Investigating the Effect of Contextual Cueing with Face Stimuli on Electrophysiological Measures in Younger and Older Adults.

Extracting repeated patterns from our surroundings plays a crucial role in contextualizing information, making predictions, and guiding our behavior implicitly. Previous research showed that contextual cueing enhances visual search performance in younger adults. In this study, we investigated whether contextual cueing could also improve older adults' performance and whether age-related differences in the neural processes underlying implicit contextual learning could be detected. Twenty-four younger and 25 older participants performed a visual search task with contextual cueing. Contextual information was generated using repeated face configurations alongside random new configurations. We measured RT difference between new and repeated configurations; ERPs to uncover the neural processes underlying contextual cueing for early (N2pc), intermediate (P3b), and late (r-LRP) processes; and multiscale entropy and spectral power density analyses to examine neural dynamics. Both younger and older adults showed similar contextual cueing benefits in their visual search efficiency at the behavioral level. In addition, they showed similar patterns regarding contextual information processing: Repeated face configurations evoked decreased finer timescale entropy (1-20 msec) and higher frequency band power (13-30 Hz) compared with new configurations. However, we detected age-related differences in ERPs: Younger, but not older adults, had larger N2pc and P3b components for repeated compared with new configurations. These results suggest that contextual cueing remains intact with aging. Although attention- and target-evaluation-related ERPs differed between the age groups, the neural dynamics of contextual learning were preserved with aging, as both age groups increasingly utilized more globally grouped representations for repeated face configurations during the learning process.

Functional brain network features specify DBS outcome for patients with treatment resistant depression.

Deep brain stimulation (DBS) has shown therapeutic benefits for treatment resistant depression (TRD). Stimulation of the subcallosal cingulate gyrus (SCG) aims to alter dysregulation between subcortical and cortex. However, the 50% response rates for SCG-DBS indicates that selection of appropriate patients is challenging. Since stimulation influences large-scale network function, we hypothesized that network features can be used as biomarkers to inform outcome. In this pilot project, we used resting-state EEG recorded longitudinally from 10 TRD patients with SCG-DBS (11 at baseline). EEGs were recorded before DBS-surgery, 1-3 months, and 6 months post surgery. We used graph theoretical analysis to calculate clustering coefficient, global efficiency, eigenvector centrality, energy, and entropy of source-localized EEG networks to determine their topological/dynamical features. Patients were classified as responders based on achieving a 50% or greater reduction in Hamilton Depression (HAM-D) scores from baseline to 12 months post surgery. In the delta band, false discovery rate analysis revealed that global brain network features (segregation, integration, synchronization, and complexity) were significantly lower and centrality of subgenual anterior cingulate cortex (ACC) was higher in responders than in non-responders. Accordingly, longitudinal analysis showed SCG-DBS increased global network features and decreased centrality of subgenual ACC. Similarly, a clustering method separated two groups by network features and significant correlations were identified longitudinally between network changes and depression symptoms. Despite recent speculation that certain subtypes of TRD are more likely to respond to DBS, in the SCG it seems that underlying brain network features are associated with ability to respond to DBS. SCG-DBS increased segregation, integration, and synchronizability of brain networks, suggesting that information processing became faster and more efficient, in those patients in whom it was lower at baseline. Centrality results suggest these changes may occur via altered connectivity in specific brain regions especially ACC. We highlight potential mechanisms of therapeutic effect for SCG-DBS.

Baseline Functional Connectivity in Resting State Networks Associated with Depression and Remission Status after 16 Weeks of Pharmacotherapy: A CAN-BIND Report.

Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. So far, findings are variable and large sample replications scarce. We aimed to replicate and extend altered functional connectivity associated with MDD and pharmacotherapy outcomes in a large, multisite sample. Resting-state fMRI data were collected from 129 patients and 99 controls through the Canadian Biomarker Integration Network in Depression. Symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Connectivity was measured as correlations between four seeds (anterior and posterior cingulate cortex, insula and dorsolateral prefrontal cortex) and all other brain voxels. Partial least squares was used to compare connectivity prior to treatment between patients and controls, and between patients reaching remission (MADRS ≤ 10) early (within 8 weeks), late (within 16 weeks), or not at all. We replicated previous findings of altered connectivity in patients. In addition, baseline connectivity of the anterior/posterior cingulate and insula seeds differentiated patients with different treatment outcomes. The stability of these differences was established in the largest single-site subsample. Our replication and extension of altered connectivity highlighted previously reported and new differences between patients and controls, and revealed features that might predict remission prior to pharmacotherapy. Trial registration:ClinicalTrials.gov: NCT01655706.

High-resolution virtual brain modeling personalizes deep brain stimulation for treatment-resistant depression: Spatiotemporal response characteristics following stimulation of neural fiber pathways.

Over the past 15 years, deep brain stimulation (DBS) has been actively investigated as a groundbreaking therapy for patients with treatment-resistant depression (TRD); nevertheless, outcomes have varied from patient to patient, with an average response rate of ∼50%. The engagement of specific fiber tracts at the stimulation site has been hypothesized to be an important factor in determining outcomes, however, the resulting individual network effects at the whole-brain scale remain largely unknown. Here we provide a computational framework that can explore each individual's brain response characteristics elicited by selective stimulation of fiber tracts. We use a novel personalized in-silico approach, the Virtual Big Brain, which makes use of high-resolution virtual brain models at a mm-scale and explicitly reconstructs more than 100,000 fiber tracts for each individual. Each fiber tract is active and can be selectively stimulated. Simulation results demonstrate distinct stimulus-induced event-related potentials as a function of stimulation location, parametrized by the contact positions of the electrodes implanted in each patient, even though validation against empirical patient data reveals some limitations (i.e., the need for individual parameter adjustment, and differential accuracy across stimulation locations). This study provides evidence for the capacity of personalized high-resolution virtual brain models to investigate individual network effects in DBS for patients with TRD and opens up novel avenues in the personalized optimization of brain stimulation.

The longitudinal relationship between BOLD signal variability changes and white matter maturation during early childhood.

Intra-individual transient temporal fluctuations in brain signal, as measured by fMRI blood oxygenation level dependent (BOLD) variability, is increasingly considered an important signal rather than measurement noise. Evidence from computational and cognitive neuroscience suggests that signal variability is a good proxy-measure of brain functional integrity and information processing capacity. Here, we sought to explore across-participant and longitudinal relationships between BOLD variability, age, and white matter structure in early childhood. We measured standard deviation of BOLD signal, total white matter volume, global fractional anisotropy (FA) and mean diffusivity (MD) during passive movie viewing in a sample of healthy children (aged 2-8 years; N = 83). We investigated how age and white matter development related to changes in BOLD variability both across- and within-participants. Our across-participant analyses using behavioural partial least squares (bPLS) revealed that the influence of age and white matter maturation on BOLD variability was highly interrelated. BOLD variability increased in widespread frontal, temporal and parietal regions, and decreased in the hippocampus and parahippocampal gyrus with age and white matter development. Our longitudinal analyses using linear mixed effects modelling revealed significant associations between BOLD variability, age and white matter microstructure. Analyses using artificial neural networks demonstrated that BOLD variability and white matter micro and macro-structure at earlier ages were strong predictors of BOLD variability at later ages. By characterizing the across-participant and longitudinal features of the association between BOLD variability and white matter micro- and macrostructure in early childhood, our results provide a novel perspective to understand structure-function relationships in the developing brain.

Increased Neural Efficiency in Visual Word Recognition: Evidence from Alterations in Event-Related Potentials and Multiscale Entropy.

Visual word recognition is a relatively effortless process, but recent research suggests the system involved is malleable, with evidence of increases in behavioural efficiency after prolonged lexical decision task (LDT) performance. However, the extent of neural changes has yet to be characterized in this context. The neural changes that occur could be related to a shift from initially effortful performance that is supported by control-related processing, to efficient task performance that is supported by domain-specific processing. To investigate this, we replicated the British Lexicon Project, and had participants complete 16 h of LDT over several days. We recorded electroencephalography (EEG) at three intervals to track neural change during LDT performance and assessed event-related potentials and brain signal complexity. We found that response times decreased during LDT performance, and there was evidence of neural change through N170, P200, N400, and late positive component (LPC) amplitudes across the EEG sessions, which suggested a shift from control-related to domain-specific processing. We also found widespread complexity decreases alongside localized increases, suggesting that processing became more efficient with specific increases in processing flexibility. Together, these findings suggest that neural processing becomes more efficient and optimized to support prolonged LDT performance.

Revisiting mental rotation with stereoscopic disparity: A new spin for a classic paradigm.

To understand how the presence of stereoscopic disparity influences cognitive and neural processing, we recorded participants' behavior and scalp electrical activity while they performed a mental rotation task. Participants wore active shutter 3D goggles, allowing us to present stimuli with or without stereoscopic disparity on a trial-by-trial basis. Participants were more accurate and faster when stimuli were presented with stereoscopic disparity. This improvement in performance was accompanied by changes in neural activity recorded from scalp electrodes at parietal and occipital regions; stereoscopic disparity produced earlier P2 peaks, larger N2 amplitudes, and earlier, smaller P300 peak amplitudes. The presence of stereoscopic disparity also produced greater neural entropy at occipital electrode sites, and lower entropy at frontal sites. These findings suggest that the nature of the benefit afforded by stereoscopic disparity occurs at both low-level perceptual processing and higher-level cognitive processing, and results in more accurate and rapid performance.

Getting a grip on sensorimotor effects in lexical-semantic processing.

One of the strategies that researchers have used to investigate the role of sensorimotor information in lexical-semantic processing is to examine the effects of words' rated body-object interaction (BOI; i.e., the ease with which the human body can interact with a word's referent). Processing tends to be facilitated for words with high as compared with low BOI, across a wide variety of tasks. Such effects have been referenced in debates over the nature of semantic representations, but their theoretical import has been limited by the fact that BOI is a fairly coarse measure of sensorimotor experience with words' referents. In the present study, we collected ratings for 621 words on seven semantic dimensions (graspability, ease of pantomime, number of actions, animacy, size, danger, and usefulness), in order to investigate which attributes are most strongly related to BOI ratings and to lexical-semantic processing. BOI ratings were obtained from previous norming studies (Bennett, Burnett, Siakaluk, & Pexman in Behavior Research Methods, 43, 1100-1109, 2011; Tillotson, Siakaluk, & Pexman in Behavior Research Methods, 40, 1075-1078, 2008), and measures of lexical-semantic processing were obtained from previous behavioral megastudies involving either the semantic categorization task (concrete/abstract decision; Pexman, Heard, Lloyd, & Yap in Behavior Research Methods, 49, 407-417, 2017) or the lexical decision task (Balota et al., Behavior Research Methods, 39, 445-459, 2007). The results showed that the motor dimensions of graspability, ease of pantomime, and number of actions were all related to BOI, and that these dimensions together explained more variance in semantic processing than did the BOI ratings alone. These ratings will be useful for researchers who wish to study how different kinds of bodily interactions influence lexical-semantic processing and cognition.

Age-related Multiscale Changes in Brain Signal Variability in Pre-task versus Post-task Resting-state EEG.

Recent empirical work suggests that, during healthy aging, the variability of network dynamics changes during task performance. Such variability appears to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into resting-state dynamics. We recorded EEG in young, middle-aged, and older adults during a "rest-task-rest" design and investigated if aging modifies the interaction between resting-state activity and external stimulus-induced activity. Using multiscale entropy as our measure of variability, we found that, with increasing age, resting-state dynamics shifts from distributed to more local neural processing, especially at posterior sources. In the young group, resting-state dynamics also changed from pre- to post-task, where fine-scale entropy increased in task-positive regions and coarse-scale entropy increased in the posterior cingulate, a key region associated with the default mode network. Lastly, pre- and post-task resting-state dynamics were linked to performance on the intervening task for all age groups, but this relationship became weaker with increasing age. Our results suggest that age-related changes in resting-state dynamics occur across different spatial and temporal scales and have consequences for information processing capacity.

Changes in cortical activity measured with EEG during a high-intensity cycling exercise.

This study investigated the effects of a high-intensity cycling exercise on changes in spectral and temporal aspects of electroencephalography (EEG) measured from 10 experienced cyclists. Cyclists performed a maximum aerobic power test on the first testing day followed by a time-to-exhaustion trial at 85% of their maximum power output on 2 subsequent days that were separated by ∼48 h. EEG was recorded using a 64-channel system at 500 Hz. Independent component (IC) analysis parsed the EEG scalp data into maximal ICs. An equivalent current dipole model was calculated for each IC, and results were clustered across subjects. A time-frequency analysis of the identified electrocortical clusters was performed to investigate the magnitude and timing of event-related spectral perturbations. Significant changes (P < 0.05) in electrocortical activity were found in frontal, supplementary motor and parietal areas of the cortex. Overall, there was a significant increase in EEG power as fatigue developed throughout the exercise. The strongest increase was found in the frontal area of the cortex. The timing of event-related desynchronization within the supplementary motor area corresponds with the onset of force production and the transition from flexion to extension in the pedaling cycle. The results indicate an involvement of the cerebral cortex during the pedaling task that most likely involves executive control function, as well as motor planning and execution.

Characterizing functional integrity: intraindividual brain signal variability predicts memory performance in patients with medial temporal lobe epilepsy.

Computational modeling suggests that variability in brain signals provides important information regarding the system's capacity to adopt different network configurations that may promote optimal responding to stimuli. Although there is limited empirical work on this construct, a recent study indicates that age-related decreases in variability across the adult lifespan correlate with less efficient and less accurate performance. Here, we extend this construct to the assessment of cerebral integrity by comparing fMRI BOLD variability and fMRI BOLD amplitude in their ability to account for differences in functional capacity in patients with focal unilateral medial temporal dysfunction. We were specifically interested in whether either of these BOLD measures could identify a link between the affected medial temporal region and memory performance (as measured by a clinical test of verbal memory retention). Using partial least-squares analyses, we found that variability in a set of regions including the left hippocampus predicted verbal retention and, furthermore, this relationship was similar across a range of cognitive tasks measured during scanning (i.e., the same pattern was seen in fixation, autobiographical recall, and word generation). In contrast, signal amplitude in the hippocampus did not predict memory performance, even for a task that reliably activates the medial temporal lobes (i.e., autobiographical recall). These findings provide a powerful validation of the concept that variability in brain signals reflects functional integrity. Furthermore, this measure can be characterized as a robust biomarker in this clinical setting because it reveals the same pattern regardless of cognitive challenge or task engagement during scanning.

Neural network configuration and efficiency underlies individual differences in spatial orientation ability.

Spatial orientation is a complex cognitive process requiring the integration of information processed in a distributed system of brain regions. Current models on the neural basis of spatial orientation are based primarily on the functional role of single brain regions, with limited understanding of how interaction among these brain regions relates to behavior. In this study, we investigated two sources of variability in the neural networks that support spatial orientation--network configuration and efficiency--and assessed whether variability in these topological properties relates to individual differences in orientation accuracy. Participants with higher accuracy were shown to express greater activity in the right supramarginal gyrus, the right precentral cortex, and the left hippocampus, over and above a core network engaged by the whole group. Additionally, high-performing individuals had increased levels of global efficiency within a resting-state network composed of brain regions engaged during orientation and increased levels of node centrality in the right supramarginal gyrus, the right primary motor cortex, and the left hippocampus. These results indicate that individual differences in the configuration of task-related networks and their efficiency measured at rest relate to the ability to spatially orient. Our findings advance systems neuroscience models of orientation and navigation by providing insight into the role of functional integration in shaping orientation behavior.

Resting-state neural dynamics changes in older adults with post-COVID syndrome and the modulatory effect of cognitive training and sex.

Post-COVID syndrome manifests with numerous neurological and cognitive symptoms, the precise origins of which are still not fully understood. As females and older adults are more susceptible to developing this condition, our study aimed to investigate how post-COVID syndrome alters intrinsic brain dynamics in older adults and whether biological sex and cognitive training might modulate these effects, with a specific focus on older females. The participants, aged between 60 and 75 years, were divided into three experimental groups: healthy old female, post-COVID old female and post-COVID old male. They underwent an adaptive task-switching training protocol. We analysed multiscale entropy and spectral power density of resting-state EEG data collected before and after the training to assess neural signal complexity and oscillatory power, respectively. We found no difference between post-COVID females and males before training, indicating that post-COVID similarly affected both sexes. However, cognitive training was effective only in post-COVID females and not in males, by modulating local neural processing capacity. This improvement was further evidenced by comparing healthy and post-COVID females, wherein the latter group showed increased finer timescale entropy (1-30 ms) and higher frequency band power (11-40 Hz) before training, but these differences disappeared following cognitive training. Our results suggest that in older adults with post-COVID syndrome, there is a pronounced shift from more global to local neural processing, potentially contributing to accelerated neural aging in this condition. However, cognitive training seems to offer a promising intervention method for modulating these changes in brain dynamics, especially among females.

One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response.

Introduction: To date, no robust electroencephalography (EEG) markers of antidepressant treatment response have been identified. Variable findings may arise from the use of group analyses, which neglect individual variation. Using a combination of group and single-participant analyses, we explored individual variability in EEG characteristics of treatment response. Methods: Resting-state EEG data and Montgomery-Åsberg Depression Rating Scale (MADRS) symptom scores were collected from 43 patients with depression before, at 1 and 12 weeks of pharmacotherapy. Partial least squares (PLS) was used to: 1) identify group differences in EEG connectivity (weighted phase lag index) and complexity (multiscale entropy) between eventual medication responders and non-responders, and 2) determine whether group patterns could be identified in individual patients. Results: Responders showed decreased alpha and increased beta connectivity, and early, widespread decreases in complexity over treatment. Non-responders showed an opposite connectivity pattern, and later, spatially confined decreases in complexity. Thus, as in previous studies, our group analyses identified significant differences between groups of patients with different treatment outcomes. These group-level EEG characteristics were only identified in ~40-60% of individual patients, as assessed quantitatively by correlating the spatiotemporal brain patterns between groups and individual results, and by independent raters through visualization. Discussion: Our single-participant analyses suggest that substantial individual variation exists, and needs to be considered when investigating characteristics of antidepressant treatment response for potential clinical applicability. Clinical trial registration: https://clinicaltrials.gov, identifier NCT00519428.

Large Individual Differences in Functional Connectivity in the Context of Major Depression and Antidepressant Pharmacotherapy.

Clinical studies of major depression (MD) generally focus on group effects, yet interindividual differences in brain function are increasingly recognized as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2, and 8 weeks during which patients received pharmacotherapy (escitalopram, N = 68) and controls (N = 39) received no intervention. The unique contributions of different sources of variation were examined by calculating how much variance in functional connectivity was shared across all participants and sessions, within/across groups (patients vs controls, responders vs nonresponders, female vs male participants), recording sessions, and individuals. Individual differences and common connectivity across groups, sessions, and participants contributed most to the explained variance (>95% across analyses). Group differences related to MD diagnosis, treatment response, and biological sex made significant but small contributions (0.3-1.2%). High individual variation was present in cognitive control and attention areas, while low individual variation characterized primary sensorimotor regions. Group differences were much smaller than individual differences in the context of MD and its treatment. These results could be linked to the variable findings and difficulty translating research on MD to clinical practice. Future research should examine brain features with low and high individual variation in relation to psychiatric symptoms and treatment trajectories to explore the clinical relevance of the individual differences identified here.

Distinct patterns of functional and effective connectivity between perirhinal cortex and other cortical regions in recognition memory and perceptual discrimination.

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched perceptual and recognition memory tasks for faces that engaged right PrC equivalently. Multivariate seed analyses revealed distinct patterns of interactions: Right ventrolateral prefrontal and posterior cingulate cortices exhibited stronger functional connectivity with PrC in recognition memory; fusiform regions were part of the pattern that displayed stronger functional connectivity with PrC in perceptual discrimination. Structural equation modeling revealed distinct patterns of effective connectivity that allowed us to constrain interpretation of these findings. Overall, they demonstrate that, even when MTL structures show similar involvement in recognition memory and perceptual discrimination, differential neural mechanisms are reflected in the interplay between the MTL and other cortical regions.

A dose-response characterization of transcranial magnetic stimulation intensity and evoked potential amplitude in the dorsolateral prefrontal cortex.

By combining transcranial magnetic stimulation (TMS) with electroencephalography, human cortical circuits can be directly interrogated. The resulting electrical trace contains TMS-evoked potential (TEP) components, and it is not known whether the amplitudes of these components are stimulus intensity dependent. We examined this in the left dorsolateral prefrontal cortex in nineteen healthy adult participants and extracted TEP amplitudes for the N40, P60, N120, and P200 components at 110%, 120%, and 130% of resting motor threshold (RMT). To probe plasticity of putative stimulus intensity dose-response relationships, this was repeated after participants received intermittent theta burst stimulation (iTBS; 600 pulses, 80% RMT). The amplitude of the N120 and P200 components exhibited a stimulus intensity dose-response relationship, however the N40 and P60 components did not. After iTBS, the N40 and P60 components continued to exhibit a lack of stimulus intensity dose-dependency, and the P200 dose-response was unchanged. In the N120 component, however, we saw evidence of change within the stimulus intensity dose-dependent relationship characterized by a decrease in absolute peak amplitudes at lower stimulus intensities. These data suggest that TEP components have heterogeneous dose-response relationships, with implications for standardizing and harmonizing methods across experiments. Moreover, the selective modification of the N120 dose-response relationship may provide a novel marker for iTBS plasticity in health and disease.

EEG complexity during mind wandering: A multiscale entropy investigation.

Our attention often drifts away from the ongoing task to task-unrelated thoughts, a phenomenon commonly referred to as mind wandering. Ample studies dedicated to delineating its electrophysiological correlates have revealed distinct event-related potentials (ERP) and spectral patterns associated with mind wandering. It remains less clear whether the complexity of the electroencephalography (EEG) changes when our minds wander, a metric that captures the predictability of the time series at varying timescales. Accordingly, this study investigated whether mind wandering impacts EEG signal complexity. We further explored whether such effects differ across timescales, and change in a context-dependent manner as indexed by global and local levels of processing. To address this, we recorded participants' EEG while they completed Navon's global and local processing task and occasionally reported whether they were on-task or mind wandering throughout the task. We found that brain signal complexity as indexed by multiscale entropy decreased at medium timescales in centro-parietal regions and increased at coarse timescales in anterior and posterior regions during mind wandering, as compared to the on-task state, for global processing. Moreover, global processing showed increased complexity at fine to medium timescales compared to local processing. Finally, behavioral performance revealed a context-dependent effect in accuracy measures, with mind wandering showing lower accuracy compared to the on-task state only during the local condition. Taken together, these results indicate that changes in brain signal complexity across timescales may be an important feature of mind wandering.

Context matters: How do task demands modulate the recruitment of sensorimotor information during language processing?

Many theories of semantic representation propose that simulations of sensorimotor experience contribute to language processing. This can be seen in the body-object interaction effect (BOI; how easily the human body can interact with a word's referent). Words with high BOI ratings (e.g., ball) are processed more quickly than words with low BOI ratings (e.g., cloud) in various language tasks. This effect can be modulated by task demands. Previous research established that when asked to decide if a word is an object (entity condition), a BOI effect is observed, but when asked to decide if a word is an action (action condition), there is no BOI effect. It is unclear whether the null behavioral effect in the action condition reflects top-down modulation of task-relevant sensorimotor information or the absence of bottom-up activation of sensorimotor simulations. We investigated this question using EEG. In Experiment 1 we replicated the previous behavioral findings. In Experiment 2, 50 participants were assigned to either the entity or action conditions and responded to the same word stimuli. In both conditions we observed differences in ERP components related to the BOI effect. In the entity condition the P2 mean amplitude was significantly more positive for high compared to low BOI words. In the action condition the N400 peak latency was significantly later for high compared to low BOI words. Our findings suggest that BOI information is generated bottom-up regardless of task demands and modulated by top-down processes that recruit sensorimotor information relevant to the task decision.

Sex differences in the relationship between age, performance, and BOLD signal variability during spatial context memory processing.

Recent work suggests that the relationship between age and memory-related brain activity are different for men and women. We sought to extend this work by examining sex differences in the association between age, memory performance, and brain signal variability during context memory tasks in neurotypical adults (aged 19-76 years; N = 128, 87 women). We measured blood oxygen level-dependent standard deviation (BOLD SD) during encoding and retrieval in easy and difficult spatial context memory tasks and investigated sex-specific, age- and performance-associated BOLD SD patterns. Behavioral analysis revealed age-related decreases in memory retrieval, but no sex differences nor an age-by-sex interaction. Imaging results indicated that both sexes showed a negative correlation between BOLD SD and retrieval accuracy in memory-related regions. We also identified significant sex differences: women exhibited age-associated increases in BOLD SD which were negatively associated with performance. Men exhibited both age-associated decreases and increases, which were not related to performance. Our results revealed sex differences in the relationship between age and BOLD SD during high-demand episodic memory tasks.