Neural Correlates Of Memory Research Articles

Epigenetics and memory: Emerging role of histone lysine methyltransferase G9a/GLP complex as bidirectional regulator of synaptic plasticity.

Various epigenetic modifications, including histone lysine methylation, play an integral role in learning and memory. The importance of the histone lysine methyltransferase complex G9a/GLP and its associated histone H3 lysine K9 dimethylation in memory formation and cognition, has garnered the attention of researchers in the past decade. Recent studies feature G9a/GLP as the 'bidirectional regulator of synaptic plasticity', the neural correlate of memory. As the 'title' suggests, G9a/GLP participates in the maintenance of both long-term potentiation (LTP) and long-term depression (LTD). This complex is demonstrated to mostly suppress LTP-related plasticity-related products (PRPs). Notably, our recent paper also shows that G9a/GLP facilitates LTD maintenance in intact hippocampal slices - shedding light on the overlooked influence of epigenetics on LTD. Although the exact mechanisms of G9a/GLP activity regulation in cognition remain elusive, pharmacological inhibition of G9a/GLP presents a new avenue of therapeutic intervention in epigenetic dysfunction-related cognitive deficits.

Long-Term Potentiation and Excitability in the Hippocampus Are Modulated Differently by θ Rhythm.

Oscillations in the brain facilitate neural processing and cognitive functions. This study investigated the dependence of long-term potentiation (LTP), a neural correlate of memory, on the phase of the hippocampal θ rhythm, a prominent brain oscillation. Multichannel field potentials and current source-sinks were analyzed in hippocampal CA1 of adult male rats under urethane anesthesia. A single burst (five pulses at 200 Hz) stimulation of stratum oriens (OR) induced LTP of the basal dendritic excitatory sink (ES), which was maximal when the burst was delivered at ∼340° and ∼160° of the distal dendritic θ rhythm. Apical dendritic sink evoked by stratum radiatum (RAD) stimulation also showed biphasic maxima at ∼30° and ∼210° of the distal dendritic θ rhythm, about 50° phase delay to basal dendritic LTP. By contrast, maximal population spike (PS) excitability, following single-pulse excitation of the basal or mid-apical dendrites, occurred at a θ phase of ∼140°, and maximal basal dendritic ES occurred at ∼20°; γ (30-57 Hz) activity recorded in CA1 RAD had maximal power at ∼300° of the distal dendritic θ rhythm, different from the phases of maximal LTP. LTP induced during the rising θ phase was NMDA receptor sensitive. It is suggested that the θ phase modulation of CA1 PS excitability is mainly provided by θ-rhythmic proximal inhibition, while dendritic LTP is also modulated by dendritic inhibition and excitation, specific to basal and apical dendrites. In summary, basal and apical dendritic synaptic plasticity and spike excitability are facilitated at different θ phases in a compartmental fashion.

Long-term effects of prenatal drug exposure on the neural correlates of memory at encoding and retrieval

The objective of the current study was to examine what stage of memory (encoding or retrieval) may be compromised in adolescents with a history of prenatal drug exposure (PDE) and how the effects of PDE on memory ability are substantiated at the neural level. To achieve this goal, we examined memory performance and associated brain activations in adolescents with and without a history of PDE via event-related fMRI during encoding and retrieval. Consistent with previous studies, we found that PDE subjects remembered fewer items than community comparison subjects. However, there were no differences in behavior after adjusting for correct rejections (i.e., d′). Novel extensions of previous work are findings that PDE is associated with changes in brain activation during memory encoding but not during retrieval. These results suggest that less optimal memory performance often observed in adolescents with a history of PDE may result from variations in encoding rather than retrieval processes.

Estrogen and Environmental Enrichment Differentially Affect Neurogenesis, Dendritic Spine Immunolabeling and Synaptogenesis in the Hippocampus of Young and Reproductively Senescent Female Rats

Background: Studies examining the ability of estrogen replacement therapy (ERT) to enhance memory in women, and in animal models, have not produced consistent results. However, studies examining the effects of activity and exposure to novel environments consistently find enhancement of memory. Methods: An animal model of reproductive aging was used to determine if estradiol (E2) replacement, activity, and/or exposure to an enriched environment could act synergistically to improve memory, and neural correlates of memory. Young (3 months) and reproductively senescent (12 months) female rats were ovariectomized and received either vehicle or E2 treatment. Rats were assigned to 1 of 3 exposures; control: rats remained in their cage; maze control: rats were put into a pen where they could move and explore; enriched maze: rats were put into a pen with various items to climb on or investigate. The amount of time rats were active in each environment was measured. On the third day of exposure, one of the items in the enriched environment was exchanged, and the amount of time animals spent investigating the new item was used as a measure of memory. Results: E2 increased activity, immunostaining for proliferating cell nuclear antigen, and synaptic markers, synaptophysin and spinophilin, in the hippocampus of all animals. However, E2- and activity-induced changes in these markers were more pronounced in young rats. Only young rats displayed improved recognition in response to E2. Conclusions: Older rats may need an extended period of ERT or increased activity before the benefits on memory become apparent.

Basic perceptual changes that alter meaning and neural correlates of recognition memory.

It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color) on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not). visual shapes (“squiggles”) were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential (ERP) correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400), implying that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition). Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates of memory. These findings are relevant to understanding similarities and distinctions between perceptual and conceptual processing as well as the functional interpretation of neural correlates of recognition memory.

Identifying neural correlates of memory and language disturbances in herpes simplex encephalitis: a voxel-based morphometry (VBM) study.

Herpes simplex encephalitis (HSE) is a severe neurological disease that often leads to persistent cognitive deficits in survivors. Memory and naming impairments have been reported most, although direct association between memory and naming performance and disease-related atrophy has not yet been demonstrated in vivo for a larger sample of patients. In the present work, a voxel-based morphometry (VBM) analysis was conducted on 3T magnetic resonance imaging (MRI) of 13 HSE survivors. The gray matter density values were correlated with scores indicating verbal memory decline, as well as errors/omissions in picture naming; both were obtained through neuropsychological assessment. Analysis of individual lesion patterns revealed a considerable inter-individual variability, mainly with atrophy in the basal forebrain, adjacent frontal cortex, medial and lateral temporal cortex, insula and thalamus. The neuropsychological data analysis revealed correlation between verbal memory decline and atrophy especially in the left hippocampal region, whereas naming problems were associated with gray matter loss especially in the lateral temporal lobe, the thalamus and the left insula. These results confirm, for the first time, the assumptions of earlier studies about the considerable variability of individual lesion patterns in HSE in a whole-brain approach in vivo, and thus the anatomical validity of VBM.

Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers

The main objective of this study is to detect the early changes in resting-state Papez circuit functional connectivity using the hippocampus as the seed, and to determine the associations between altered functional connectivity (FC) and the episodic memory performance in cognitively intact middle-aged apolipoprotein E4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26 age-, sex-, and education-matched noncarriers were studied. The resting-state FC of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers. APOE4 carriers showed significantly decreased FC in brain areas that involve learning and memory functions, including the frontal, cingulate, thalamus and basal ganglia regions. Multiple linear regression analysis showed significant correlations between HFC and the episodic memory performance. Conjunction analysis between neural correlates of memory and altered HFC showed the overlapping regions, especially the subcortical regions such as thalamus, caudate nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in connectivity in the Papez circuit may be used as an early risk detection for AD.

P.1.030 Three week bright-light intervention has dose-related effects on threat-related corticolimbic reactivity and functional coupling

The main objective of this study is to detect the early changes in resting-state Papez circuit functional connectivity using the hippocampus as the seed, and to determine the associations between altered functional connectivity (FC) and the episodic memory performance in cognitively intact middle-aged apolipoprotein E4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26 age-, sex-, and education-matched noncarriers were studied. The resting-state FC of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers. APOE4 carriers showed significantly decreased FC in brain areas that involve learning and memory functions, including the frontal, cingulate, thalamus and basal ganglia regions. Multiple linear regression analysis showed significant correlations between HFC and the episodic memory performance. Conjunction analysis between neural correlates of memory and altered HFC showed the overlapping regions, especially the subcortical regions such as thalamus, caudate nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in connectivity in the Papez circuit may be used as an early risk detection for AD.

Remembering forward: Neural correlates of memory and prediction in human motor adaptation

We used functional MR imaging (FMRI), a robotic manipulandum and systems identification techniques to examine neural correlates of predictive compensation for spring-like loads during goal-directed wrist movements in neurologically-intact humans. Although load changed unpredictably from one trial to the next, subjects nevertheless used sensorimotor memories from recent movements to predict and compensate upcoming loads. Prediction enabled subjects to adapt performance so that the task was accomplished with minimum effort. Population analyses of functional images revealed a distributed, bilateral network of cortical and subcortical activity supporting predictive load compensation during visual target capture. Cortical regions--including prefrontal, parietal and hippocampal cortices--exhibited trial-by-trial fluctuations in BOLD signal consistent with the storage and recall of sensorimotor memories or "states" important for spatial working memory. Bilateral activations in associative regions of the striatum demonstrated temporal correlation with the magnitude of kinematic performance error (a signal that could drive reward-optimizing reinforcement learning and the prospective scaling of previously learned motor programs). BOLD signal correlations with load prediction were observed in the cerebellar cortex and red nuclei (consistent with the idea that these structures generate adaptive fusimotor signals facilitating cancelation of expected proprioceptive feedback, as required for conditional feedback adjustments to ongoing motor commands and feedback error learning). Analysis of single subject images revealed that predictive activity was at least as likely to be observed in more than one of these neural systems as in just one. We conclude therefore that motor adaptation is mediated by predictive compensations supported by multiple, distributed, cortical and subcortical structures.

Neural correlates of memory in depression measured by brain perfusion SPECT at rest

Brain metabolism activated studies have indicated associations between memory and the anterior cingulate cortex and hippocampus in patients with depression. The aim of the present study was therefore to investigate memory function, measured as performance on the Wechsler Memory Scale-Revised (WMS-R), and its relationship to brain perfusion using single-photon emission computed tomography (SPECT) at rest in patients with depression. The Hamilton Rating Scale for Depression (HAMD) and WMS-R were measured for 17 patients with depression by an independent clinical evaluation team. Voxel-based correlation analyses were performed with statistical parametric mapping at an extent threshold of 200 voxels. Associations were controlled for state and trait factors. WMS-R measurements of verbal, visual, and general memory were inversely correlated with brain perfusion in the right anterior cingulate cortex, left premotor cortices, and both regions, respectively. The HAMD directly correlated with brain perfusion in the right anterior cingulate cortex. Brain perfusion SPECT measurements of the anterior cingulate cortex at rest were associated with the severity of depression and immediate memory scores measured with the WMS-R.