanning task. 1...number) FIELD GROUP SUB-GROUP L ocalization of cognitive processes; alpha-band suppression; memory scanning for tones; silent speech; visual image

Differences in brain morphology and working memory capacity across childhood.

PubMed

Bathelt, Joe; Gathercole, Susan E; Johnson, Amy; Astle, Duncan E

2018-05-01

Working memory (WM) skills are closely associated with learning progress in key areas such as reading and mathematics across childhood. As yet, however, little is known about how the brain systems underpinning WM develop over this critical developmental period. The current study investigated whether and how structural brain correlates of components of the working memory system change over development. Verbal and visuospatial short-term and working memory were assessed in 153 children between 5.58 and 15.92 years, and latent components of the working memory system were derived. Fractional anisotropy and cortical thickness maps were derived from T1-weighted and diffusion-weighted MRI and processed using eigenanatomy decomposition. There was a greater involvement of the corpus callosum and posterior temporal white matter in younger children for performance associated with the executive part of the working memory system. For older children, this was more closely linked with the thickness of the occipitotemporal cortex. These findings suggest that increasing specialization leads to shifts in the contribution of neural substrates over childhood, moving from an early dependence on a distributed system supported by long-range connections to later reliance on specialized local circuitry. Our findings demonstrate that despite the component factor structure being stable across childhood, the underlying brain systems supporting working memory change. Taking the age of the child into account, and not just their overall score, is likely to be critical for understanding the nature of the limitations on their working memory capacity. © 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

Dissociable brain biomarkers of fluid intelligence.

PubMed

Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

2016-08-15

Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Coactivation of lower leg muscles during body weight-supported treadmill walking decreases with age in adolescents.

PubMed

Deffeyes, Joan E; Karst, Gregory M; Stuberg, Wayne A; Kurz, Max J

2012-08-01

The kinematics of children's walking are nearly adult-like by about age 3-4 years, but metabolic efficiency of walking does not reach adult values until late in adolescence or early adulthood, perhaps due to higher coactivation of agonist/antagonist muscle pairs in adolescents. Additionally, it is unknown how use of a body weight-supported treadmill device affects coactivation, but because unloading will alter the activity of anti-gravity muscles, it was hypothesized that muscle coactivation will be altered as well. Muscle coactivation during treadmill walking was evaluated for adolescents (ages 10 to 17 years, M = 13.2, SD = 2.2) and adults (ages 22 to 35 years, M = 25.2, SD = 4.3), for thigh muscles (vastus lateralis/biceps femoris) and lower leg muscles (tibialis anterior/gastrocnemius). Conditions included body weight unloadings from nearly 0% to 80% of body weight, while walking at a preferred speed (self-selected, overground speed) or a reduced speed. Unloading was accomplished using a lower body positive pressure support system. Coactivation was found to be higher in adolescents than in adults, but only for the lower leg muscles.

HER4 selectively coregulates estrogen stimulated genes associated with breast tumor cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Wen; Jones, Frank E., E-mail: fjones3@tulane.edu

2014-01-10

Highlights: •HER4/4ICD is an obligate coactivator for 37% of estrogen regulated genes. •HER4/4ICD coactivated genes selectively regulate estrogen stimulated proliferation. •Estrogen stimulated tumor cell migration occurs independent of HER4/4ICD. •Disrupting HER4/4ICD and ER coactivated gene expression may suppress breast cancer. -- Abstract: The EGFR-family member HER4 undergoes regulated intramembrane proteolysis (RIP) to generate an intracellular domain (4ICD) that functions as a transcriptional coactivator. Accordingly, 4ICD coactivates the estrogen receptor (ER) and associates with ER at target gene promoters in breast tumor cells. However, the extent of 4ICD coactivation of ER and the functional significance of the 4ICD/ER transcriptional complex ismore » unclear. To identify 4ICD coactivated genes we performed a microarray gene expression analysis of β-estradiol treated cells comparing control MCF-7 breast cancer cells to MCF-7 cells where HER4 expression was stably suppressed using a shRNA. In the MCF-7 cell line, β-estradiol significantly stimulated or repressed by 2-fold or more 726 or 53 genes, respectively. Significantly, HER4/4ICD was an obligate coactivator for 277 or 38% of the β-estradiol stimulated genes. Ingenuity Pathway Analysis of β-estradiol regulated genes identified significant associations with multiple cellular functions regulating cellular growth and proliferation, cell cycle progression, cancer metastasis, decreased hypoplasia, tumor cell migration, apoptotic resistance of tumor cells, and increased transcription. Genes coactivated by 4ICD displayed functional specificity by only significantly contributing to cellular growth and proliferation, cell cycle progression, and decreased hypoplasia. In direct concordance with these in situ results we show that HER4 knockdown in MCF-7 cells results in a loss of estrogen stimulated tumor cell proliferation and cell cycle progression, whereas, estrogen stimulated tumor cell migration was unaffected by loss of HER4 expression. In summary, we demonstrate for the first time that a cell surface receptor functions as an obligate ER coactivator with functional specificity associated with breast tumor cell proliferation and cell cycle progression. Nearly 90% of ER positive tumors coexpress HER4, therefore we predict that the majority of breast cancer patients would benefit from a strategy to therapeutic disengage ER/4ICD coregulated tumor cell proliferation.« less

Remembering tips

MedlinePlus

Memory aids; Alzheimer disease - remembering tips; Early memory loss - remembering tips; Dementia - remembering tips ... harder for your brain to create a new memory, even while you can remember actions and events ...

False memories and confabulation.

PubMed

Johnson, M K; Raye, C L

1998-04-01

Memory distortions range from the benign (thinking you mailed a check that you only thought about mailing), to the serious (confusing what you heard after a crime with what you actually saw), to the fantastic (claiming you piloted a spaceship). We review theoretical ideas and empirical evidence about the source monitoring processes underlying both true and false memories. Neuropsychological studies show that certain forms of brain damage (such as combined frontal and medial-temporal lesions) might result in profound source confusions, called confabulations. Neuroimaging techniques provide new evidence regarding more specific links between underlying brain mechanisms and the normal cognitive processes involved in evaluating memories. One hypothesis is that the right prefrontal cortex (PFC) subserves heuristic judgments based on easily assessed qualities (such as familiarity or perceptual detail) and the left PFC (or the right and left PFC together) subserves more systematic judgments requiring more careful analysis of memorial qualities or retrieval and evaluation of additional supporting or disconfirming information. Such heuristic and systematic processes can be disrupted not only by brain damage but also, for example, by hypnosis, social demands and motivational factors, suggesting caution in the methods used by `memory exploring' professions (therapists, police officers, lawyers, etc.) in order to avoid inducing false memories.

Cortical connectivity and memory performance in cognitive decline: A study via graph theory from EEG data.

PubMed

Vecchio, F; Miraglia, F; Quaranta, D; Granata, G; Romanello, R; Marra, C; Bramanti, P; Rossini, P M

2016-03-01

Functional brain abnormalities including memory loss are found to be associated with pathological changes in connectivity and network neural structures. Alzheimer's disease (AD) interferes with memory formation from the molecular level, to synaptic functions and neural networks organization. Here, we determined whether brain connectivity of resting-state networks correlate with memory in patients affected by AD and in subjects with mild cognitive impairment (MCI). One hundred and forty-four subjects were recruited: 70 AD (MMSE Mini Mental State Evaluation 21.4), 50 MCI (MMSE 25.2) and 24 healthy subjects (MMSE 29.8). Undirected and weighted cortical brain network was built to evaluate graph core measures to obtain Small World parameters. eLORETA lagged linear connectivity as extracted by electroencephalogram (EEG) signals was used to weight the network. A high statistical correlation between Small World and memory performance was found. Namely, higher Small World characteristic in EEG gamma frequency band during the resting state, better performance in short-term memory as evaluated by the digit span tests. Such Small World pattern might represent a biomarker of working memory impairment in older people both in physiological and pathological conditions. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Modality-specific alpha modulations facilitate long-term memory encoding in the presence of distracters.

PubMed

Jiang, Haiteng; van Gerven, Marcel A J; Jensen, Ole

2015-03-01

It has been proposed that long-term memory encoding is not only dependent on engaging task-relevant regions but also on disengaging task-irrelevant regions. In particular, oscillatory alpha activity has been shown to be involved in shaping the functional architecture of the working brain because it reflects the functional disengagement of specific regions in attention and memory tasks. We here ask if such allocation of resources by alpha oscillations generalizes to long-term memory encoding in a cross-modal setting in which we acquired the ongoing brain activity using magnetoencephalography. Participants were asked to encode pictures while ignoring simultaneously presented words and vice versa. We quantified the brain activity during rehearsal reflecting subsequent memory in the different attention conditions. The key finding was that successful long-term memory encoding is reflected by alpha power decreases in the sensory region of the to-be-attended modality and increases in the sensory region of the to-be-ignored modality to suppress distraction during rehearsal period. Our results corroborate related findings from attention studies by demonstrating that alpha activity is also important for the allocation of resources during long-term memory encoding in the presence of distracters.

Memory in multiple sclerosis is linked to glutamate concentration in grey matter regions

PubMed Central

Muhlert, Nils; Atzori, Matteo; De Vita, Enrico; Thomas, David L; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Geurts, Jeroen J G; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2014-01-01

Objective Glutamate is the principal excitatory neurotransmitter and is involved in normal brain function. Cognitive impairment is common in multiple sclerosis (MS), and understanding its mechanisms is crucial for developing effective treatments. We used structural and metabolic brain imaging to test two hypotheses: (i) glutamate levels in grey matter regions are abnormal in MS, and (ii) patients show a relationship between glutamate concentration and memory performance. Methods Eighteen patients with relapsing-remitting MS and 17 healthy controls were cognitively assessed and underwent 1H-magnetic resonance spectroscopy at 3 T to assess glutamate levels in the hippocampus, thalamus, cingulate and parietal cortices. Regression models investigated the association between glutamate concentration and memory performance independently of magnetisation transfer ratio values and grey matter lesions withint he same regions, and whole-brain grey matter volume. Results Patients had worse visual and verbal memory than controls. A positive relationship between glutamate levels in the hippocampal, thalamic and cingulate regions and visuospatial memory was detected in patients, but not in healthy controls. Conclusions The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS. PMID:24431465

Is bigger always better? A critical appraisal of the use of volumetric analysis in the study of the hippocampus.

PubMed

Roth, Timothy C; Brodin, Anders; Smulders, Tom V; LaDage, Lara D; Pravosudov, Vladimir V

2010-03-27

A well-developed spatial memory is important for many animals, but appears especially important for scatter-hoarding species. Consequently, the scatter-hoarding system provides an excellent paradigm in which to study the integrative aspects of memory use within an ecological and evolutionary framework. One of the main tenets of this paradigm is that selection for enhanced spatial memory for cache locations should specialize the brain areas involved in memory. One such brain area is the hippocampus (Hp). Many studies have examined this adaptive specialization hypothesis, typically relating spatial memory to Hp volume. However, it is unclear how the volume of the Hp is related to its function for spatial memory. Thus, the goal of this article is to evaluate volume as a main measurement of the degree of morphological and physiological adaptation of the Hp as it relates to memory. We will briefly review the evidence for the specialization of memory in food-hoarding animals and discuss the philosophy behind volume as the main currency. We will then examine the problems associated with this approach, attempting to understand the advantages and limitations of using volume and discuss alternatives that might yield more specific hypotheses. Overall, there is strong evidence that the Hp is involved in the specialization of spatial memory in scatter-hoarding animals. However, volume may be only a coarse proxy for more relevant and subtle changes in the structure of the brain underlying changes in behaviour. To better understand the nature of this brain/memory relationship, we suggest focusing on more specific and relevant features of the Hp, such as the number or size of neurons, variation in connectivity depending on dendritic and axonal arborization and the number of synapses. These should generate more specific hypotheses derived from a solid theoretical background and should provide a better understanding of both neural mechanisms of memory and their evolution.

Post-traumatic stress avoidance is attenuated by corticosterone and associated with brain levels of steroid receptor co-activator-1 in rats.

PubMed

Whitaker, Annie M; Farooq, Muhammad A; Edwards, Scott; Gilpin, Nicholas W

2016-01-01

Individuals with post-traumatic stress disorder (PTSD) avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal (HPA) axis activation at the time of stress. Our rodent model of stress mimics the avoidance symptom cluster of PTSD. Rats are classified as "Avoiders" or "Non-Avoiders" post-stress based on the avoidance of a predator-odor paired context. Previously, we found Avoiders exhibit an attenuated HPA stress response to predator odor. We hypothesized that corticosterone administration before stress would reduce the magnitude and incidence of stress-paired context avoidance. Furthermore, we also predicted that Avoiders would exhibit altered expression of glucocorticoid receptor (GR) signaling machinery elements, including steroid receptor co-activator (SRC)-1. Male Wistar rats (n = 16) were pretreated with corticosterone (25 mg/kg) or saline and exposed to predator-odor stress paired with a context and tested for avoidance 24 h later. A second group of corticosterone-naïve rats (n = 24) were stressed (or not), indexed for avoidance 24 h later, and killed 48 h post-odor exposure to measure phosphorylated GR, FKBP51 and SRC-1 levels in the paraventricular nucleus (PVN), central amygdala (CeA) and ventral hippocampus (VH), all brain sites that highly express GRs and regulate HPA function. Corticosterone pretreatment reduced the magnitude and incidence of avoidance. In Avoiders, predator-odor exposure led to lower SRC-1 expression in the PVN and CeA, and higher SRC-1 expression in the VH. SRC-1 expression in PVN, CeA and VH was predicted by prior avoidance behavior. Hence, a blunted HPA stress response may contribute to stress-induced neuroadaptations in central SRC-1 levels and behavioral dysfunction in Avoider rats.

Multifaceted brain networks reconfiguration in disorders of consciousness uncovered by co-activation patterns.

PubMed

Di Perri, Carol; Amico, Enrico; Heine, Lizette; Annen, Jitka; Martial, Charlotte; Larroque, Stephen Karl; Soddu, Andrea; Marinazzo, Daniele; Laureys, Steven

2018-01-01

Given that recent research has shown that functional connectivity is not a static phenomenon, we aim to investigate the dynamic properties of the default mode network's (DMN) connectivity in patients with disorders of consciousness. Resting-state fMRI volumes of a convenience sample of 17 patients in unresponsive wakefulness syndrome (UWS) and controls were reduced to a spatiotemporal point process by selecting critical time points in the posterior cingulate cortex (PCC). Spatial clustering was performed on the extracted PCC time frames to obtain 8 different co-activation patterns (CAPs). We investigated spatial connectivity patterns positively and negatively correlated with PCC using both CAPs and standard stationary method. We calculated CAPs occurrences and the total number of frames. Compared to controls, patients showed (i) decreased within-network positive correlations and between-network negative correlations, (ii) emergence of "pathological" within-network negative correlations and between-network positive correlations (better defined with CAPs), and (iii) "pathological" increases in within-network positive correlations and between-network negative correlations (only detectable using CAPs). Patients showed decreased occurrence of DMN-like CAPs (1-2) compared to controls. No between-group differences were observed in the total number of frames CONCLUSION: CAPs reveal at a more fine-grained level the multifaceted spatial connectivity reconfiguration following the DMN disruption in UWS patients, which is more complex than previously thought and suggests alternative anatomical substrates for consciousness. BOLD fluctuations do not seem to differ between patients and controls, suggesting that BOLD response represents an intrinsic feature of the signal, and therefore that spatial configuration is more important for consciousness than BOLD activation itself. Hum Brain Mapp 39:89-103, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

From episodic to habitual prospective memory: ERP-evidence for a linear transition

PubMed Central

Meier, Beat; Matter, Sibylle; Baumann, Brigitta; Walter, Stefan; Koenig, Thomas

2014-01-01

Performing a prospective memory task repeatedly changes the nature of the task from episodic to habitual. The goal of the present study was to investigate the neural basis of this transition. In two experiments, we contrasted event-related potentials (ERPs) evoked by correct responses to prospective memory targets in the first, more episodic part of the experiment with those of the second, more habitual part of the experiment. Specifically, we tested whether the early, middle, or late ERP-components, which are thought to reflect cue detection, retrieval of the intention, and post-retrieval processes, respectively, would be changed by routinely performing the prospective memory task. The results showed a differential ERP effect in the middle time window (450–650 ms post-stimulus). Source localization using low resolution brain electromagnetic tomography analysis suggests that the transition was accompanied by an increase of activation in the posterior parietal and occipital cortex. These findings indicate that habitual prospective memory involves retrieval processes guided more strongly by parietal brain structures. In brief, the study demonstrates that episodic and habitual prospective memory tasks recruit different brain areas. PMID:25071519

Task positive and default mode networks during a working memory in children with primary monosymptomatic nocturnal enuresis and healthy controls.

PubMed

Zhang, Kaihua; Ma, Jun; Lei, Du; Wang, Mengxing; Zhang, Jilei; Du, Xiaoxia

2015-10-01

Nocturnal enuresis is a common developmental disorder in children, and primary monosymptomatic nocturnal enuresis (PMNE) is the dominant subtype. This study investigated brain functional abnormalities that are specifically related to working memory in children with PMNE using function magnetic resonance imaging (fMRI) in combination with an n-back task. Twenty children with PMNE and 20 healthy children, group-matched for age and sex, participated in this experiment. Several brain regions exhibited reduced activation during the n-back task in children with PMNE, including the right precentral gyrus and the right inferior parietal lobule extending to the postcentral gyrus. Children with PMNE exhibited decreased cerebral activation in the task-positive network, increased task-related cerebral deactivation during a working memory task, and longer response times. Patients exhibited different brain response patterns to different levels of working memory and tended to compensate by greater default mode network deactivation to sustain normal working memory function. Our results suggest that children with PMNE have potential working memory dysfunction.

Memory recall and spike-frequency adaptation

NASA Astrophysics Data System (ADS)

Roach, James P.; Sander, Leonard M.; Zochowski, Michal R.

2016-05-01

The brain can reproduce memories from partial data; this ability is critical for memory recall. The process of memory recall has been studied using autoassociative networks such as the Hopfield model. This kind of model reliably converges to stored patterns that contain the memory. However, it is unclear how the behavior is controlled by the brain so that after convergence to one configuration, it can proceed with recognition of another one. In the Hopfield model, this happens only through unrealistic changes of an effective global temperature that destabilizes all stored configurations. Here we show that spike-frequency adaptation (SFA), a common mechanism affecting neuron activation in the brain, can provide state-dependent control of pattern retrieval. We demonstrate this in a Hopfield network modified to include SFA, and also in a model network of biophysical neurons. In both cases, SFA allows for selective stabilization of attractors with different basins of attraction, and also for temporal dynamics of attractor switching that is not possible in standard autoassociative schemes. The dynamics of our models give a plausible account of different sorts of memory retrieval.

Encoding-related brain activity during deep processing of verbal materials: a PET study.

PubMed

Fujii, Toshikatsu; Okuda, Jiro; Tsukiura, Takashi; Ohtake, Hiroya; Suzuki, Maki; Kawashima, Ryuta; Itoh, Masatoshi; Fukuda, Hiroshi; Yamadori, Atsushi

2002-12-01

The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.

Angular default mode network connectivity across working memory load.

PubMed

Vatansever, D; Manktelow, A E; Sahakian, B J; Menon, D K; Stamatakis, E A

2017-01-01

Initially identified during no-task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large-scale brain networks. Nevertheless, its contribution to whole-brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI-based n-back paradigm with parametric increases in difficulty. Using a voxel-wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of n-back task load. Subsequent seed-based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large-scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n-back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands. Hum Brain Mapp 38:41-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Individual Differences in Dynamic Functional Brain Connectivity across the Human Lifespan.

PubMed

Davison, Elizabeth N; Turner, Benjamin O; Schlesinger, Kimberly J; Miller, Michael B; Grafton, Scott T; Bassett, Danielle S; Carlson, Jean M

2016-11-01

Individual differences in brain functional networks may be related to complex personal identifiers, including health, age, and ability. Dynamic network theory has been used to identify properties of dynamic brain function from fMRI data, but the majority of analyses and findings remain at the level of the group. Here, we apply hypergraph analysis, a method from dynamic network theory, to quantify individual differences in brain functional dynamics. Using a summary metric derived from the hypergraph formalism-hypergraph cardinality-we investigate individual variations in two separate, complementary data sets. The first data set ("multi-task") consists of 77 individuals engaging in four consecutive cognitive tasks. We observe that hypergraph cardinality exhibits variation across individuals while remaining consistent within individuals between tasks; moreover, the analysis of one of the memory tasks revealed a marginally significant correspondence between hypergraph cardinality and age. This finding motivated a similar analysis of the second data set ("age-memory"), in which 95 individuals, aged 18-75, performed a memory task with a similar structure to the multi-task memory task. With the increased age range in the age-memory data set, the correlation between hypergraph cardinality and age correspondence becomes significant. We discuss these results in the context of the well-known finding linking age with network structure, and suggest that hypergraph analysis should serve as a useful tool in furthering our understanding of the dynamic network structure of the brain.

Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls

PubMed Central

Huppert, T. J.; Beluk, N. H.; Elbin, R. J.; Henry, L. C.; French, J.; Dakan, S. M.; Collins, M. W.

2016-01-01

There is no accepted clinical imaging modality for concussion, and current imaging modalities including fMRI, DTI, and PET are expensive and inaccessible to most clinics/ patients. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable, and low-cost imaging modality that can measure brain activity. The purpose of this study was to compare brain activity as measured by fNIRS in concussed and age-matched controls during the performance of cognitive tasks from a computerized neurocognitive test battery. Participants included nine currently symptomatic patients aged 18–45 years with a recent (15–45 days) sport-related concussion and five age-matched healthy controls. The participants completed a computerized neurocognitive test battery while wearing the fNIRS unit. Our results demonstrated reduced brain activation in the concussed subject group during word memory, (spatial) design memory, digit-symbol substitution (symbol match), and working memory (X’s and O’s) tasks. Behavioral performance (percent-correct and reaction time respectively) was lower for concussed participants on the word memory, design memory, and symbol match tasks than controls. The results of this preliminary study suggest that fNIRS could be a useful, portable assessment tool to assess reduced brain activation and augment current approaches to assessment and management of patients following concussion. PMID:24477579

Cerebralcare Granule(®), a Chinese Herb Compound Preparation, Attenuates D-Galactose Induced Memory Impairment in Mice.

PubMed

Qu, Zhuo; Yang, Honggai; Zhang, Jingze; Huo, Liqin; Chen, Hong; Li, Yuming; Liu, Changxiao; Gao, Wenyuan

2016-09-01

Cerebralcare granule(®) (CG) is a preparation of Traditional Chinese Medicine that widely used in China. It was approved by the China State Food and Drug Administration for treatment of headache and dizziness associated with cerebrovascular diseases. In the present study, we aimed to investigate whether CG had protective effect against D-galactose (gal)-induced memory impairment and to explore the mechanism of its action. D-gal was administered (100 mg/kg, subcutaneously) once daily for 8 weeks to induced memory deficit and neurotoxicity in the brain of aging mouse and CG (7.5, 15, and 30 g/kg) were simultaneously administered orally. The present study demonstrates that CG can alleviate aging in the mouse brain induced by D-gal through improving behavioral performance and reducing brain cell damage in the hippocampus. CG prevents aging mainly via suppression of oxidative stress response, such as decreasing NO and MDA levels, renewing activities of SOD, CAT, and GPx, as well as decreasing AChE activity in the brain of D-gal-treated mice. In addition, CG prevents aging through inhibiting NF-κB-mediated inflammatory response and caspase-3-medicated neurodegeneration in the brain of D-gal treated mice. Taken together, these data clearly demonstrates that subcutaneous injection of D-gal produced memory deficit, meanwhile CG can protect neuron from D-gal insults and improve memory ability.

Differences in visual vs. verbal memory impairments as a result of focal temporal lobe damage in patients with traumatic brain injury.

PubMed

Ariza, Mar; Pueyo, Roser; Junqué, Carme; Mataró, María; Poca, María Antonia; Mena, Maria Pau; Sahuquillo, Juan

2006-09-01

The aim of the present study was to determine whether the type of lesion in a sample of moderate and severe traumatic brain injury (TBI) was related to material-specific memory impairment. Fifty-nine patients with TBI were classified into three groups according to whether the site of the lesion was right temporal, left temporal or diffuse. Six-months post-injury, visual (Warrington's Facial Recognition Memory Test and Rey's Complex Figure Test) and verbal (Rey's Auditory Verbal Learning Test) memories were assessed. Visual memory deficits assessed by facial memory were associated with right temporal lobe lesion, whereas verbal memory performance assessed with a list of words was related to left temporal lobe lesion. The group with diffuse injury showed both verbal and visual memory impairment. These results suggest a material-specific memory impairment in moderate and severe TBI after focal temporal lesions and a non-specific memory impairment after diffuse damage.

Slime mold uses an externalized spatial "memory" to navigate in complex environments.

PubMed

Reid, Chris R; Latty, Tanya; Dussutour, Audrey; Beekman, Madeleine

2012-10-23

Spatial memory enhances an organism's navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold Physarum polycephalum constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem--a classic test of autonomous navigational ability commonly used in robotics--requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism's ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms.

Integrative assessment of brain function in PTSD: brain stability and working memory.

PubMed

Veltmeyer, Melinda D; McFarlane, Alexander C; Bryant, Richard A; Mayo, Therese; Gordon, Evian; Clark, C Richard

2006-03-01

Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

Effects of cinnamic acid on memory deficits and brain oxidative stress in streptozotocin-induced diabetic mice

PubMed Central

Hemmati, Ali Asghar; Ahangarpour, Akram

2018-01-01

The present study aimed to evaluate the cinnamic acid effect on memory impairment, oxidative stress, and cholinergic dysfunction in streptozotocin (STZ)-induced diabetic model in mice. In this experimental study, 48 male Naval Medical Research Institute (NMRI) mice (30–35 g) were chosen and were randomly divided into six groups: control, cinnamic acid (20 mg/kg day, i.p. ), diabetic, and cinnamic acid-treated diabetic (10, 20 and 40 mg/kg day, i.p. ). Memory was impaired by administering an intraperitoneal STZ injection of 50 mg/kg. Cinnamic acid was injected for 40 days starting from the 21st day after confirming STZ-induced dementia to observe its therapeutic effect. Memory function was assessed using cross-arm maze, morris water maze and passive avoidance test. After the administration, biochemical parameters of oxidative stress and cholinergic function were estimated in the brain. Present data indicated that inducing STZ caused significant memory impairment, whereas administration of cinnamic acid caused significant and dose-dependent memory improvement. Assessment of brain homogenates indicated cholinergic dysfunction, increase in lipid peroxidation and reactive oxygen species (ROS) levels, and decrease in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the diabetic group compared to the control animals, whereas cinnamic acid administration ameliorated these indices in the diabetic mice. The present study demonstrated that cinnamic acid improves memory by reducing the oxidative stress and cholinergic dysfunction in the brain of diabetic mice. PMID:29719448

Effects of cinnamic acid on memory deficits and brain oxidative stress in streptozotocin-induced diabetic mice.

PubMed

Hemmati, Ali Asghar; Alboghobeish, Soheila; Ahangarpour, Akram

2018-05-01

The present study aimed to evaluate the cinnamic acid effect on memory impairment, oxidative stress, and cholinergic dysfunction in streptozotocin (STZ)-induced diabetic model in mice. In this experimental study, 48 male Naval Medical Research Institute (NMRI) mice (30-35 g) were chosen and were randomly divided into six groups: control, cinnamic acid (20 mg/kg day, i.p. ), diabetic, and cinnamic acid-treated diabetic (10, 20 and 40 mg/kg day, i.p. ). Memory was impaired by administering an intraperitoneal STZ injection of 50 mg/kg. Cinnamic acid was injected for 40 days starting from the 21st day after confirming STZ-induced dementia to observe its therapeutic effect. Memory function was assessed using cross-arm maze, morris water maze and passive avoidance test. After the administration, biochemical parameters of oxidative stress and cholinergic function were estimated in the brain. Present data indicated that inducing STZ caused significant memory impairment, whereas administration of cinnamic acid caused significant and dose-dependent memory improvement. Assessment of brain homogenates indicated cholinergic dysfunction, increase in lipid peroxidation and reactive oxygen species (ROS) levels, and decrease in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the diabetic group compared to the control animals, whereas cinnamic acid administration ameliorated these indices in the diabetic mice. The present study demonstrated that cinnamic acid improves memory by reducing the oxidative stress and cholinergic dysfunction in the brain of diabetic mice.

Sex differences in the neural basis of emotional memories.

PubMed

Canli, Turhan; Desmond, John E; Zhao, Zuo; Gabrieli, John D E

2002-08-06

Psychological studies have found better memory in women than men for emotional events, but the neural basis for this difference is unknown. We used event-related functional MRI to assess whether sex differences in memory for emotional stimuli is associated with activation of different neural systems in men and women. Brain activation in 12 men and 12 women was recorded while they rated their experience of emotional arousal in response to neutral and emotionally negative pictures. In a recognition memory test 3 weeks after scanning, highly emotional pictures were remembered best, and remembered better by women than by men. Men and women activated different neural circuits to encode stimuli effectively into memory even when the analysis was restricted to pictures rated equally arousing by both groups. Men activated significantly more structures than women in a network that included the right amygdala, whereas women activated significantly fewer structures in a network that included the left amygdala. Women had significantly more brain regions where activation correlated with both ongoing evaluation of emotional experience and with subsequent memory for the most emotionally arousing pictures. Greater overlap in brain regions sensitive to current emotion and contributing to subsequent memory may be a neural mechanism for emotions to enhance memory more powerfully in women than in men.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Yirui; Scheuermann, Thomas H.; Partch, Carrie L.

The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor,more » we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. Furthermore, these findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.« less

Perspectives from the symposium: The role of nutrition in infant and toddler brain and behavioral development.

PubMed

Rosales, Francisco J; Zeisel, Steven H

2008-06-01

This symposium examined current trends in neuroscience and developmental psychology as they apply to assessing the effects of nutrients on brain and behavioral development of 0-6-year-olds. Although the spectrum of nutrients with brain effects has not changed much in the last 25 years, there has been an explosion in new knowledge about the genetics, structure and function of the brain. This has helped to link the brain mechanistic pathway by which these nutrients act with cognitive functions. A clear example of this is linking of brain structural changes due to hypoglycemia versus hyperglycemia with cognitive functions by using magnetic resonance imaging (MRI) to assess changes in brain-region volumes in combination with cognitive test of intelligence, memory and processing speed. Another example is the use of event-related potential (ERP) studies to show that infants of diabetic mothers have impairments in memory from birth through 8 months of age that are consistent with alterations in mechanistic pathways of memory observed in animal models of perinatal iron deficiency. However, gaps remain in the understanding of how nutrients and neurotrophic factors interact with each other in optimizing brain development and function.

Gender similarities and differences in brain activation strategies: Voxel-based meta-analysis on fMRI studies.

PubMed

AlRyalat, Saif Aldeen

2017-01-01

Gender similarities and differences have long been a matter of debate in almost all human research, especially upon reaching the discussion about brain functions. This large scale meta-analysis was performed on functional MRI studies. It included more than 700 active brain foci from more than 70 different experiments to study gender related similarities and differences in brain activation strategies for three of the main brain functions: Visual-spatial cognition, memory, and emotion. Areas that are significantly activated by both genders (i.e. core areas) for the tested brain function are mentioned, whereas those areas significantly activated exclusively in one gender are the gender specific areas. During visual-spatial cognition task, and in addition to the core areas, males significantly activated their left superior frontal gyrus, compared with left superior parietal lobule in females. For memory tasks, several different brain areas activated by each gender, but females significantly activated two areas from the limbic system during memory retrieval tasks. For emotional task, males tend to recruit their bilateral prefrontal regions, whereas females tend to recruit their bilateral amygdalae. This meta-analysis provides an overview based on functional MRI studies on how males and females use their brain.

EEG-based research on brain functional networks in cognition.

PubMed

Wang, Niannian; Zhang, Li; Liu, Guozhong

2015-01-01

Recently, exploring the cognitive functions of the brain by establishing a network model to understand the working mechanism of the brain has become a popular research topic in the field of neuroscience. In this study, electroencephalography (EEG) was used to collect data from subjects given four different mathematical cognitive tasks: recite numbers clockwise and counter-clockwise, and letters clockwise and counter-clockwise to build a complex brain function network (BFN). By studying the connectivity features and parameters of those brain functional networks, it was found that the average clustering coefficient is much larger than its corresponding random network and the average shortest path length is similar to the corresponding random networks, which clearly shows the characteristics of the small-world network. The brain regions stimulated during the experiment are consistent with traditional cognitive science regarding learning, memory, comprehension, and other rational judgment results. The new method of complex networking involves studying the mathematical cognitive process of reciting, providing an effective research foundation for exploring the relationship between brain cognition and human learning skills and memory. This could help detect memory deficits early in young and mentally handicapped children, and help scientists understand the causes of cognitive brain disorders.

Is magnetite a universal memory molecule?

PubMed

Størmer, Fredrik C

2014-11-01

Human stem cells possess memory, and consequently all living human cells must have a memory system. How memory is stored in cells and organisms is an open question. Magnetite is perhaps the best candidate to be a universal memory molecule. Magnetite may give us a clue, because it is the Earth's most distributed and important magnetic material. It is found in living organisms with no known functions except for involvement in navigation in some organisms. In humans magnetite is found in the brain, heart, liver and spleen. Humans suffer from memory dysfunctions in many cases when iron is out of balance. Anomalous concentrations of magnetite is known to be associated with a neurodegenerative disorder like Alzheimer's disease. Due to the rapid speed and accuracy of our brain, memory and its functions must be governed by quantum mechanics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Filopodia: A Rapid Structural Plasticity Substrate for Fast Learning

PubMed Central

Ozcan, Ahmet S.

2017-01-01

Formation of new synapses between neurons is an essential mechanism for learning and encoding memories. The vast majority of excitatory synapses occur on dendritic spines, therefore, the growth dynamics of spines is strongly related to the plasticity timescales. Especially in the early stages of the developing brain, there is an abundant number of long, thin and motile protrusions (i.e., filopodia), which develop in timescales of seconds and minutes. Because of their unique morphology and motility, it has been suggested that filopodia can have a dual role in both spinogenesis and environmental sampling of potential axonal partners. I propose that filopodia can lower the threshold and reduce the time to form new dendritic spines and synapses, providing a substrate for fast learning. Based on this proposition, the functional role of filopodia during brain development is discussed in relation to learning and memory. Specifically, it is hypothesized that the postnatal brain starts with a single-stage memory system with filopodia playing a significant role in rapid structural plasticity along with the stability provided by the mushroom-shaped spines. Following the maturation of the hippocampus, this highly-plastic unitary system transitions to a two-stage memory system, which consists of a plastic temporary store and a long-term stable store. In alignment with these architectural changes, it is posited that after brain maturation, filopodia-based structural plasticity will be preserved in specific areas, which are involved in fast learning (e.g., hippocampus in relation to episodic memory). These propositions aim to introduce a unifying framework for a diversity of phenomena in the brain such as synaptogenesis, pruning and memory consolidation. PMID:28676753

Neural overlap in processing music and speech.

PubMed

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L

2015-03-19

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Neural overlap in processing music and speech

PubMed Central

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

2015-01-01

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

Shared neural processes support semantic control and action understanding

PubMed Central

Davey, James; Rueschemeyer, Shirley-Ann; Costigan, Alison; Murphy, Nik; Krieger-Redwood, Katya; Hallam, Glyn; Jefferies, Elizabeth

2015-01-01

Executive–semantic control and action understanding appear to recruit overlapping brain regions but existing evidence from neuroimaging meta-analyses and neuropsychology lacks spatial precision; we therefore manipulated difficulty and feature type (visual vs. action) in a single fMRI study. Harder judgements recruited an executive–semantic network encompassing medial and inferior frontal regions (including LIFG) and posterior temporal cortex (including pMTG). These regions partially overlapped with brain areas involved in action but not visual judgements. In LIFG, the peak responses to action and difficulty were spatially identical across participants, while these responses were overlapping yet spatially distinct in posterior temporal cortex. We propose that the co-activation of LIFG and pMTG allows the flexible retrieval of semantic information, appropriate to the current context; this might be necessary both for semantic control and understanding actions. Feature selection in difficult trials also recruited ventral occipital–temporal areas, not implicated in action understanding. PMID:25658631

Environment enrichment rescues the neurodegenerative phenotypes in presenilins-deficient mice.

PubMed

Dong, Suzhen; Li, Chunxia; Wu, Pu; Tsien, Joe Z; Hu, Yinghe

2007-07-01

Presenilin (PS) 1 and 2 conditional double knockout (cDKO) mice show progressive memory dysfunction and forebrain degeneration. Gene expression profiling results revealed a strong activation of immunity and inflammation responses in the brains of 10-month-old cDKO mice. As environmental enrichment (EE) has been shown to be able to improve memory and induce neurogenesis of the brain, we assessed the effects of EE on the memory performance and the neurodegeneration in cDKO mice. We found that EE effectively enhanced memory and partially rescued the forebrain atrophy of the cDKO mice. Our results suggest that immunity and inflammation could play important roles in the neurodegeneration of cDKO mice. Furthermore, the beneficial effects of EE may be associated with the inhibition of the expression of immunity and inflammation-related genes in the brain.

Efficacy of memory aids after traumatic brain injury: A single case series.

PubMed

Bos, Hannah R; Babbage, Duncan R; Leathem, Janet M

2017-01-01

Individuals living with traumatic brain injury commonly have difficulties with prospective memory-the ability to remember a planned action at the intended time. Traditionally a memory notebook has been recommended as a compensatory memory aid. Electronic devices have the advantage of providing a cue at the appropriate time to remind participants to refer to the memory aid and complete tasks. Research suggests these have potential benefit in neurorehabilitation. This study aimed to investigate the efficacy of a memory notebook and specifically a smartphone as a compensatory memory aid. A single case series design was used to assess seven participants. A no-intervention baseline was followed by training and intervention with either the smartphone alone, or a memory notebook and later the smartphone. Memory was assessed with weekly assigned memory tasks. Participants using a smartphone showed improvements in their ability to complete assigned memory tasks accurately and within the assigned time periods. Use of a smartphone provided additional benefits over and above those already seen for those who received a memory notebook first. Smartphones have the potential to be a useful and cost effective tool in neurorehabilitation practice.

Greater neural pattern similarity across repetitions is associated with better memory.

PubMed

Xue, Gui; Dong, Qi; Chen, Chuansheng; Lu, Zhonglin; Mumford, Jeanette A; Poldrack, Russell A

2010-10-01

Repeated study improves memory, but the underlying neural mechanisms of this improvement are not well understood. Using functional magnetic resonance imaging and representational similarity analysis of brain activity, we found that, compared with forgotten items, subsequently remembered faces and words showed greater similarity in neural activation across multiple study in many brain regions, including (but not limited to) the regions whose mean activities were correlated with subsequent memory. This result addresses a longstanding debate in the study of memory by showing that successful episodic memory encoding occurs when the same neural representations are more precisely reactivated across study episodes, rather than when patterns of activation are more variable across time.

Working Memory Training: Improving Intelligence--Changing Brain Activity

ERIC Educational Resources Information Center

Jausovec, Norbert; Jausovec, Ksenija

2012-01-01

The main objectives of the study were: to investigate whether training on working memory (WM) could improve fluid intelligence, and to investigate the effects WM training had on neuroelectric (electroencephalography--EEG) and hemodynamic (near-infrared spectroscopy--NIRS) patterns of brain activity. In a parallel group experimental design,…

Patterns of Brain-Electrical Activity during Declarative Memory Performance in 10-Month-Old Infants

ERIC Educational Resources Information Center

Morasch, Katherine C.; Bell, Martha Ann

2009-01-01

This study of infant declarative memory concurrently examined brain-electrical activity and deferred imitation performance in 10-month-old infants. Continuous electroencephalogram (EEG) measures were collected throughout the activity-matched baseline, encoding (modeling) and retrieval (delayed test) phases of a within-subjects deferred imitation…

Human Performance on the Temporal Bisection Task

ERIC Educational Resources Information Center

Kopec, Charles D.; Brody, Carlos D.

2010-01-01

The perception and processing of temporal information are tasks the brain must continuously perform. These include measuring the duration of stimuli, storing duration information in memory, recalling such memories, and comparing two durations. How the brain accomplishes these tasks, however, is still open for debate. The temporal bisection task,…

Combinatorial semantics strengthens angular-anterior temporal coupling.

PubMed

Molinaro, Nicola; Paz-Alonso, Pedro M; Duñabeitia, Jon Andoni; Carreiras, Manuel

2015-04-01

The human semantic combinatorial system allows us to create a wide number of new meanings from a finite number of existing representations. The present study investigates the neural dynamics underlying the semantic processing of different conceptual constructions based on predictions from previous neuroanatomical models of the semantic processing network. In two experiments, participants read sentences for comprehension containing noun-adjective pairs in three different conditions: prototypical (Redundant), nonsense (Anomalous) and low-typical but composable (Contrastive). In Experiment 1 we examined the processing costs associated to reading these sentences and found a processing dissociation between Anomalous and Contrastive word pairs, compared to prototypical (Redundant) stimuli. In Experiment 2, functional connectivity results showed strong co-activation across conditions between inferior frontal gyrus (IFG) and posterior middle temporal gyrus (MTG), as well as between these two regions and middle frontal gyrus (MFG), anterior temporal cortex (ATC) and fusiform gyrus (FG), consistent with previous neuroanatomical models. Importantly, processing of low-typical (but composable) meanings relative to prototypical and anomalous constructions was associated with a stronger positive coupling between ATC and angular gyrus (AG). Our results underscore the critical role of IFG-MTG co-activation during semantic processing and how other relevant nodes within the semantic processing network come into play to handle visual-orthographic information, to maintain multiple lexical-semantic representations in working memory and to combine existing representations while creatively constructing meaning. Copyright © 2015 Elsevier Ltd. All rights reserved.

On ways to overcome the magical capacity limit of working memory.

PubMed

Turi, Zsolt; Alekseichuk, Ivan; Paulus, Walter

2018-04-01

The ability to simultaneously process and maintain multiple pieces of information is limited. Over the past 50 years, observational methods have provided a large amount of insight regarding the neural mechanisms that underpin the mental capacity that we refer to as "working memory." More than 20 years ago, a neural coding scheme was proposed for working memory. As a result of technological developments, we can now not only observe but can also influence brain rhythms in humans. Building on these novel developments, we have begun to externally control brain oscillations in order to extend the limits of working memory.

[Sleep-wake cycle and memory consolidation].

PubMed

Baratti, Carlos M; Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B

2007-01-01

Although several hypothesis and theories have been advanced as explanations for the functions of sleep, a unified theory of sleep function remains elusive. Sleep has been implicated in the plastic cerebral changes that underlie learning and memory, in particular those related to memory consolidation of recently acquired new information. Despite steady accumulations of positive findings over the last ten years, the precise role of sleep in memory and brain plasticity is unproven at all. This situation might be solved by more integrated approaches that combine behavioral and neurophysiological measurements in well described in vivo models of neuronal activity and brain plasticity.

Kagan Structures, Processing, and Excellence in College Teaching

ERIC Educational Resources Information Center

Kagan, Spencer

2014-01-01

Frequent student processing of lecture content (1) clears working memory, (2) increases long-term memory storage, (3) produces retrograde memory enhancement, (4) creates episodic memories, (5) increases alertness, and (6) activates many brain structures. These outcomes increase comprehension of and memory for content. Many professors now…

Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome.

PubMed

Jiménez-Maldonado, Alberto; Ying, Zhe; Byun, Hyae Ran; Gomez-Pinilla, Fernando

2018-01-01

Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Region-specific differences in bioenergetic proteins and protein response to acute high fat diet in brains of low and high capacity runner rats.

PubMed

Gan, Li; Ma, Delin; Li, Min; Yang, Fu-Chen; Rogers, Robert S; Wheatley, Joshua L; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C; Stanford, John A

2018-05-01

Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions. LCR rats exhibited lower levels of mitochondrial proteins (PGC1-α, Nrf-1, TFAM), and greater p-AMPK, in striatum, but not in the other brain regions. Mitochondrial protein levels were greater in HFD LCR striatum, while p-AMPK was lower in this group. Markers of lower mitochondrial biogenesis and increased metabolic demand were limited to the LCR striatum, which nevertheless maintained the capacity to respond to an acute HFD challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

This Is Your Brain: A Decision-Making Machine

DTIC Science & Technology

2015-11-01

brain has vast comput-ing power that performs a plethora of vital tasks. It regu-lates your bodily functions, movements and emotions . It processes and...system beneath the cerebrum and associated with long-term memory and emotions . In our “The brain is a wonderful organ. It starts working when you get...presence of perceived danger. Long-term memories and experiences also are stored here, often along with their emotional connections to pain or

Interictal Epileptiform Discharges Impair Word Recall in Multiple Brain Areas

PubMed Central

Horak, Peter C.; Meisenhelter, Stephen; Song, Yinchen; Testorf, Markus E.; Kahana, Michael J.; Viles, Weston D.; Bujarski, Krzysztof A.; Connolly, Andrew C.; Robbins, Ashlee A.; Sperling, Michael R.; Sharan, Ashwini D.; Worrell, Gregory A.; Miller, Laura R.; Gross, Robert E.; Davis, Kathryn A.; Roberts, David W.; Lega, Bradley; Sheth, Sameer A.; Zaghloul, Kareem A.; Stein, Joel M.; Das, Sandhitsu R.; Rizzuto, Daniel S.; Jobst, Barbara C.

2016-01-01

Summary Objectives Interictal epileptiform discharges (IEDs) have been linked to memory impairment, but the spatial and temporal dynamics of this relationship remain elusive. In the present study, we aim to systematically characterize the brain areas and times at which IEDs affect memory. Methods Eighty epilepsy patients participated in a delayed free recall task while undergoing intracranial EEG monitoring. We analyzed the locations and timing of IEDs relative to the behavioral data in order to measure their effects on memory. Results Overall IED rates did not correlate with task performance across subjects (r = 0.03, p = 0.8). However, at a finer temporal scale, within-subject memory was negatively affected by IEDs during the encoding and recall periods of the task but not during the rest and distractor periods (p < 0.01, p < 0.001, p = 0.3, and p = 0.8 respectively). The effects of IEDs during encoding and recall were stronger in the left hemisphere than in the right (p < 0.05). Out of six brain areas analyzed, IEDs in the inferior temporal, medial temporal, and parietal areas significantly affected memory (false discovery rate < 0.05). Significance These findings reveal a network of brain areas sensitive to IEDs with key nodes in temporal as well as parietal lobes. They also demonstrate the time-dependent effects of IEDs in this network on memory. PMID:27935031

Memory and anatomical change in severe non missile traumatic brain injury: ∼1 vs. ∼8 years follow-up.

PubMed

Tomaiuolo, Francesco; Bivona, Umberto; Lerch, Jason P; Di Paola, Margherita; Carlesimo, Giovanni A; Ciurli, Paola; Matteis, Mariella; Cecchetti, Luca; Forcina, Antonio; Silvestro, Daniela; Azicnuda, Eva; Sabatini, Umberto; Di Giacomo, Dina; Caltagirone, Carlo; Petrides, Michael; Formisano, Rita

2012-03-10

In previous studies, we investigated a group of subjects who had suffered from a severe non missile traumatic brain injury (nmTBI) without macroscopic focal lesions and we found brain atrophy involving the hippocampus, fornix, corpus callosum, optic chiasm, and optic radiations. Memory test scores correlated mainly with fornix volumes [37,38]. In the present study, we re-examined 11 of these nmTBI subjects approximately 8 yr later. High-spatial resolution T1 weighted magnetic resonance images of the brain (1mm(3)) and standardised memory tests were performed once more in order to compare brain morphology and memory performance originally assessed 3-13 months after head injury (first study) and after 8-10 yr (present study). An overall improvement of memory test performance was demonstrated in the latest assessment, indicating that cognitive recovery in severe nmTBI subjects had not been completed within 3-13 months post-injury. It is notable that the volumes of the fornix and the hippocampus were reduced significantly from normal controls, but these volumes do not differ appreciatively between nmTBI subjects at first (after ∼1 yr) and at second (after ∼8 yr) scans. On the contrary, a clear reduction in the volume of the corpus callosus can be observed after ∼1 yr and a further significant reduction is evident after ∼8 yr, indicating that the neural degeneration in severe nmTBI continues long after the head trauma and relates to specific structures and not to the overall brain. Copyright © 2012 Elsevier Inc. All rights reserved.

Synaptic clustering within dendrites: an emerging theory of memory formation

PubMed Central

Kastellakis, George; Cai, Denise J.; Mednick, Sara C.; Silva, Alcino J.; Poirazi, Panayiota

2015-01-01

It is generally accepted that complex memories are stored in distributed representations throughout the brain, however the mechanisms underlying these representations are not understood. Here, we review recent findings regarding the subcellular mechanisms implicated in memory formation, which provide evidence for a dendrite-centered theory of memory. Plasticity-related phenomena which affect synaptic properties, such as synaptic tagging and capture, synaptic clustering, branch strength potentiation and spinogenesis provide the foundation for a model of memory storage that relies heavily on processes operating at the dendrite level. The emerging picture suggests that clusters of functionally related synapses may serve as key computational and memory storage units in the brain. We discuss both experimental evidence and theoretical models that support this hypothesis and explore its advantages for neuronal function. PMID:25576663

Face Encoding and Recognition in the Human Brain

NASA Astrophysics Data System (ADS)

Haxby, James V.; Ungerleider, Leslie G.; Horwitz, Barry; Maisog, Jose Ma.; Rapoport, Stanley I.; Grady, Cheryl L.

1996-01-01

A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition. The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations.

False memories to emotional stimuli are not equally affected in right- and left-brain-damaged stroke patients.

PubMed

Buratto, Luciano Grüdtner; Zimmermann, Nicolle; Ferré, Perrine; Joanette, Yves; Fonseca, Rochele Paz; Stein, Lilian Milnitsky

2014-10-01

Previous research has attributed to the right hemisphere (RH) a key role in eliciting false memories to visual emotional stimuli. These results have been explained in terms of two right-hemisphere properties: (i) that emotional stimuli are preferentially processed in the RH and (ii) that visual stimuli are represented more coarsely in the RH. According to this account, false emotional memories are preferentially produced in the RH because emotional stimuli are both more strongly and more diffusely activated during encoding, leaving a memory trace that can be erroneously reactivated by similar but unstudied emotional items at test. If this right-hemisphere hypothesis is correct, then RH damage should result in a reduction in false memories to emotional stimuli relative to left-hemisphere lesions. To investigate this possibility, groups of right-brain-damaged (RBD, N=15), left-brain-damaged (LBD, N=15) and healthy (HC, N=30) participants took part in a recognition memory experiment with emotional (negative and positive) and non-emotional pictures. False memories were operationalized as incorrect responses to unstudied pictures that were similar to studied ones. Both RBD and LBD participants showed similar reductions in false memories for negative pictures relative to controls. For positive pictures, however, false memories were reduced only in RBD patients. The results provide only partial support for the right-hemisphere hypothesis and suggest that inter-hemispheric cooperation models may be necessary to fully account for false emotional memories. Copyright © 2014 Elsevier Inc. All rights reserved.

[Application of spatial working memory task fMRI in evaluation of primary insomnia patient's cognitive dysfunction].

PubMed

Dou, Shewei; Wang, Enfeng; Zhang, Hongju; Tong, Li; Zhang, Xiaoqi; Shi, Dapeng; Cheng, Jingliang; Li, Yongli

2015-06-02

To explore abnormal brain activation of spatial working memory in primary insomnia and its potential neuromechanism. we recruited 30 cases primary insomnia (PI) patients and 30 cases age, gender matched healthy control (HC) subjects from July 2013 to December 2013, the diagnosis of primary insomnia matched the diagnosis criterion of DSM-IV and Classification and diagnostic criteria of mental disorders in China third edition (CCMD-3). All the subjects attended the tests of PSQI, HAMA, HAMD and index of spatial working memory. And then, we collected the data of routine MRI and spatial working memory task fMRI on 3.0 T MRI scanner. After that, we used SPM8 and REST1.8 to analyze the fMRI data, compared difference of PSQI, HAMA, HAMD, index of spatial working memory and brain activation of spatial working memory between PI group and HC group. There were significant difference between PI group and HC group in PSQI, HAMA, HAMD and index of spatial working memory (P < 0.05). In the spatial working memory related activate brain region, compared with HC group, left temporal lobe, occipital lobe and right frontal lobe activation increased and bilateral parahippocampalis, temporal cortex, frontal cortex and superior parietal lobule activation reduced in PI group. Spatial working memory task fMRI revealed the pathological mechanisms of cognitive dysfunction of clinical spatial working memory and emotional disorder in primary insomnia patients.

Brain-based Learning.

ERIC Educational Resources Information Center

Weiss, Ruth Palombo

2000-01-01

Discusses brain research and how new imaging technologies allow scientists to explore how human brains process memory, emotion, attention, patterning, motivation, and context. Explains how brain research is being used to revise learning theories. (JOW)

Improvement and decline in tactile discrimination behavior after cortical plasticity induced by passive tactile coactivation.

PubMed

Hodzic, Amra; Veit, Ralf; Karim, Ahmed A; Erb, Michael; Godde, Ben

2004-01-14

Perceptual learning can be induced by passive tactile coactivation without attention or reinforcement. We used functional MRI (fMRI) and psychophysics to investigate in detail the specificity of this type of learning for different tactile discrimination tasks and the underlying cortical reorganization. We found that a few hours of Hebbian coactivation evoked a significant increase of primary (SI) and secondary (SII) somatosensory cortical areas representing the stimulated body parts. The amount of plastic changes was strongly correlated with improvement in spatial discrimination performance. However, in the same subjects, frequency discrimination was impaired after coactivation, indicating that even maladaptive processes can be induced by intense passive sensory stimulation.

The "memory kinases": roles of PKC isoforms in signal processing and memory formation.

PubMed

Sun, Miao-Kun; Alkon, Daniel L

2014-01-01

The protein kinase C (PKC) isoforms, which play an essential role in transmembrane signal conduction, can be viewed as a family of "memory kinases." Evidence is emerging that they are critically involved in memory acquisition and maintenance, in addition to their involvement in other functions of cells. Deficits in PKC signal cascades in neurons are one of the earliest abnormalities in the brains of patients suffering from Alzheimer's disease. Their dysfunction is also involved in several other types of memory impairments, including those related to emotion, mental retardation, brain injury, and vascular dementia/ischemic stroke. Inhibition of PKC activity leads to a reduced capacity of many types of learning and memory, but may have therapeutic values in treating substance abuse or aversive memories. PKC activators, on the other hand, have been shown to possess memory-enhancing and antidementia actions. PKC pharmacology may, therefore, represent an attractive area for developing effective cognitive drugs for the treatment of many types of memory disorders and dementias. © 2014 Elsevier Inc. All rights reserved.

Sharpen Kids' Memory to Raise Test Scores

ERIC Educational Resources Information Center

Willis, Judy

2005-01-01

By understanding the different types of memory, the neurophysiology of brain chemical and anatomical changes associated with memory, and the ways to enhance the memory process, teachers can utilize proven technique--and develop their own--to guide students over that bleak terrain of memorization. From simplest recall of awareness, memory skills…

Neuroenhancement of Memory for Children with Autism by a Mind–Body Exercise

PubMed Central

Chan, Agnes S.; Han, Yvonne M. Y.; Sze, Sophia L.; Lau, Eliza M.

2015-01-01

The memory deficits found in individuals with autism spectrum disorder (ASD) may be caused by the lack of an effective strategy to aid memory. The executive control of memory processing is mediated largely by the timely coupling between frontal and posterior brain regions. The present study aimed to explore the potential effect of a Chinese mind–body exercise, namely Nei Gong, for enhancing learning and memory in children with ASD, and the possible neural basis of the improvement. Sixty-six children with ASD were randomly assigned to groups receiving Nei Gong training (NGT), progressive muscle relaxation (PMR) training, or no training for 1 month. Before and after training, the participants were tested individually on a computerized visual memory task while EEG signals were acquired during the memory encoding phase. Children in the NGT group demonstrated significantly enhanced memory performance and more effective use of a memory strategy, which was not observed in the other two groups. Furthermore, the improved memory after NGT was consistent with findings of elevated EEG theta coherence between frontal and posterior brain regions, a measure of functional coupling. The scalp EEG signals were localized by the standardized low resolution brain electromagnetic tomography method and found to originate from a neural network that promotes effective memory processing, including the prefrontal cortex, the parietal cortex, and the medial and inferior temporal cortex. This alteration in neural processing was not found in children receiving PMR or in those who received no training. The present findings suggest that the mind–body exercise program may have the potential effect on modulating neural functional connectivity underlying memory processing and hence enhance memory functions in individuals with autism. PMID:26696946

Neuroenhancement of Memory for Children with Autism by a Mind-Body Exercise.

PubMed

Chan, Agnes S; Han, Yvonne M Y; Sze, Sophia L; Lau, Eliza M

2015-01-01

The memory deficits found in individuals with autism spectrum disorder (ASD) may be caused by the lack of an effective strategy to aid memory. The executive control of memory processing is mediated largely by the timely coupling between frontal and posterior brain regions. The present study aimed to explore the potential effect of a Chinese mind-body exercise, namely Nei Gong, for enhancing learning and memory in children with ASD, and the possible neural basis of the improvement. Sixty-six children with ASD were randomly assigned to groups receiving Nei Gong training (NGT), progressive muscle relaxation (PMR) training, or no training for 1 month. Before and after training, the participants were tested individually on a computerized visual memory task while EEG signals were acquired during the memory encoding phase. Children in the NGT group demonstrated significantly enhanced memory performance and more effective use of a memory strategy, which was not observed in the other two groups. Furthermore, the improved memory after NGT was consistent with findings of elevated EEG theta coherence between frontal and posterior brain regions, a measure of functional coupling. The scalp EEG signals were localized by the standardized low resolution brain electromagnetic tomography method and found to originate from a neural network that promotes effective memory processing, including the prefrontal cortex, the parietal cortex, and the medial and inferior temporal cortex. This alteration in neural processing was not found in children receiving PMR or in those who received no training. The present findings suggest that the mind-body exercise program may have the potential effect on modulating neural functional connectivity underlying memory processing and hence enhance memory functions in individuals with autism.

Autobiographical memory and hyperassociativity in the dreaming brain: implications for memory consolidation in sleep

PubMed Central

Horton, Caroline L.; Malinowski, Josie E.

2015-01-01

In this paper we argue that autobiographical memory (AM) activity across sleep and wake can provide insight into the nature of dreaming, and vice versa. Activated memories within the sleeping brain reflect one’s personal life history (autobiography). They can appear in largely fragmentary forms and differ from conventional manifestations of episodic memory. Autobiographical memories in dreams can be sampled from non-REM as well as REM periods, which contain fewer episodic references and become more bizarre across the night. Salient fragmented memory features are activated in sleep and re-bound with fragments not necessarily emerging from the same memory, thus de-contextualizing those memories and manifesting as experiences that differ from waking conceptions. The constructive nature of autobiographical recall further encourages synthesis of these hyper-associated images into an episode via recalling and reporting dreams. We use a model of AM to account for the activation of memories in dreams as a reflection of sleep-dependent memory consolidation processes. We focus in particular on the hyperassociative nature of AM during sleep. PMID:26191010

Autobiographical memory and hyperassociativity in the dreaming brain: implications for memory consolidation in sleep.

PubMed

Horton, Caroline L; Malinowski, Josie E

2015-01-01

In this paper we argue that autobiographical memory (AM) activity across sleep and wake can provide insight into the nature of dreaming, and vice versa. Activated memories within the sleeping brain reflect one's personal life history (autobiography). They can appear in largely fragmentary forms and differ from conventional manifestations of episodic memory. Autobiographical memories in dreams can be sampled from non-REM as well as REM periods, which contain fewer episodic references and become more bizarre across the night. Salient fragmented memory features are activated in sleep and re-bound with fragments not necessarily emerging from the same memory, thus de-contextualizing those memories and manifesting as experiences that differ from waking conceptions. The constructive nature of autobiographical recall further encourages synthesis of these hyper-associated images into an episode via recalling and reporting dreams. We use a model of AM to account for the activation of memories in dreams as a reflection of sleep-dependent memory consolidation processes. We focus in particular on the hyperassociative nature of AM during sleep.

Programmable Payload Release from Transient Polymer Microcapsules Triggered by a Specific Ion Coactivation Effect.

PubMed

Tang, Shijia; Tang, Liuyan; Lu, Xiaocun; Liu, Huiying; Moore, Jeffrey S

2018-01-10

Stimuli-responsive materials activated by a pair of molecular or ionic species are of interest in the design of chemical logic gates and signal amplification schemes. There are relatively few materials whose coactivated response has been well-characterized. Here, we demonstrate a specific ion coactivation (SICA) effect at the interfaces of transient polymer solids and liquid solutions. We found that depolymerization of the transient polymer, cyclic poly(phthalaldehyde) (cPPA), exhibited a SICA effect when the cPPA core-shell microcapsules were suspended in ion-containing acidic methanol solutions. Significant acceleration in cPPA depolymerization rate is triggered by the combination of acid and ion coactivators. Intriguingly, the SICA effect is related to the Hofmeister behavior. The SICA effect is primarily determined by anions, and cations exhibit a secondary effect that modulates the coactivation strength. Based on these observations, we developed cPPA programmable microcapsules whose payload release rates depend on the composition and concentration of the salt/acidic-methanol solutions.

Blood Alcohol Concentration-Related Lower Performance in Immediate Visual Memory and Working Memory in Adolescent Binge Drinkers

PubMed Central

Vinader-Caerols, Concepción; Duque, Aránzazu; Montañés, Adriana; Monleón, Santiago

2017-01-01

The binge drinking (BD) pattern of alcohol consumption is prevalent during adolescence, a period characterized by critical changes to the structural and functional development of brain areas related with memory and cognition. There is considerable evidence of the cognitive dysfunctions caused by the neurotoxic effects of BD in the not-yet-adult brain. Thus, the aim of the present study was to evaluate the effects of different blood alcohol concentrations (BAC) on memory during late adolescence (18–19 years old) in males and females with a history of BD. The sample consisted of 154 adolescents (67 males and 87 females) that were classified as refrainers if they had never previously drunk alcoholic drinks and as binge drinkers if they had drunk six or more standard drink units in a row for men or five or more for women at a minimum frequency of three occasions in a month, throughout the previous 12 months. After intake of a high acute dose of alcohol by binge drinkers or a control refreshment by refrainers and binge drinkers, subjects were distributed into four groups for each gender according to their BAC: BAC0-R (0 g/L, in refrainers), BAC0-BD (0 g/L, in binge drinkers), BAC1 (0.3 – 0.5 g/L, in binge drinkers) or BAC2 (0.54 – 1.1 g/L, in binge drinkers). The subjects’ immediate visual memory and working memory were then measured according to the Wechsler Memory Scale (WMS-III). The BAC1 group showed lower scores of immediate visual memory but not of working memory, while lower performance in both memories were found in the BAC2 group. Therefore, the brain of binge drinkers with moderate BAC could be employing compensatory mechanisms from additional brain areas to perform a working memory task adequately, but these resources would be undermined when BAC is higher (>0.5 g/L). No gender differences were found in BAC-related lower performance in immediate visual memory and working memory. In conclusion, immediate visual memory is more sensitive than working memory to the neurotoxic effects of alcohol in adolescent binge drinkers of both genders, being a BAC-related lower performance, and without obvious differences between males and females. PMID:29046656

Blood Alcohol Concentration-Related Lower Performance in Immediate Visual Memory and Working Memory in Adolescent Binge Drinkers.

PubMed

Vinader-Caerols, Concepción; Duque, Aránzazu; Montañés, Adriana; Monleón, Santiago

2017-01-01

The binge drinking (BD) pattern of alcohol consumption is prevalent during adolescence, a period characterized by critical changes to the structural and functional development of brain areas related with memory and cognition. There is considerable evidence of the cognitive dysfunctions caused by the neurotoxic effects of BD in the not-yet-adult brain. Thus, the aim of the present study was to evaluate the effects of different blood alcohol concentrations (BAC) on memory during late adolescence (18-19 years old) in males and females with a history of BD. The sample consisted of 154 adolescents (67 males and 87 females) that were classified as refrainers if they had never previously drunk alcoholic drinks and as binge drinkers if they had drunk six or more standard drink units in a row for men or five or more for women at a minimum frequency of three occasions in a month, throughout the previous 12 months. After intake of a high acute dose of alcohol by binge drinkers or a control refreshment by refrainers and binge drinkers, subjects were distributed into four groups for each gender according to their BAC: BAC0-R (0 g/L, in refrainers), BAC0-BD (0 g/L, in binge drinkers), BAC1 (0.3 - 0.5 g/L, in binge drinkers) or BAC2 (0.54 - 1.1 g/L, in binge drinkers). The subjects' immediate visual memory and working memory were then measured according to the Wechsler Memory Scale (WMS-III). The BAC1 group showed lower scores of immediate visual memory but not of working memory, while lower performance in both memories were found in the BAC2 group. Therefore, the brain of binge drinkers with moderate BAC could be employing compensatory mechanisms from additional brain areas to perform a working memory task adequately, but these resources would be undermined when BAC is higher (>0.5 g/L). No gender differences were found in BAC-related lower performance in immediate visual memory and working memory. In conclusion, immediate visual memory is more sensitive than working memory to the neurotoxic effects of alcohol in adolescent binge drinkers of both genders, being a BAC-related lower performance, and without obvious differences between males and females.

Using event-related potentials to study perinatal nutrition and brain development in infants of diabetic mothers.

PubMed

deRegnier, Raye-Ann; Long, Jeffrey D; Georgieff, Michael K; Nelson, Charles A

2007-01-01

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birth weights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant.

Using Event-Related Potentials to Study Perinatal Nutrition and Brain Development in Infants of Diabetic Mothers

PubMed Central

deRegnier, Raye-Ann; Long, Jeffrey D.; Georgieff, Michael K.; Nelson, Charles A.

2009-01-01

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birthweights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant. PMID:17559331

Studies on the effects of aspartame on memory and oxidative stress in brain of mice.

PubMed

Abdel-Salam, O M E; Salem, N A; El-Shamarka, M E S; Hussein, J S; Ahmed, N A S; El-Nagar, M E S

2012-12-01

The dipeptide aspartame (N-L-alpha-aspartyl-Lphenylalanine, 1-methyl ester; alpha-APM) is one of the most widely used artificial sweeteners. The present study aimed to investigate the effect of repeated administration of aspartame in the working memory version of Morris water maze test, on oxidative stress and brain monoamines in brain of mice. Aspartame (0.625, 1.875 or 5.625 mg/kg) was administered once daily subcutaneously for 2 weeks and mice were examined four times a week for their ability to locate a submerged plate. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide levels (the concentrations of nitrite/nitrate) and glucose were determined in brain. Only at the highest dose of 5.625 mg/kg, did aspartame significantly impaired water maze performance. The mean time taken to find the escape platform (latency) over 2 weeks was significantly delayed by aspartame 5.625 mg/kg, compared with the saline-treated control group. Significant differences occurred only on the first trial to find the escape platform. Significant increase in brain MDA by 16.5% and nitric oxide by 16.2% and a decrease in GSH by 25.1% and glucose by 22.5% occurred after treatment with aspartame at 1.875 mg/kg. Aspartame administered at 5.625 mg/kg significantly increased brain MDA by 43.8%, nitric oxide by 18.6% and decreased GSH by 32.7% and glucose by 25.8%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine. These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration. The impaired memory performance is likely to involve increased oxidative stress as well as decreased brain glucose availability.

Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

PubMed

Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

2017-08-01

Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

Anxiety, cognition, and habit: a multiple memory systems perspective.

PubMed

Packard, Mark G

2009-10-13

Consistent with a multiple systems approach to memory organization in the mammalian brain, numerous studies have differentiated the roles of the hippocampus and dorsal striatum in "cognitive" and "habit" learning and memory, respectively. Additional research indicates that activation of efferent projections of the basolateral amygdala (BLA), a brain region implicated in mammalian emotion, modulates memory processes occurring in other brain structures. The present brief review describes research designed to link these general concepts by examining the manner in which emotional state may influence the relative use of multiple memory systems. In a dual-solution plus-maze task that can be acquired using either hippocampus-dependent or dorsal striatal-dependent learning, acute pre-training or pre-retrieval emotional arousal (restraint stress/inescapable foot shock, exposure to the predator odor TMT, or peripheral injection of anixogenic drugs) biases rats towards the use of habit memory. Moreover, intra-BLA injection of anxiogenic drugs is sufficient to bias rats towards the use of dorsal striatal-dependent habit memory. In single-solution plus-maze tasks that require the use of either cognitive or habit learning, intra-BLA infusions of anxiogenic drugs result in a behavioral profile indicating an impairing effect on hippocampus-dependent memory that effectively produces enhanced habit learning by eliminating competitive interference between cognitive and habit memory systems. It is speculated that the predominant use of habit memory that can be produced by anxious and/or stressful emotional states may have implications for understanding the role of learning and memory processes in various human psychopathologies, including for example post-traumatic stress disorder and drug addiction.

A trade-off between local and distributed information processing associated with remote episodic versus semantic memory.

PubMed

Heisz, Jennifer J; Vakorin, Vasily; Ross, Bernhard; Levine, Brian; McIntosh, Anthony R

2014-01-01

Episodic memory and semantic memory produce very different subjective experiences yet rely on overlapping networks of brain regions for processing. Traditional approaches for characterizing functional brain networks emphasize static states of function and thus are blind to the dynamic information processing within and across brain regions. This study used information theoretic measures of entropy to quantify changes in the complexity of the brain's response as measured by magnetoencephalography while participants listened to audio recordings describing past personal episodic and general semantic events. Personal episodic recordings evoked richer subjective mnemonic experiences and more complex brain responses than general semantic recordings. Critically, we observed a trade-off between the relative contribution of local versus distributed entropy, such that personal episodic recordings produced relatively more local entropy whereas general semantic recordings produced relatively more distributed entropy. Changes in the relative contributions of local and distributed entropy to the total complexity of the system provides a potential mechanism that allows the same network of brain regions to represent cognitive information as either specific episodes or more general semantic knowledge.

Exploring novel objective functions for simulating muscle coactivation in the neck.

PubMed

Mortensen, J; Trkov, M; Merryweather, A

2018-04-11

Musculoskeletal modeling allows for analysis of individual muscles in various situations. However, current techniques to realistically simulate muscle response when significant amounts of intentional coactivation is required are inadequate. This would include stiffening the neck or spine through muscle coactivation in preparation for perturbations or impacts. Muscle coactivation has been modeled previously in the neck and spine using optimization techniques that seek to maximize the joint stiffness by maximizing total muscle activation or muscle force. These approaches have not sought to replicate human response, but rather to explore the possible effects of active muscle. Coactivation remains a challenging feature to include in musculoskeletal models, and may be improved by extracting optimization objective functions from experimental data. However, the components of such an objective function must be known before fitting to experimental data. This study explores the effect of components in several objective functions, in order to recommend components to be used for fitting to experimental data. Four novel approaches to modeling coactivation through optimization techniques are presented, two of which produce greater levels of stiffness than previous techniques. Simulations were performed using OpenSim and MATLAB cooperatively. Results show that maximizing the moment generated by a particular muscle appears analogous to maximizing joint stiffness. The approach of optimizing for maximum moment generated by individual muscles may be a good candidate for developing objective functions that accurately simulate muscle coactivation in complex joints. This new approach will be the focus of future studies with human subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Destination memory in traumatic brain injuries.

PubMed

Wili Wilu, Amina; Coello, Yann; El Haj, Mohamad

2018-06-01

Destination memory, which is socially driven, refers to the ability to remember to whom one has sent information. Our study investigated destination memory in patients with traumatic brain injuries (TBIs). Patients and control participants were invited to tell proverbs (e.g., "the pen is mightier than the sword") to pictures of celebrities (e.g., Barack Obama). Then they were asked to indicate to which celebrity they had previously told the proverbs. Besides the assessment of destination memory, participants performed a binding task in which they were required to associate letters with their corresponding location. Analysis demonstrated less destination memory and binding in patients with TBIs than in controls. In both populations, significant correlations were observed between destination memory and performances on the binding task. These findings demonstrate difficulty in the ability to attribute information to its appropriate destination in TBI patients, perhaps owing to difficulties in binding separate information together to form a coherent representation of an event in memory.

Slime mold uses an externalized spatial “memory” to navigate in complex environments

PubMed Central

Reid, Chris R.; Latty, Tanya; Dussutour, Audrey; Beekman, Madeleine

2012-01-01

Spatial memory enhances an organism’s navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold Physarum polycephalum constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem—a classic test of autonomous navigational ability commonly used in robotics—requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism’s ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms. PMID:23045640

The Future of Memory: Remembering, Imagining, and the Brain

PubMed Central

Schacter, Daniel L.; Addis, Donna Rose; Hassabis, Demis; Martin, Victoria C.; Spreng, R. Nathan; Szpunar, Karl K.

2013-01-01

During the past few years, there has been a dramatic increase in research examining the role of memory in imagination and future thinking. This work has revealed striking similarities between remembering the past and imagining or simulating the future, including the finding that a common brain network underlies both memory and imagination. Here we discuss a number of key points that have emerged during recent years, focusing in particular on the importance of distinguishing between temporal and non-temporal factors in analyses of memory and imagination, the nature of differences between remembering the past and imagining the future, the identification of component processes that comprise the default network supporting memory-based simulations, and the finding that this network can couple flexibly with other networks to support complex goal-directed simulations. This growing area of research has broadened our conception of memory by highlighting the many ways in which memory supports adaptive functioning. PMID:23177955

The importance of hippocampal dynamic connectivity in explaining memory function in multiple sclerosis.

PubMed

van Geest, Quinten; Hulst, Hanneke E; Meijer, Kim A; Hoyng, Lieke; Geurts, Jeroen J G; Douw, Linda

2018-05-01

Brain dynamics (i.e., variable strength of communication between areas), even at the scale of seconds, are thought to underlie complex human behavior, such as learning and memory. In multiple sclerosis (MS), memory problems occur often and have so far only been related to "stationary" brain measures (e.g., atrophy, lesions, activation and stationary (s) functional connectivity (FC) over an entire functional scanning session). However, dynamics in FC (dFC) between the hippocampus and the (neo)cortex may be another important neurobiological substrate of memory impairment in MS that has not yet been explored. Therefore, we investigated hippocampal dFC during a functional (f) magnetic resonance imaging (MRI) episodic memory task and its relationship with verbal and visuospatial memory performance outside the MR scanner. Thirty-eight MS patients and 29 healthy controls underwent neuropsychological tests to assess memory function. Imaging (1.5T) was obtained during performance of a memory task. We assessed hippocampal volume, functional activation, and sFC (i.e., FC of the hippocampus with the rest of the brain averaged over the entire scan, using an atlas-based approach). Dynamic FC of the hippocampus was calculated using a sliding window approach. No group differences were found in hippocampal activation, sFC, and dFC. However, stepwise forward regression analyses in patients revealed that lower dFC of the left hippocampus (standardized β = -0.30; p  =   .021) could explain an additional 7% of variance (53% in total) in verbal memory, in addition to female sex and larger left hippocampal volume. For visuospatial memory, lower dFC of the right hippocampus (standardized β = -0.38; p  =   .013) could explain an additional 13% of variance (24% in total) in addition to higher sFC of the right hippocampus. Low hippocampal dFC is an important indicator for maintained memory performance in MS, in addition to other hippocampal imaging measures. Hence, brain dynamics may offer new insights into the neurobiological mechanisms underlying memory (dys)function.

Short-term memory and critical clusterization in brain neurons spike series

NASA Astrophysics Data System (ADS)

Bershadskii, A.; Dremencov, E.; Yadid, G.

2003-06-01

A new phenomenon: critical clusterization, is observed in the neuron firing of a genetically defined rat model of depression. The critical clusterization is studied using a multiscaling analysis of the data obtained from the neurons belonging to the Red Nucleus area of the depressive brains. It is suggested that this critical phenomenon can be partially responsible for the observed ill behavior of the depressive brains: loss of short-term motor memory and slow motor reaction.

The Event-Related Brain Potential as an Index of Information Processing and Cognitive Activity: A Program of Basic Research.

DTIC Science & Technology

1988-02-29

reciprocity: An event- related brain potentials analysis. Acta Psychologica. Submitted for publication. 21. Stolar, N., Sparenborg, S., Donchin, E...in press) argued that it is a manifestation of a process related to the updating of models of the environment or context in working memory. Such an...suggemng " ees ud e may involve working memory, but they do am hold any privileged relation to working memory.u However, he immedi- ately proceeds to narrow

Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2010-01-01

Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…

Improving Reasoning Skills in Secondary History Education by Working Memory Training

ERIC Educational Resources Information Center

Ariës, Roel Jacobus; Groot, Wim; van den Brink, Henriette Maassen

2015-01-01

Secondary school pupils underachieve in tests in which reasoning abilities are required. Brain-based training of working memory (WM) may improve reasoning abilities. In this study, we use a brain-based training programme based on historical content to enhance reasoning abilities in history courses. In the first experiment, a combined intervention…