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OBJECTIVE: The risk of seizure relapse after antiepileptic drug (AED) discontinuation in children has been reported to vary between 6% and 40%. It has been suggested that neurologic deficit and mental retardation are poor prognostic factors for seizure relapse after AED discontinuation. Because epileptic children with cerebral palsy (CP) have neurologic deficits, and many have mental retardation, it is important to know their risk for seizure relapse. METHODS: AED treatment was discontinued in 65 children with CP and histories of epilepsy after 2 seizure-free years. All of the patients were followed until they had seizure relapses or for at least 2 years without seizures after AEDs were stopped. Multiple factors were analyzed for possible association with seizure relapse. RESULTS: Twenty-seven patients (41.5%) had seizure relapses. Patients with spastic hemiparesis had the highest relapse rate (61.5%), and those with spastic diplegia had the lowest rate (14.3%). No other factor correlated significantly with the risk of seizure relapse. CONCLUSIONS: Discontinuation of AEDs in children with CP can, and should, be practiced when possible after patients have been seizure-free for at least 2 years. AED discontinuation in patients with spastic hemiparesis is significantly more likely to lead to seizure relapse than in patients with other CP types, but no other factor is yet known to increase the chance of relapse. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This report describes the consensus outcome of an interdisciplinary workshop that was held at the National Institutes of Health in April 2001. The purpose of the workshop and this article are to define the terms 'spasticity,' 'dystonia,' and 'rigidity' as they are used to describe clinical features of hypertonia in children. The definitions presented here are designed to allow differentiation of clinical features even when more than 1 is present simultaneously. METHODS: A consensus agreement was obtained on the best current definitions and their application in clinical situations. RESULTS: 'Spasticity' is defined as hypertonia in which 1 or both of the following signs are present: 1) resistance to externally imposed movement increases with increasing speed of stretch and varies with the direction of joint movement, and/or 2) resistance to externally imposed movement rises rapidly above a threshold speed or joint angle. 'Dystonia' is defined as a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. 'Rigidity' is defined as hypertonia in which all of the following are true: 1) the resistance to externally imposed joint movement is present at very low speeds of movement, does not depend on imposed speed, and does not exhibit a speed or angle threshold; 2) simultaneous co-contraction of agonists and antagonists may occur, and this is reflected in an immediate resistance to a reversal of the direction of movement about a joint; 3) the limb does not tend to return toward a particular fixed posture or extreme joint angle; and 4) voluntary activity in distant muscle groups does not lead to involuntary movements about the rigid joints, although rigidity may worsen. CONCLUSION: We have provided a set of definitions for the purpose of identifying different components of childhood hypertonia. We encourage the development of clinical rating scales that are based on these definitions, and we encourage research to relate the degree of hypertonia to the degree of functional ability, change over time, and societal participation in children with motor disorders. [ABSTRACT FROM AUTHOR]

Holoprosencephaly (HPE) is a brain malformation characterized by incomplete cleavage of the cerebral hemispheres and deep brain structures. Epilepsy is a common problem in children with HPE and a vast majority will have abnormal EEGs. A variety of EEG findings, including spike-and-slow-wave complexes, hypsarrhythmia, isoelectric patterns, periodic discharges, fast anterior rhythms, posterior gradient flattening, asynchronous high amplitude rhythmic activity, and paroxysmal hypersynchronous patterns, are reported in the literature. About half of the children with HPE evaluated at Texas Scottish Rite Hospital for Children have epilepsy. These children have various seizure types; however, there are some consistent EEG findings such as hypersynchronous theta during sleep, hypersynchronous theta while awake, hypersynchronous beta during sleep, and episodic attenuation of cerebral activity, in addition to a spectrum of epileptiform discharges. This article is a review of the clinical and neuroimaging features of HPE and includes discussion of what is known about EEC findings in the disorder. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of interests J.A.R., P.L., and W.B.: The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratory. P.L. and W.B.: Baylor College of Medicine (BCM) and Miraca Holdings Inc. have formed a joint venture with shared ownership and governance of Baylor Genetics, which performs genetic testing and derives revenue. P.L. and W.B. are employees of BCM and derive support through a professional services agreement with Baylor Genetics., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: High drive and high effort during spontaneous breathing can generate patient self-inflicted lung injury (P-SILI) due to uncontrolled high transpulmonary and transvascular pressures, with deterioration of respiratory failure. P-SILI has been demonstrated in experimental studies and supported in recent computational models. Different treatment strategies have been proposed according to the phenotype of elastance of the respiratory system (Ers) for patients with COVID-19. This study aimed to investigate the effect of three spontaneous ventilation modes on respiratory drive and muscle effort in clinical practice and their relationship with different phenotypes. This was achieved by obtaining the following respiratory signals: airway pressure (Paw), flow (V´) and volume (V) and calculating muscle pressure (Pmus)., Methods: A physiologic observational study of a series of cases in a university medical-surgical ICU involving 11 mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing was conducted. Three spontaneous ventilation modes were evaluated in each of the patients: pressure support ventilation (PSV), airway pressure release ventilation (APRV), and BiLevel positive airway pressure ventilation (BIPAP). Pmus was calculated through the equation of motion. For this purpose, we acquired the signals of Paw, V´ and V directly from the data transmission protocol of the ventilator (Dräger). The main physiological measurements were calculation of the respiratory drive (P0.1), muscle effort through the ΔPmus, pressure‒time product (PTP/min) and work of breathing of the patient in joules multiplied by respiratory frequency (WOBp, J/min)., Results: Ten mechanically ventilated patients with COVID-19 pneumonia at the initiation of spontaneous breathing were evaluated. Our results showed similar high drive and muscle effort in each of the spontaneous ventilatory modes tested, without significant differences between them: median (IQR): P0.1 6.28 (4.92-7.44) cm H 2 O, ∆Pmus 13.48 (11.09-17.81) cm H 2 O, PTP 166.29 (124.02-253.33) cm H 2 O*sec/min, and WOBp 12.76 (7.46-18.04) J/min. High drive and effort were found in patients even with low Ers. There was a significant relationship between respiratory drive and WOBp and Ers, though the coefficient of variation widely varied., Conclusions: In our study, none of the spontaneous ventilatory methods tested succeeded in reducing high respiratory drive or muscle effort, regardless of the Ers, with subsequent risk of P-SILI., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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).

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., (© 2023. The Psychonomic Society, Inc.)

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.

The opportunity to exert control in one's environment is desirable, and individuals are willing to seek out control, even at a financial cost. Additionally, control-related activation of reward regions in the brain and the positive affect associated with the opportunity to exert control suggest that control is rewarding. The present study explores whether there are age-related differences in the preference for control. Older and younger adults chose whether to maintain control and play a guessing game themselves or to cede this control to the computer. Maintaining and ceding control were associated with different amounts of monetary reward that could be banked upon a successful guess. This required participants to weigh the value associated with control compared to monetary rewards. We found that older adults preferred control and traded monetary reward for control, similar to younger adults. The results suggest that the preference for exerting control may be preserved across age. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Here, we present the complete chloroplast genomes of Quercus × morehus , Q. wislizeni , and Q. kelloggii from California. The genomes are 161,119 to 161,130 bp and encode 132 genes. Quercus × morehus and Q. wislizeni are identical in sequence but differ from Q. kelloggii by three indels and eight SNPs.

PAX5 is a transcription factor associated with abnormal posterior midbrain and cerebellum development in mice. PAX5 is highly loss-of-function intolerant and missense constrained, and has been identified as a candidate gene for autism spectrum disorder (ASD). We describe 16 individuals from 12 families who carry deletions involving PAX5 and surrounding genes, de novo frameshift variants that are likely to trigger nonsense-mediated mRNA decay, a rare stop-gain variant, or missense variants that affect conserved amino acid residues. Four of these individuals were published previously but without detailed clinical descriptions. All these individuals have been diagnosed with one or more neurodevelopmental phenotypes including delayed developmental milestones (DD), intellectual disability (ID), and/or ASD. Seizures were documented in four individuals. No recurrent patterns of brain magnetic resonance imaging (MRI) findings, structural birth defects, or dysmorphic features were observed. Our findings suggest that PAX5 haploinsufficiency causes a neurodevelopmental disorder whose cardinal features include DD, variable ID, and/or ASD., (© 2022 Wiley Periodicals LLC.)

Purpose: BRG1/BRM-associated factor (BAF) complex is a chromatin remodeling complex that plays a critical role in gene regulation. Defects in the genes encoding BAF subunits lead to BAFopathies, a group of neurodevelopmental disorders with extensive locus and phenotypic heterogeneity., Methods: We retrospectively analyzed data from 16,243 patients referred for clinical exome sequencing (ES) with a focus on the BAF complex. We applied a genotype-first approach, combining predicted genic constraints to propose candidate BAFopathy genes., Results: We identified 127 patients carrying pathogenic variants, likely pathogenic variants, or de novo variants of unknown clinical significance in 11 known BAFopathy genes. Those include 34 patients molecularly diagnosed using ES reanalysis with new gene-disease evidence (n = 21) or variant reclassifications in known BAFopathy genes (n = 13). We also identified de novo or predicted loss-of-function variants in 4 candidate BAFopathy genes, including ACTL6A, BICRA (implicated in Coffin-Siris syndrome during this study), PBRM1, and SMARCC1., Conclusion: We report the mutational spectrum of BAFopathies in an ES cohort. A genotype-driven and pathway-based reanalysis of ES data identified new evidence for candidate genes involved in BAFopathies. Further mechanistic and phenotypic characterization of additional patients are warranted to confirm their roles in human disease and to delineate their associated phenotypic spectrums., Competing Interests: Conflict of Interest Baylor College of Medicine and Miraca Holdings Inc have formed a joint venture with shared ownership and governance of Baylor Genetics, formerly the Baylor Miraca Genetics Laboratories, which performs chromosomal microarray analysis and clinical exome sequencing. J.L., W.Z., L.W., V.P., A.D., H.Da., L.M., F.X., W.B., P.L., and C.M.E. are employees of Baylor College of Medicine and derive support through a professional services agreement with Baylor Genetics. J.R.L. serves on the Scientific Advisory Board of the Regeneron Genetics Center and has stock ownership in 23andMe. All other authors declare no conflicts of interest., (Copyright © 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association between the Observational Gait Scale (OGS) and the Gross Motor Function Classification System (GMFCS) in walking children with cerebral palsy (CP)., Methods: The charts of 512 children with CP GMFCS levels I to IV were reviewed for the OGS score and GMFCS level at their initial visit., Results: The OGS score decreased with increasing GMFCS levels. The average OGS for GMFCS level I was 13.1 (2.8), level II was 11.3 (2.7), level III was 7.7 (2.7), and level IV was 6.1 (2.0). A significant negative relationship was seen between the OGS and the GMFCS. In particular, each GMFCS level was different across all levels in a pairwise comparison. In addition, multivariate modeling analysis confirmed that the association between the OGS and the GMFCS was still valid, after adjusting for age and gender., Conclusions: The OGS is a quick tool to rate gait and help confirm a child's GMFCS level., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Finding positive meaning in past negative memories is associated with enhanced mental health. Yet it remains unclear whether it leads to updates in the memory representation itself. Since memory can be labile after retrieval, this leaves the potential for modification whenever its reactivated. Across four experiments, we show that positively reinterpreting negative memories adaptively updates them, leading to the re-emergence of positivity at future retrieval. Focusing on the positive aspects after negative recall leads to enhanced positive emotion and changes in memory content during recollection one week later, remaining even after two months. Consistent with a reactivation-induced reconsolidation account, memory updating occurs only after a reminder and twenty four hours, but not a one hour delay. Multi-session fMRI showed adaptive updates are reflected in greater hippocampal and ventral striatal pattern dissimilarity across retrievals. This research highlights the mechanisms by which updating of maladaptive memories occurs through a positive emotion-focused strategy., (© 2021. The Author(s).)

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2-4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2-4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment. Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8-6 U/kg), the brachioradialis in 83.8% (0.4-3 U/kg), the flexor carpi ulnaris in 82.4% (0.5-3 U/kg) and the flexor carpi radialis in 79.5% (0.5-4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3-3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1-2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5-2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5-6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group. Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need., Competing Interests: This study was funded by Ipsen. The authors employed or contracted by Ipsen SP, BR, and CT were involved in interpretation of the data; and in review, approval of, and decision to submit the manuscript. The funder had no other role in study conduct or preparation of this report. JO, AT, JC, ND, MB, ED, and MD were investigators in Ipsen-sponsored clinical trials and they or their institutions have received payment for participation. In addition, JO reports consultancy fees for Ipsen and Allergan. AT reports research support and educational grants from Ipsen and personal fees for consultancy from Ipsen. JC reports personal fees for consultancy and speaking from Ipsen. ND reports research support from Ipsen, Allergan, and Merz and personal fees for consultancy and speaking from Ipsen and Allergan. MB reports research support from Ipsen, Allergan, and Merz and personal fees for consultancy and speaking from Ipsen and Allergan. ED reports personal fees from Ipsen and Allergan for speaking, Solstice Neurosciences for consultancy and serves on a US speaker bureau. MD reports personal fees from Ipsen, Allergan and Kashiv Pharma for consultancy., (Copyright © 2021 Oleszek, Tilton, Carranza del Rio, Dursun, Bonikowski, Dabrowski, Page, Regnault, Thompson and Delgado.)

The propensity to perceive and exert control in our environment contributes to both our adaptive behavior and general well-being. Prior studies have shown that humans have an inherent behavioral bias toward control-conferring environments and that this bias translates into greater subjective affect and is protective of our well-being. As such, it is vital to understand contextual factors that can alter our preference for control. In our previous work, we demonstrated that the behavioral bias toward control can be captured experimentally as the subjective value of control using a novel Value of Control task. We adapted this task in two experiments to study whether one's subjective value of control is (a) tied to overestimation of success probability or outcome magnitude (Experiment 1) and (b) affected by the contextual valence of a decision (e.g., gain, loss; Experiment 2). Using a within-subjects design (Experiment 1), we found that participants showed similar behavioral bias toward control regardless of whether probability or magnitude was manipulated, suggesting that the perception of control can increase both how much a reward is subjectively worth and the probability estimation for obtaining the given reward. Using a between-subjects design (Experiment 2), we showed that when the outcome was framed as a potential loss, participants significantly lowered their subjective value of control, suggesting that outcome valence plays a role in shaping how much perceived control influences our behavior. Collectively, these findings offer further insight into the malleability of an individual's perception of control and drive to perform control-seeking behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background : Negative emotion is associated with substance craving and use in individuals recovering from substance use disorders, including prescription opioid use disorder (POUD). Decisions to abandon or persist towards a goal after negative emotion-eliciting events, and neural responses that shape such decisions, may be important in maintaining recovery from POUD. Objectives : We examined differences in neural responses to negative events and subsequent persistence decisions in individuals recovering from POUD without a history of a substance use disorder. Methods : 20 individuals with POUD (POUD group: 4 females, abstinent 2-3 weeks after admission to an inpatient treatment facility post-detoxification, no other substance use disorder), and 20 individuals with no substance use history (control group: 6 females) completed a persistence-after-setbacks task during functional magnetic resonance imaging. Participants advanced along a path toward a reward; after encountering each negative event (i.e., progress-erasing setback), participants made decisions to persist or abandon the path. Persistence decision rates were compared between groups and blood-oxygen-level-dependent signal to negative events was analyzed within a striatum region of interest (ROI) as well as whole-brain. Results : The POUD group persisted less (t(38) = 2.293, p = .028, d = .725) and showed lower striatum (left ventral putamen) signal to negative events compared to the control group ( p < .05, corrected for striatum ROI). Conclusions : In POUD, neural and behavioral responses to negative events differ from controls. These differences are a target for research to address whether POUD treatment increases persistence and striatum responses to negative events and improves recovery outcomes.

Aim: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP)., Method: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4., Results: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively)., Interpretation: Treatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles., What This Paper Adds: AbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year., (© 2020 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

The ability to perceive and exercise control is a major contributor to our mental and physical wellbeing. When faced with uncontrollable aversive stimuli, organisms develop heightened anxiety and become unwilling to exert effort to avoid the stimuli. In contrast, when faced with controllable aversive stimuli, organisms demonstrate behavioral vigor via avoidance attempts toward trying to seek and exercise control over the environment. As such, controllability confers protective effects against reduced avoidance motivation trigged by aversive environments. These observations beg the question of whether controllability can be potent enough to reverse passivity following repeated exposure to uncontrollable aversive stimuli and how this protective effect is encoded neurally. Human participants performed a Control in Aversive Domain (CAD) task where they were first subjected to a series of repeated uncontrollable aversive stimuli (i.e., aversive tones) across several contexts that were followed by a series of controllable aversive stimuli in a novel context. Faced with persistent uncontrollability, participants significantly reduced their avoidance attempts over time and biased toward giving up. However, the subsequent presence of controllability rescued participants' avoidance behavior. Strikingly, participants who responded more strongly to the protective effects of control also had greater ventromedial prefrontal cortical (vmPFC) activation-a region previously observed to be associated with encoding the subjective value of control. Taken together, these findings highlighted the protective effect conferred by perceived control against passivity and offered insights into the potential role of the vmPFC in controllable environments, with implications for understanding the beneficial influence of perceived control on adaptive behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang and Delgado.)

De novo germline variation in POLR2A was recently reported to associate with a neurodevelopmental disorder. We report twelve individuals harboring putatively pathogenic de novo or inherited variants in POLR2A , detail their phenotypes, and map all known variants to the domain structure of POLR2A and crystal structure of RNA polymerase II. Affected individuals were ascertained from a local data lake, pediatric genetics clinic, and an online community of families of affected individuals. These include six affected by de novo missense variants (including one previously reported individual), four clinical laboratory samples affected by missense variation with unknown inheritance-with yeast functional assays further supporting altered function-one affected by a de novo in-frame deletion, and one affected by a C-terminal frameshift variant inherited from a largely asymptomatic mother. Recurrently observed phenotypes include ataxia, joint hypermobility, short stature, skin abnormalities, congenital cardiac abnormalities, immune system abnormalities, hip dysplasia, and short Achilles tendons. We report a significantly higher occurrence of epilepsy (8/12, 66.7%) than previously reported (3/15, 20%) (p value = 0.014196; chi-square test) and a lower occurrence of hypotonia (8/12, 66.7%) than previously reported (14/15, 93.3%) (p value = 0.076309). POLR2A -related developmental disorders likely represent a spectrum of related, multi-systemic developmental disorders, driven by distinct mechanisms, converging at a single locus., Competing Interests: Declaration of interests J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron Pharmaceuticals, and is a co-inventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from clinical genetic testing offered in the Baylor Genetics Laboratory.

Aim: To determine the acceptability and effects of a pediatric constraint induced movement therapy (P-CIMT) camp for children with hemiplegic cerebral palsy (hCP) augmented by use of an exoskeleton to play games in virtual reality (VR)., Method: 31 children with hCP attended a P-CIMT camp 6 hours per day for 10 days over 2 successive weeks (60 hours) that included 30 minutes of unilateral training with the Hocoma Armeo ® Spring Pediatric that combines the assistance of an exoskeleton and VR games. The primary outcome measure was the Assisting Hand Assessment (AHA); secondary outcome measures were the Melbourne Assessment of Uni-lateral Hand Function (MUUL), and the Canadian Occupational Performance Measure (COPM). Assessments were completed at pre-intervention, post-intervention, and 6 months following intervention., Results: Participants demonstrated clinically and statistically significant improvement in bimanual performance (AHA) ( p < .001) and COPM Performance ( p < .001) and Satisfaction with performance ( p < .001). Improvement in unilateral performance (MUUL) was statistically ( p < .001) but not clinically significant., Conclusions: A P-CIMT camp augmented by the Hocoma Armeo ® Spring Pediatric was feasible and accepted by participants. Bimanual hand function and occupational performance improved immediately following intervention, and the treatment effects persisted 6 months following intervention.

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD) SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 ± 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 ± 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 ± 5.1 years, SD) and later tetraplegia (mean age: 16.1 ± 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 ± 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 ± 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Botulinum toxin-A is a well-established treatment for adult and pediatric spastic paresis and cervical dystonia. While guidelines and approved labels indicate that treatment should not occur more frequently than every 12 weeks, studies and real-world evidence show that the timing of symptom recurrence between treatments may vary. Methods: We report retreatment criteria and response duration (retreatment intervals) from four pivotal, double-blind, placebo-controlled studies with open-label extensions involving patients treated with abobotulinumtoxinA (aboBoNTA) for upper limb (NCT01313299) or lower limb (NCT01249404) spastic paresis in adults, lower limb spastic paresis in children (NCT01249417), and cervical dystonia in adults (NCT00257660). We review results in light of recently available preclinical data. Results: In spastic paresis, 24.0-36.9% of upper limb patients treated with aboBoNTA and 20.1-32.0% of lower limb patients did not require retreatment before 16 weeks. Moreover, 72.8-93.8% of aboBoNTA-treated pediatric patients with lower limb spastic paresis did not require retreatment before 16 weeks (17.7-54.0% did not require retreatment before 28 weeks). In aboBoNTA-treated patients with cervical dystonia, 72.6-81.5% did not require retreatment before 16 weeks. Conclusion: AboBoNTA, when dosed as recommended, offers symptom relief beyond 12 weeks to many patients with spastic paresis and cervical dystonia. From recently available preclinical research, the amount of active neurotoxin administered with aboBoNTA might be a factor in explaining this long duration of response., (Copyright © 2020 Esquenazi, Delgado, Hauser, Picaut, Foster, Lysandropoulos and Gracies.)

Aim: To assess the neural and non-neural contributions to spasticity in the impaired ankle of children with cerebral palsy (CP)., Method: Instrumented tapping of the Achilles tendon was done isometrically to minimize non-neural contributions and elicit neural contributions. Robot-controlled ankle stretching was done at various velocities, including slow stretching, with minimized neural contributions. Spasticity was assessed as having neural (phasic and tonic stretch reflex torque, tendon reflex gain, contraction rate, and half relaxation rate) and non-neural origin (elastic stiffness and viscous damping) in 17 children with CP (six females and 11 males; mean age [SD] 10y 8mo [3y 11mo], range 4y-18y) and 17 typically developing children (six females and 11 males; mean age [SD] 12y 7mo [2y 9mo], range 7y-18y). All torques were normalized to weight×height., Results: Children with CP showed increased phasic and tonic stretch reflex torque (p=0.004 and p=0.001 respectively), tendon reflex gain (p=0.02), contraction rate (p=0.038), half relaxation rate (p=0.02), elastic stiffness (p=0.01), and viscous damping (p=0.01) compared to typically developing children., Interpretation: Controlled stretching and instrumented tendon tapping allow the systematic quantification of various neural and non-neural changes in CP, which can be used to guide impairment-specific treatment., What This Paper Adds: Ankle spasticity is associated with increased phasic and tonic stretch reflexes, tendon reflex gain, and contraction and half relaxation rates. Ankle spasticity is also associated with increased elastic stiffness and viscous damping., (© 2020 Mac Keith Press.)

Purpose : This secondary analysis of a randomized, double-blind study plus open-label extension (NCT01249417/NCT01251380) evaluated the efficacy of abobotulinumtoxinA versus placebo in improving gait pattern in children with dynamic equinus due to cerebral palsy (CP) as assessed by the observational gait scale (OGS). Methods : Ambulatory children with CP (N = 241, aged 2-17) and dynamic equinus were randomized to treatment with abobotulinumtoxinA (10 or 15U/kg/leg) or placebo injected into the gastrocsoleus. All children received abobotulinumtoxinA in the open-label phase. Results : In the double-blind phase, abobotulinumtoxinA significantly improved OGS total scores versus placebo at Week 4 (treatment effect vs. placebo: 10U/kg/leg: 1.5 [0.7, 2.3], p = .0003; 15U/kg/leg: 1.1 [0.3, 1.9], p = .01). In the open-label phase, treatment with abobotulinumtoxinA continued to improve the OGS score at the same magnitude as seen in the double-blind study. Conclusion : Repeat treatment with abobotulinumtoxinA improved gait in children with dynamic equinus.

Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses 1 . The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset 2-5 . Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Reciprocated trust plays a critical role in forming and maintaining relationships, and has consistently been shown to implicate neural circuits involved in reward-related processing and social cognition. Less is known about neural network connectivity during social interactions involving trust, however, particularly as a function of closeness between an investor and a trustee. We examined network reactivity and connectivity in participants who played an economic trust game with close friends, strangers and a computer. Network reactivity analyses showed enhanced activation of the default-mode network (DMN) to social relative to non-social outcomes. A novel network psychophysiological interaction (nPPI) analysis revealed enhanced connectivity between the DMN and the superior frontal gyrus and superior parietal lobule when experiencing reciprocated vs violated trust from friends relative to strangers. Such connectivity tracked with differences in self-reported social closeness with these partners. Interestingly, reactivity of the executive control network (ECN), involved in decision processes, demonstrated no social vs non-social preference, and ECN-ventral striatum connectivity did not track social closeness. Taken together, these novel findings suggest that DMN interacts with components of attention and control networks to signal the relative importance of positive experiences with close others vs strangers., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND)., Methods: Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex., Results: Subjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners., Conclusions: A consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.

Positive memory retrieval generates pleasant feelings that can counteract negative affective states and improve mood. However, not all positive memories are created equal. Our most treasured memories are likely experiences we shared with other people (e.g., birthday party) rather than something we did alone (e.g., receiving good grades). Here, we explored whether the social context within a positive memory enhanced its subjective value and contributed to an individual's well-being. In Study 1, participants were asked how much they would be willing to pay to reexperience positive memories that occurred with socially close others (high-social), with acquaintances (low-social) or alone (nonsocial). When controlling for the memory's positivity, participants were still willing to pay 1.5 times as much for high-social than for low-social or nonsocial memories. Likewise, participants chose to reminisce about high-social memories more frequently than less social ones of equal positive feeling. In Study 2, recalling memories rich in social context recruited regions previously implicated in mentalizing and reward (e.g., caudate), which further correlated with greater ability to savor positive emotions in daily life. Finally, we examined the benefit of social context by asking participants to recall positive memories that varied in social context after acute stress exposure. In Study 3, recalling memories that included higher social context led to a greater dampening of the physiological stress response (i.e., cortisol). Taken together, these findings suggest that social context inherent in a positive memory enhances its value, providing a possible mechanism by which positive reminiscence aids stress coping and enhances well-being. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Congenital scoliosis (CS) is a birth defect with variable clinical and anatomical manifestations due to spinal malformation. The genetic etiology underlying about 10% of CS cases in the Chinese population is compound inheritance by which the gene dosage is reduced below that of haploinsufficiency. In this genetic model, the trait manifests as a result of the combined effect of a rare variant and common pathogenic variant allele at a locus. From exome sequencing (ES) data of 523 patients in Asia and two patients in Texas, we identified six TBX6 gene-disruptive variants from 11 unrelated CS patients via ES and in vitro functional testing. The in trans mild hypomorphic allele was identified in 10 of the 11 subjects; as anticipated these 10 shared a similar spinal deformity of hemivertebrae. The remaining case has a homozygous variant in TBX6 (c.418C>T) and presents a more severe spinal deformity phenotype. We found decreased transcriptional activity and abnormal cellular localization as the molecular mechanisms for TBX6 missense loss-of-function alleles. Expanding the mutational spectrum of TBX6 pathogenic alleles enabled an increased molecular diagnostic detection rate, provided further evidence for the gene dosage-dependent genetic model underlying CS, and refined clinical classification., (© 2019 Wiley Periodicals, Inc.)

The ability to perceive and exercise control over an outcome is both desirable and beneficial to our well-being. It has been shown that animals and humans alike exhibit behavioral bias towards seeking control and that such bias recruits the ventromedial prefrontal cortex (vmPFC) and striatum. Yet, this bias remains to be quantitatively captured and studied neurally. Here, we employed a behavioral task to measure the preference for control and characterize its neural underpinnings. Participants made a series of binary choices between having control and no-control over a game for monetary reward. The mere presence of the control option evoked activity in the ventral striatum. Importantly, we manipulated the expected value (EV) of each choice pair to extract the pairing where participants were equally likely to choose either option. The difference in EV between the options at this point of equivalence was inferred as the subjective value of control. Strikingly, perceiving control inflated the reward value of the associated option by 30% and this value inflation was tracked by the vmPFC. Altogether, these results capture the subjective value of perceived control inherent in decision making and highlight the role of corticostriatal circuitry in the perception of control., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)