Corrigendum: Motor learning in developmental coordination disorder: behavioral and neuroimaging study.

[This corrects the article DOI: 10.3389/fnins.2023.1187790.].

Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.

BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.

Prefrontal Cortex Responses to Social Video Stimuli in Young Children with and without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting individuals worldwide and characterized by deficits in social interaction along with the presence of restricted interest and repetitive behaviors. Despite decades of behavioral research, little is known about the brain mechanisms that influence social behaviors among children with ASD. This, in part, is due to limitations of traditional imaging techniques specifically targeting pediatric populations. As a portable and scalable optical brain monitoring technology, functional near infrared spectroscopy (fNIRS) provides a measure of cerebral hemodynamics related to sensory, motor, or cognitive function. Here, we utilized fNIRS to investigate the prefrontal cortex (PFC) activity of young children with ASD and with typical development while they watched social and nonsocial video clips. The PFC activity of ASD children was significantly higher for social stimuli at medial PFC, which is implicated in social cognition/processing. Moreover, this activity was also consistently correlated with clinical measures, and higher activation of the same brain area only during social video viewing was associated with more ASD symptoms. This is the first study to implement a neuroergonomics approach to investigate cognitive load in response to realistic, complex, and dynamic audiovisual social stimuli for young children with and without autism. Our results further confirm that new generation of portable fNIRS neuroimaging can be used for ecologically valid measurements of the brain function of toddlers and preschool children with ASD.

Exploring Social Impairment in Those with Opioid Use Disorder: Linking Impulsivity, Childhood Trauma, and the Prefrontal Cortex.

Background: Challenges with social functioning, which is a hallmark of opioid use disorder (OUD), are a drawback in treatment adherence and maintenance. Yet, little research has explored the underlying mechanisms of this impairment. Impulsivity, a known risk factor for OUD, and corresponding neural alterations may be at the center of this issue. Childhood adversity, which has been linked to both impulsivity and poorer treatment outcomes, could also affect this relationship. This study aims to understand the relationship between impulsivity and social functioning in those recovering from OUD. Differences in the prefrontal cortex will be analyzed, as well as potential moderating effects of childhood trauma. Methods: Participants with (N = 16) and without (N = 19) social impairment completed a survey (e.g., social functioning, Barrat's Impulsivity Scale, Adverse Childhood Experiences (ACEs) and cognitive tasks while undergoing neuroimaging. Functional near infrared spectroscopy (fNIRS), a modern, portable, wearable and low-cost neuroimaging technology, was used to measure prefrontal cortex activity during a behavioral inhibition task (Go/No-Go task). Results: Those who social functioning survey scores indicated social impairment (n = 16) scored significantly higher on impulsivity scale (t(33)= -3.4, p < 0.01) and reported more depressive symptoms (t(33) = -2.8, p < 0.01) than those reporting no social impairment (n = 19). Social functioning was negatively correlated with impulsivity (r=-0.7, p < 0.001), such that increased impulsivity corresponded to decreased social functioning. Childhood trauma emerged as a moderator of this relationship, but only when controlling for the effects of depression, B=-0.11, p = 0.023. Although both groups had comparable Go/No-Go task performance, the socially impaired group displayed greater activation in the dorsolateral (F(1,100.8) = 7.89, p < 0.01), ventrolateral (F(1,88.8) = 7.33, p < 0.01), and ventromedial (F(1,95.6) = 7.56, p < 0.01) prefrontal cortex during impulse control. Conclusion: In addition to being more impulsive, individuals with social impairment exhibited differential activation in the prefrontal cortex when controlling responses. Furthermore, the impact of impulsivity on social functioning varies depending on ACEs demonstrating that it must be considered in treatment approaches. These findings have implications for addressing social needs and impulsivity of those in recovery, highlighting the importance of a more personalized, integrative, and trauma-informed approach to intervention.

Impaired Cortico-Thalamo-Cerebellar Integration Across Schizophrenia, Bipolar II, and Attention Deficit Hyperactivity Disorder Patients Suggests Potential Neural Signatures for Psychiatric Illness.

Understanding aberrant functional changes between brain regions has shown promise for characterizing and differentiating the symptoms associated with progressive psychiatric disorders. The functional integration between the thalamus and cerebellum significantly influences learning and memory in cognition. Observed in schizophrenic patients, dysfunction within the corticalthalamocerebellar (CTC) circuitry is linked to challenges in prioritizing, processing, coordinating, and responding to information. This study explored whether abnormal CTC functional network connectivity patterns are present across schizophrenia (SCHZ) patients, bipolar II disorder (BIPOL) patients, and ADHD patients by examining both task- and task-free conditions compared to healthy volunteers (HC). Leveraging fMRI data from 135 participants (39 HC, 27 SCHZ patients, 38 BIPOL patients, and 31 ADHD patients), we analyzed functional network connectivity (FNC) patterns across 115 cortical, thalamic, subcortical, and cerebellar regions of interest (ROIs). Guiding our investigation: First, do the brain regions of the CTC circuit exhibit distinct abnormal patterns at rest in SCHZ, ADHD, and BIPOL? Second, do working memory tasks in these patients engage common regions of the circuit in similar or unique patterns? Consistent with previous findings, our observations revealed FNC patterns constrained in the cerebellar, thalamic, striatal, hippocampal, medial prefrontal and insular cortices across all three psychiatric cohorts when compared to controls in both task and task-free conditions. Post hoc analysis suggested a predominance in schizophrenia and ADHD patients during rest, while the task condition demonstrated effects across all three disorders. Factor-by-covariance GLM MANOVA further specified regions associated with clinical symptoms and trait assessments. Our study provides evidence suggesting that dysfunctional CTC circuitry in both task-free and task-free conditions may be an important broader neural signature of psychiatric illness.

Mental workload assessment by monitoring brain, heart, and eye with six biomedical modalities during six cognitive tasks.

Introduction: The efficiency and safety of complex high precision human-machine systems such as in aerospace and robotic surgery are closely related to the cognitive readiness, ability to manage workload, and situational awareness of their operators. Accurate assessment of mental workload could help in preventing operator error and allow for pertinent intervention by predicting performance declines that can arise from either work overload or under stimulation. Neuroergonomic approaches based on measures of human body and brain activity collectively can provide sensitive and reliable assessment of human mental workload in complex training and work environments. Methods: In this study, we developed a new six-cognitive-domain task protocol, coupling it with six biomedical monitoring modalities to concurrently capture performance and cognitive workload correlates across a longitudinal multi-day investigation. Utilizing two distinct modalities for each aspect of cardiac activity (ECG and PPG), ocular activity (EOG and eye-tracking), and brain activity (EEG and fNIRS), 23 participants engaged in four sessions over 4 weeks, performing tasks associated with working memory, vigilance, risk assessment, shifting attention, situation awareness, and inhibitory control. Results: The results revealed varying levels of sensitivity to workload within each modality. While certain measures exhibited consistency across tasks, neuroimaging modalities, in particular, unveiled meaningful differences between task conditions and cognitive domains. Discussion: This is the first comprehensive comparison of these six brain-body measures across multiple days and cognitive domains. The findings underscore the potential of wearable brain and body sensing methods for evaluating mental workload. Such comprehensive neuroergonomic assessment can inform development of next generation neuroadaptive interfaces and training approaches for more efficient human-machine interaction and operator skill acquisition.

Cognitive Effort during Visuospatial Problem Solving in Physical Real World, on Computer Screen, and in Virtual Reality.

Spatial cognition plays a crucial role in academic achievement, particularly in science, technology, engineering, and mathematics (STEM) domains. Immersive virtual environments (VRs) have the growing potential to reduce cognitive load and improve spatial reasoning. However, traditional methods struggle to assess the mental effort required for visuospatial processes due to the difficulty in verbalizing actions and other limitations in self-reported evaluations. In this neuroergonomics study, we aimed to capture the neural activity associated with cognitive workload during visuospatial tasks and evaluate the impact of the visualization medium on visuospatial task performance. We utilized functional near-infrared spectroscopy (fNIRS) wearable neuroimaging to assess cognitive effort during spatial-reasoning-based problem-solving and compared a VR, a computer screen, and a physical real-world task presentation. Our results reveal a higher neural efficiency in the prefrontal cortex (PFC) during 3D geometry puzzles in VR settings compared to the settings in the physical world and on the computer screen. VR appears to reduce the visuospatial task load by facilitating spatial visualization and providing visual cues. This makes it a valuable tool for spatial cognition training, especially for beginners. Additionally, our multimodal approach allows for progressively increasing task complexity, maintaining a challenge throughout training. This study underscores the potential of VR in developing spatial skills and highlights the value of comparing brain data and human interaction across different training settings.

A Miniature Ultrasound Source for Neural Modulation.

This work describes a unique ultrasound (US) exposure system designed to create very localized ( [Formula: see text]) sound fields at operating frequencies that are currently being used for preclinical US neuromodulation. This system can expose small clusters of neuronal tissue, such as cell cultures or intact brain structures in target animal models, opening up opportunities to examine possible mechanisms of action. We modified a dental descaler and drove it at a resonance frequency of 96 kHz, well above its nominal operating point of 28 kHz. A ceramic microtip from an ultrasonic wire bonder was attached to the end of the applicator, creating a 100- [Formula: see text] point source. The device was calibrated with a polyvinylidene difluoride (PVDF) membrane hydrophone, in a novel, air-backed, configuration. The experimental results were confirmed by simulation using a monopole model. The results show a consistent decaying sound field from the tip, well-suited to neural stimulation. The system was tested on an existing neurological model, Drosophila melanogaster, which has not previously been used for US neuromodulation experiments. The results show brain-directed US stimulation induces or suppresses motor actions, demonstrated through synchronized tracking of fly limb movements. These results provide the basis for ongoing and future studies of US interaction with neuronal tissue, both at the level of single neurons and intact organisms.

Neurophysiological and gait outcomes during a dual-task gait assessment in concussed adolescents.

BACKGROUND: Gait deficits are common after concussion in adolescents. However, the neurophysiological underpinnings of these gait deficiencies are currently unknown. Thus, the goal of this study was to compare spatiotemporal gait metrics, prefrontal cortical activation, and neural efficiency between concussed adolescents several weeks from injury and uninjured adolescents during a dual-task gait assessment. METHODS: Fifteen concussed (mean age[SD]: 17.4[0.6], 13 female, days since injury: 26.3[9.9]) and 17 uninjured adolescents (18.0[0.7], 10 female) completed a gait assessment with three conditions repeated thrice: single-task walking, single-task subtraction, and dual-task, which involved walking while completing a subtraction task simultaneously. Gait metrics were measured using an inertial sensor system. Prefrontal cortical activation was captured via functional near-infrared spectroscopy. Neural efficiency was calculated by relating gait metrics to prefrontal cortical activity. Differences between groups and conditions were examined, with corrections for multiple comparisons. FINDINGS: There were no significant differences in gait metrics between groups. Compared to uninjured adolescents, concussed adolescents displayed significantly greater prefrontal cortical activation during the single-task subtraction (P = 0.01) and dual-task (P = 0.01) conditions with lower neural efficiency based on cadence (P = 0.02), gait cycle duration (P = 0.03), step duration (P = 0.03), and gait speed (P = 0.04) during the dual-task condition. INTERPRETATION: Our findings suggest that several weeks after injury concussed adolescents demonstrate lower neural efficiency and display a cost to gait performance when cognitive demand is high, e.g., while multitasking, suggesting that the concussed adolescent brain is less able to compensate when attention is divided between two concurrent tasks.

Motor learning in developmental coordination disorder: behavioral and neuroimaging study.

Developmental coordination disorder (DCD) is characterized by motor learning deficits that are poorly understood within whole-body activities context. Here we present results of one of the largest non-randomized interventional trials combining brain imaging and motion capture techniques to examine motor skill acquisition and its underpinning mechanisms in adolescents with and without DCD. A total of 86 adolescents with low fitness levels (including 48 with DCD) were trained on a novel stepping task for a duration of 7 weeks. Motor performance during the stepping task was assessed under single and dual-task conditions. Concurrent cortical activation in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS). Additionally, structural and functional magnetic resonance imaging (MRI) was conducted during a similar stepping task at the beginning of the trial. The results indicate that adolescents with DCD performed similarly to their peers with lower levels of fitness in the novel stepping task and demonstrated the ability to learn and improve motor performance. Both groups showed significant improvements in both tasks and under single- and dual-task conditions at post-intervention and follow-up compared to baseline. While both groups initially made more errors in the Stroop task under dual-task conditions, at follow-up, a significant difference between single- and dual-task conditions was observed only in the DCD group. Notably, differences in prefrontal activation patterns between the groups emerged at different time points and task conditions. Adolescents with DCD exhibited distinct prefrontal activation responses during the learning and performance of a motor task, particularly when complexity was increased by concurrent cognitive tasks. Furthermore, a relationship was observed between MRI brain structure and function measures and initial performance in the novel stepping task. Overall, these findings suggest that strategies that address task and environmental complexities, while simultaneously enhancing brain activity through a range of tasks, offer opportunities to increase the participation of adolescents with low fitness in physical activity and sports.

Use of functional near-infrared spectroscopy to quantify neurophysiological deficits after repetitive head impacts in adolescent athletes.

There is concern that repetitive head impact exposure (RHIE) may lead to neurophysiological deficits in adolescents. Twelve high school varsity soccer players (5 female) completed the King-Devick (K-D) and complex tandem gait (CTG) assessments pre- and post-season while wearing a functional near-infrared spectroscopy (fNIRS) sensor. The average head impact load (AHIL) for each athlete-season was determined via a standardised protocol of video-verification of headband-based head impact sensor data. Linear mixed effect models were used to determine the effects of AHIL and task condition (3 K-D cards or 4 CTG conditions) on the change in mean prefrontal cortical activation measured by fNIRS, and performance on K-D and CTG, from pre- to post-season. Although there was no difference in the pre- to post-season change in K-D or CTG performance, greater AHIL was associated with greater cortical activation at post-season in comparison to pre-season during the most challenging conditions of K-D (p = 0.003) and CTG (p = 0.02), suggesting that greater RHIE necessitates increased cortical activation to complete the more challenging aspects of these assessments at the same level of performance. These results describe the effect of RHIE on neurofunction and suggest the need for further study of the time course of these effects.

Simultaneous fMRI and tDCS for Enhancing Training of Flight Tasks.

There is a gap in our understanding of how best to apply transcranial direct-current stimulation (tDCS) to enhance learning in complex, realistic, and multifocus tasks such as aviation. Our goal is to assess the effects of tDCS and feedback training on task performance, brain activity, and connectivity using functional magnetic resonance imaging (fMRI). Experienced glider pilots were recruited to perform a one-day, three-run flight-simulator task involving varying difficulty conditions and a secondary auditory task, mimicking real flight requirements. The stimulation group (versus sham) received 1.5 mA high-definition HD-tDCS to the right dorsolateral prefrontal cortex (DLPFC) for 30 min during the training. Whole-brain fMRI was collected before, during, and after stimulation. Active stimulation improved piloting performance both during and post-training, particularly in novice pilots. The fMRI revealed a number of tDCS-induced effects on brain activation, including an increase in the left cerebellum and bilateral basal ganglia for the most difficult conditions, an increase in DLPFC activation and connectivity to the cerebellum during stimulation, and an inhibition in the secondary task-related auditory cortex and Broca's area. Here, we show that stimulation increases activity and connectivity in flight-related brain areas, particularly in novices, and increases the brain's ability to focus on flying and ignore distractors. These findings can guide applied neurostimulation in real pilot training to enhance skill acquisition and can be applied widely in other complex perceptual-motor real-world tasks.

Prefrontal cortex activation by binge-eating status in individuals with obesity while attempting to reappraise responses to food using functional near infrared spectroscopy.

PURPOSE: Difficulty reappraising drives to consume palatable foods may promote poorer inhibition and binge eating (BE) in adults with obesity, but neural underpinnings of food-related reappraisal are underexamined. METHODS: To examine neural correlates of food-related reappraisal, adults with obesity with and without BE wore a portable neuroimaging tool, functional near-infrared spectroscopy (fNIRS). fNIRS measured activity in the prefrontal cortex while participants watched videos of food and attempt to "resist" the food stimuli (i.e., "consider the negative consequences of eating the food"). RESULTS: Participants (N = 32, 62.5% female; BMI 38.6 [Formula: see text] 7.1; 43.5 [Formula: see text] 13.4 y) had a BMI > 30 kg/m2. Eighteen adults (67.0% female; BMI 38.2 [Formula: see text] 7.6) reported BE (≥ 12 BE-episodes in preceding 3 months). The control group comprised 14 adults who denied BE (64.0% female; BMI 39.2 [Formula: see text] 6.6). Among the entire sample, mixed models showed significant, small hyperactivation during crave and resist compared to watch (relax) condition bilaterally in the medial superior frontal gyrus, dorsolateral areas, and middle frontal gyrus (optodes 5, 7, 9, 10, 11, and 12) in the total sample. No statistically significant differences in neural activation were observed between the BE and control group. Moreover, there were no significant group by condition interactions on neural activation. CONCLUSION: Among adults with obesity, BE status was not linked to differential activation in inhibitory prefrontal cortex areas during a food-related reappraisal task. Future research is needed with larger samples, adults without obesity, and inhibition paradigms with both behavioral and cognitive components. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies. TRIAL REGISTRATION: # NCT03113669, date April 13, 2017.

Haptic shared control improves neural efficiency during myoelectric prosthesis use.

Clinical myoelectric prostheses lack the sensory feedback and sufficient dexterity required to complete activities of daily living efficiently and accurately. Providing haptic feedback of relevant environmental cues to the user or imbuing the prosthesis with autonomous control authority have been separately shown to improve prosthesis utility. Few studies, however, have investigated the effect of combining these two approaches in a shared control paradigm, and none have evaluated such an approach from the perspective of neural efficiency (the relationship between task performance and mental effort measured directly from the brain). In this work, we analyzed the neural efficiency of 30 non-amputee participants in a grasp-and-lift task of a brittle object. Here, a myoelectric prosthesis featuring vibrotactile feedback of grip force and autonomous control of grasping was compared with a standard myoelectric prosthesis with and without vibrotactile feedback. As a measure of mental effort, we captured the prefrontal cortex activity changes using functional near infrared spectroscopy during the experiment. It was expected that the prosthesis with haptic shared control would improve both task performance and mental effort compared to the standard prosthesis. Results showed that only the haptic shared control system enabled users to achieve high neural efficiency, and that vibrotactile feedback was important for grasping with the appropriate grip force. These results indicate that the haptic shared control system synergistically combines the benefits of haptic feedback and autonomous controllers, and is well-poised to inform such hybrid advancements in myoelectric prosthesis technology.

Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies.

Objective: The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric symptoms using cognitive task performance, functional brain imaging, and a prospective population survey. Methods: Study 1 was a laboratory study conducted between 3 May 2022 and 16 Nov 2022 involving 120 fully vaccinated community dwelling adults between 18 and 84 years of age (Mage = 31.96 (SD = 20.71), 63.3% female). In this cross-sectional study we examined the association between symptomatic COVID-19 infection history and performance on three computer tasks assessing cognitive function (Flanker interference, delay discounting and simple reaction time) and measured oxygen saturation within the prefrontal cortex using functional near infrared spectroscopy (fNIRS). Study 2 was a 2-wave population survey undertaken between 28 September 2021 and 21 March 2022, examining the prospective relationship between symptomatic COVID-19 and self-reported symptoms of cognitive dysfunction, depressive symptoms, anxiety symptoms, and agitation at 6-month follow up. The sample (N = 2,002, M age = 37.0, SD = 10.4; 60.8% female) was collected using a quota process to ensure equal numbers of vaccinated and unvaccinated individuals. Structural equation modelling with latent variables was performed on the population-level data, evaluating the fit of the proposed mediational model of symptomatic COVID-19 to psychiatric symptoms through cognitive dysfunction. Results: Findings from Study 1 revealed significant effects of symptomatic COVID-19 history on Flanker interference and delay discounting. Effects on flanker performance were significantly stronger among older adult women (effect: 9.603, SE = 4.452, t = 2.157, p = .033), and were accompanied by task-related changes cerebral oxygenation at the right superior frontal gyrus (F (1, 143.1) = 4.729, p = .031). Additionally, those with a symptomatic COVID-19 infection history showed evidence of amplified delay discounting (coefficient = 0.4554, SE = 0.2208, t = 2.0629, p = .041). In Study 2, baseline symptomatic COVID-19 history was associated with self-reported cognitive dysfunction and a latent variable reflecting psychiatric symptoms of anxiety, depression and agitation at follow-up. Mediational analyses revealed evidence of cognitive mediation of clinically significant psychiatric outcomes: depression (indirect effect = 0.077, SE = 0.026, p = .003) and generalized anxiety (indirect effect = 0.060, SE = 0.021, p = .004). Conclusions: Converging findings from laboratory and population survey data support the conclusion that symptomatic COVID-19 infection is associated with task-related, functional imaging and self-reported indices of cognitive dysfunction as well as psychiatric symptoms. In some cases, these findings appear to be more amplified among women than men, and among older women than younger.