Acute psychosocial stress modulates neural and behavioral substrates of cognitive control.

Acute psychosocial stress affects learning, memory, and attention, but the evidence for the influence of stress on the neural processes supporting cognitive control remains mixed. We investigated how acute psychosocial stress influences performance and neural processing during the Go/NoGo task-an established cognitive control task. The experimental group underwent the Trier Social Stress Test (TSST) acute stress induction, whereas the control group completed personality questionnaires. Then, participants completed a functional magnetic resonance imaging (fMRI) Go/NoGo task, with self-report, blood pressure and salivary cortisol measurements of induced stress taken intermittently throughout the experimental session. The TSST was successful in eliciting a stress response, as indicated by significant Stress > Control between-group differences in subjective stress ratings and systolic blood pressure. We did not identify significant differences in cortisol levels, however. The stress induction also impacted subsequent Go/NoGo task performance, with participants who underwent the TSST making fewer commission errors on trials requiring the most inhibitory control (NoGo Green) relative to the control group, suggesting increased vigilance. Univariate analysis of fMRI task-evoked brain activity revealed no differences between stress and control groups for any region. However, using multivariate pattern analysis, stress and control groups were reliably differentiated by activation patterns contrasting the most demanding NoGo trials (i.e., NoGo Green trials) versus baseline in the medial intraparietal area (mIPA, affiliated with the dorsal attention network) and subregions of the cerebellum (affiliated with the default mode network). These results align with prior reports linking the mIPA and the cerebellum to visuomotor coordination, a function central to cognitive control processes underlying goal-directed behavior. This suggests that stressor-induced hypervigilance may produce a facilitative effect on response inhibition which is represented neurally by the activation patterns of cognitive control regions.

Characterization of the interaction between the Sec61 translocon complex and ppαF using optical tweezers.

The Sec61 translocon allows the translocation of secretory preproteins from the cytosol to the endoplasmic reticulum lumen during polypeptide biosynthesis. These proteins possess an N-terminal signal peptide (SP) which docks at the translocon. SP mutations can abolish translocation and cause diseases, suggesting an essential role for this SP/Sec61 interaction. However, a detailed biophysical characterization of this binding is still missing. Here, optical tweezers force spectroscopy was used to characterize the kinetic parameters of the dissociation process between Sec61 and the SP of prepro-alpha-factor. The unbinding parameters including off-rate constant and distance to the transition state were obtained by fitting rupture force data to Dudko-Hummer-Szabo models. Interestingly, the translocation inhibitor mycolactone increases the off-rate and accelerates the SP/Sec61 dissociation, while also weakening the interaction. Whereas the translocation deficient mutant containing a single point mutation in the SP abolished the specificity of the SP/Sec61 binding, resulting in an unstable interaction. In conclusion, we characterize quantitatively the dissociation process between the signal peptide and the translocon, and how the unbinding parameters are modified by a translocation inhibitor.

Development of GO Move: A Website for Children With Unilateral Cerebral Palsy.

It is unknown if an online tool is wanted by therapists and parents of individuals with unilateral cerebral palsy (UCP) to support implementation of goal-directed home programs, and if wanted, the recommended features for the tool. The objective was to explore the experiences of therapists and parents who have implemented home programs, seek guidance on translating a paper-based home program toolbox into a mobile website, and develop the website. Qualitative descriptive methodology guided data collection using semi-structured interviews and thematic analysis, validated with field notes and member checking. A team science, iterative approach was used to integrate the themes into the development of the mobile website. Five primary themes including recommendations for the functionality, features, content, and naming of the mobile website were identified. Parents and therapists value home programs. Participants provided recommendations regarding content and features, and the GO Move mobile website was developed based on the recommendations.

Development of Go Move: A Website for Children With Unilateral Cerebral PalsyTherapists and parents of children with unilateral cerebral palsy were interviewed to understand their experience of home programs and gain input for creating a mobile website with information on goal setting and implementing home programs. The interviews provided valuable information about the functionality, features, content, and naming of the website. GO Move, a mobile website aimed to provide information on goal setting, activity selection, and tracking of exercises and activities in the home environment for children with unilateral cerebral palsy, was developed based on the information from the interviews.

Mindfulness-oriented recovery enhancement in opioid use disorder: Extended emotional regulation and neural effects and immediate effects of guided meditation in a pilot sample.

OBJECTIVE: Mindfulness-Oriented Recovery Enhancement (MORE) is an efficacious intervention to aid recovery from substance use disorder. This study in a pilot sample of individuals in treatment for opioid use disorder (OUD) characterizes longer-term changes after the MORE intervention and immediate effects of a brief MORE guided meditation session. DESIGN: Twelve female participants in residential treatment for OUD completed an 8-week MORE intervention. Participants completed two sessions: one before and one after the 8-week MORE intervention. Each session included an emotional regulation questionnaire outside an MRI scanner first and then a 10-minute guided MORE meditation inside the scanner during which functional magnetic resonance imaging (fMRI) data were collected. Emotional regulation was measured after 8-weeks of MORE intervention. In addition, functional connectivity (i.e. correlated fMRI signal) between regions in a hypothesized affect regulation network was measured during the meditation state to assess change in brain network function due to 8-weeks of MORE. For each 10-min guided meditation, we also assessed their mood and opioid craving. RESULTS: Nine participants completed all measurements. Participants' emotional regulation difficulty significantly decreased after 8-weeks of MORE intervention. Furthermore, after 8-weeks of MORE, there was significantly increased connectivity between left ventromedial prefrontal cortex and left amygdala and between left ventrolateral prefrontal cortex and left nucleus accumbens captured during a meditation state. In both sessions, positive mood significantly increased after 10-min of guided mediation, however opioid craving was not significantly influenced. CONCLUSIONS: This pilot study characterizes potential benefits of 8-week MORE intervention in improving emotional regulation difficulty and brain function. A 10-min guided MORE meditation may immediately improve mood, with potential to reduce acute stress- or cue-provoked craving. These results warrant future studies with larger sample size.

RAB1A haploinsufficiency phenocopies the 2p14-p15 microdeletion and is associated with impaired neuronal differentiation.

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and a mosaic missense mutation (c.83T>C [p.Leu28Pro]), were identified in three individuals with similar neurodevelopmental presentations. In rescue experiments, production of the full-length, but not the truncated, RAB1a rescued Golgi structure and cell proliferation in Rab1-depleted cells. In contrast, the missense-variant RAB1a disrupted Golgi structure despite intact Rab1 expression, suggesting a dominant-negative function of the mosaic missense mutation. Knock-down of RAB1A in cultured human embryonic stem cell-derived neurons resulted in impaired neuronal arborization. Finally, RAB1A is located within the 2p14-p15 microdeletion syndrome locus. The similar clinical presentations of individuals with RAB1A loss-of-function mutations and the 2p14-p15 microdeletion syndrome implicate loss of RAB1A in the pathogenesis of neurodevelopmental manifestations of this microdeletion syndrome. Our study identifies a RAB1A-related neurocognitive disorder with speech and motor delay, demonstrates an essential role for RAB1a in neuronal differentiation, and implicates RAB1A in the etiology of the neurodevelopmental sequelae associated with the 2p14-p15 microdeletion syndrome.

Characterizing the mechanisms of social connection.

Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority as a result of the increased focus on the epidemic of loneliness and the myriad protective benefits conferred by social connection. In this review, we highlight the psychological and neural mechanisms that enable us to connect with others, which in turn help buffer against the consequences of stress and isolation. Central to this process is the experience of rewards derived from positive social interactions, which encourage the sharing of perspectives and preferences that unite individuals. Sharing affective states with others helps us to align our understanding of the world with another's, thereby continuing to reinforce bonds and strengthen relationships. These psychological processes depend on neural systems supporting reward and social cognitive function. Lastly, we also consider limitations associated with pursuing healthy social connections and outline potential avenues of future research.

A Qualitative Examination of the Impact of Suicidal Thoughts and Behavior on Help-Seeking Among University Students in Colombia and Mexico.

This study examined descriptions of suicidal thoughts and behavior (STB) to identify risk and protective factors that may present in clinical settings among university students from Latin America. Our focus was on answering the following key questions: How are suicidal thoughts and behavior described? What are reasons for wanting to die and for living? What impact do STBs have on motivations to seek or avoid psychological treatment? To this end, 55 qualitative interviews were completed with university students from Colombia and Mexico who recently endorsed emotional difficulties in the World Mental Health International College Student (WMH-ICS) surveys. Interviews were coded to identify themes specific to STBs. Findings revealed insight on symptom presentations and consequences of STBs. Participants described uncontrollable somatic symptoms during periods of high suicide risk, which serves as a relevant clinical marker for health providers. An important reason for living was to avoid suffering for family, which was protective against suicide and motivates familial involvement in treatment planning. Participants sought solutions to emotional problems after experiencing STBs, including psychological treatment. Cultural stigma of mental illness induced feelings of shame and burden, which led to avolition, avoidance, and nondisclosure of symptom severity. This study provides insight into the utility of evaluating cultural context in (a) detecting antecedents to STBs frequently reported as somatic symptoms, (b) identifying protective factors against suicide, and (c) recognizing how stigma of mental illness and suicide, shame avoidance, and familism might influence personal motivations to seek or avoid help for emotional distress.

Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

Social feedback promotes positive social sharing, trust, and closeness.

Positive social sharing is an interpersonal emotion regulation strategy that enhances positive affect and social belonging, particularly when met with positive social feedback. Despite the ubiquity of positive social sharing both in person and online, what drives this behavior is not well understood. We hypothesized that positive social feedback serves as a reward that reinforces sharing behavior and strengthens social bonds. Participants made trial-by-trial choices about whether to share social media photos with peers who returned positive ("likes") or negative ("dislikes") feedback. Unbeknownst to participants, peer conditions were manipulated to yield varying amounts of positive and negative feedback. Social bonding was subsequently measured using a trust game and subjective closeness ratings. Participants shared more with peers who provided greater rates of positive feedback. This effect generalized to trust decisions and subjective feelings of closeness and varied individually as a function of interpersonal emotion regulation in daily life. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Goal Attainment after Treatment with Abobotulinumtoxina and a Tailored Home Therapy Programme in Children with Upper Limb Spasticity: Descriptive, Exploratory Analysis of a Large Randomized, Controlled Study

OBJECTIVE: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). METHODS: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which included stretches and exercises specifically chosen to facilitate goal achievement and engagement in activities. RESULTS: For cycle 1, most children had active function goals set as their primary goal (69.7% vs 19.2% passive function goals). GAS T- scores and goal responder rates at week 16 indicated that most types of primary goal were achieved at least as expected during cycle 1 (all groups). Primary goal GAS T-scores were generally maintained for the first 3 abobotulinumtoxinA treatment cycles. CONCLUSION: Most children with upper limb spasticity treated with repeat cycles of abobotulinumtoxinA supported by an individualized home exercises therapy programme achieved their functional goals.