Cerebral Cortex Communications

Moderate-to-severe traumatic brain injury (msTBI) is recognized as a chronic and evolving neurological condition characterized by progressive structural brain changes and persistent cognitive impairment. While prior studies have demonstrated widespread atrophy following msTBI, less is known regarding the longitudinal trajectory of gray matter (GM) changes during recovery and post-rehabilitation. The current study used longitudinal voxel-based morphometry (VBM) to characterize GM volume changes over a period of 9 months, in individuals with msTBI relative to healthy controls (HC). Associations between regional GM volume and neuropsychological functioning were examined. Twenty-eight participants (14 msTBI, 14 HC) completed MRI and neuropsychological assessments across three timepoints spanning outpatient rehabilitation and follow-up. Longitudinal VBM analyses revealed significant group and time interactions within subcortical and limbic regions. Relative to HC, individuals with msTBI showed lower GM volume in these regions at baseline, with trajectories that converged toward HC values (right hippocampus) or increased relative to HC over the rehabilitation period (bilateral pulvinar), whereas the right amygdala and inferior cerebellar vermis remained persistently reduced. Significant longitudinal improvements in memory and psychomotor speed during the rehabilitation period were demonstrated in msTBI. Greater (preserved) GM volume within the right hippocampus, thalamus, and bilateral pulvinar was associated with better performance across measures of verbal memory, processing speed, executive functioning, and cognitive flexibility. These findings suggest that msTBI is associated with dynamic structural brain changes involving subcortical, limbic, and cerebellar networks, and that the rehabilitation period was accompanied by relative volumetric stabilization in these regions and by meaningful cognitive improvement.

Human long-term memory for visual scenes is remarkably robust, yet the neural mechanisms supporting memory encoding and retrieval remain poorly understood when both processes must operate at the same time. For instance, this might happen when we encounter a familiar place while simultaneously forming new memories of this encounter. We investigated electrophysiological correlates of visual recognition memory using a continuous recognition task (CRT), in which participants judged a continuous stream of scene photographs as previously seen or new, such that encoding and retrieval occurred in parallel on every trial. To make recognition particularly demanding, stimuli were drawn from only four scene categories. Thirty-one participants performed the task while EEG was recorded, and we analyzed canonical ERP markers of retrieval (mid-frontal FN400, 300-550 ms; late parietal effect, LPE, 550-800 ms) and encoding (subsequent memory effect, SME) as a function of stimulus repetition and lag between consecutive presentations. FN400 showed robust old/new effects for both repetitions, whereas LPE differences emerged only at the second repetition. While FN400 amplitude was insensitive to lag, LPE amplitude decreased systematically with increasing lag, mirroring the behavioral pattern of declining accuracy and slower responses. A significant SME emerged selectively for images subsequently recognized on both repetitions, indicating that the SME in continuous recognition is specific for the most robustly encoded items and reflects the strength of encoding. Together, these findings show that canonical ERP markers of recognition memory are preserved even when encoding and retrieval operate concurrently, but their expression depends on how often and how recently an item has previously been encoded - parameters that can be flexibly manipulated within the CRT. This demonstrates that the CRT is sensitive to fine-grained temporal dynamics of memory formation and retrieval that could be missed under standard single-repetition designs.

We investigated the dimensions of output zones affecting specific combinations of forelimb muscles in the precentral "motor" cortex of macaque monkeys. Single-pulse intracortical microstimulation (S-ICMS) was used to evoke subthreshold effects in multiple wrist and finger muscles. Results indicate that each motor cortex site represents a different combination of muscles. The effects evoked from cortical sites separated by several hundred microns invariably involved different profiles of muscle activity. The muscle fields of remote CM cells were rarely identical, while the fields of neighboring CM cells were often similar. Given the number of unrecorded muscles, we conclude that primate motor cortex is a mosaic of output sites representing forelimb muscles in different combinations.

Object representations in the human ventral occipitotemporal cortex (VOTC) are organized along multiple dimensions, including shape (rectilinear vs. curvilinear), real-world size (large vs. small), and mobility (stationary vs. mobile). However, these dimensions are strongly correlated in naturalistic vision, making their separate contributions to VOTC organization unclear. For example, large objects (e.g., a wardrobe, a house) are typically rectilinear and stationary, while small objects (e.g., a ball, a cup) are more curvilinear and mobile. Here, we used fMRI, together with a new stimulus set that orthogonally manipulates shape, size, and mobility, to investigate the separate influences of these dimensions on VOTC organization. Example stimuli include air balloon (large, curvilinear, mobile), radar dish (large, curvilinear, stationary), and mailbox (small, rectilinear, stationary). Contrasts revealed that large (vs. small), rectilinear (vs. curvilinear), and stationary (vs. mobile) dimensions all independently evoked strong and overlapping activity in medio-anterior VOTC. This overlapping activity was at the intersection of the parahippocampal place area (PPA) and the ventral place-memory area (VPMA). Similar results were found at the intersection of the scene-selective occipital place area and the lateral place-memory area (LPMA). Finally, large (vs. small), but not rectilinear (vs. curvilinear) or stationary (vs. mobile) activity, was found in additional posterior ventral scene-selective regions, as well as in early visual cortex. Overall, these results indicate that object shape, real-world size, and mobility dimensions all independently activate scene-selective PPA and OPA, showing joint selectivity for distinct low- and high-level object properties that are highly correlated in naturalistic vision.

Sleep supports episodic memory consolidation, yet it remains unclear how naturalistic post-encoding sleep quality relates to the neural reinstatement of episodic representations across adulthood. The present study examined whether sleep discontinuity during the retention interval predicted delayed context memory and encoding-retrieval similarity (ERS) of EEG in younger and older adults. Participants completed an object-scene context memory task with immediate and delayed retrieval, while EEG was recorded during encoding and retrieval. Actigraphy was used to measure sleep across the post-encoding retention period, and principal component analysis identified sleep discontinuity and sleep time components. Behavioral results showed that greater post-encoding sleep discontinuity, but not sleep time, was associated with poorer delayed memory accuracy for mismatching object-context pairs across age. ERS analyses further showed that greater sleep discontinuity was associated with reduced ERS for correctly rejected mismatching pairs across frontal and posterior spatiotemporal clusters. Age moderated sleep-ERS associations: greater sleep discontinuity was generally related to lower ERS in younger adults, whereas some spatiotemporal clusters showed positive associations in older adults, potentially reflecting compensatory or effortful retrieval-related processing in poorer sleepers. Together, these findings suggest that sleep continuity during the post-encoding retention interval is important for preserving high-fidelity episodic representations needed for later context discrimination. More broadly, the results demonstrate that naturalistic sleep fragmentation is linked to both behavioral memory outcomes and neural reinstatement across adults.

Neural activity in frontal-striatal circuits underlies reinforcement learning. Traditional theories suggest that reinforcement signals, which drive learning, strengthen connections within the basal ganglia. This strengthening is believed to shift information processing from cortical regions to subcortical regions as learning becomes established over time. To examine this hypothesis, we trained macaques to associate multiple sets of images with their values. Selecting different images led to either an increase (+2, +1) or a decrease (-1, -2) in the number of tokens, which subsequently determined the amount of juice reward the macaques received. We simultaneously recorded neuronal activity from orbitofrontal cortex, ventral striatum, amygdala, and dorsomedial thalamic nucleus, analyzing the dynamic changes in these brain regions during both the initial learning and overlearned stages. The results indicated that as learning progressed from the initial stage to the overlearned stage, information processing shifted from the ventral striatum to the orbitofrontal cortex, corresponding to the abstraction from stimulus value to state value. This finding challenges traditional theories and provides a new perspective on the neural circuit mechanisms of learning.

Voluntary movement requires the central nervous system to transform and integrate visual and somatosensory information into coordinated motor outputs. Although mirrorlike neuronal activity during both action execution and observation has been extensively described in premotor, motor, and parietal cortices, it remains unknown whether the primary somatosensory cortex (S1) also participates in the action observation network. Here, we recorded single-unit activity from cytoarchitectonically defined areas 3a, 3b, 1, and 2 in macaque S1 while monkeys either executed or observed grasping movements. Approximately one-third of neurons across S1 modulated their firing during action observation, with the proportion of responsive neurons increasing from area 3 to areas 1 and 2, consistent with the hierarchical organization of somatosensory processing. Most action observation neurons showed congruent activity during action execution and observation, suggesting that these responses may reflect top-down motor-related or integrated visuomotor signals and are unlikely to be explained by visual input alone. The higher prevalence of action observation neurons in areas 1 and 2 suggests that action observation-related signals preferentially influence later stages of somatosensory processing, potentially via cortico-cortical interactions with motor and parietal regions.

Audiovisual semantic matching can be achieved using either written words or pictures, yet whether these formats engage shared semantic matching representations with similar temporal dynamics remains unclear. We recorded electroencephalography from 27 participants while they performed audiovisual semantic matching tasks in which spoken words were paired with either written words or pictures. Stimuli included both natural and man-made objects. Time-resolved multivariate pattern analyses (MVPA or decoding), cross-decoding, and temporal generalization analyses were used to characterize the temporal dynamics of semantic processing. Reliable decoding of matching versus mismatching judgments emerged in both word and picture conditions. Decoding onset that significant above chance level occurred earlier for written words than for pictures and cross-decoding analyses revealed successful generalization between word and picture formats. Temporal generalization analyses further demonstrated distinct representational dynamics across formats, with word processing characterized by predominantly time-specific neural representations and picture processing showing more sustained and temporally stable representations. In addition, matching-related discrimination emerged earlier for natural objects than for man-made objects across both formats. The results suggest that speech-word matching shows earlier neural evidence of audiovisual alignment than speech-picture matching, potentially reflecting differences in how auditory linguistic input is integrated with visual information across representational formats.

Episodic memory plays a critical role in supporting adaptive behavior; however, whether it can be causally regulated in humans via deep subcortical stimulation remains unclear. In the present study, we investigated the differential effects of substantia nigra (SN) and subthalamic nucleus (STN) stimulation on episodic memory, as well as the underlying mechanisms of its associated brain networks, using a recognition memory task combined with concurrent functional magnetic resonance imaging in patients with Parkinson's disease. SN-DBS increased recognition sensitivity and reduced false alarms at both frequencies, whereas 10 Hz STN-DBS reduced sensitivity and increased false alarms. Functional connectivity analyses in the absence of DBS stimulation identified a false recognition-related network linking nigral, pallidal, subthalamic, medial temporal, frontal, and occipital regions. SN-DBS-related false alarm reduction tracked modulation of this circuit and was marked by its baseline vulnerability state. These behavioral effects mapped onto target-dependent parieto-occipital and SN-visual retrieval pathways, supporting a model in which DBS bidirectionally regulates recognition memory through target- and frequency-dependent subcortical-cortical circuits.

Sleep is thought to promote memory consolidation through the offline reactivation and reorganization of newly acquired information. However, most studies assess memory shortly after sleep, leaving unresolved whether an initial post-learning sleep episode produces enduring modifications that influence how memories respond to later reactivation. Importantly, the absence of behavioral differences after prolonged retention intervals does not necessarily imply that sleep failed to modify the original memory. Instead, sleep-dependent changes may persist in latent forms that are not readily captured by conventional memory assessments. Here, we investigated whether post-learning sleep produces lasting changes in declarative memories that influence their subsequent response to reactivation. In Study 1, participants learned a declarative memory task and were assigned to either a short nap, a wake condition, or an exploratory long-nap condition that included both NREM and REM sleep. Memory was assessed one week later. Despite substantial forgetting across the retention interval, no significant differences in memory performance were observed between groups. In Study 2, participants learned the same task and subsequently underwent either a short nap or wakefulness. Memory was reactivated six days after learning using an incomplete reminder previously shown to induce memory updating in human declarative memory, and memory was tested one day later. Under these conditions, participants who slept after learning showed better memory performance than wake controls. Moreover, sleep physiological measures predicted the magnitude of the post-reactivation memory benefit. These findings suggest that post-learning sleep induces enduring modifications in declarative memories that are not readily detectable through delayed memory testing alone. Instead, these sleep-dependent changes become evident when memories are challenged through subsequent reactivation. Our results indicate that sleep-dependent consolidation influences the future expression of memory, shaping how memories respond to later reactivation experiences and providing new insight into the relationship between consolidation and reconsolidation.

Visual areas V2 and V4 are critical for the perception of visual forms in primates. Neurons in area V4 of macaque monkeys are often sensitive to the curvature of specific boundary segments within shapes, but it is unknown how curvature tuning is represented in the developing brain. To address this, we recorded multiunit neural activity from areas V2 and V4 of two macaque monkeys, at both 30 and 58 weeks of age, in response to shape stimuli which primarily varied in curvature along a single segment. Observable curvature tuning was adult-like from 30 weeks of age in both V2 and V4. We compared the tuning of sites to shapes presented at multiple positions. We saw evidence of position-invariant tuning in V4, but not in V2. Position invariance in V4 was stable from 30 weeks of age. Finally, we fit two models - a stimulus-centric model of boundary curvature tuning, and a simple linear model based on the spike-triggered average response to all stimuli. We found many sites in both V2 and V4 whose responses could be captured by one or both models, but no evidence of age-related changes in curvature tuning within the space of either model. Our results suggest that the neural representation of curvature in both areas reaches maturity soon after birth, and that object-centric representations of curvature first emerge in V4, not V2.

Insulin resistance, an often-untreated precursor of type 2 diabetes mellitus (T2DM), is implicated in cognitive decline in adults, yet its impact on the developing brain in youth with obesity remains poorly understood. We investigate whether insulin resistance moderates the relation between hippocampal volume and unhealthy food-seeking in overweight and depressed youth ages 9-17 who completed an oral glucose tolerance test and a cognitive task assessing unhealthy food-seeking motivation at baseline, 6-, and 24-months follow-up, and structural MRI at baseline and 6-months follow-up. Insulin sensitivity moderated this relation: smaller baseline hippocampal subfield volumes predicted increased unhealthy food-seeking over 24 months (ps<0.05). Categorical grouping revealed subfield CA2/3 and 4 volumes predicted this relation among insulin-resistant (ps<0.05), but not insulin-sensitive (ps>0.10), youth, suggesting that threshold criteria for insulin resistance are physiologically meaningful. These findings identify a neuro-metabolic risk phenotype that precedes T2DM and may accelerate unhealthy food-seeking severity in youth with obesity.

Whether and how various visual sensory areas contribute to the perceived location of visual stimuli remains unknown. To test the role of neurons in extrastriate area V4 in generating alterations in spatial perception during saccadic eye movements (saccades), we examined perisaccadic mislocalization--the perceptual phenomenon in which visual stimuli appearing around the time of a saccade are perceived at a different position than their actual location. We designed and implemented a combined behavioral and electrophysiological framework in non-human primates to directly relate trial-by-trial spatial perception reports during saccades to neuronal firing rates in V4 populations. We measured monkeys perception of stimulus location behaviorally and found perisaccadic mislocalization opposite to the saccade direction. We also quantified population responses by computing the center of mass of firing rate activity across probe locations for V4 neurons with receptive fields close to the saccade target. While perisaccadic neuronal responses showed shifts toward the saccade target, these shifts did not systematically vary with the magnitude of perceptual mislocalization across trials. In conclusion, receptive field shifts based on the perisaccadic firing rate of V4 neurons are not sufficient to account for the magnitude of perceptual mislocalization in each trial, suggesting that more complex neural representation of perisaccadic visual information may be critical for linking extrastriate neural activity to saccade-induced perception.

Adaptive decision-making under ambiguity requires constant integration of reward- and loss-related information to guide behaviour. In humans and rodents, not all individuals maximise gains in decision-making tasks, such as the Iowa Gambling task or its rodent version, the Rat Gambling task (rGT). While the prefrontal and insular cortices have each been shown independently to support optimal probabilistic decision-making, how they interact functionally to shape individual differences in performance remains unclear. Here, we investigated the consequences of bilateral baclofen/muscimol-mediated inactivation of the prelimbic cortex (PLC) or the anterior insular cortex (AIC) vs. their functional disconnection on the performance of Sprague Dawley rats identified as safe (SDMs) or risky decision makers (RDMs) in the RGT. AIC inhibition decreased advantageous choice in SDMs, whereas it increased win-stay responding in RDMs. In contrast, PLC inhibition primarily affected lose-shift behaviour, reducing sensitivity to losses in SDMs while enhancing adaptive switching in RDMs. Functionally disconnecting the PLC from the AIC, which had no effect on the performance of SDMs, improved decision-making in RDMs by increasing loss-guided behavioural adaptation. Together, these findings identify parallel versus serial AIC-PLC processing as a potential neural mechanism underlying the tendency some individuals have to make suboptimal decisions.

Post-encoding sleep plays an essential role in episodic memory consolidation. Much of the existing literature on sleep and memory relies on deprivation paradigms or laboratory-controlled sleep. Relatively few studies have examined how naturalistic post-encoding sleep relates to memory retrieval and its supporting neural activity, or whether age-related impairments in this sleep are linked to those in episodic memory. In the present study, we used actigraphy and electroencephalography to examine how post-encoding sleep quality relates to context memory performance and retrieval-related ERPs supporting performance in younger and older adults. Participants encoded object-scene pairs and were tested on matching and mismatching pairs after a 96-hour sleep-filled delay. We found that greater post-encoding sleep continuity predicted better delayed context memory performance for mismatching pairs across age groups. Post-encoding sleep continuity was also associated with larger ERP differences between context hits and misses for context-matching pairs, for ERP effects associated with post-retrieval monitoring operations across age groups. Together, these findings suggest that more continuous, naturalistic post-encoding sleep facilitates episodic memory performance and neural mechanisms supporting episodic memory retrieval across adult age.

Children often outperform adults in probabilistic statistical learning tasks, yet the mechanisms underlying this developmental advantage remain poorly understood. Here, we used eye-tracking measures of belief updating to examine how children and adults acquire and update predictions in a probabilistic sequence-learning task. Using the standard (oculomotor) reaction time measure, children showed stronger statistical learning than adults, replicating previous behavioral findings while revealing a more detailed profile of developmental differences in statistical learning. Critically, children updated their predictions more frequently: they were less likely to repeat previous predictions and more likely to shift their expectations in response to new input. Adults, in contrast, showed greater persistence, tending to maintain prior predictions even when those predictions were inconsistent with the underlying statistical structure. Despite these pronounced differences in updating behavior, the processing and use of prediction errors were remarkably similar across age groups. These findings indicate that developmental differences in statistical learning do not primarily arise from how prediction errors are computed, but rather from how prior beliefs and incoming information are weighted during belief updating. Children's enhanced learning may therefore reflect reduced reliance on stable priors and greater sensitivity to current sensory evidence, supporting a more exploratory learning strategy. Adults, by contrast, appear to favor an exploitative strategy that stabilizes existing predictions but reduces flexibility in probabilistic environments. More broadly, the results suggest that developmental changes in statistical learning may reflect age-related differences in how readily learners revise their predictions in response to incoming evidence. By integrating sensitive oculomotor measures with analyses that probe the mechanisms underlying belief updating, the present study provides a more fine-grained account of how predictive learning changes across development and offers a framework for reconciling previously inconsistent developmental findings in statistical learning.

Audiovisual cues ("bells and whistles") are ubiquitous in commercial gambling products. Pairing wins with sound and light cues in laboratory-based gambling paradigms increases risky choice, but the neurocognitive basis of this effect is unclear. Here we compared patterns of neural activation using functional MRI in healthy volunteers (n = 31) while they performed a two-choice lottery task. Reward-paired cues were either present or absent in a mixed-block, event-related design. As predicted, participants made riskier choices on cued trials. Choice latencies were also longer when cues were present, particularly on trials following a win. Activity within the nucleus accumbens and orbitofrontal cortex was greater during the decision phase when participants made risky choices. Nucleus accumbens signal was also greater when participants were anticipating risky outcomes, and in response to risky wins. Contrary to our pre-registered hypotheses, cue condition did not alter patterns of activity across any task phase, in either of these a priori regions of interest. As such, cue-induced risky choice does not appear to be driven by altered representation of risk or value within this canonically reward-sensitive circuitry. Instead, exploratory analyses revealed that the anterior insula was selectively activated by cued, risky wins. Such activation may signal the saliency of these events, or their emotional impact, and may reflect one mechanism through which cue-induced craving develops in vulnerable individuals.

Recurrent processing involves feedforward, feedback and lateral connections and is thought to allow efficient visual processing. Anatomical and behavioral studies in humans have suggested that feedback connections mature later in development than feedforward connections and thus were proposed to depend to a larger degree on experience. In order to isolate feedforward from feedback activity and to investigate the role of early visual experience, we assessed seven individuals with reversed congenital cataracts and nine sighted controls using an "occlusion paradigm" with 7T magnetic resonance imaging (Smith & Muckli, 2010): Grayscale images of scenes were presented with the lower right quadrant covered by a white rectangle. We examined whether information about category (beaches, buildings, highways) and individual scenes could be extracted from early visual region vertices (V1 - V3) associated with the occluded quadrant of the visual field, in the absence of bottom-up visual input. This was achieved by decoding individual category or scene context utilizing a linear support vector machine. In addition, bidirectional information flow was assessed using connective field modeling. While both groups showed successful decoding of scene and category from vertices receiving bottom-up visual input, the accuracy was higher in normally sighted individuals than in individuals with reversed congenital cataracts. When bottom-up input was removed, decoding of categories remained successful in both groups, but decoding of individual scenes was only possible in normally sighted control individuals. Connective field modeling results indicated a less precise alignment of feedforward and feedback processing during visual stimulation in individuals with reversed congenital cataracts. These findings suggest that early visual experience is crucial for the refinement of feedback activity which in turn is crucial for well-tuned feedforward processing.

ABSTRACT IMPORTANCE Childhood obesity is a growing global health concern associated with adverse physical, psychiatric, and neurodevelopmental outcomes. Although previous neuroimaging studies have linked obesity to widespread alterations in brain structure and function, it remains unclear how well multimodal neuroimaging measures and genetic markers can predict future weight gain and inform early intervention strategies. OBJECTIVE To evaluate the predictive utility of multimodal MRI measures and polygenic risk scores for obesity in estimating proportional body weight at baseline and predicting weight gain over one year in preadolescent children. DESIGN, SETTING, AND PARTICIPANTS This study used data from the Adolescent Brain Cognitive Development (ABCD) Study, a large-scale, multisite longitudinal cohort of children aged 9 to 10 years (N = 11,880). Analyses included baseline data collected between 2016 and 2018, and one-year follow-up data collected between 2018 and 2020 across multiple imaging sites. MAIN OUTCOMES AND MEASURES Elastic net regression models were applied to structural MRI (including diffusion tensor imaging) and resting-state functional MRI data to predict baseline triponderal mass index (TMI), a weight-for-height measure that more accurately reflects adiposity in children than body-mass index (BMI). Longitudinal classification models were developed to predict excess weight gain relative to normative developmental trajectories at one-year follow-up. Models were evaluated with and without the inclusion of polygenic risk scores and other non-imaging covariates. Generalizability was assessed using leave-one-site-out cross-validation. RESULTS Structural MRI measures predicted baseline TMI with an R^2 of 0.21, whereas resting-state functional MRI measures predicted TMI with an R^2 of 0.08. Classification models predicted one-year weight gain with area under the receiver operating characteristic curve (AUC) values of 0.73 for structural MRI and 0.60 for resting-state functional MRI. Including polygenic risk scores and other covariates improved model performance (structural MRI: R^2 = 0.25, AUC = 0.75; resting-state functional MRI: R^2 = 0.15, AUC = 0.69). Leave-one-site-out cross-validation revealed reduced generalizability across imaging sites (structural MRI R^2 = 0.13-0.17; resting-state functional MRI R^2 = 0.02-0.09; structural MRI AUC = 0.73-0.74; resting-state functional MRI AUC = 0.60-0.67). CONCLUSIONS AND RELEVANCE Multimodal MRI measures were associated with proportional body weight and demonstrated modest predictive utility for future weight gain in preadolescent children, explaining up to one fifth of the variance in weight-related outcomes. The addition of genetic and non-imaging variables improved prediction accuracy, underscoring the multifactorial nature of childhood obesity. However, the observed decline in performance under site-wise cross-validation highlights the need to address site-related variability to enhance reproducibility and generalizability in neuroimaging-based predictive models of pediatric obesity.

Sleep deprivation amplifies emotional reactivity to brief, overt threats in the external environment. However, its effects on emotional responses to prolonged, ambiguous threat remain unclear. In this pre-registered study, we combined virtual reality, psychophysiology and multidimensional experience sampling to test the hypothesis that sleep deprivation disrupts emotional adaptation to sustained or resolving threat. Following a night of restful sleep or total sleep deprivation, healthy young adults navigated an immersive virtual world that alternated between ambiguously threatening and non-threatening contexts. Despite initial increases in emotional arousal, sleep-rested individuals quickly downregulated affective responses to ambiguous threat, reflecting efficient adaptation to the aversive virtual environment. Sleep-deprived individuals, by contrast, were unable to overturn elevated arousal responses, and exhibited a breakdown of goal-orientated, emotional control. Interestingly, resting heart rate variability, an index of affective regulatory capacity, mitigated arousal responses to ambiguous threat after sleep deprivation. These findings suggest that insufficient sleep prevents an adaptive renormalisation of emotional arousal during prolonged and ambiguous threat, giving rise to a maladaptive state of anxiety.