ArticleLiterature Review

Cabeza, R. & Nyberg, L. Neural bases of learning and memory: functional neuroimaging evidence. Curr. Opin. Neurol. 13, 415-421

September 2000
Current Opinion in Neurology 13(4):415-21

DOI:10.1097/00019052-200008000-00008

Source
PubMed

Authors:

Roberto Cabeza

Duke University

Lars Nyberg

Umeå University

Positron emission tomography and functional magnetic resonance imaging studies have identified brain regions associated with different forms of memory. Working memory has been associated primarily with the bilateral prefrontal and parietal regions; semantic memory with the left prefrontal and temporal regions; episodic memory encoding with the left prefrontal and medial temporal regions; episodic memory retrieval with the right prefrontal, posterior midline and medial temporal regions; and skill learning with the motor, parietal, and subcortical regions. Recent studies have provided higher specificity, by dissociating the neural correlates of different subcomponents of complex memory tasks, and the cognitive roles of different subregions of larger brain areas.

Working Memory Workload When Making Complex Decisions: A Behavioral and EEG Study

Article

Full-text available

Sep 2024
SENSORS-BASEL

Working memory (WM) is crucial for adequate performance execution in effective decision-making, enabling individuals to identify patterns and link information by focusing on current and past situations. This work explored behavioral and electrophysiological (EEG) WM correlates through a novel decision-making task, based on real-life situations, assessing WM workload related to contextual variables. A total of 24 participants performed three task phases (encoding, retrieval, and metacognition) while their EEG activity (delta, theta, alpha, and beta frequency bands) was continuously recorded. From the three phases, three main behavioral indices were computed: Efficiency in complex Decision-making, Tolerance of Decisional Complexity, and Metacognition of Difficulties. Results showed the central role of alpha and beta bands during encoding and retrieval: decreased alpha/beta activity in temporoparietal areas during encoding might indicate activation of regions related to verbal WM performance and a load-related effect, while decreased alpha activity in the same areas and increased beta activity over posterior areas during retrieval might indicate, respectively, active information processing and focused attention. Evidence from correlational analysis between the three indices and EEG bands are also discussed. Integration of behavioral and metacognitive data gathered through this novel task and their interrelation with EEG correlates during task performance proves useful to assess WM workload during complex managerial decision-making.

Enhancing memory capacity by experimentally slowing theta frequency oscillations using combined EEG-tACS

Article

Full-text available

Aug 2022

The coupling of gamma oscillation (~ 40+ Hz) amplitude to the phase of ongoing theta (~ 6 Hz) oscillations has been proposed to be directly relevant for memory performance. Current theories suggest that memory capacity scales with number of gamma cycles that can be fitted into the preferred phase of a theta cycle. Following this logic, transcranial alternating current stimulation (tACS) may be used to adjust theta cycles (increasing/decreasing theta frequency) to decrease or increase memory performance during stimulation. Here, we used individualized EEG-informed theta tACS to (1) experimentally “slow down” individual theta frequency (ITF), (2) evaluate cognitive after effects on a battery of memory and learning tasks, and (3) link the cognitive performance changes to tACS-induced effects on theta-band oscillations as measured by post EEG. We found frequency- and task-specific tACS after effects demonstrating a specific enhancement in memory capacity. This tACS-induced cognitive enhancement was specific to the visual memory task performed immediately after tACS offset, and specific to the ITF-1 Hz (slowing) stimulation condition and thus following a protocol specifically designed to slow down theta frequency to enhance memory capacity. Follow-up correlation analyses in this group linked the enhanced memory performance to increased left frontal-parietal theta-band connectivity. Interestingly, resting-state theta power immediately after tACS offset revealed a theta power increase not for the ITF-1 Hz group, but only for the ITF group where the tACS frequency was ‘optimal’ for entrainment. These results suggest that while individually calibrated tACS at peak frequency maximally modulates resting-state oscillatory power, tACS stimulation slightly below this optimal peak theta frequency is better suited to enhance memory capacity performance. Importantly, our results further suggest that such cognitive enhancement effects can last beyond the period of stimulation and are linked to increased network connectivity, opening the door towards more clinical and applied relevance of using tACS in cognitive rehabilitation and/or neurocognitive enhancement.

Limited carry-over effects of socioemotional manipulations on subsequent unrelated memory tasks

Article

Full-text available

Oct 2024
PLOS ONE

Although age is typically associated with significant impairments in memory performance, several domains exist in which these impairments are reduced or even eliminated. These “pockets of preservation” in older adults’ memory can be seen in tasks involving socioemotional processing and may be supported by distinct encoding or retrieval modes relative to neutral content. The current study examines whether engaging in socioemotional tasks prior to encoding or retrieval allows older adults to enter an encoding or retrieval mode that better supports memory performance. In two online studies, adults across the lifespan were asked to complete a memory task where they incidentally encoded and retrieved neutral (Experiment 1, N = 1621) or emotional (Experiment 2, N = 409) word-image pairs. Participants were randomly assigned to a control (i.e., no manipulation), pre-encoding, or pre-retrieval socioemotional manipulation condition. There were no main effects of manipulation condition, suggesting that such manipulations may not reliably enhance memory. However, future research is needed to follow up on exploratory analyses that highlighted particular conditions under which these manipulations may convey benefits. There were also no age-by-manipulation interactions. While these null effects may suggest that these manipulations are not better suited to older adults, this may also be a result of the unexpected age-related increases (Experiment 1) and age invariance (Experiment 2) in overall memory accuracy in the current study. Socioemotional manipulations should also be examined in older adults who underperform younger adults.

The mesolimbic system and the loss of higher order network features in schizophrenia when learning without reward

Article

Full-text available

Sep 2024

Introduction Schizophrenia is characterized by a loss of network features between cognition and reward sub-circuits (notably involving the mesolimbic system), and this loss may explain deficits in learning and cognition. Learning in schizophrenia has typically been studied with tasks that include reward related contingencies, but recent theoretical models have argued that a loss of network features should be seen even when learning without reward. We tested this model using a learning paradigm that required participants to learn without reward or feedback. We used a novel method for capturing higher order network features, to demonstrate that the mesolimbic system is heavily implicated in the loss of network features in schizophrenia, even when learning without reward. Methods fMRI data (Siemens Verio 3T) were acquired in a group of schizophrenia patients and controls (n=78; 46 SCZ, 18 ≤ Age ≤ 50) while participants engaged in associative learning without reward-related contingencies. The task was divided into task-active conditions for encoding (of associations) and cued-retrieval (where the cue was to be used to retrieve the associated memoranda). No feedback was provided during retrieval. From the fMRI time series data, network features were defined as follows: First, for each condition of the task, we estimated 2nd order undirected functional connectivity for each participant (uFC, based on zero lag correlations between all pairs of regions). These conventional 2nd order features represent the task/condition evoked synchronization of activity between pairs of brain regions. Next, in each of the patient and control groups, the statistical relationship between all possible pairs of 2nd order features were computed. These higher order features represent the consistency between all possible pairs of 2nd order features in that group and embed within them the contributions of individual regions to such group structure. Results From the identified inter-group differences (SCZ ≠ HC) in higher order features, we quantified the respective contributions of individual brain regions. Two principal effects emerged: 1) SCZ were characterized by a massive loss of higher order features during multiple task conditions (encoding and retrieval of associations). 2) Nodes in the mesolimbic system were over-represented in the loss of higher order features in SCZ, and notably so during retrieval. Discussion Our analytical goals were linked to a recent circuit-based integrative model which argued that synergy between learning and reward circuits is lost in schizophrenia. The model’s notable prediction was that such a loss would be observed even when patients learned without reward. Our results provide substantial support for these predictions where we observed a loss of network features between the brain’s sub-circuits for a) learning (including the hippocampus and prefrontal cortex) and b) reward processing (specifically constituents of the mesolimbic system that included the ventral tegmental area and the nucleus accumbens. Our findings motivate a renewed appraisal of the relationship between reward and cognition in schizophrenia and we discuss their relevance for putative behavioral interventions.

Exploring the correlation between childhood trauma experiences, inflammation, and brain activity in first-episode, drug-naive major depressive disorder

Article

Full-text available

Jul 2024
EUR ARCH PSY CLIN N

Background Childhood trauma experiences and inflammation are pivotal factors in the onset and perpetuation of major depressive disorder (MDD). However, research on brain mechanisms linking childhood trauma experiences and inflammation to depression remains insufficient and inconclusive. Methods Resting-state fMRI scans were performed on fifty-six first-episode, drug-naive MDD patients and sixty healthy controls (HCs). A whole-brain functional network was constructed by thresholding 246 brain regions, and connectivity and network properties were calculated. Plasma interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assays in MDD patients, and childhood trauma experiences were evaluated through the Childhood Trauma Questionnaire (CTQ). Results Negative correlations were observed between CTQ total (r = -0.28, p = 0.047), emotional neglect (r = -0.286, p = 0.042) scores, as well as plasma IL-6 levels (r = -0.294, p = 0.036), with mean decreased functional connectivity (FC) in MDD patients. Additionally, physical abuse exhibited a positive correlation with the nodal clustering coefficient of the left thalamus in patients (r = 0.306, p = 0.029). Exploratory analysis indicated negative correlations between CTQ total and emotional neglect scores and mean decreased FC in MDD patients with lower plasma IL-6 levels (n = 28), while these correlations were nonsignificant in MDD patients with higher plasma IL-6 levels (n = 28). Conclusions This finding enhances our understanding of the correlation between childhood trauma experiences, inflammation, and brain activity in MDD, suggesting potential variations in their underlying pathophysiological mechanisms.

‘Nip it in the bud’: Low-frequency rTMS of the prefrontal cortex disrupts threat memory consolidation in humans

Article

Full-text available

Apr 2024
BEHAV RES THER

It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories.

Does attachment in adolescence predict neural responses to handholding in adulthood? A functional magnetic resonance imaging study

Article

Mar 2024
J SOC PERS RELAT

Objective: Early life experiences, including attachment-related experiences, inform internal working models that guide adult relationship behaviors. Few studies have examined the association between adolescent attachment and adult relationship behavior on a neural level. The current study examined attachment in adolescence and its associations with neural correlates of relationship behaviors in adulthood. Method: 85 participants completed the Adult Attachment Interview (AAI) at age 14. Ten years later, at age 24, participants underwent functional brain image when participants were under the threat of electric shock alone, holding the hand of a stranger, or their partner. Results: We found that adolescents who were securely attached at age 14 showed increased activation in regions commonly associated with cognitive, affective, and reward processing when they held the hand of their partner and stranger compared to being alone. Adolescents with higher preoccupied attachment scores showed decreased activation in similar regions only during the stranger handholding condition compared to being alone. Conclusions: These findings suggest that adolescent attachment predicts adult social relationship behaviors on a neural level, in regions largely consistent with previous literature. Broadly, this study has implications for understanding long-term links between attachment and adult relationship behaviors and has potential for informing intervention.

Working Memory Training in Norwegian Children with Cerebral Palsy (CP) Show Minimal Evidence of Near and No Far Transfer Effects

Article

Sep 2023

In children with cerebral palsy (CP), learning disabilities are well documented, and impairments in executive functions, such as attention, inhibition, shifting and working memory, represent significant burdens on patients, their families and the society. The aim of this study was to evaluate whether Cogmed RM working memory training could improve working memory in children with CP and investigate whether increased working memory capacity would generalize to other cognitive functions. Twenty-eight children completed the training and the results were compared to a waitlist control group (n = 32). The results yielded three main findings. First, children with CP improved with practice on trained working memory tasks. Second, the intervention group showed minimal near transfer effects to non-trained working memory tasks. Third, no effects on cognitive and behavioral far transfer measures were found.

IL-6 Enhances the Negative Impact of Cortisol on Cognition among Community-Dwelling Older People without Dementia

Article

Full-text available

Mar 2023

There is growing evidence that high basal cortisol levels and systemic inflammation independently contribute to cognitive decline among older people without dementia. The present cross-sectional study examined (a) the potential synergistic effect of cortisol levels and systemic inflammation on executive function and (b) whether this effect is more prominent among older people with mild cognitive impairment (MCI). A sub-sample of 99 patients with MCI and 84 older people without cognitive impairment (CNI) (aged 73.8 ± 7.0 years) were recruited from a large population-based cohort in Crete, Greece, and underwent comprehensive neuropsychiatric and neuropsychological evaluation and a single morning measurement of cortisol and IL-6 plasma levels. Using moderated regression models, we found that the relation between cortisol and executive function in the total sample was moderated by IL-6 levels (b = −0.994, p = 0.044) and diagnostic group separately (b = −0.632, p < 0.001). Moreover, the interaction between cortisol and IL-6 levels was significant only among persons with MCI (b = −0.562, p < 0.001). The synergistic effect of stress hormones and systemic inflammation on cognitive status appears to be stronger among older people who already display signs of cognitive decline. Targeting hypercortisolemia and inflammation may be a promising strategy toward improving the course of cognitive decline.

Home-based transcranial direct current stimulation in mild neurocognitive disorder due to possible Alzheimer’s disease. A randomised, single-blind, controlled-placebo study

Article

Full-text available

Jan 2023

Introduction Mild neurocognitive disorder (mNCD), a pre-dementia stage close to Mild Cognitive Impairment, shows a progressive and constant decline in the memory domain. Of the non-pharmacological therapeutic interventions that may help to decelerate the neurodegenerative progress, transcranial direct current stimulation (tDCS) shows beneficial effects on the learning curve, immediate recall, immediate verbal memory and executive functions. The purpose of this research was to study the effect of tDCS on general cognition, immediate and delayed memory and executive functions by comparing an active group with a placebo group of mNCD patients. Methods Participants were 33 mNCD due to possible AD, randomly assigned to two groups: 17 active tDCS and 16 placebo tDCS. Ten sessions of tDCS were conducted over the left dorsolateral prefrontal cortex. Several neuropsychological scales were administered to assess the primary outcome measures of general cognitive function, immediate and delayed memory and learning ability, whereas the secondary outcome measures included executive function tests. All participants were evaluated at baseline and at the end of the intervention. Mixed ANOVAs were performed. Results Significant effects were obtained on general cognitive function, immediate and delayed memory and learning ability, with increases in scores in the active tDCS group. However, there were no significant effects on executive function performance. Conclusion The present study demonstrated the effectiveness of tDCS in an active tDCS group, compared to a placebo group, in improving general cognition and immediate and delayed memory, as previous studies found. Taken together, our data suggest that tDCS is a simple, painless, reproducible and easy technique that is useful for treating cognitive alterations found in neurodegenerative diseases.

Working memory-related alterations in neural oscillations reveal the influence of in-vehicle toluene on cognition at low concentration

Article

Full-text available

Oct 2022
ENVIRON SCI POLLUT R

Although toluene is a typical in-vehicle pollutant, the impacts of in-vehicle toluene exposure on cognitive functions remain unestablished. Therefore, this study aimed to investigate the effects of short-term toluene exposure in vehicles on working memory based on neural oscillations. In total, 24 healthy adults were recruited. Each subject was exposed to four different concentrations of toluene and divided into 0 ppb, 17.5 ppb, 35 ppb, and 70 ppb groups for self-control studies. After 4 h of exposure to each concentration of toluene, a behavioral test of visual working memory was performed while 19-channel electroencephalogram (EEG) signals were collected. Meanwhile, the power spectral density (PSD) and spatial distribution of working memory encoding, maintenance, and extraction periods were calculated by short-time Fourier transform to clarify the characteristic frequency bands, major brain regions, and characteristic channels of each period. To compare the changes in the characteristic patterns of neural oscillations under the effect of different concentrations of toluene. There was no significant difference in working memory reaction time and correct rate between the groups at different toluene concentrations (p > 0.05). The characteristic frequency band of the working memory neural oscillations in each group was the theta frequency band; the PSD of the theta frequency band was predominantly concentrated in the frontal area, and the characteristic channel was the Fz channel. The whole brain (F = 3.817, p < 0.05; F = 4.758, p < 0.01; F = 3.694, p < 0.05), the frontal area (F = 2.505, p < 0.05; F = 2.839, p < 0.05; F = 6.068, p < 0.05), the Fz channel (F = 3.522, p < 0.05; F = 3.745, p < 0.05; F = 6.526, p < 0.05), and the PSD of working memory in the theta frequency band was significantly increased in the 70 ppb group compared with the other three groups during the coding, maintenance, and retrieval phases of working memory. When the in-vehicle toluene exposure concentration was 70 ppb, the PSD of the characteristic frequency bands of working memory was significantly increased in the whole brain, major brain regions, and characteristic channels.

The role of the serum response factor in the pathogenesis of Huntington's disease

Thesis

Mar 2021

Ali Awada

Huntington's Huntington's disease (HD) is a progressive neurodegenerative disease. It is caused by an abnormal expansion of CAG repeats in the gene coding for the Huntingtin protein (HTT). Neurons in the striatum are affected by the toxicity of the mutation. HD is characterized by motor, cognitive and psychiatric symptoms. Studies in the lab have shown that the genes that define striatal identity and the genes involved in the mechanisms of neuronal plasticity are down-regulated in patients and mouse models of HD. The mechanism of transcriptional deregulation could involve the transcription factor Serum Response Factor (SRF), promoting synaptic plasticity and memory processes. The objective of my thesis work was to characterize the regulation of SRF in the context of HD and to evaluate its role in pathogenesis. Indeed, the analysis of SRF at the transcriptional and/or protein level shows that it is down-regulated at an early stage in the striatum of mouse models of HD. To establish a possible causal link between SRF down-regulation in the striatum and Huntington's phenotypes, we used an AAV-based viral approach to over-express SRF in the striatum of R6/1 transgenic mouse, a model of HD. Using different behavioral tests, we showed that overexpression of the full length of SRF in the striatum of transgenic mice leads to an aggravation of motor symptoms. Moreover, histological and molecular analyses (q-RT-PCR, RNAseq and Western-blot) showed no rescue of SRF targets in the striatum of R6/1 mice, despite its high overexpression. Our results suggest that the striatal regulation of SRF and its target genes is altered by mutated HTT. We then overexpressed a construct consisting of the fusion of the SRF binding domain with the VP16 transactivation domain (SRF-VP16) in the striatum of R6/1 mice. Our data indicate that although neuronal plasticity genes are up-regulated by this construct, the behavioral phenotype of R6/1 mice is not improved, probably due to the absence of a major effect of SRF-VP16 on the striatal identity genes. This could suggest that restoring the level of SRF in the HD is not sufficient to significantly rescue HD pathogenesis.

Determinants of quality, specificity, and stability of emotional episodic memories in a fine-dining context

Article

Full-text available

Mar 2022

For theoretical and practical reasons, it is of great interest to understand how accurate and persistent episodic memories of enjoyable experiences are formed and maintained, for example, in the context of gastronomy and other instances of experience design. Here, we investigated factors that might affect the quality (a measure of coherence) of immediate and long-term emotional episodic memories of individual dishes of a long and complex dinner in a fine-dining restaurant. We also assessed long-term recognition memory for pictures of the dishes. Intra-class correlations revealed good immediate emotional episodic memory, which remained stable over three months. Contributing factors to these kinds of memory were assessed with path modelling. The quality of emotional episodic memory was enhanced by the hedonic intensity of the most valued dishes during the meal and was impaired with the hedonic intensity of the least valued dishes. Enjoying the final dish positively affects emotional memory after the experience. Interestingly, when diners reported to have been distracted from the meal, presumably by communicating with their meal companions about the food, it had a positive effect on the long-term emotional episodic memory. Personality traits of the diners had no substantial impact on either type of memory. Alcohol intake during the meal modestly affected recognition memory but – interestingly – had no statistically significant effect on emotional episodic memory. Altogether, this study provides novel information about the main determinants of the precision and temporal stability of emotional episodic memory and nonemotional recognition memory for a meal. These findings contribute to the psychological foundations of designing memorable experiences in gastronomy and other areas. Implications for gastronomy Knowing what factors may determine whether a gastronomic experience would be memorable to diners is the holy grail of any chef. The design of a gastronomic experience should provide intense emotional moments to the diners aiming to increase the quality of emotional memory of those moments. Different factors contribute to this stability, for instance, how the diner interacts with the food and the food itself. In this regard, serving in a dining course very tasty and less delicious dishes thereafter can enhance the memorability of the former, but not so much of the latter, as it may be disturbing for the diner. Critically, enjoying the final dish positively affects emotional memory after the experience. In addition, most gastronomic events are shared with companions. Far from being a distracting element, social relationships in a table seem to increase the memorability of the experience, as communication deeply elaborates and reinforces memory traces. In the reinforcement of emotional memories for foods, alcohol has a negligible effect. Although our findings have been obtained in a fine-dining context, the implications of our current findings might be generalizable to other, more standard contexts. The critical point is to focus on having positive specific episodes rather than having a positive global valuation. All these outcomes would converge to increase the probability of repeating the gastronomic experience, regardless of whether it is a high-level restaurant or a standard one.

The association of basal cortisol levels with episodic memory in older adults is mediated by executive function

Article

Feb 2022
NEUROBIOL LEARN MEM

Elevated basal cortisol levels in elderly may indicate dysregulation of the internal stress-related system, as well as dysfunction and structural alterations in brain structures necessary for cognition, such as hippocampus and prefrontal cortex. Because of the close relation of executive functions and episodic memory processing, in this study we explored whether the association of elevated cortisol levels on episodic memory could be partly attributed to cortisol effects on executive functions. In this cross-sectional study we analyzed data from a sample of 236 community-dwelling older adults from the Cretan Aging Cohort aged 75.56 ± 7.21 years [53 with dementia due to probable Alzheimer’s disease, 99 with Mild Cognitive Impairment (MCI) and 84 cognitively non-impaired participants (NI)]. Morning serum cortisol levels were higher in the probable AD as compared to the NI group (p = .031). Mediated regression models in the total sample supported the hypothesis that the negative association of basal cortisol levels with delayed memory was fully mediated by the relation of basal cortisol levels with executive functions and immediate memory (adjusted for age and self-reported depression symptoms). Moderated mediation regression models revealed that the direct effect of cortisol on executive function and the effect of executive function on delayed memory performance were statistically significant among participants diagnosed with MCI, while the immediate memory effect on delayed memory was more pronounced in AD patients, as compared to the NI group. The current findings corroborate neuroimaging research highlighting cortisol effects on executive functions and immediate memory and further suggest that dysregulation of systems involved in these functions may account for the purported detrimental long-term effects of high cortisol levels on delayed memory.

Differential associations of regional cerebellar volume with gait speed and working memory

Article

Full-text available

Feb 2022

The relationship between gait speed and working memory is well-understood in older adults. However, it remains to be determined whether this relationship also exists in younger adults; and there is little known regarding the possible neural mechanism underlying the association between gait speed and working memory. The aims of this study are to determine if there is: (1) an association between gait speed and working memory performance; and (2) a mediating role of cerebellar subregion volume in the correlation between gait speed and working memory in healthy younger adults. 1054 younger adults (28.7 ± 3.6 years) from the Human Connectome Project were included in the analyses. A four-meter gait test was used to assess gait speed. The 2-back task was used to measure working memory performance [accuracy and response time (RT)]. T1-weighted structural MRI data (obtained using Siemens 3 T MRI scanner) was used to assess cerebellar subregion volumes. Linear regression and mediation analysis were used to examine the relationships between the variables after controlling for age, sex, and education. There was no association between gait speed and 2-back working memory performance in younger adults. Greater Crus I and whole cerebellar volumes were associated with better 2-back working memory accuracy. Greater VIIIa volume was associated with faster gait speed. Greater Crus 1 and VIIIa volumes were also associated with higher fluid cognition. The present study suggests that specific subregions of the cerebellar volumes are distinctively associated with gait speed and working memory performance in healthy younger adults.

Hippocampal Asymmetry of Regional Development and Structural Covariance in Preterm Neonates

Article

Dec 2021
CEREB CORTEX

Premature birth is associated with a high prevalence of neurodevelopmental impairments in surviving infants. The hippocampus is known to be critical for learning and memory, yet the putative effects of hippocampal dysfunction remain poorly understood in preterm neonates. In particular, while asymmetry of the hippocampus has been well noted both structurally and functionally, how preterm birth impairs hippocampal development and to what extent the hippocampus is asymmetrically impaired by preterm birth have not been well delineated. In this study, we compared volumetric growth and shape development in the hippocampal hemispheres and structural covariance (SC) between hippocampal vertices and cortical thickness in cerebral cortex regions between two groups. We found that premature infants had smaller volumes of the right hippocampi only. Lower thickness was observed in the hippocampal head in both hemispheres for preterm neonates compared with full-term peers, though preterm neonates exhibited an accelerated age-related change of hippocampal thickness in the left hippocampi. The SC between the left hippocampi and the limbic lobe of the premature infants was severely impaired compared with the term-born neonates. These findings suggested that the development of the hippocampus during the third trimester may be altered following early extrauterine exposure with a high degree of asymmetry.

Resting state network activation and functional connectivity in the dying brain

Article

Dec 2021
CLIN NEUROPHYSIOL

Objective To characterize electrophysiological functional connectivity within both the default mode network (DMN) and the task-positive network (TPN) among a small group of unresponsive hospice patients at the end of life. Methods EEG recordings from resting state were analysed to identify brain regions in the DMN and TPN of 30 young, healthy controls, and of 9 hospice patients when they were responsive and of 5 patients when they became unresponsive during the last hours of life. Results The prevalence of activation and connectivity within the DMN was similar across all participant groups. Overall functional connectivity was higher between brain regions within the DMN than between brain regions within TPN for all participant groups. The number of functional connections within the DMN, however, was greater than those within the TPN among controls and responsive hospice patients but not among unresponsive hospice patients. Conclusions Some unresponsive patients may have the functional architecture to support internally-oriented thought at the end of life. Resting state default mode - task positive network anticorrelations may be present among some unresponsive hospice patients. Significance Some unresponsive end of life patients may be able to mind-wander. Implications for internally-oriented awareness at the end of life are discussed.

Animal models of developmental dyslexia: Where we are and what we are missing

Article

Oct 2021
NEUROSCI BIOBEHAV R

Developmental dyslexia (DD) is a complex neurodevelopmental disorder and the most common learning disability among both school-aged children and across languages. Recently, sensory and cognitive mechanisms have been reported to be potential endophenotypes (EPs) for DD, and nine DD-candidate genes have been identified. Animal models have been used to investigate the etiopathological pathways that underlie the development of complex traits, as they enable the effects of genetic and/or environmental manipulations to be evaluated. Animal research designs have also been linked to cutting-edge clinical research questions by capitalizing on the use of EPs. For the present scoping review, we reviewed previous studies of murine models investigating the effects of DD-candidate genes. Moreover, we highlighted the use of animal models as an innovative way to unravel new insights behind the pathophysiology of reading (dis)ability and to assess cutting-edge preclinical models.

Transcranial Magnetic Stimulation Trains at 1 Hz Frequency of the Right Posterior Parietal Cortex Facilitate Recognition Memory

Article

Full-text available

Oct 2021
FRONT HUM NEUROSCI

Neuroimaging, neuropsychological, and brain stimulation studies have led to contrasting findings regarding the potential roles of the lateral parietal lobe in episodic memory. Studies using brain stimulation methods reported in the literature do not offer unequivocal findings on the interactions with stimulation location (left vs. right hemisphere) or timing of the stimulation (encoding vs. retrieval). To address these issues, active and sham 1 Hz repetitive transcranial magnetic stimulation (rTMS) trains of 600 stimuli were applied over the right or left posterior parietal cortex (PPC) before the encoding or before the retrieval phase of a recognition memory task of unknown faces in a group of 40 healthy subjects. Active rTMS over the right but not the left PPC significantly improved non-verbal recognition memory performance without any significant modulation of speed of response when applied before the retrieval phase. In contrast, rTMS over the right or the left PPC before the encoding phase did not modulate memory performance. Our results support the hypothesis that the PPC plays a role in episodic memory retrieval that appears to be dependent on both the hemispheric lateralization and the timing of the stimulation (encoding vs. retrieval).

The Effects of Concussive and Sub-concussive Head Impacts on Brain Activity.

Thesis

Jan 2016

Richelle M. Williams

Context: 7 million athletes participate in high school sports annually. Approximately 1 million of these athletes participate in football, which is associated with repetitive head impacts. Concussion literature suggests sub-concussive impacts may lead to declines in brain function across a season of football. Furthermore, recent research suggests following clinical concussion recovery, metabolic and neurophysiological recovery may not be complete. Objective: The purpose of this study was to monitor head impacts and cognitive function during (72hour, asymptomatic) and after concussion and longer term over a full football season (pre-season, mid-season, post-season). Participants: 106 male adolescent (46 football-athletes, 42 controls for football-athletes, 9 concussed-athletes, 9 controls for concussed-athletes). Outcome measures: The Head Impact Telemetry System encoder was used to track the location and magnitude of head impacts during football participation. Psychophysiology was measured using Electroencephalography and was quantified using a 256 channel system to record brain activity during an auditory oddball task. All Participants completed Axon neurocognitive testing, clinical reaction time task (CRT), symptom inventory and two Health Related Quality of Life Surveys (Health Behavior Inventory, Satisfaction with Life) throughout the above testing time-points. Results: Football-athletes sustained a mean of 482 head impacts during all practices and games. Mixed measures ANOVA indicated a significant decrement on one BNA output score, Target amplitude, with lower post-season scores (p<0.05). No other BNA output scores, Axon, CRT, SWL, or HBI measurements showed significant deficits post-season (p>0.05). Furthermore, P3a amplitudes were significantly larger and N2 latency was longer during post-season testing. Mixed measured ANOVAs indicated no significant deficits in BNA output scores, Axon performance, CRT, and HRQOL, for concussed and matched controls across post-injury time points. Additionally, there was a significantly longer P3a latency post-season latencies across groups and smaller P3a amplitudes at post-season for concussed compared to controls (p<0.05). Conclusion: Overall, these findings suggest electrophysiology changes between pre and post-season testing among football athletes and control participants without concussion, with the majority demonstrating improved cognitive function. Therefore, no negative effects may be associated with repeated head impacts in one season of football. Furthermore, no cognitive deficits were present during asymptomatic testing following concussion.

The Neural Correlates of Computational Thinking: Collaboration of Distinct Cognitive Components Revealed by fMRI

Article

Jul 2021

Recent technical advance attracts great attention to the promotion of programming skills, in particular, and computational thinking (CT), in general, as a new intellectual competency. However, the understanding of its cognitive substrates is limited. The present study used functional magnetic resonance imaging to examine the neural correlates of programming to understand the cognitive substrates of CT. Specifically, magnetic resonance imaging signals were collected while the participants were mentally solving programming problems, and we found that CT recruited distributed cortical regions, including the posterior parietal cortex, the medial frontal cortex, and the left lateral frontal cortex. These regions showed extensive univariate and multivariate resemblance with arithmetic, reasoning, and spatial cognition tasks. Based on the resemblance, clustering analyses revealed that cortical regions involved in CT can be divided into Reasoning, Calculation, Visuospatial, and Shared components. Further, connectivity increased during programming within the CT network constructed by these four components and decreased between the CT network and other cortical regions. In sum, our study revealed the cognitive components underlying CT and their neural correlates and further suggests that CT is not a simple sum of parallel cognitive processes, but a composite cognitive process integrating a set of intellectual abilities, particularly those in the science, technology, engineering, and math domains.

Memories are not written in stone: Re-writing fear memories by means of non-invasive brain stimulation and optogenetic manipulations

Article

Apr 2021

The acquisition of fear associative memory requires brain processes of coordinated neural activity within the amygdala, prefrontal cortex (PFC), hippocampus, thalamus and brainstem. After fear consolidation, a suppression of fear memory in the absence of danger is crucial to permit adaptive coping behavior. Acquisition and maintenance of fear extinction critically depend on amygdala-PFC projections. The robust correspondence between the brain networks encompassed cortical and subcortical hubs involved into fear processing in humans and in other species underscores the potential utility of comparing the modulation of brain circuitry in humans and animals, as a crucial step to inform the comprehension of fear mechanisms and the development of treatments for fear-related disorders. The present review is aimed at providing a comprehensive description of the literature on recent clinical and experimental researches regarding the noninvasive brain stimulation and optogenetics. These innovative manipulations applied over specific hubs of fear matrix during fear acquisition, consolidation, reconsolidation and extinction allow an accurate characterization of specific brain circuits and their peculiar interaction within the specific fear processing.

Rôle de l’amygdale dans les symptômes émotionnels de la Maladie de Huntington : étude d’un modèle de rat transgénique, BACHD

Thesis

Jan 2016

Charlotte Lamirault

La Maladie de Huntington (MH) est une pathologie génétique neurodégénérative, causée par un nombre anormalement élevé de répétitions du codon CAG dans le gène codant pour la protéine huntingtine (htt). A un stade pré-symptomatique (avant les symptômes moteurs), des troubles émotionnels sont souvent observés chez les patients MH, tels une agitation, une anxiété, une irritabilité ainsi qu’une tendance à la dépression, une apathie et une perte du contrôle émotionnel. Dans le but d’étudier la physiopathologie sous-jacentes aux (dys)fonctions émotionnelles de la MH, nous analysons le rôle de l’amygdale (en particulier le noyau central (CeA)). Cette structure est connue pour être impliquée dans la régulation du processus émotionnel et avoir un volume réduit ainsi qu’un grand nombre d’agrégats chez les patients et chez des modèles animaux transgéniques.Afin d’étudier les symptômes émotionnels de la MH, nous avons utilisé un modèle de rats transgéniques récent, les BACHD. Nos résultats montrent que ces animaux sont hyper-anxieux et hyper-réactifs face aux situations menaçantes à un stade précoce de la maladie. Ces rats BACHD présentent également un nombre élevé d’agrégats de grande taille augmentant en fonction de l’âge spécifiquement dans le CeA par rapport au noyau basolateral (BLA). De plus, la modulation pharmacologique du CeA entraine un effet comportemental différentiel chez les rats BACHD par rapport aux rats normaux, attestant d’un défaut fonctionnel de cette structure à un stade précoce de la maladie. Finalement, l’hyper-activité cellulaire observée dans le CeA (partie médiane) des rats BACHD pourrait expliquer l’hyper-réactivité émotionnelle de ces animaux et participer aux troubles émotionnels de la MH.

Methylphenidate for attention problems in epilepsy patients: Safety and efficacy

Article

Feb 2021

Children with attention deficit hyperactivity disorder (ADHD) have an increased risk of seizures, and children with epilepsy have an increased prevalence of ADHD. Adults with epilepsy often have varying degrees of attentional dysfunction due to multiple factors, including anti-seizure medications, frequent seizures, interictal discharges, underlying lesions, and psychiatric comorbidities. Currently, there are no approved medications for the treatment of epilepsy-related attentional dysfunction. Methylphenidate (MPH) is a stimulant, FDA-approved for the treatment of ADHD, and often used for ADHD in the setting of pediatric epilepsy. Large database and registry studies indicate safety of MPH in children with ADHD and epilepsy, with no significant effect on seizure frequency. Small single-dose and open-label studies suggest efficacy of MPH in adults with epilepsy-related attention deficits. Methylphenidate represents a possible treatment for attentional dysfunction due to epilepsy, but large, randomized, placebo-controlled, double-blinded studies are needed.

Hippocampal Asymmetry of Regional Development and Structural Covariance in Preterm Neonates

Preprint

Nov 2020

Premature birth is associated with high prevalence of neurodevelopmental impairments in surviving infants. The hippocampus is known to be critical for learning and memory, the putative role of hippocampus dysfunction remains poorly understood in preterm neonates. Particularly, hemispherical asymmetry of the hippocampus has been well-noted, either structurally or functionally. How the preterm birth impairs the hippocampal development, and to what extent the hippocampus was impaired by preterm birth asymmetrical has not been well studied. In this study, we compared regional and local hippocampal development in term born neonates (n=361) and prematurely born infants at term-born equivalent age on MRI studies (n = 53) using T2 MRI images collected from the Developing Human Connectome Project (dHCP); We compared 1) volumetric growth; 2) shape development in the hippocampal hemispheres using Laplace–Beltrami eigen-projection and boundary deformation between the two groups; and 3) structural covariance between hippocampal vertices and the cortical thickness in cerebral cortex regions. We demonstrated that premature infants have smaller volume for the right hippocampi, while no difference was observed for the left hippocampi. Lower thickness was observed in the hippocampal head in both hemispheres for preterm neonates compared to full-term peers, while an accelerated hippocampal thickness growth rate was found in left hippocampus only. Structural covariance analysis demonstrated that in premature infants, the structural covariance between hippocampi and limbic lobe were severely impaired compared to healthy term neonates only in left hemisphere. These data suggest that the development of the hippocampus during the third trimester may be altered following early extrauterine exposure, with high degree of asymmetry. These findings suggested that the hippocampus shows high degree of vulnerability, particularly asymmetrical vulnerability or plasticity, in preterm neonates at the term-born equivalent age compared to full-term healthy controls.

Functional and neural mechanisms of human fear conditioning: studies in healthy and brain-damaged individuals

Thesis

Full-text available

Mar 2020

Simone Battaglia

Fear conditioning represents the learning process by which a stimulus, after repeated pairing with an aversive event, comes to evoke fear and becomes intrinsically aversive. This learning is essential to organisms throughout the animal kingdom and represents one the most successful laboratory paradigm to reveal the psychological processes that govern the expression of emotional memory and explore its neurobiological underpinnings. Although a large amount of research has been conducted on the behavioural or neural correlates of fear conditioning, some key questions remain unanswered. Accordingly, this thesis aims to respond to some unsolved theoretic and methodological issues, thus furthering our understanding of the neurofunctional basis of human fear conditioning both in healthy and brain-damaged individuals. Specifically, in this thesis, behavioural, psychophysiological, lesion and non-invasive brain stimulation studies were reported. Study 1 examined the influence of normal aging on context-dependent recall of extinction of fear conditioned stimulus. Results showed that older adults were less able to use contextual information to recall extinction memory and modulate the expression of defensive responses to threat in a context-dependent manner, despite their preserved ability to acquire and extinguish a conditioned response. This deficit may be linked to age-related changes in the neural structures underpinning context-dependent behaviour such as hippocampus and prefrontal cortex (PFC). Study 2 aimed to determine the causal role of the ventromedial PFC (vmPFC) in the acquisition of fear conditioning by systematically test the effect of bilateral vmPFC brain-lesion. Results suggest that vmPFC is a crucial brain structure for fear conditioning in humans, impairing the ability to shape defensive anticipatory responses to the fear conditioned stimulus, but nevertheless sparing the ability to learn explicit contingencies regarding the conditioning. Study 3 aimed to interfere with the reconsolidation process of fear memory by the means of non-invasive brain stimulation (i.e. TMS) disrupting PFC neural activity. Results showed that interfering with activity in both left and right PFC prevents the recall of fear, in contrast to control groups. These results suggest that non-invasive stimulation of PFC may attenuate the expression of learned fear, arguing in favour of a critical role of the PFC in the neural network underlying fear memory reconsolidation in humans. Finally, Study 4 aimed to investigate whether the parasympathetic – vagal – modulation of heart rate might reflect the anticipation of fearful, as compared to neutral, events during classical fear conditioning paradigm. Results indicate that fear conditioned stimuli elicit a strong and selective vagal response, supporting bradycardia during the acquisition of aversive conditioning. Evidence reported in this PhD thesis might therefore provide key insights and deeper understanding of critical issues concerning the neurofunctional mechanisms underlying the acquisition, the extinction and the reconsolidation of fear memories in humans.

Altered Brain Activation in Youth following Concussion: Using a Dual-task Paradigm

Article

Oct 2020

A concussion is known as a functional injury affecting brain communication, integration, and processing. There is a need to objectively measure how concussions disrupt brain activation while completing ecologically relevant tasks. The objective of this study was to compare brain activation patterns between concussion and comparison groups (non-concussed youth) during a cognitive-motor single and dual-task paradigm utilizing functional near-infrared spectroscopy (fNIRS) in regions of the frontal-parietal attention network and compared to task performance. Youth with concussion generally exhibited hyperactivation and recruitment of additional brain regions in the dorsal lateral prefrontal (DLPFC), superior (SPC) and inferior parietal cortices (IPC), which are associated with processing, information integration, and response selection. Additionally, hyper- or hypo-activation patterns were associated with slower processing speed on the cognitive task. Our findings corroborate the growing literature suggesting that neural recovery may be delayed compared to the restoration of behavioral performance post-concussion. Concussion, near-infrared spectroscopy, dual-task paradigm, cognitive, motor, brain activation

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals

Article

Full-text available

Sep 2020

Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains in healthy young individuals. Fifty-six subjects were randomly assigned to either increased oxygen supply using hyperbaric oxygen (two atmospheres of 100% oxygen) or to a "sham" treatment (a simulation of increased pressure in a chamber with normal air). While in the chamber, participants went through a battery of tests evaluating the major cognitive domains including information processing speed, episodic memory, working memory, cognitive flexibility, and attention. The results demonstrated that from all evaluated cognitive domains, a statistically significant improvement was found in the episodic memory of the hyper-oxygenized group. The hyper-oxygenized group demonstrated a better learning curve and a higher resilience to interference. To conclude, oxygen delivery is a rate-limiting factor for memory function even in healthy young individuals under normal conditions. Understanding the biological limitations of our cognitive functions is important for future development of interventional tools that can be used in daily clinical practice.

State-Dependent TMS over Prefrontal Cortex Disrupts Fear-Memory Reconsolidation and Prevents the Return of Fear

Article

Jul 2020
CURR BIOL

Erasing maladaptive memories has been a challenge for years. A way to change fear memories is to target theprocess of reconsolidation, during which a retrieved memory transiently returns to a labile state, amenable tomodification [1, 2]. Disruption of human fear-memory reconsolidation has been classically attempted withpharmacological [3] or behavioral (e.g., extinction) [4] treatments that, however, do not clarify the underlyingbrain mechanism. To address this issue, in 84 healthy humans submitted to six experiments, here, we com-bined a differential fear conditioning paradigm with repetitive transcranial magnetic stimulation (rTMS)administered in a state-dependent manner. In a critical condition, we stimulated the dorsolateral prefrontalcortex (dlPFC) 10 min after a reminder cue that reactivated a fear memory acquired 1 day before. At testing,24 h after rTMS, participants exhibited decreased physiological expression of fear, as shown by their skinconductance response. Similar reductions were observed when targeting the left and the right dlPFC. Incontrast, no decrease was observed in participants tested immediately after dlPFC-rTMS or in participantsreceiving either control rTMS (i.e., active control site and sham stimulations) or dlPFC-rTMS without preced-ing fear-memory reactivation, thus showing both the site and time specificity and state dependency of ourrTMS intervention. Expression of fear was indeed reduced only when dlPFC-rTMS was administered withinthe reconsolidation time window. Moreover, dlPFC-rTMS prevented subsequent return of fear after extinc-tion training. These findings highlight the causal role of dlPFC in fear-memory reconsolidation and suggestthat rTMS can be used in humans to prevent the return of fear.

Asymmetric tumor‐related alterations of network‐specific intrinsic functional connectivity in glioma patients

Article

Full-text available

Jul 2020
HUM BRAIN MAPP

Resting‐state functional MRI (rs‐fMRI) allows mapping temporally coherent brain networks, and intra‐ and inter‐network alterations have been described in different diseases. This prospective study investigated hemispheric resting‐state functional connectivity (RSFC) differences in the default‐mode network (DMN) and fronto‐parietal network (FPN) between patients with left‐ and right‐hemispheric gliomas (LH PAT, RH PAT), addressing asymmetry effects the tumor might have on network‐specific intrinsic functional connectivity under consideration of the prognostically relevant isocitrate‐dehydrogenase (IDH) mutation status. Twenty‐seven patients (16 LH PAT, 12 IDH‐wildtype) and 27 healthy controls underwent anatomical and rs‐fMRI as well as neuropsychological assessment. Independent component analyses were performed to identify the DMN and FPN. Hemispheric DMN‐ and FPN‐RSFC were computed, compared across groups, and correlated with cognitive performance. Patient groups did not differ in tumor volume, grade or location. RH PAT showed higher contra‐tumoral DMN‐RSFC than controls and LH PAT. With regard to the FPN, contra‐tumoral RSFC was increased in both patient groups as compared to controls. Higher contra‐tumoral RSFC was associated with worse cognitive performance in patients, which, however, seemed to apply mainly to IDH‐wildtype patients. The benefit of RSFC alterations for cognitive performance varied depending on the affected hemisphere, cognitive demand, and seemed to be altered by IDH‐mutation status.

Decreased interhemispheric resting-state functional connectivity in male adolescents with conduct disorder

Article

Full-text available

Jun 2021
BRAIN IMAGING BEHAV

Conduct disorder (CD) is a common psychiatric disorder defined by a repetitive and persistent pattern of aggressive and antisocial behaviors. Although numerous task-based and resting-state functional magnetic resonance imaging (rsfMRI) studies have emphasized the disrupted functional connectivity in CD, the CD-related alterations in functional interactions between the bilateral cerebral hemispheres are rarely investigated directly. In this study, a voxel-mirrored homotopic connectivity (VMHC) method based on rsfMRI was employed for the first time to examine the abnormalities of interhemispheric functional connectivity in patients with CD. The VMHC was compared between eighteen pure CD patients and eighteen typically developing (TD) healthy controls. In CD patients, reduced homotopic connectivity was observed relative to TDs in the middle occipital gyrus (MOG), pre- and postcentral gyrus, rolandic operculum and paracentral lobe (PCL) which were the components of visual and motor networks. Furthermore, the VMHC of the MOG and PCL was found to be negatively correlated with clinical scores in the CD group. Moreover, the regions with altered VMHC exhibited a relative good and robust ability to discriminate CD patients from TDs. This study provided a novel angle to identify the important role of interhemispheric coordination in the pathophysiology underlying CD and further indicated that the aberrant homotopic connectivity could be a potential clinical neural marker for CD diagnosis.

Aerobic fitness as a moderator of acute aerobic exercise effects on executive function

Article

Apr 2024

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30 min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.

FMRI correlates of autobiographical memory: Comparing silent retrieval with narrated retrieval

Article

Feb 2024
NEUROPSYCHOLOGIA

Good Moments to Stimulate the Brain – A randomized controlled double-blinded study on anodal transcranial direct current stimulation of the ventromedial prefrontal cortex on two different time points in a two-day fear conditioning paradigm

Article

Dec 2023
BEHAV BRAIN RES

Learning without contingencies: A loss of synergy between memory and reward circuits in schizophrenia

Article

Jul 2023

Motivational deficits in schizophrenia may interact with foundational cognitive processes including learning and memory to induce impaired cognitive proficiency. If such a loss of synergy exists, it is likely to be underpinned by a loss of synchrony between the brains learning and reward sub-networks. Moreover, this loss should be observed even during tasks devoid of explicit reward contingencies given that such tasks are better models of real world performance than those with artificial contingencies. Here we applied undirected functional connectivity (uFC) analyses to fMRI data acquired while participants engaged in an associative learning task without contingencies or feedback. uFC was estimated and inter-group differences (between schizophrenia patients and controls, n = 54 total, n = 28 patients) were assessed within and between reward (VTA and NAcc) and learning/memory (Basal Ganglia, DPFC, Hippocampus, Parahippocampus, Occipital Lobe) sub-networks. The task paradigm itself alternated between Encoding, Consolidation, and Retrieval conditions, and uFC differences were quantified for each of the conditions. Significantly reduced uFC dominated the connectivity profiles of patients across all conditions. More pertinent to our motivations, these reductions were observed within and across classes of sub-networks (reward-related and learning/memory related). We suggest that disrupted functional connectivity between reward and learning sub-networks may drive many of the performance deficits that characterize schizophrenia. Thus, cognitive deficits in schizophrenia may in fact be underpinned by a loss of synergy between reward-sensitivity and cognitive processes.

Mediating Role of Cerebellar Subregion Volume in the Relationship Between Gait Speed and Working Memory

Preprint

Full-text available

Jul 2021

Introduction: The relationship between gait speed and working memory is well-understood in older adults. However, it remains to be determined whether this relationship also exists in younger adults; and there is little known regarding the possible neural mechanism underlying the association between gait speed and working memory. The aims of this study are to determine if there is: 1) an association between gait speed and working memory performance; and 2) a mediating role of cerebellar subregion volume in the correlation between gait speed and working memory in healthy younger adults. Methods: 1054 younger adults (28.7±3.6 years) from the Human Connectome Project were included in the analyses. A four-meter gait test was used to assess gait speed. The N-back task was conducted to measure working memory performance [accuracy and response time(RT)]. T1-weighted structural MRI data (obtained using Siemens 3T MRI scanner) was used to assess cerebellar subregion volumes. Linear regression and mediation analysis were used to examine the relationships between the variables after controlling for age, sex, and education. Results: Faster gait speed was associated with faster working memory RT in younger adults. Greater cerebellar subregion volumes were associated with faster gait speed and better working memory performance. Faster gait speed was correlated with faster working memory RT through greater volume of cerebellar region VIIIa. Conclusions: The present study suggests faster gait speed is associated with faster RT during working memory tasks in younger individuals. The specific subregion of the cerebellum (VIIIa) may serve as an important neural basis linking gait speed and working memory.

The effect of tDCS electrode montage on attention and working memory

Article

Dec 2022
NEUROPSYCHOLOGIA

The effects of transcranial direct current stimulation (tDCS) for improving attention and working memory have been generally mixed and small, potentially due to variability between studies with montages, stimulus parameters and outcome measures. The tDCS montage is an important parameter which determines the degree and intensity of stimulation in targeted brain regions. This study aimed to examine the effects of using three different montages for modulating attention and working memory performance: Bi-frontal, Broad-frontal and Broad-parietal. Ninety-three healthy adults participated in a counterbalanced cross-over study. Participants received both active and sham tDCS with either the Bi-frontal, Broad-frontal or Broad-parietal montage during performance of both a 1- and 2-back task. TDCS montage moderated 2-back working memory reaction time performance, though not accuracy, with faster reaction times observed for active compared to sham tDCS with the Broad-frontal montage only (F (1,90) = 5.26, p = .024, η2 = 0.06). TDCS montage did not significantly moderate performance on the 1-back task. The cognitive effects of tDCS varied according to montage, task, and outcome measure. TDCS administered with the cathode placed extracephalically in a Broad-frontal montage may be beneficial for improving working memory.

Procesos de codificación, almacenamiento y recuperación en pacientes con epilepsia del lóbulo temporal mesial izquierdo

Article

Full-text available

Dec 2018

La epilepsia del lóbulo temporal mesial (ELTm) se considera clave para el estudio de aspectos relacionados con el procesamiento de la memoria. La integridad del lóbulo temporal mesial es determinante en la formación de nuevos aprendizajes. Por este motivo la ETLm supone una oportunidad de estudiar estos procesos. En este estudio se plantea la hipótesis de que el daño en esta estructura compromete a los procesos de codificación, almacenamiento y recuperación de la memoria episódica. En el presente trabajo se analiza cada uno de estos procesos y su relación con otras funciones cognitivas –velocidad de procesamiento, atención y memoria de trabajo-. Para la evaluación de las fases de memoria se emplearon un conjunto de índices del TAVEC. La muestra estaba compuesta por 14 sujetos con diagnóstico de ELTmi y 14 sujeto sanos pareados por edad sexo y nivel educacional. Los resultados muestran un déficit en los procesos de codificación y recuperación.

Cortica Explain to me : How learning and memory operate in the brain ?

Article

Sep 2022

The building blocks of a human healthy life are assembled in the brain. Cognitive and emotional neural systems interact based on genetic and epigenetic factors, hence entangling our experiences for better or for worse. During childhood and through adolescence traumatic experiences may embrace our lifelong behaviours creating a shaky brain-behaviour relationship, hence affecting learning and memory. Fortunately, such a relationship is not static. In this course we will work together to understand how the human brain encompasses learning and memory during normal and traumatic experiences. Let’s discover together how these systems are organised in the brain!

Functional near-infrared spectroscopy as a potential objective evaluation technique in neurocognitive disorders after traumatic brain injury

Article

Full-text available

Jul 2022

Most patients with neurocognitive disorders after traumatic brain injury (TBI) show executive dysfunction, in which the pre-frontal cortex (PFC) plays an important role. However, less objective evaluation technique could be used to assess the executive dysfunction in these patients. Functional near-infrared spectroscopy (fNIRS), which is a non-invasive technique, has been widely used in the study of psychiatric disorders, cognitive dysfunction, etc. The present study aimed to explore whether fNIRS could be a technique to assess the damage degree of executive function in patients with neurocognitive disorders after TBI by using the Stroop and N-back tasks in PFC areas. We enrolled 37 patients with neurocognitive disorders after TBI and 60 healthy controls. A 22-channel fNIRS device was used to record HbO during Stroop, 1-back and 2-back tasks. The results showed that patients made significantly more errors and had longer response times than healthy controls. There were statistically significant differences in HbO level variation in bilateral frontopolar, bilateral inferior frontal gyrus and left middle temporal gyrus during Stroop color word consistency tasks and in left frontopolar during Stroop color word inconsistency tasks. During 2-back tasks, there were also statistically significant differences in HbO level variation in bilateral frontopolar, bilateral inferior frontal gyrus, bilateral dorsolateral pre-frontal cortex. According to brain activation maps, the patients exhibited lower but more widespread activation during the 2-back and Stroop color word consistency tasks. The fNIRS could identify executive dysfunction in patients with neurocognitive disorders after TBI by detecting HbO levels, which suggested that fNIRS could be a potential objective evaluation technique in neurocognitive disorders after TBI.

Impulsivity, Self-control, Interpersonal Influences, and Maladaptive Cognitions as Factors of Internet Gaming Disorder Among Adolescents in China: Cross-sectional Mediation Study

Article

Full-text available

Oct 2021
J MED INTERNET RES

Background Gaming disorder, including internet gaming disorder (IGD), was recently defined by the World Health Organization as a mental disease in the 11th Revision of the International Classification of Diseases (ICD-11). Thus, reducing IGD is warranted. Maladaptive cognitions related to internet gaming (MCIG) have been associated with IGD, while impulsivity, self-control, parental influences, and peer influences are key risk factors of IGD. Previous literature suggests that MCIG is associated with the aforementioned 4 risk factors and IGD, and may thus mediate between these risk factors and IGD. These potential mediations, if significant, imply that modification of MCIG may possibly alleviate these risk factors’ harmful impacts on increasing IGD. These mediation hypotheses were tested in this study for the first time. Objective This study tested the mediation effects of MCIG between intrapersonal factors (impulsivity and self-control) and IGD, and between interpersonal factors (parental influences and peer influences) and IGD among adolescents in China. Methods An anonymous, cross-sectional, and self-administered survey was conducted among secondary school students in classroom settings in Guangzhou and Chengdu, China. All grade 7 to 9 students (7 to 9 years of formal education) of 7 secondary schools were invited to join the study, and 3087 completed the survey. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) checklist was used to assess IGD. MCIG was assessed by using the Chinese version of the Revised Internet Gaming Cognition Scale. Impulsivity, self-control, and parental or peer influences were measured by using the motor subscale of the Barratt Impulsiveness Scale, the Brief Self-Control Scale, and the modified interpersonal influence scale, respectively. Structural equation modeling was conducted to examine the mediation effects of MCIG between these risk factors and IGD. Results The prevalence of IGD was 13.57% (418/3081) and 17.67% (366/2071) among all participants and adolescent internet gamers, respectively. The 3 types of MCIG (perceived rewards of internet gaming, perceived urges for playing internet games, and perceived unwillingness to stop playing without completion of gaming tasks) were positively associated with IGD. Impulsivity, self-control, parental influences, and peer influences were all significantly associated with the 3 types of MCIG and IGD. The 3 types of MCIG partially mediated the associations between the studied factors and IGD (effect size of 30.0% to 37.8%). Conclusions Impulsivity, self-control, and interpersonal influences had both direct and indirect effects via MCIG on IGD. Modifications of the 3 types of MCIG can potentially reduce the harmful impacts of impulsivity and interpersonal influences on IGD and enhance the protective effect of self-control against IGD. Future longitudinal studies are warranted.

Mentalisation et attachement

Chapter

Jan 2021

The Neural Basis of Decision-Making During Time-Based Inter-Role Conflict

Article

Sep 2021
BIOL PSYCHOL

Time-based inter-role conflict is a type of conflict in which individuals are faced with simultaneous role pressures from different role domains. Some researchers have applied a decision-making perspective to investigate inter-role conflict; however, the neural basis of inter-role decision-making has rarely been discussed. In the current study, a collection of inter-role conflict scenarios with high/low levels of conflict were selected, and sixty college students were recruited to make choices between the conflicting student and family/friend demands in each scenario while their brain activities were recorded using functional magnetic resonance imaging. Blood oxygen level-dependent conjunction analysis found that making decisions in inter-role conflict activated brain areas, including the bilateral medial prefrontal cortex (mPFC), bilateral temporoparietal conjunction (TPJ), bilateral posterior cingulate cortex (PCC), and bilateral anterior temporal lobe. Direct comparisons between high versus low conflict situations showed increased activation of the left dorsal anterior cingulate. A generalized psychophysiological interaction analysis further showed enhanced connectivity among the mPFC, PCC, and bilateral TPJ in high conflict versus low conflict situations. Our study improved understanding of the relationship between brain and inter-role decision-making and provided an empirical examination on the psychological process propositions.

Amyloid and anatomical correlates of executive functioning in middle-aged offspring of patients with late-onset Alzheimer`s Disease.

Article

Aug 2021
PSYCHIAT RES-NEUROIM

A traditional hallmark of cognitive impairment associated with late-onset Alzheimer´s disease (LOAD) is episodic memory impairment. However, early alterations have been identified in brain regions associated with executive function in asymptomatic, middle-age offspring of patients with LOAD (O-LOAD) compared to those with no family history. We hypothesized that executive function among O-LOAD would correlate with structural and amyloid brain imaging differently from those without a family history of LOAD (control subjects, CS). Executive function, cortical thickness, and in-vivo Aβ deposits were quantified in 30 O-LOAD and 25 CS. Associations were observed among O-LOAD only. Cortical thickness in the left lateral orbitofrontal cortex was positively associated with Design Fluency. The Stroop Color and Word Test, correlated positively with right rostral mid-frontal cortex thickness. Trails Making Test-B was inversely related to left medial orbitofrontal thickness. Tower of London total time was positively associated with β-amyloid deposition in the right precuneus. These results support previous evidence that early executive dysfunction might reflect subtle, early changes in persons at risk of LOAD and suggests that executive function alterations deserve further exploration in the LOAD literature.

Tract-specific MRI measures explain learning and recall differences in multiple sclerosis

Article

Full-text available

Apr 2021

Cognitive difficulties are common and a key concern for people with multiple sclerosis. Advancing knowledge of the role of white matter pathology in multiple sclerosis-related cognitive impairment is essential as both occur early in the disease with implications for early intervention. Consequently, this cross-sectional study asked whether quantifying the relationships between lesions and specific white matter structures could better explain co-existing cognitive differences than whole brain imaging measures. Forty participants with relapse-onset multiple sclerosis underwent cognitive testing and MRI at 3 Tesla. They were classified as cognitively impaired (n = 24) or unimpaired (n = 16) and differed across verbal fluency, learning and recall tasks corrected for intelligence and education (corrected P-values = 0.007–0.04). The relationships between lesions and white matter were characterized across six measures: conventional voxel-based T2 lesion load, whole brain tractogram load (lesioned volume/whole tractogram volume), whole bundle volume, bundle load (lesioned volume/whole bundle volume), Tractometry (diffusion-tensor and high angular resolution diffusion measures sampled from all bundle streamlines) and lesionometry (diffusion measures sampled from streamlines traversing lesions only). The tract-specific measures were extracted from corpus callosum segments (genu and isthmus), striato-prefrontal and -parietal pathways, and the superior longitudinal fasciculi (sections I, II and III). White matter measure-task associations demonstrating at least moderate evidence against the null hypothesis (Bayes Factor threshold < 0.2) were examined using independent t-tests and covariate analyses (significance level P < 0.05). Tract-specific measures were significant predictors (all P-values < 0.05) of task-specific clinical scores and diminished the significant effect of group as a categorical predictor in Story Recall (isthmus bundle load), Figure Recall (right striato-parietal lesionometry) and Design Learning (left superior longitudinal fasciculus III volume). Lesion load explained the difference in List Learning, whereas Letter Fluency was not associated with any of the imaging measures. Overall, tract-specific measures outperformed the global lesion and tractogram load measures. Variation in regional lesion burden translated to group differences in tract-specific measures, which in turn, attenuated differences in individual cognitive tasks. The structural differences converged in temporo-parietal regions with particular influence on tasks requiring visuospatial-constructional processing. We highlight that measures quantifying the relationships between tract-specific structure and multiple sclerosis lesions uncovered associations with cognition masked by overall tract volumes and global lesion and tractogram loads. These tract-specific white matter quantifications show promise for elucidating the relationships between neuropathology and cognition in multiple sclerosis.

Comparison of Resting-State Spontaneous Brain Activity between Treatment-Naive Patients with Schizophrenia and Obsessive-Compulsive Disorder

Preprint

Full-text available

Apr 2021

Background: Schizophrenia (SZ) and Obsessive-compulsive disorder (OCD) share many demographic and clinical symptoms, genetic risk factors, pathophysiological underpinnings, and brain structure and function. However, the differences in the spontaneous brain activity patterns between the two diseases remain unclear. Here this study aimed to compare the features of intrinsic brain activity in treatment-naive patients with schizophrenia (SZ) and obsessive-compulsive disorder (OCD) and to explore the relationship between spontaneous brain activity and the severity of symptoms. Methods: Twenty-two treatment-naive patients with SZ, twenty-seven treatment-naive patients with OCD, and sixty healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree of centrality (DC) of SZ group, OCD group and healthy control (HC) group were compared. Results: Compared with SZ group and HC group, patients with OCD had significantly higher ALFF in the right angular gyrus and the left middle frontal gyrus/precentral gyrus, and significantly lower ALFF in the left superior temporal gyrus/insula/rolandic operculum and the left postcentral gyrus. Compared with HC group, lower ALFF values in the right supramarginal gyrus/inferior parietal lobule and DC values of the right lingual gyrus/calcarine fissure and surrounding cortex of the two patient groups, higher ReHo values in OCD group and lower ReHo values in SZ group in the right angular gyrus/middle occipital gyrus brain region, and higher DC values in the right inferior parietal lobule/angular gyrus in SZ group were documented in the present study. In addition, the ALFF values of the left postcentral gyrus were positively correlated with positive subscale score and general psychopathology subscale score respectively on the Positive and Negative Syndrome Scale (PANSS) in SZ group. The ALFF values in the left superior temporal gyrus/insula/rolandic operculum of patients with OCD were positively correlated with compulsion subscale score and total score respectively on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Conclusion: Our data showed various patterns of spontaneous brain activity damage in resting-state between treatment-naive patients with SZ and OCD, which might imply different underlying neurobiological mechanisms in SZ and OCD.

Mentalisation et attachement

Chapter

Jan 2015

Hippocampal Functional Connectivity Development During the First Two Years Indexes 4-year Working Memory Performance

Article

Feb 2021
CORTEX

The hippocampus is a key limbic region involved in higher-order cognitive processes including learning and memory. Although both typical and atypical functional connectivity patterns of the hippocampus have been well-studied in adults, the developmental trajectory of hippocampal connectivity during infancy and how it relates to later working memory performance remains to be elucidated. Here we used resting state fMRI (rsfMRI) during natural sleep to examine the longitudinal development of hippocampal functional connectivity using a large cohort (N=202) of infants at 3 weeks (neonate), 1 year, and 2 years of age. Next, we used multivariate modeling to investigate the relationship between both cross-sectional and longitudinal growth in hippocampal connectivity and 4-year working memory outcome. Results showed robust local functional connectivity of the hippocampus in neonates with nearby limbic and subcortical regions, with dramatic maturation and increasing connectivity with key default mode network (DMN) regions resulting in adult-like topology of the hippocampal functional connectivity by the end of the first year. This pattern was stabilized and further consolidated by 2 years of age. Importantly, cross-sectional and longitudinal measures of hippocampal connectivity in the first year predicted subsequent behavioral measures of working memory at 4 years of age. Taken together, our findings provide insight into the development of hippocampal functional circuits underlying working memory during this early critical period.

Temporal dynamic changes of intrinsic brain activity in Alzheimer’s disease and mild cognitive impairment patients: a resting-state functional magnetic resonance imaging study

Article

Full-text available

Jan 2021

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment. Previous studies have largely focused on alterations of static brain activity occurring in patients with AD. Few studies to date have explored the characteristics of dynamic brain activity in cognitive impairment, and their predictive ability in AD patients. Methods: One hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (HC) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) and the dynamic fraction amplitude of low-frequency fluctuation (dfALFF) were used to assess the temporal variability of local brain activity in patients with AD or mild cognitive impairment (MCI). Pearson's correlation coefficients were calculated between the metrics and subjects' behavioral scores. Results: The results of analysis of variance indicated that the AD, MCI, and HC groups showed significant variability of dALFF in the cerebellar posterior and middle temporal lobes. In AD patients, these brain regions had high dALFF variability. Significant dfALFF variability was found between the three groups in the left calcarine cortex and white matter. The AD group showed lower dfALFF than the MCI group in the left calcarine cortex. Conclusions: Compared to HC, AD patients were found to have increased dALFF variability in the cerebellar posterior and temporal lobes. This abnormal pattern may diminish the capacity of the cerebellum and temporal lobes to participate in the cerebrocerebellar circuits and default mode network (DMN), which regulate cognition and emotion in AD. The findings above indicate that the analysis of dALFF and dfALFF based on functional magnetic resonance imaging data may give a new insight into the neurophysiological mechanisms of AD.

Why is Internet gaming disorder more prevalent among Chinese male than female adolescents? The role of cognitive mediators

Article

Aug 2020
ADDICT BEHAV

Background Adolescent males were consistently reported to have a higher prevalence of Internet gaming disorder (IGD) than females. The mechanisms underlying the sex difference were potentially important for designing sex-specific interventions but were under-researched. Maladaptive cognitions were potential mediators between sex and adolescent IGD, as they were positively associated with both sex and adolescent IGD. Methods A total of 3,075 students participated in a cross-sectional survey that was conducted in Guangzhou and Chengdu, China. IGD was measured by using the DSM-5 checklist and maladaptive cognitions were measured by the validated Chinese version of Revised Internet Gaming Cognition Scale (C-RIGCS). Structural equation modeling was used to test the mediation hypotheses. Results Adolescent males showed a significantly higher prevalence of IGD than females (19.2% versus 7.8%, p<.05). Significant positive associations were found between sex and both maladaptive cognitions and IGD. The sex difference in IGD prevalence was partially mediated by the overall scale of C-RIGCS and its three subscales (i.e., perceived overvaluation of rewards of Internet gaming, perceived urges for playing Internet games, and perceived unwillingness to stop playing without completion of gaming tasks), with large mediation effect sizes ranging from 35.0% to 60.0% (Sobel test, p<.001). Conclusions The higher levels of maladaptive cognitions among adolescent males explained a relatively large part of the substantially higher prevalence of IGD among adolescent males than females. Interventions targeting adolescent males may consider modifying such cognitions to reduce their IGD.

Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study

Article

Full-text available

Oct 1999
BRAIN

Andrew J Saykin

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, ~1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior–posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

PET studies of encoding and retrieval: The HERA model

Article

Full-text available

Jun 1996
PSYCHON B REV

We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval.

Functional Neuroanatomy of Recall and Recognition: A PET Study of Episodic Memory

Article

Full-text available

Mar 1997
J COGNITIVE NEUROSCI

The purpose of this study was to directly compare the brain regions involved in episodic-memory recall and recognition. Changes in regional cerebral blood flow were measured by positron emission tomography while young healthy test persons were either recognizing or recalling previously studied word pairs. Reading of previously nonstudied pairs served as a reference task for subtractive comparisons. Compared to reading, both recall and recognition were associated with higher blood flow (activation) at identical sites in the right prefrontal cortex (areas 47, 45, and 10) and the anterior cingulate. Compared to recognition, recall was associated with higher activation in the anterior cingulate, globus pallidus, thalamus, and cerebellum, suggesting that these components of the cerebello-frontal pathway play a role in recall processes that they do not in recognition. Compared to recall, recognition was associated with higher activation in the right inferior parietal cortex (areas 39, 40, and 19), suggesting a larger perceptual component in recognition than in recall. Contrary to the expectations based on lesion data, the activations of the frontal regions were indistinguishable in recall and recognition. This finding is consistent with the notion that frontal activations in explicit memory tasks are related to the general episodic retrieval mode or retrieval attempt, rather than to specific mechanisms of ecphory (recovery of stored information).

From the Cover: Prefrontal cortex and episodic memory retrieval mode

Article

Full-text available

Jan 2000

A multistudy analysis of positron emission tomography data identified three right prefrontal and two left prefrontal cortical sites, as well as a region in the anterior cingulate gyrus, where neuronal activity is correlated with the maintenance of episodic memory retrieval mode (REMO), a basic and necessary condition of remembering past experiences. The right prefrontal sites were near the frontal pole [Brodmann's area (BA) 10], frontal operculum (BA 47/45), and lateral dorsal area (BA 8/9). The two left prefrontal sites were homotopical with the right frontal pole and opercular sites. The same kinds of REMO sites were not observed in any other cerebral region. Many previous functional neuroimaging studies of episodic memory retrieval have reported activations near the frontal REMO sites identified here, although their function has not been clear. Many of these, too, probably have signaled their involvement in REMO. We propose that REMO activations largely if not entirely account for the frontal hemispheric asymmetry of retrieval as described by the original hemispheric encoding retrieval asymmetry model.

Article

Full-text available

Feb 2000
J COGNITIVE NEUROSCI

Positron emission tomography (PET) was used to inves-tigate the hypothesis that older adults' difficulties with temporal-order memory are related to deficits in frontal function. Young (mean 24.7 years) and old (mean 68.6 years) participants studied a list of words, and were then scanned while retrieving information about what words were in the list (item retrieval) or when they occurred within the list (temporal-order retrieval). There were three main results. First, whereas the younger adults engaged right prefrontal regions more during temporal-order retrieval than during item retrieval, the older adults did not. This result is consistent with the hypothesis that context memory deficits in older adults are due to frontal dysfunction. Second, ventromedial temporal activity during item memory was relatively unaffected by aging. This finding concurs with evidence that item memory is relatively preserved in old adults and with the notion that medial temporal regions are involved in automatic retrieval operations. Finally, replicating the result of a previous study (Cabeza,, the old adults showed weaker activations than the young adults in the right prefrontal cortex but stronger activations in the left prefrontal cortex. The age-related increase in left prefrontal activity may be interpreted as compensatory. Taken together, the results suggest that age-related changes in brain activity are rather process-and region-specific, and that they involve increases as well as decreases in neural activity. &

Prefrontal cortex and episodic memory retrieval mode

Article

Full-text available

Jan 2000

A resource model of the neural basis of executive working memory

Article

Full-text available

Apr 2000

Working memory (WM) refers to the temporary storage and processing of goal-relevant information. WM is thought to include domain-specific short-term memory stores and executive processes, such as coordination, that operate on the contents of WM. To examine the neural substrates of coordination, we acquired functional magnetic resonance imaging data while subjects performed a WM span test designed specifically to measure executive WM. Subjects performed two tasks (sentence reading and short-term memory for five words) either separately or concurrently. Dual-task performance activated frontal-lobe areas to a greater extent than performance of either task in isolation, but no new area was activated beyond those activated by either component task. These findings support a resource theory of WM executive processes in the frontal lobes.

Article

Full-text available

Aug 1995

The participation of the medial temporal cortex and other cerebral structures in the memory impairment that accompanies aging was examined by means of positron emission tomography. Cerebral blood flow (rCBF) was measured during encoding and recognition of faces. Young people showed increased rCBF in the right hippocampus and the left prefrontal and temporal cortices during encoding and in the right prefrontal and parietal cortex during recognition. Old people showed no significant activation in areas activated during encoding in young people but did show right prefrontal activation during recognition. Age-related impairments of memory may be due to a failure to encode the stimuli adequately, which is reflected in the lack of cortical and hippocampal activation during encoding.

Tulving, E., Kapur, S., Craik, F.I.M., Moscovitch, M. & Houle, S. Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proc. Natl. Acad. Sci. USA 91, 2016-2020

Article

Full-text available

Apr 1994

Data are reviewed from positron emission tomography studies of encoding and retrieval processes in episodic memory. These data suggest a hemispheric encoding/retrieval asymmetry model of prefrontal involvement in encoding and retrieval of episodic memory. According to this model, the left and right prefrontal lobes are part of an extensive neuronal network that subserves episodic remembering, but the two prefrontal hemispheres play different roles. Left prefrontal cortical regions are differentially more involved in retrieval of information from semantic memory and in simultaneously encoding novel aspects of the retrieved information into episodic memory. Right prefrontal cortical regions, on the other hand, are differentially more involved in episodic memory retrieval.

Paulesu E, Frith CD, Frackowiak RSThe neural correlates of the verbal component of working memory. Nature 362:342-345

Article

Full-text available

Apr 1993

By repeating words 'in our head', verbal material (such as telephone numbers) can be kept in working memory almost indefinitely. This 'articulatory loop' includes a subvocal rehearsal system and a phonological store. Little is known about neural correlates of this model of verbal short-term memory. We therefore measured regional cerebral blood flow, an index of neuronal activity, in volunteers performing a task engaging both components of the articulatory loop (short-term memory for letters) and a task which engages only the subvocal rehearsal system (rhyming judgement for letters). Stimuli were presented visually and the subjects did not speak. We report here that comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area. This is, to our knowledge, the first demonstration of the normal anatomy of the components of the 'articulatory loop'.

PET Activation of Posterior Temporal Regions during Auditory Word Presentation and Verb Generation

Article

Full-text available

Jan 1996

Previous studies using positron emission tomography (PET) report blood flow changes in superior and middle temple gyri associated with auditory and language tasks (Petersen et al., 1988, 1989; Wise et al., 1991; Demonet et al., 1992; Howard et al., 1992; Sergent et al., 1992; Zatorre et al., 1992; Petrides et al., 1993; Raichle et al., 1994; Fiez et al., 1995). An important issue is whether these changes reflect the activation of a single functional region or multiple regions with distinct functional contributions. In the present study, we examined this issue by focusing upon two tasks for which we have previously reported posterior temporal blood flow changes: listening to auditorily presented words (Petersen et al., 1988, 1989), and generation of a verb in response to a visually presented noun (Raichle et al., 1994); see also Wise et al. (1991). We began by further characterizing a left temporoparietal region of change previously associated with auditory word presentation. This previously reported response was replicated, and the results were extended by demonstrating presentation of pseudowords also produced activation. We next asked whether the activation associated with auditory word presentation could be distinguished from that associated with the generation of verbs in response to visually presented nouns. It was found that the activations associated with these two tasks could be both functionally and spatially dissociated. Thus, two posterior temporal areas associated with auditory word presentation and verb generation appear to represent distinct areas concerned with word processing. More generally, the results demonstrate an approach for assessing the independence of two activated areas.

Article

Full-text available

Feb 1997

Positron emission tomography (PET) was used to compare regional cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling word pairs. A multivariate partial-least-squares (PLS) analysis of the data was used to identify age-related neural changes associated with (1) encoding versus retrieval and (2) recognition versus recall. Young subjects showed higher activation than old subjects (1) in left prefrontal and occipito-temporal regions during encoding and (2) in right prefrontal and parietal regions during retrieval. Old subjects showed relatively higher activation than young subjects in several regions, including insular regions during encoding, cuneus/precuneus regions during recognition, and left prefrontal regions during recall. Frontal activity in young subjects was left-lateralized during encoding and right-lateralized during recall [hemispheric encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal activity during encoding and a more bilateral pattern of frontal activation during retrieval. In young subjects, activation in recall was higher than that in recognition in cerebellar and cingulate regions, whereas recognition showed higher activity in right temporal and parietal regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in other regions. Taken together, the results indicate that advanced age is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1) age-related decreases in local regional activity, which may signal less efficient processing by the old, and (2) age-related increases in activity, which may signal functional compensation.

Differential activation of the prefrontal cortex in successful and unsuccessful memory retrieval

Article

Full-text available

Jan 1997

Six subjects underwent PET scans while they performed three versions of a recognition memory test for words and three versions of a control task. In each memory condition, the subjects discriminated between words presented in a prescan study list and words new to the experiment. During the 30 s scanning interval, the ratio of old and new words was 0:20, 4:16 or 16:4, depending on the experimental condition. Outside this interval, the ratio was 50:50 in all three conditions. The requirement in the control task was to discriminate between two character strings, the ratios of which were also manipulated during the 30 s scanning interval. Employing the control task as a covariate, analysis with statistical parametric mapping revealed that regional cerebral blood flow (rCBF) covaried with increasing density of old items in three regions of prefrontal cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex, especially in the right hemisphere, is more active when a retrieval attempt succeeds than when it fails. This finding is consistent with the idea that the prefrontal cortex supports processes that operate selectively on the products of memory retrieval.

Role of Left Inferior Prefrontal Cortex in Retrieval of Semantic Knowledge: A Reevaluation

Article

Full-text available

Jan 1998

A number of neuroimaging findings have been interpreted as evidence that the left inferior frontal gyrus (IFG) subserves retrieval of semantic knowledge. We provide a fundamentally different interpretation, that it is not retrieval of semantic knowledge per se that is associated with left IFG activity but rather selection of information among competing alternatives from semantic memory. Selection demands were varied across three semantic tasks in a single group of subjects. Functional magnetic resonance imaging signal in overlapping regions of left IFG was dependent on selection demands in all three tasks. In addition, the degree of semantic processing was varied independently of selection demands in one of the tasks. The absence of left IFG activity for this comparison counters the argument that the effects of selection can be attributed solely to variations in degree of semantic retrieval. Our findings suggest that it is selection, not retrieval, of semantic knowledge that drives activity in the left IFG.

Inhibition in verbal working memory revealed by brain activity

Article

Full-text available

Aug 1998

There are many occasions in which humans and other animals must inhibit the production of some behavior or inhibit the processing of some internal representation. Success in inhibitory processing under normal circumstances can be revealed by the fact that certain brain pathologies render inhibitory processing ineffective. These pathologies often have been associated with damage to frontal cortex, including lateral and inferior aspects. We provide behavioral evidence of a verbal working memory task that, by hypothesis, engaged inhibitory processing, and we show (by using positron emission tomograpny) that the inhibitory processing is associated with a lateral portion of the left prefrontal cortex. The task in which subjects engaged was item-recognition: Four target letters were presented for storage followed, after a brief interval, by a probe letter that could match a target letter or not. On some trials, when the probe did not match a target letter and therefore required a "no" response, the probe had matched a target letter of the previous trial, so on these trials a "yes" response was prepotent and had to be inhibited, by hypothesis. Compared with a condition in which no prepotent response was created, this condition yielded brain activation in left inferior frontal gyrus, in the region of Brodmann's area 45.

Building Memories: Remembering and Forgetting of Verbal Experiences as Predicted by Brain Activity

Article

Full-text available

Sep 1998

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.

Brewer, J. B., Zhao, Z., Desmond, J. E., Glover, G. H. & Gabrieli, J. D. E. Making memories: brain activity that predicts how well visual experience will be remembered. Science 281, 1185-1187

Article

Full-text available

Sep 1998

Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.

Hippocampal, but not Amygdala, Activity at Encoding Correlates with Long-Term, Free Recall of Nonemotional Information

Article

Full-text available

Dec 1998

Participation of two medial temporal lobe structures, the hippocampal region and the amygdala, in long-term declarative memory encoding was examined by using positron emission tomography of regional cerebral glucose. Positron emission tomography scanning was performed in eight healthy subjects listening passively to a repeated sequence of unrelated words. Memory for the words was assessed 24 hr later with an incidental free recall test. The percentage of words freely recalled then was correlated with glucose activity during encoding. The results revealed a striking correlation (r = 0.91, P < 0.001) between activity of the left hippocampal region (centered on the dorsal parahippocampal gyrus) and word recall. No correlation was found between activity of either the left or right amygdala and recall. The findings provide evidence for hippocampal involvement in long-term declarative memory encoding and for the view that the amygdala is not involved with declarative memory formation for nonemotional material.

Regional brain activity during taks devoted to the central executive of working memory

Article

Full-text available

Feb 1999
Cognit Brain Res

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation

Article

May 1999
BRAIN

Giuseppe Esposito

We used PET to explore the neurophysiological changes that accompany cognitive disability in ageing, with a focus on the frontal lobe. Absolute regional cerebral blood flow (rCBF) was measured in 41 healthy volunteers, evenly distributed across an age range of 18–80 years, during two task paradigms: (i) the Wisconsin Card Sorting Test (WCST), which depends heavily on working memory and is particularly sensitive to dysfunction of the dorsolateral prefrontal cortex (DLPFC); and (ii) Raven's Progressive Matrices (RPM), which may also have a working memory component, but depends more on visuo-spatial processing and is most sensitive to dysfunction of postrolandic regions. We used voxel-wise correlational mapping to determine age-related changes in WCST and RPM activation and developed a method to quantitate and localize statistical differences between the correlation maps for the two task paradigms. Because both WCST and RPM performance declined with age, as expected, correlational analyses were performed with and without partialling out the effect of task performance. Task-specific reductions of rCBF activation with age were found in the DLPFC during the WCST and in portions of the inferolateral temporal cortex involved in visuo-spatial processing during the RPM. We also found reduced ability to suppress rCBF in the right hippocampal region during the WCST and in mesial and polar portions of the prefrontal cortex during both task conditions. Task-dependent alterations with age in the relationship between the DLPFC and the hippocampus were also documented; because the collective pattern of changes in the hippocampal–DLPFC relationship with ageing was opposite to that seen in a previous study using dextroamphetamine, we postulated a dopaminergic mechanism. These results indicate that, despite some cognitive overlap between the two tasks and the age-related cognitive decline in both, many of the changes in rCBF activation with age were task-specific, reflecting functional alteration of the different neural circuits normally engaged by young subjects during the WCST and RPM. Reduced activation of areas critical for task performance (i.e. the DLPFC during the WCST and posterior visual association areas of the inferolateral temporal cortex during the RPM), in conjunction with the inability to suppress areas normally not involved in task performance (i.e. the left hippocampal region during the WCST and mesial polar prefrontal cortex during both the WCST and RPM), suggest that, overall, reduced ability to focus neural activity may be impaired in older subjects. The context dependency of the age-related changes is most consistent with systems failure and disordered connectivity.

Direct comparison of the neural substrates of recognition memory for words and faces

Article

Jun 1999
BRAIN

J. J. Kim

For the purpose of identifying the relatively specific brain regions related to word and face recognition memory on the one hand and the regions common to both on the other, regional cerebral blood flow associated with different cognitive tasks for recognition memory was examined using [H215O]PET in healthy volunteers. The tasks consisted of recognizing two types of stimuli (faces and words) in two conditions (novel and familiar), and two baseline tasks (reading words and gender classification). The statistical analyses used to identify the specific regions consisted of three subtractions: novel words minus novel faces, familiar words minus familiar faces, and reading words minus gender classification. These analyses revealed relative differences in the brain circuitry used for recognizing words and for recognizing faces within a defined level of familiarity. In order to find the regions common to both face and word recognition, overlapping areas in four subtractions (novel words minus reading words, novel faces minus gender classification, familiar words minus reading words, and familiar faces minus gender classification) were identified. The results showed that the activation sites in word recognition tended to be lateralized to the left hemisphere and distributed as numerous small loci, and particularly included the posterior portion of the left middle and inferior temporal gyri. These regions may be related to lexical retrieval during written word recognition. In contrast, the activated regions for face recognition tended to be lateralized to the right hemisphere and located in a large aggregated area, including the right lingual and fusiform gyri. These findings suggest that strikingly different neural pathways are engaged during recognition memory for words and for faces, in which a critical role in discrimination is played by semantic cueing and perceptual loading, respectively. In addition, the investigation of the regions common to word and face recognition indicates that the anterior and posterior cingulate have dissociable functions in recognition memory that vary with familiarity, and that the cerebellum may serve as the co-ordinator of all four types of recognition memory processes.

The Effects of Age on the Neural Correlates of Episodic Encoding

Article

Dec 1999
CEREB CORTEX

Cheryl L. Grady

Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.

Brain Activation in Young and Older Adults During Implicit and Explicit Retrieval

Article

May 1997
J COGNITIVE NEUROSCI

Positron emission tomography was used to study regional cerebral blood flow (H215O method) in groups of young and older adults during implicit and explicit retrieval, following a procedure devised by Squire et al. (1992). At study, subjects were exposed to four lists of words. Following list presentation, subjects were presented with three-letter word stems under four conditions: (1) silent viewing, (2) completion of word stems that could not form words from the study list, with the instruction to provide the first word that came to mind (baseline), (3) completion of word stems, half of which could form words from the study list, with the instruction to provide the first word that came to mind (priming), and (4) completion of word stems, half of which could form words from the study list, with the instruction to use the stems as cues for recall of list words (memory). The behavioral data indicated an agerelated deficit in cued recall that was reduced in priming. Both age groups showed a similar decrease of blood flow in right posterior cortex during priming relative to baseline. During cued recall, bilateral increases of blood flow were observed in prefrontal cortex and anterior cingulate gyrus for both age groups. The young adults showed selective increases of activity in left cerebellum and Wernicke's area, whereas the older adults showed a selective bilateral activation in the perirhinal region of the medial-temporal cortex during cued recall. The results suggest a simiiar biological basis of priming in both age groups: a decrease in the neural activity required to process a particular stimulus during a subsequent encounter compared with a previous one. In addition, the importance of prefrontal regions for conscious retrieval was substantiated and extended to late adulthood. Finally, the agedifferential activations observed during cued recall were discussed relative to prominent concepts in the current literature on cognitive aging (e.g., speed of processing, self-initiated operations, cross-modal recoding).

Hippocampal system and declarative (relational) memory: Summarizing from functional neuroimaging studies

Article

Jan 1999
HIPPOCAMPUS

In the last several years there have been impressive strides in the ability to explore the nature of hippocampal system functioning in humans by employing functional neuroimaging methods, permitting such methods to be used in conjunction with neuropsychological methods to better understand the role of the hippocampal system in memory. In this paper, we review the literature on functional imaging studies of the hippocampal system, summarizing the data and testing these data against a number of theories or explanatory accounts of hippocampal function. We consider five alternative explanatory accounts of, or ideas about, hippocampal function— some from already existing work, for which the functional imaging data can provide a new test, and others that have emerged directly from the functional imaging work, and that have yet to be tested for their fit of data from neuropsychological methods. We conclude that the relational (declarative) memory account, in which it is proposed that the hippocampal system plays a critical role in binding together multiple inputs to permit representations of the relations among the constituent elements of scenes or events, can better accomodate the full range of imaging (and other existing) data than any other explanatory account of hippocampal function. Hippocampus 1999;9:83–98. © 1999 Wiley-Liss, Inc.

Redefining the functional organization of working memory processes within human lateral prefrontal cortex

Article

Feb 1999
EUR J NEUROSCI

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non-spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid-dorsolateral and mid-ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non-spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a ‘spatial span' task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood-flow was observed in the right mid-ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid-dorsolateral frontal-lobe region. By contrast, during a ‘2-back' task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid-ventrolateral and mid-dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid-dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

I. PET Studies of Memory: Novel and Practiced Free Recall of Complex Narratives

Article

Jan 1996

Positron Emission Tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers during two experimental memory tasks, one of which was well-practiced and the other of which was novel. The materials used for the memory tasks consisted of two complex narratives (Story A and Story B from the Wechsler Memory Scale). Natural language materials were chosen because they similate experimentally the natural learning situation and permit study of the neural mechanisms by which recall memory becomes more fluid, automatic, or "rote." One week before the PET study, subjects were trained to perfect recall of Story A, while they were exposed to Story B only 60s prior to PET data acquisition. Despite the substantial differences in level of familiarity (and in free recall performance), patterns of activation were quite similar; activations presumed to reflect recall in both tasks included frontal, inferior temporal, thalamic, anterior cingulate, and cerebellar regions. Many regions were smaller during recall of the familiar story, however, presumably reflecting greater neural efficiency due to practice. In addition, the novel task activated an additional left frontal region that is presumed to reflect more active encoding. The similarity and multiplicity of the activations in the two tasks suggest that the brain uses a multinodal general network for memory tasks such as free recall, while the differences suggest that some nodes in the network may be used for specific components of memory such as encoding and retrieval.

II. PET Studies of Memory: Novel versus Practiced Free Recall of Word Lists

Article

Jan 1996

Positron emission tomography (PET) with the tracer Ha215O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or task-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.

Cabeza, R. & Nyberg, L. Neural bases of learning and memory: functional neuroimaging evidence. Curr. Opin. Neurol. 13, 415-421

Abstract

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