The Behavioral Profile of SYNGAP1-Related Intellectual Disability.

This study aimed to describe the behavioral profile of individuals with SYNGAP1-ID. Parents/carers of 30 individuals aged 3-18 years old with a diagnosis of SYNGAP1-ID and 21 typically developing individuals completed the Vineland-3 Adaptive Behavior Scale and the Child Behavior Checklist. We found that those with SYNGAP1-ID showed fewer adaptive behaviors and higher levels of internalizing and externalizing behaviors across almost all domains compared to typically developing controls. There was some evidence that these differences were greatest in older children, and more apparent in those with co-occuring epilepsy. This characterization of the phenotype of SYNGAP1-ID significantly aids our understanding of the behavioral profile of this population and is a step towards the development of tailored interventions.

The Important Role of the Right Dorsolateral Prefrontal Cortex in Conflict Adaptation: A Combined Voxel-Based Morphometry and Continuous Theta Burst Stimulation Study.

Humans can flexibly adjust their executive control to resolve conflicts. Conflict adaptation and conflict resolution are crucial aspects of conflict processing. Functional neuroimaging studies have associated the dorsolateral prefrontal cortex (DLPFC) with conflict processing, but its causal role remains somewhat controversial. Moreover, the neuroanatomical basis of conflict processing has not been thoroughly examined. In this study, the Stroop task, a well-established measure of conflict, was employed to investigate (1) the neuroanatomical basis of conflict resolution and conflict adaptation with the voxel-based morphometry analysis, (2) the causal role of DLPFC in conflict processing with the application of the continuous theta burst stimulation to DLPFC. The results revealed that the Stroop effect was correlated to the gray matter volume of the precuneus, postcentral gyrus, and cerebellum, and the congruency sequence effect was correlated to the gray matter volume of superior frontal gyrus, postcentral gyrus, and lobule paracentral gyrus. These findings indicate the neuroanatomical basis of conflict resolution and adaptation. In addition, the continuous theta burst stimulation over the right DLPFC resulted in a significant reduction in the Stroop effect of RT after congruent trials compared with vertex stimulation and a significant increase in the Stroop effect of accuracy rate after incongruent trials than congruent trials, demonstrating the causal role of right DLPFC in conflict adaptation. Moreover, the DLPFC stimulation did not affect the Stroop effect of RT and accuracy rate. Overall, our study offers further insights into the neural mechanisms underlying conflict resolution and adaptation.

Task-general or specific: The alertness modulates post-error adjustment.

Previous studies have shown that alertness is closely related to executive control function, but its impact on components of post-error adjustment is unknown. This study applied the Attentional Networks Test and the Four-choice Flanker task with three response stimulus intervals (RSIs) to explore the correlation between alertness and post-error adjustment. The linear mixed-effects model of alertness and RSI on the post-error processing indicators showed a significant negative correlation between the alertness and post-error slowing (PES) under 200 ms RSI , as well as between alertness and post-error improvement in accuracy (PIA) under both 700 ms RSI and 1200 ms RSI. Participants with lower alertness showed larger post-error slowing in the early stages, while those with higher alertness had smaller PIA in later stages. This study revealed the effects of alertness on different processing components of post-error adjustment. The control strategies utilized by individuals with high and low levels of alertness differed in preparation for performance monitoring. Alertness improved post-error response speed in a task-unspecific manner, but not post-error adaptation.

Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress.

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.

Recent Opioid Use Impedes Range Adaptation in Reinforcement Learning in Human Addiction.

BACKGROUND: Drugs like opioids are potent reinforcers thought to co-opt value-based decisions by overshadowing other rewarding outcomes, but how this happens at a neurocomputational level remains elusive. Range adaptation is a canonical process of fine-tuning representations of value based on reward context. Here, we tested whether recent opioid exposure impacts range adaptation in opioid use disorder, potentially explaining why shifting decision making away from drug taking during this vulnerable period is so difficult. METHODS: Participants who had recently (<90 days) used opioids (n = 34) or who had abstained from opioid use for ≥ 90 days (n = 20) and comparison control participants (n = 44) completed a reinforcement learning task designed to induce robust contextual modulation of value. Two models were used to assess the latent process that participants engaged while making their decisions: 1) a Range model that dynamically tracks context and 2) a standard Absolute model that assumes stationary, objective encoding of value. RESULTS: Control participants and ≥90-days-abstinent participants with opioid use disorder exhibited choice patterns consistent with range-adapted valuation. In contrast, participants with recent opioid use were more prone to learn and encode value on an absolute scale. Computational modeling confirmed the behavior of most control participants and ≥90-days-abstinent participants with opioid use disorder (75%), but a minority in the recent use group (38%), was better fit by the Range model than the Absolute model. Furthermore, the degree to which participants relied on range adaptation correlated with duration of continuous abstinence and subjective craving/withdrawal. CONCLUSIONS: Reduced context adaptation to available rewards could explain difficulty deciding about smaller (typically nondrug) rewards in the aftermath of drug exposure.

The bidirectional effect of stress and functionality in multiple sclerosis and the interaction role of anxiety, coping and social support.

OBJECTIVE: The present study aims to analyse the bidirectional hypothesis between stress and multiple sclerosis with several measures of stress, impairment and functionality, considering also the interaction role of stress-related psychosocial factors such as anxiety, coping and social support. METHODS: A one-year follow-up was conducted with 26 people with multiple sclerosis. Participants reported i) at baseline, anxiety (State-Trait Anxiety Inventory), and social support (Multidimensional Scale of Perceived Social Support); ii) daily, Ecological Momentary Assessment through self-reported diaries of stressful events and coping strategies; iii) monthly, the perceived stress (Perceived Stress Scale), iv) trimonthly, the self-reported functionality (Functionality Assessment in multiple sclerosis) and v) at baseline and at the end, neurologist rated impairment (Expanded Disability Status Scale). Mixed-effect regression models were conducted. RESULTS: The bidirectional hypothesis was confirmed with perceived stress and self-reported functionality, which were negatively related in both directions. Coping and anxiety showed an interaction effect: active coping increased functionality only with high levels of stress, and high-trait anxiety showed lower functionality whereas low-trait anxiety showed higher functionality but only with low stress levels. CONCLUSION: People with multiple sclerosis may benefit from different types of psychological therapies, from gold-standard therapies like Cognitive Behavioural Therapy to third-waves therapies like Dialectical Behaviour Therapy or mindfulness, that focus on dealing with stress and affective symptoms, adjusting to the disease, and to improving their overall quality of life. More research is needed in this field under the biopsychosocial model.

Coping With Stress: The Mitokine GDF-15 as a Biomarker of COVID-19 Severity.

Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-ß superfamily cytokine that plays a central role in metabolism regulation. Produced in response to mitochondrial stress, tissue damage or hypoxia, this cytokine has emerged as one of the strongest predictors of disease severity during inflammatory conditions, cancers and infections. Reports suggest that GDF-15 plays a tissue protective role via sympathetic and metabolic adaptation in the context of mitochondrial damage, although the exact mechanisms involved remain uncertain. In this review, we discuss the emergence of GDF-15 as a distinctive marker of viral infection severity, especially in the context of COVID-19. We will critically review the role of GDF-15 as an inflammation-induced mediator of disease tolerance, through metabolic and immune reprogramming. Finally, we discuss potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Altogether, this cytokine seems to be involved in disease tolerance to viral infections including SARS-CoV-2, paving the way for novel therapeutic interventions.

Chain Mediation Model of Perceived Stress, Resilience, and Social Support on Coping Styles of Chinese Patients on Hemodialysis During COVID-19 Pandemic Lockdown.

BACKGROUND The recurrence of COVID-19 and the continuous escalation of prevention and control policies can lead to an increase in mental health problems. This study aimed to investigate the perceived stress, coping style, resilience, and social support among patients on maintenance hemodialysis (MHD) during the COVID-19 epidemic lockdown in China. MATERIAL AND METHODS This cross-sectional observational study enrolled 197 patients on MHD from the Guangdong Province Traditional Chinese Medical Hospital and the Hedong Hospital of Guangzhou Liwan District People's Hospital during July 2021. AMOS 24.0 and PROCESS Macro 3.1 model 6 were used for analyses of moderating mediating effects. RESULTS Perceived stress was negatively correlated with positive coping style (r=-0.305, P<0.001) and resilience (r=-0.258, P<0.001), whereas resilience (r=0.631, P<0.001) and social support (r=0.300, P<0.001) were positively correlated with positive coping style among patients on MHD. In the moderated mediating model, perceived stress had significant direct predictive effects on positive coping style (95% CI -0.33, -0.07), and perceived stress had significant indirect predictive effects on positive coping styles through resilience (95% CI -0.26, -0.06) or social support (95% CI 0.01, 0.06). Perceived stress had significant indirect predictive effects on positive coping style through both resilience and social support (95% CI -0.04, -0.01). CONCLUSIONS Perceived stress not only predicted coping style directly, but also indirectly predicted coping style through resilience and social support. Coping style was affected by internal and external factors during the COVID-19 pandemic lockdown period.

Cerebellar connectivity maps embody individual adaptive behavior in mice.

The cerebellar cortex encodes sensorimotor adaptation during skilled locomotor behaviors, however the precise relationship between synaptic connectivity and behavior is unclear. We studied synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs) in murine acute cerebellar slices using photostimulation of caged glutamate combined with patch-clamp in developing or after mice adapted to different locomotor contexts. By translating individual maps into graph network entities, we found that synaptic maps in juvenile animals undergo critical period characterized by dissolution of their structure followed by the re-establishment of a patchy functional organization in adults. Although, in adapted mice, subdivisions in anatomical microzones do not fully account for the observed spatial map organization in relation to behavior, we can discriminate locomotor contexts with high accuracy. We also demonstrate that the variability observed in connectivity maps directly accounts for motor behavior traits at the individual level. Our findings suggest that, beyond general motor contexts, GC-PC networks also encode internal models underlying individual-specific motor adaptation.

The Emotion Dynamics Conundrum in Developmental Psychopathology: Similarities, Distinctions, and Adaptiveness of Affective Variability and Socioaffective Flexibility.

A recent emphasis in developmental psychopathology research has been on emotion dynamics, or how emotional experience changes over time in response to context, and how those emotion dynamics affect psychosocial functioning. Two prominent emotion dynamics constructs have emerged in the developmental psychopathology literature: affective variability and socioaffective flexibility. Affective variability is most often measured using momentary methods (e.g., EMA) and is theorized to reflect reactivity and regulation in response to context, whereas socioaffective flexibility is typically measured in the context of parent-child interactions and theorized as the ability to move effectively through a range of affective states. Notably, affective variability is considered broadly maladaptive; however, socioaffective flexibility is theorized to be fundamentally adaptive. Despite these diametric views on adaptability, these two constructs share an underlying dependency on non-effortful emotion change in response to context, which raises questions about whether these constructs are, at their core, more similar than dissimilar. This review examined the literatures on affective variability and socioaffective flexibility in child and adolescent samples, examining associations with psychosocial and clinical correlates, as well as conceptual and methodological similarities and distinctions. Findings indicate that despite considerable theoretical overlap, there are sufficient differences-albeit largely methodological-that justify continuing to treat these constructs as distinct, most notably the influence of parents in socioaffective flexibility. The review closes with several recommendations for future study targeted at further clarifying the distinctions (or lack thereof) between affective variability and socioaffective flexibility.

Constructing neural network models from brain data reveals representational transformations linked to adaptive behavior.

The human ability to adaptively implement a wide variety of tasks is thought to emerge from the dynamic transformation of cognitive information. We hypothesized that these transformations are implemented via conjunctive activations in "conjunction hubs"-brain regions that selectively integrate sensory, cognitive, and motor activations. We used recent advances in using functional connectivity to map the flow of activity between brain regions to construct a task-performing neural network model from fMRI data during a cognitive control task. We verified the importance of conjunction hubs in cognitive computations by simulating neural activity flow over this empirically-estimated functional connectivity model. These empirically-specified simulations produced above-chance task performance (motor responses) by integrating sensory and task rule activations in conjunction hubs. These findings reveal the role of conjunction hubs in supporting flexible cognitive computations, while demonstrating the feasibility of using empirically-estimated neural network models to gain insight into cognitive computations in the human brain.

Risk perception and coping response to COVID-19 mediated by positive and negative emotions: A study on Chinese college students.

This study aimed to assess the mediating roles of positive and negative emotions on the relationship between COVID-19-related risk perception and coping behaviours adopted by Chinese college students in response to the COVID-19 pandemic. We conducted an internet-based questionnaire survey from mid February-late October 2020, among 1038 college students, from six Chinese universities (females = 73.41%), ranging within 17-26 years. The survey questionnaire included three major components-the COVID-19-Related Risk Perception Scale (CRPS), the Positive and Negative Affect Scale (PANAS-Revision), and Coping Response of COVID-19 Scale (CRCS). Descriptive statistics and a mediated model were used to analyse the collected data. A partial mediation relationship was found between COVID-19-related risk perception and 1) active-response behaviour (ß = 0.05, 95% Confidence Interval [CI: 0.03, 0.08]), 2) self-protection behaviour through positive emotions (ß = 0.03, CI [0.01, 0.04]), and 3) risk-taking behaviour through negative emotions (ß = -0.04, CI [-0.07, -0.02]). This study's double-mediation model has been shown to detect the effect coping mechanisms to COVID-19. Furthermore, it implies that public health managers should consider the differences in coping mechanisms and the diverse mediating roles of positive and negative emotions for coping with public health emergencies.

Emerging experience-dependent dynamics in primary somatosensory cortex reflect behavioral adaptation.

Behavioral experience and flexibility are crucial for survival in a constantly changing environment. Despite evolutionary pressures to develop adaptive behavioral strategies in a dynamically changing sensory landscape, the underlying neural correlates have not been well explored. Here, we use genetically encoded voltage imaging to measure signals in primary somatosensory cortex (S1) during sensory learning and behavioral adaptation in the mouse. In response to changing stimulus statistics, mice adopt a strategy that modifies their detection behavior in a context dependent manner as to maintain reward expectation. Surprisingly, neuronal activity in S1 shifts from simply representing stimulus properties to transducing signals necessary for adaptive behavior in an experience dependent manner. Our results suggest that neuronal signals in S1 are part of an adaptive framework that facilitates flexible behavior as individuals gain experience, which could be part of a general scheme that dynamically distributes the neural correlates of behavior during learning.

Feasibility study of immersive virtual prism adaptation therapy with depth-sensing camera using functional near-infrared spectroscopy in healthy adults.

Prism Adaptation (PA) is used to alleviate spatial neglect. We combined immersive virtual reality with a depth-sensing camera to develop virtual prism adaptation therapy (VPAT), which block external visual cues and easily quantify and monitor errors than conventional PA. We conducted a feasibility study to investigate whether VPAT can induce behavioral adaptations by measuring after-effect and identifying which cortical areas were most significantly activated during VPAT using functional near-infrared spectroscopy (fNIRS). Fourteen healthy subjects participated in this study. The experiment consisted of four sequential phases (pre-VPAT, VPAT-10°, VPAT-20°, and post-VPAT). To compare the most significantly activated cortical areas during pointing in different phases against pointing during the pre-VPAT phase, we analyzed changes in oxyhemoglobin concentration using fNIRS during pointing. The pointing errors of the virtual hand deviated to the right-side during early pointing blocks in the VPAT-10° and VPAT-20° phases. There was a left-side deviation of the real hand to the target in the post-VPAT phase, demonstrating after-effect. The most significantly activated channels during pointing tasks were located in the right hemisphere, and possible corresponding cortical areas included the dorsolateral prefrontal cortex and frontal eye field. In conclusion, VPAT may induce behavioral adaptation with modulation of the dorsal attentional network.

Reciprocal midbrain-extended amygdala circuit activity in preclinical models of alcohol use and misuse.

Alcohol dependence is characterized by a shift in motivation to consume alcohol from positive reinforcement (i.e., increased likelihood of future alcohol drinking based on its rewarding effects) to negative reinforcement (i.e., increased likelihood of future alcohol drinking based on alcohol-induced reductions in negative affective symptoms, including but not limited to those experienced during alcohol withdrawal). The neural adaptations that occur during this transition are not entirely understood. Mesolimbic reinforcement circuitry (i.e., ventral tegmental area [VTA] neurons) is activated during early stages of alcohol use, and may be involved in the recruitment of brain stress circuitry (i.e., extended amygdala) during the transition to alcohol dependence, after chronic periods of high-dose alcohol exposure. Here, we review the literature regarding the role of canonical brain reinforcement (VTA) and brain stress (extended amygdala) systems, and the connections between them, in acute, sub-chronic, and chronic alcohol response. Particular emphasis is placed on preclinical models of alcohol use.

Impaired control in addiction involves cognitive distortions and unreliable self-control, not compulsive desires and overwhelmed self-control.

Impaired control in addiction involves a characteristic but obscure kind of partial control. Certain aspects of control over drug use are clearly reduced, reflected in difficulty cutting back and relapse. However, other aspects of control are clearly preserved, as reflected in substantial sensitivity to situational incentives-for example, the ability to defer use when needed. This juxtaposition is puzzling, and a clear mechanistically precise understanding of impaired control has yet to emerge. In this article, a Distortion model of impaired control is put forward. The key insight of the model is that the puzzling pattern of partial control seen in addiction can be understood in terms of unreliable control. The model posits large populations of distorted automatic thoughts (e.g., about drugs, one's self, one's circumstances, and one's abilities to cope), coupled with unreliable control over these distorted thoughts. These distorted thoughts, typically gradually and cumulatively, lead to illusion-like misvaluation of costs and benefits of drug use, in turn eventually leading to decisions to use. The model captures an elusive middle ground in addiction in which substantially preserved control over drug use for briefer intervals coexists with difficulty maintaining sobriety over the long-term. Moreover, the model explains a range of clinical findings in addiction that are not easily accommodated on leading alternative views.

Prioritizing Multidimensional Interdependent Factors Influencing COVID-19 Risk.

COVID-19 has significantly affected various industries and domains worldwide. Since such pandemics are considered as rare events, risks associated with pandemics are generally managed through reactive approaches, which involve seeking more information about the severity of the pandemic over time and adopting suitable strategies accordingly. However, policy-makers at a national level must devise proactive strategies to minimize the harmful impacts of such pandemics. In this article, we use a country-level data-set related to humanitarian crises and disasters to explore critical factors influencing COVID-19 related hazard and exposure, vulnerability, lack of coping capacity, and the overall risk for individual countries. The main contribution is to establish the relative importance of multidimensional factors associated with COVID-19 risk in a probabilistic network setting. This study provides unique insights to policy-makers regarding the identification of critical factors influencing COVID-19 risk and their relative importance in a network setting.

Protective Role of Caregiver Preparedness on the Relationship Between Depression and Quality of Life in Stroke Dyads.

BACKGROUND AND PURPOSE: Depression and quality of life (QOL) have an interdependent and transactional nature in stroke survivor-caregiver dyads. While the strong relationship between depression and physical and emotional QOL in stroke survivor-caregiver dyads is well known, it is less clear if this relationship is moderated by caregiver preparedness, which could easily be targeted with interventions. In this study, we examined the moderating role of caregiver preparedness on the association between depression and QOL in stroke survivor-caregiver dyads. METHODS: We used a longitudinal design with follow-ups every 3 months over a 1-year period. Considering the nonindependent nature of the data (survivors and their caregivers), we used multilevel modeling to analyze data at the dyad level. We implemented 4 longitudinal dyadic moderation models (one for each QOL domain: physical, psychological, social, and environmental) using hierarchical linear modeling. RESULTS: A sample of 222 stroke survivor-caregiver dyads was analyzed. Stroke survivors were older (M=70.8, SD=11.9) than their caregivers (M=52.4, SD=13.1). Stroke survivors predominantly had an ischemic stroke, equally distributed by site. Caregivers were primarily female (66%), with a medium to high educational level (57%). Caregiver preparedness significantly moderated the association between survivor depression and survivor psychological (B=0.56, P<0.01) and environmental (B=0.58, P<0.01) QOL at baseline and social QOL over time (B=0.24, P<0.05). Similarly, caregiver preparedness significantly moderated the association between caregiver depression and caregiver physical (B=0.25, P<0.01) and environmental (B=0.18, P<0.05) QOL over time. CONCLUSIONS: Caregiver preparedness has a positive influence on both members of the dyad. Assessment of stroke-caregiver preparedness could be helpful to motivate clinicians to develop and implement interventions for stroke survivor-caregiver dyads.

Prediction of Learned Resistance or Helplessness by Hippocampal-Prefrontal Cortical Network Activity during Stress.

The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (PFC) and the hippocampus (HPC) are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded HPC and PFC neural activities in male rats during the exposure to controllable, uncontrollable, or no shocks and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from nonstressed animals and predict resistant (R) or helpless (H) individuals based on hippocampal-cortical oscillatory dynamics. Remarkably, R animals exhibited an increase in theta power during CS, while H exhibited a decrease. Furthermore, R exhibited higher HPC to PFC θ synchronization during stress. Notably, HPC-PFC θ connectivity in the initial stress exposure showed strong correlations with escape performance evaluated days later. R rats also showed stronger θ coupling to both γ oscillations and neuronal firing in the PFC. Finally, we found that these distinct features of network dynamics collectively formed a pattern that accurately predicted learned resistance and was lacking in H individuals. Our findings suggest that hippocampal-prefrontal network θ activity supports cognitive mechanisms of stress coping, whose impairment may underlie vulnerability to stress-related disorders.SIGNIFICANCE STATEMENT The appraisal of adversities as controllable or uncontrollable is key in determining resilience or risk for stress-related disorders. Here, we performed the first electrophysiological investigation during controllable or uncontrollable stress. Pharmacological studies showed that the prefrontal cortex (PFC) and the hippocampus (HPC) encode stressor controllability, and here we identified the neural activity underlying this process. This "neural signature of stressor controllability" accurately predicted resistance to future stressors and was characterized by increased HPC-PFC oscillatory activity in the θ frequency (4-10 Hz). Our findings suggest a new role of frontal θ oscillations in adaptive stress coping, integrating its emotional and cognitive functions. We also endorse the potential of this biomarker to guide neurophysiologically-informed and rhythm-based stimulation therapies for depression.