The multiscale topological organization of the functional brain network in adolescent PTSD.

The experience of an extremely aversive event can produce enduring deleterious behavioral, and neural consequences, among which posttraumatic stress disorder (PTSD) is a representative example. Although adolescence is a period of great exposure to potentially traumatic events, the effects of trauma during adolescence remain understudied in clinical neuroscience. In this exploratory work, we aim to study the whole-cortex functional organization of 14 adolescents with PTSD using a data-driven method tailored to our population of interest. To do so, we built on the network neuroscience framework and specifically on multilayer (multisubject) community analysis to study the functional connectivity of the brain. We show, across different topological scales (the number of communities composing the cortex), a hyper-colocalization between regions belonging to occipital and pericentral regions and hypo-colocalization in middle temporal, posterior-anterior medial, and frontal cortices in the adolescent PTSD group compared to a nontrauma exposed group of adolescents. These preliminary results raise the question of an altered large-scale cortical organization in adolescent PTSD, opening an interesting line of research for future investigations.

[The dynamic brain-network model of PTSD]. / Les sciences des réseaux appliquées à l'étude du Trouble de Stress Post-Traumatique.

The brain is a highly complex system whose functioning is critical for our interaction with the world. Neural elements, from single cells to brain systems, constantly fluctuate in their dynamics, accompanying the plethora of possible exchanges between our environment and ourselves. However, sometimes things go awry. An unfortunate example is post-traumatic stress disorder (PTSD), a debilitating clinical condition that can appear after exposure to a threatening life event. In this work, using complexity as a framework, we aim to introduce the dynamic brain network model of PTSD. We hope this model will allow the generation of novel specific hypotheses concerning brain organization and dynamics in PTSD research. We first introduce how the network framework complements the localizationist approach centered in specific brain regions or subsets of brain regions, with a whole brain approach considering brain regions' dynamic relationships. Then, we review key concepts in network neuroscience, focusing on the importance of the network topology and dynamics to understand the organizational principles of the brain, that is, functional segregation and integration. In the third part, we apply this knowledge to describe the possible trajectories conducting a brain system to present PTSD alterations. Accordingly, we introduce the Dynamic Brain Network Model (DBNM) of PTSD, a concrete framework built on the network approach and resilience theory to study the transition of a brain network from state 1 (e.g., before the traumatic event) to state 2 (e.g., after the traumatic event). To conclude, we provide a summary of metrics for quantifying elements on the DBNM and its potential use in computational models of PTSD.

Title: Les sciences des réseaux appliquées à l'étude du Trouble de Stress Post-Traumatique. Abstract: Cet article expose la manière dont les sciences des réseaux peuvent contribuer à la compréhension du Trouble de Stress Post-Traumatique (TSPT). Nous soulignons l'intérêt de concevoir le cerveau comme un système complexe et dynamique pour affiner la description et la prédiction des réponses cérébrales après exposition à un évènement traumatique. À partir des modèles de résilience au stress et sous le prisme des sciences des réseaux, nous proposons une ligne temporelle du TSPT, partant des facteurs de résilience intrinsèques au réseau, présents avant l'évènement traumatique, jusqu'à la réponse cérébrale ayant lieu après l'évènement traumatique. Dans ce cadre, il est essentiel de considérer la topologie du cerveau et les dynamiques cérébrales dans des processus permettant d'utiliser ces facteurs de résilience. Ainsi, nous proposons un cadre concret, autorisant la formulation d'hypothèses explicites sur des aspects potentiellement critiques de l'organisation et des dynamiques des réseaux cérébraux impliqués dans le TSPT.

Intact memory storage but impaired retrieval in visual memory in autism: New insights from an electrophysiological study.

In a recent study on visual episodic memory (Desaunay, Clochon, et al., 2020), we have shown event-related potentials (ERPs) differences associated with priming (150-300 msec), familiarity (350-470 msec), and recollection (600-700 msec), in young people with autism spectrum disorders (ASD) compared with typical development (TD). To go further into the study of the processes of storage and retrieval of the memory trace, we re-analyzed Desaunay, Clochon, et al's data using time-frequency analysis, that is, event-related synchronization and desynchronization (ERS/ERD). This allows a decomposition of the spectral power within frequency bands associated with these ERPs. We focused both on the same time windows and the same regions of interest as previously published. We mainly identified, in ASD compared with TD, reduced ERS in low-frequencies (delta, theta) in early time-windows, and non-significant differences in ERD in higher frequencies (alpha, beta1) in all time-windows. Reduced ERS during recognition confirmed previously reported diminution of priming effects and difficulties in manipulation and retrieval of both semantic and episodic information. Conversely, preserved ERD corroborates a preservation of memory storage processes. These observations are consistent with a cognitive model of memory in ASD, that suggests difficulties in cognitive operations or executive demand at retrieval, subsequent to successful long-term storage of information. LAY SUMMARY: We assessed the EEG synchronization and desynchronization, during visual episodic recognition. We observed, in youth with Autism, reduced synchronization in low-frequencies (delta, theta), suggesting reduced access to and manipulation of long-term stored information. By contrast, non-significant differences in desynchronization at higher frequencies (alpha, beta frequency bands), that support long-term stored semantic and episodic information, suggested preserved memory traces.

EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism.

BACKGROUND: Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD. METHODS: Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched). RESULTS: We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band. CONCLUSION: These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts.

Variations in response to trauma and hippocampal subfield changes.

Models of posttraumatic stress disorder (PTSD) suggest that the hippocampus is key to the persistence of traumatic memory. Yet very little is known about the precise changes that take place in this structure, nor their relation with PTSD symptoms. Previous studies have mostly used magnetic resonance imaging (MRI) at low resolutions, making it impossible to identify sensitive anatomical landmarks, or compared groups often unequally matched in terms of traumatic exposure. The present cross-sectional study included 92 individuals who had all been exposed to the terrorist attacks in Paris on November 13, 2015 (53 of whom subsequently developed PTSD) and 56 individuals who had not been exposed. Hippocampal subfield volumes were estimated using cross-validated automatic segmentation of high-resolution MRI images. Results revealed changes in CA1 and CA2-3/dentate gyrus (DG) volumes in individuals with PTSD, but not in resilient (i.e., exposed but without PTSD) individuals, after controlling for potential nuisance variables such as previous traumatic exposure and substance abuse. In line with current models of hippocampal subfield functions, CA1 changes were linked to the uncontrollable re-experiencing of intrusive memories, while CA2-3/DG changes, potentially exacerbated by comorbid depression, fostered the overgeneralization of fear linked to avoidance and hypervigilance behaviors. Additional analyses revealed that CA1 integrity was linked to optimum functioning of the memory control network in resilient individuals. These findings shed new light on potential pathophysiological mechanisms in the hippocampus subtending the development of PTSD and the failure to recover from trauma.

Local Processing Bias Impacts Implicit and Explicit Memory in Autism.

Autism spectrum disorder (ASD) is characterized by atypical perception, including processing that is biased toward local details rather than global configurations. This bias may impact on memory. The present study examined the effect of this perception on both implicit (Experiment 1) and explicit (Experiment 2) memory in conditions that promote either local or global processing. The first experiment consisted of an object identification priming task using two distinct encoding conditions: one favoring local processing (Local condition) and the other favoring global processing (Global condition) of drawings. The second experiment focused on episodic (explicit) memory with two different cartoon recognition tasks that favored either local (i.e., processing specific details) or a global processing (i.e., processing each cartoon as a whole). In addition, all the participants underwent a general clinical cognitive assessment aimed at documenting their cognitive profile and enabling correlational analyses with experimental memory tasks. Seventeen participants with ASD and 17 typically developing (TD) controls aged from 10 to 16 years participated to the first experiment and 13 ASD matched with 13 TD participants were included for the second experiment. Experiment 1 confirmed the preservation of priming effects in ASD but, unlike the Comparison group, the ASD group did not increase his performance as controls after a globally oriented processing. Experiment 2 revealed that local processing led to difficulties in discriminating lures from targets in a recognition task when both lures and targets shared common details. The correlation analysis revealed that these difficulties were associated with processing speed and inhibition. These preliminary results suggest that natural perceptual processes oriented toward local information in ASD may impact upon their implicit memory by preventing globally oriented processing in time-limited conditions and induce confusion between explicit memories that share common details.

Autobiographical Memory and Social Identity in Autism: Preliminary Results of Social Positioning and Cognitive Intervention.

Autobiographical memory (AM) is closely linked to the self-concept, and fulfills directive, identity, social, and adaptive functions. Individuals with autism spectrum disorder (ASD) are now known to have atypical AM, which may be closely associated with social communication difficulties. This may result in qualitatively different autobiographical narratives, notably regarding social identity. In the present study, we sought to investigate this concept and develop a cognitive intervention targeting individuals with ASD. First, 13 adolescents with ASD and 13 typically developing adolescents underwent an AM interview featuring an original coding system designed to analyze the social self. We observed that the narratives produced by the ASD group focused more on the family than on extended social spheres, compared with those of the comparison group. Moreover, participants with ASD did not include themselves in the social groups they mentioned, and produced more references to others, compared with typically developing participants. Second, we designed a cognitive intervention program consisting of individual and group sessions that targeted AM. We conducted a pilot study among three adolescents with ASD aged 12, 16, and 17 years. Preliminary results showed that the program increased extra-family narrative references by the two youngest adolescents, who produced more social integration markers. Our study of autobiographical narratives yielded interesting findings about social positioning in ASD and showed how AM can be targeted in rehabilitation programs as a vector of social interaction.

Exploring the Event-Related Potentials' Time Course of Associative Recognition in Autism.

Behavioral data on episodic recollection in autism spectrum disorders (ASD) point limited relational memory functioning. However, the involvement of successive memory processes in the profile of episodic memory in ASD needs more study. Here, we used event-related potentials (ERP) to investigate the time course of episodic recollection with an associative recognition paradigm with picture pairs. Twenty-two participants with ASD and 32 with typical development (TD), all right-handed, were included. Behavioral results confirmed difficulties in correctly recognizing identical pairs in the ASD relative to TD group. We found an unexpected amplitude decrement on the P2 (220-270 msec) and FN400 (350-470 msec) potentials, suggesting diminished priming and familiarity effects in the ASD relative to TD group. However, ERP data revealed that the recognition of associative information relies on the same electrophysiological process (old/new effect in the 600-700-msec late positive component) in ASD participants as in TD ones, with a parietal extension in the ASD group. These results suggest that the electrophysiological processes of associative recognition are qualitatively similar in individuals with and without ASD but may differ quantitatively. This difference may be driven by the reduced early processing of picture pairs that may in turn lead to their diminished integration into the semantic memory system, being partially compensated by a greater involvement of associative memory during the recollection process. Other studies would be useful to go further in identifying these cognitive processes involved in atypical recognition in ASD and their neural substrates. Autism Res 2020, 13: 1998-2016. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: We identified diminished performance on the associative recognition of picture pairs in adolescents and young adults with autism when compared to typical development. Electrophysiological data revealed qualitative similarities but quantitative differences between-group, with diminished priming and familiarity processes partially compensated by an enhanced parietal recollection process.

Short-Term Memory Span and Cross-Modality Integration in Younger and Older Adults With and Without Autism Spectrum Disorder.

This study tested whether adults with autism spectrum disorder (ASD) show the same pattern of difficulties and absence of age-related differences in short-term memory (STM) as those that have been reported in episodic long-term memory (LTM). Fifty-three adults with ASD (age range: 25-65 years) were compared to 52 age-, biological sex-, and intelligence-matched typically developing (TD; age range: 21-67 years) adults on three STM span tasks, which tested STM performance for letters (Verbal), grid locations (Visuospatial), or letters in grid locations (Multimodal). A subsample of 34 TD and 33 ASD participants ranging in age from 25 to 64 years completed a fourth Multimodal Integration task. We also administered the Color Trails Test as a measure of executive function. ASD participants' accuracy was lower than that of the TD participants on the three span tasks (Cohen's d: 0.26-0.50). The Integration task difference was marginally significant (p = .07) but had a moderate effect size (Cohen's d = 0.50). Regression analyses confirmed reduced STM performance only for older TD participants. Analyses also indicated that executive processes played a greater role in the ASD group's performance. The demonstration of similar difficulties and age-related patterning of STM in ASD to those documented for LTM and the greater recruitment of executive processes by older ASD participants on the Integration task suggest a compensatory role of frontal processes both as a means of achieving undiminished task performance and as a possible protection against older age cognitive decline in ASD. Longitudinal research is needed to confirm this. Autism Res 2020, 13: 1970-1984. © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC. LAY SUMMARY: Little is known about short-term memory (STM) in younger and older adults with autism spectrum disorder (ASD). This study tested different kinds of STM and showed that ASD adults remembered shorter sequences of letters, crosses, or letters in grid cells less well than matched participants with typical development. However, older ASD individuals performed similarly to younger ASD individuals, nor showing the reduction in performance usually seen with older age. The data suggest that ASD individuals use different underlying mechanisms when performing the tasks and that this might help protect their memory as they grow older.

Memory in autism spectrum disorder: A meta-analysis of experimental studies.

To address inconsistencies in the literature on memory in autism spectrum disorder (ASD), we report the first ever meta-analysis of short-term memory (STM) and episodic long-term memory (LTM) in ASD, evaluating the effects of type of material, type of retrieval and the role of interitem relations. Analysis of 64 studies comparing individuals with ASD and typical development (TD) showed greater difficulties in ASD compared with TD individuals in STM (Hedges' g = -0.53, 95% CI [-0.90, -0.16], p = .005, I² = 96%) compared with LTM (g = -0.30, 95% CI [-0.42, -0.17], p < .00001, I² = 24%), a small difficulty in verbal LTM (g = -0.21, p = .01), contrasting with a medium difficulty for visual LTM (g = -0.41, p = .0002) in ASD compared with TD individuals. We also found a general diminution in free recall compared with cued recall and recognition (LTM, free recall: g = -0.38, p < .00001, cued recall: g = -0.08, p = .58, recognition: g = -0.15, p = .16; STM, free recall: g = -0.59, p = .004, recognition: g = -0.33, p = .07). We discuss these results in terms of their relation to semantic memory. The limited diminution in verbal LTM and preserved overall recognition and cued recall (supported retrieval) may result from a greater overlap of these tasks with semantic long-term representations which are overall preserved in ASD. By contrast, difficulties in STM or free recall may result from less overlap with the semantic system or may involve additional cognitive operations and executive demands. These findings highlight the need to support STM functioning in ASD and acknowledge the potential benefit of using verbal materials at encoding and broader forms of memory support at retrieval to enhance performance. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Prospective Memory in Adolescents with Autism: A Preliminary Study of the Impact of Memory Load.

We evaluated event-based prospective memory (EBPM) in adolescents with Autism, varying the load of the to-be-performed intentions. We included measures of inhibition, working memory and binding. Results showed that increasing the retrospective memory load reduced performance in controls. In Autism, adolescents were impaired in the low load condition with normal performance for the ongoing task, with the reverse pattern in the high load condition. EBPM may be impacted in Autism due to difficulty to process ongoing and EBPM tasks simultaneously possibly because of restricted inhibitory control.

Positive Effect of Visual Cuing in Episodic Memory and Episodic Future Thinking in Adolescents With Autism Spectrum Disorder.

Cognitive studies generally report impaired autobiographical memory in individuals with autism spectrum disorder (ASD), but mostly using verbal paradigms. In the present study, we therefore investigated the properties of both past and future autobiographical productions using visual cues in 16 boys with ASD and 16 typically developing (TD) participants aged between 10 and 18 years. We focused on sensory properties, emotional properties, and recollection, probing past and future productions for both near and distant time periods. Results showed that the ASD group performed more poorly than controls on free recall for recent periods, but performed like them when provided with visual cues. In addition, the ASD group reported fewer sensory details than controls and exhibited difficulties in the experience of recollection for the most remote events. These data suggest a combination of consolidation and binding deficits. Finally, our findings reveal the relevance of using visual cues to probe autobiographical memory, with possible perspectives for memory rehabilitation.

Altered default mode network connectivity in adolescents with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.

Hippocampal subfields alterations in adolescents with post-traumatic stress disorder.

Reexperiencing symptoms in adolescent Post-Traumatic Stress Disorder (PTSD) are characterized by the apparition of vivid intrusive images of the traumatic event. The emergence of these intrusions is thought to be related to a deficiency in context processing and could then be related to hippocampal alterations. The hippocampus is a complex structure which can be divided into several subfields, namely, the Cornu Ammonis (CA1, CA2, and CA3), the subiculum, and the dentate gyrus (DG). As each subfield presents different histological characteristics and functions, it appears more relevant to consider hippocampal subfields, instead of only assessing the whole hippocampus, to understand the neurobiology of PTSD. Hence, this study presents the first investigation of structural alterations within hippocampal subfields and their links to reexperiencing symptoms in adolescent PTSD. Hippocampal subfields were manually delineated on high-resolution MRI images in 15 adolescents (13-18 years old) with PTSD and 24 age-matched healthy controls. The volume of the region CA2-3/DG region was significantly smaller in the PTSD group compared to controls in both hemispheres. No other significant difference was found for other subfields. Moreover, the volume of the left CA2-3/DG was negatively correlated with the intrusion score (as measured by the Impact of Events Scale-Revised) in the PTSD group. To conclude, an alteration in the hippocampal subregion CA2-3/DG, known to resolve interferences between new and similar stored memories, could participate in the apparition of intrusive trauma memories in adolescents with PTSD.

Impact of Semantic Relatedness on Associative Memory: An ERP Study.

Encoding and retrieval processes in memory for pairs of pictures are thought to be influenced by inter-item similarity and by features of individual items. Using Event-Related Potentials (ERP), we aimed to identify how these processes impact on both the early mid-frontal FN400 and the Late Positive Component (LPC) potentials during associative retrieval of pictures. Twenty young adults undertook a sham task, using an incidental encoding of semantically related and unrelated pairs of drawings. At test, we conducted a recognition task in which participants were asked to identify target identical pairs of pictures, which could be semantically related or unrelated, among new and rearranged pairs. We observed semantic (related and unrelated pairs) and condition effects (old, rearranged and new pairs) on the early mid-frontal potential. First, a lower amplitude was shown for identical and rearranged semantically related pairs, which might reflect a retrieval process driven by semantic cues. Second, among semantically unrelated pairs, we found a larger negativity for identical pairs, compared to rearranged and new ones, suggesting additional retrieval processing that focuses on associative information. We also observed an LPC old/new effect with a mid-parietal and a right occipito-parietal topography for semantically related and unrelated old pairs, demonstrating a recollection phenomenon irrespective of the degree of association. These findings suggest that associative recognition using visual stimuli begins at early stages of retrieval, and differs according to the degree of semantic relatedness among items. However, either strategy may ultimately lead to recollection processes.

Functional brain alterations during self-reference processing in adolescents with sexual abuse-related post-traumatic stress disorder: A preliminary report.

We proposed to explore the functional brain changes during a self-reference processing (SRP) task in adolescents with sexual abuse-related post-traumatic stress disorder (N = 10), compared with healthy adolescents (N = 10). While patients showed no behavioral disturbances in (SRP), they exhibited changes in activity and connectivity in regions involved in emotional regulation (amygdala and dorsal prefrontal cortex) and semantic memory (temporal and ventrolateral prefrontal regions). These preliminary results suggest that these alterations may have an effect on self-esteem which may contribute to a possible retention and impairment of symptoms in adulthood.

Rhythms dysregulation: A new perspective for understanding PTSD?

Post-traumatic stress disorder (PTSD) is a complex syndrome that may occur after exposure to one or more traumatic events. It associates physiological, emotional, and cognitive changes Brain and hormonal modifications contribute to some impairments in learning, memory, and emotion regulation. Some of these biological dysfunctions may be analyzed in terms of rhythms dysregulation that would be expressed through endocrine rhythmicity, sleep organization, and temporal synchrony in brain activity. In the first part of this article, we report studies on endocrine rhythmicity revealing that some rhythms abnormalities are frequently observed, although not constantly, for both cortisol and sympathetic nervous system (SNS) activity. The most typical changes are a flattening of the diurnal secretion of cortisol and the hyperactivation of the SNS. These results may explain why cognitive functioning, in particular consolidation of emotional memories, attention, learning, vigilance and arousal, is altered in patients with PTSD. The second part of this article focuses on sleep disturbances, one of the core features of PTSD. Abnormal REM sleep reported in various studies may have a pathophysiological role in PTSD and may exacerbate some symptoms such as emotional regulation and memory. In addition, sleep disorders, such as paradoxical insomnia, increase the risk of developing PTSD. We also discuss the potential impact of sleep disturbances on cognition. Finally, temporal synchrony of brain activity and functional connectivity, explored using electroencephalography and functional magnetic resonance imaging, are addressed. Several studies reported abnormalities in alpha, beta and gamma frequency bands that may affect both attentional and memory processes. Other studies confirmed abnormalities in connectivity and recent fMRI data suggest that this could limit top-down control and may be associated with flashback intrusive memories. These data illustrate that a better knowledge of the different patterns of biological rhythms contributes to explain the heterogeneity of PTSD and shed new light on the association with some frequent medical disorders.

Neural Correlates of Self and Its Interaction With Memory in Healthy Adolescents.

Adolescence is marked by the development of personal identity and is associated with structural and functional changes in brain regions associated with Self processing. Yet, little is known about the neural correlates of self-reference processing and self-reference effect in adolescents. This functional magnetic resonance imaging study consists of a self-reference paradigm followed by a recognition test proposed to 30 healthy adolescents aged 13-18 years old. Results showed that the rostral anterior cingulate cortex is specifically involved in self-reference processing and that this specialization develops gradually from 13 to 18 years old. The self-reference effect is associated with increased brain activation changes during encoding, suggesting that the beneficial effect of Self on memory may occur at encoding of self-referential information, rather than at retrieval.

Binding in working memory and frontal lobe in normal aging: is there any similarity with autism?

Some studies highlight similarities between Autism Spectrum Disorder (ASD) and healthy aging. Indeed, the decline in older individuals' ability to create a unified representation of the individual features of an event is thought to arise from a disruption of binding within the episodic buffer of working memory (WM) as the same way as observed in ASD. In both cases, this deficit may result from an abnormal engagement of a frontohippocampal network. The objective of the present study is to identify both cognitive processes and neural substrates associated with the deficit of binding in WM in healthy aging. We studied the capacity of binding and the cognitive processes that might subtend its decline in 72 healthy participants aged 18-84 years. We examined the behavioral data in relation to the changes in brain metabolism associated with the age-related decline in a subgroup of 34 healthy participants aged 20-77 years using the resting-state [(18)F] fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). Forward stepwise regression analyses showed that the age-related decline in binding was partially explained by a decline in inhibition and processing speed. PET correlation analyses indicated that metabolism of the frontal regions, anterior and middle cingulate cortices is implicated in this phenomenon. These data suggest that executive functions and processing speed may play a crucial role in the capacity to integrate unified representations in memory in aging. Possible implications are discussed in ASD.