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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A model of optimal timing for a predictive adaptive response.

Predictive adaptive responses (PARs) are a form of developmental plasticity in which the developmental response to an environmental cue experienced early in life is delayed and yet, at the same time, the induced phenotype anticipates (i.e., is completely developed before) exposure to the eventual environmental state predicted by the cue, in which the phenotype is adaptive. We model this sequence of events to discover, under various assumptions concerning the cost of development, what lengths of delay, developmental time, and anticipation are optimal. We find that in many scenarios modeled, development of the induced phenotype should be completed at the exact same time that the environmental exposure relevant to the induced phenotype begins: that is, in contrast to our observed cases of PARs, there should be no anticipation. Moreover, unless slow development is costly, development should commence immediately after the cue: there should be no delay. Thus, PARs, which normally have non-zero delays and/or anticipation, are highly unusual. Importantly, the exceptions to these predictions of zero delays and anticipation occurred when developmental time was fixed and delaying development was increasingly costly. We suggest, therefore, that PARs will only evolve under three kinds of circumstances: (i) there are strong timing constraints on the cue and the environmental status, (ii) delaying development is costly, and development time is either fixed or slow development is costly, or (iii) when the period between the cue and the eventual environmental change is variable and the cost of not completing development before the change is high. These predictions are empirically testable.

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.

COVID-19 pandemic related excessive electronic media exposure and mental health in Saudi Arabia.

OBJECTIVE: Due to the continued spread of COVID-19 and the emergence of novel mutated viral variants, families all over the world are experiencing wide-ranging stressors that threaten not only their financial well-being but also their physical and mental health. The present study assessed the association between excessive electronic media exposure of pandemic-related news and mental health of the residents of Ha'il Province, Saudi Arabia. The present study also assessed the prevalence of perceived stress, fear of COVID-19, anxiety, depression, and loneliness due to COVID-19-related restrictions in the same population. MATERIALS AND METHODS: A total of 490 residents of Ha'il Province participated in a cross-sectional online survey during a two-month period (March to April 2021). A validated 38-item self-report survey was used to collect the data. RESULTS: Significant associations were reported between excessive electronic media exposure and the prevalence of perceived stress (χ2=140.56; p<.001), generalized anxiety (χ2=74.55; p<.001), depression (χ2=71.58; p<.001), COVID-19-related fear (χ2=24.54; p<.001), and loneliness (χ2=11.46; p<.001). It was also found that participants without depressive symptoms were 0.28 times less likely to have been exposed to excessive electronic media exposure (AOR: 0.28; C.I. 0.16-0.48; p<.001). Similarly, participants with no stress/mild stress were 0.32 times less likely to have been exposed to excessive electronic media exposure (AOR: 0.32; C.I. 0.19-0.52; p<.001). CONCLUSIONS: The findings of the present study suggest an urgent need for educational resilience programs (online and in-person) for susceptible individuals (females, unemployed, urban residents, etc.). Such programs would help them to develop skills to cope with the psychological impact of the COVID-19 pandemic.

Internal state effects on behavioral shifts in freely behaving praying mantises (Tenodera sinensis).

How we interact with our environment largely depends on both the external cues presented by our surroundings and the internal state from within. Internal states are the ever-changing physiological conditions that communicate the immediate survival needs and motivate the animal to behaviorally fulfill them. Satiety level constitutes such a state, and therefore has a dynamic influence on the output behaviors of an animal. In predatory insects like the praying mantis, hunting tactics, grooming, and mating have been shown to change hierarchical organization of behaviors depending on satiety. Here, we analyze behavior sequences of freely hunting praying mantises (Tenodera sinensis) to explore potential differences in sequential patterning of behavior as a correlate of satiety. First, our data supports previous work that showed starved praying mantises were not just more often attentive to prey, but also more often attentive to further prey. This was indicated by the increased time fraction spent in attentive bouts such as prey monitoring, head turns (to track prey), translations (closing the distance to the prey), and more strike attempts. With increasing satiety, praying mantises showed reduced time in these behaviors and exhibited them primarily towards close-proximity prey. Furthermore, our data demonstrates that during states of starvation, the praying mantis exhibits a stereotyped pattern of behavior that is highly motivated by prey capture. As satiety increased, the sequenced behaviors became more variable, indicating a shift away from the necessity of prey capture to more fluid presentations of behavior assembly.

Evolutionary change in the construction of the nursery environment when parents are prevented from caring for their young directly.

Parental care can be partitioned into traits that involve direct engagement with offspring and traits that are expressed as an extended phenotype and influence the developmental environment, such as constructing a nursery. Here, we use experimental evolution to test whether parents can evolve modifications in nursery construction when they are experimentally prevented from supplying care directly to offspring. We exposed replicate experimental populations of burying beetles (Nicrophorus vespilloides) to different regimes of posthatching care by allowing larvae to develop in the presence (Full Care) or absence of parents (No Care). After only 13 generations of experimental evolution, we found an adaptive evolutionary increase in the pace at which parents in the No Care populations converted a dead body into a carrion nest for larvae. Cross-fostering experiments further revealed that No Care larvae performed better on a carrion nest prepared by No Care parents than did Full Care larvae. We conclude that parents construct the nursery environment in relation to their effectiveness at supplying care directly, after offspring are born. When direct care is prevented entirely, they evolve to make compensatory adjustments to the nursery in which their young will develop. The rapid evolutionary change observed in our experiments suggests there is considerable standing genetic variation for parental care traits in natural burying beetle populations-for reasons that remain unclear.

Protein Appetite at the Interface between Nutrient Sensing and Physiological Homeostasis.

Feeding behavior is guided by multiple competing physiological needs, as animals must sense their internal nutritional state and then identify and consume foods that meet nutritional needs. Dietary protein intake is necessary to provide essential amino acids and represents a specific, distinct nutritional need. Consistent with this importance, there is a relatively strong body of literature indicating that protein intake is defended, such that animals sense the restriction of protein and adaptively alter feeding behavior to increase protein intake. Here, we argue that this matching of food consumption with physiological need requires at least two concurrent mechanisms: the first being the detection of internal nutritional need (a protein need state) and the second being the discrimination between foods with differing nutritional compositions. In this review, we outline various mechanisms that could mediate the sensing of need state and the discrimination between protein-rich and protein-poor foods. Finally, we briefly describe how the interaction of these mechanisms might allow an animal to self-select between a complex array of foods to meet nutritional needs and adaptively respond to changes in either the external environment or internal physiological state.