History of conditioned reward association disrupts inhibitory control: an examination of neural correlates.

The neural processes that support inhibitory control in the face of stimuli with a history of reward association are not yet well understood. Yet, the ability to flexibly adapt behavior to changing reward-contingency contexts is important for daily functioning and warrants further investigation. This study aimed to characterize neural and behavioral impacts of stimuli with a history of conditioned reward association on motor inhibitory control in healthy young adults by investigating group-level effects as well as individual variation in the ability to inhibit responses to stimuli with a reward history. Participants (N = 41) first completed a reward conditioning phase, during which responses to rewarded stimuli were associated with money and responses to unrewarded stimuli were not. Rewarded and unrewarded stimuli from training were carried forward as No-Go targets in a subsequent go/no-go task to test the effect of reward history on inhibitory control. Participants underwent functional brain imaging during the go/no-go portion of the task. On average, a history of reward conditioning disrupted inhibitory control. Compared to inhibition of responses to stimuli with no reward history, trials that required inhibition of responses to previously rewarded stimuli were associated with greater activity in frontal and striatal regions, including the inferior frontal gyrus, insula, striatum, and thalamus. Activity in the insula and thalamus during false alarms and in the ventromedial prefrontal cortex during correctly withheld trials predicted behavioral performance on the task. Overall, these results suggest that reward history serves to disrupt inhibitory control and provide evidence for diverging roles of the insula and ventromedial prefrontal cortex while inhibiting responses to stimuli with a reward history.

Computer-based inhibitory control training in children with Attention-Deficit/Hyperactivity Disorder (ADHD): Evidence for behavioral and neural impact.

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychological disorder of childhood. Medication and cognitive behavioral therapy are effective treatments for many children; however, adherence to medication and therapy regimens is low. Thus, identifying effective adjunct treatments is imperative. Previous studies exploring computerized training programs as supplementary treatments have targeted working memory or attention. However, many lines of research suggest inhibitory control (IC) plays a central role in ADHD pathophysiology, which makes IC a potential intervention target. In this randomized control trial (NCT03363568), we target IC using a modified stop-signal task (SST) training designed by NeuroScouting, LLC in 40 children with ADHD, aged 8 to 11 years. Children were randomly assigned to adaptive treatment (n = 20) or non-adaptive control (n = 20) with identical stimuli and task goals. Children trained at home for at least 5 days a week (about 15m/day) for 4-weeks. Relative to the control group, the treatment group showed decreased relative theta power in resting EEG and trending improvements in parent ratings of attention (i.e. decreases in inattentive behaviors). Both groups showed improved SST performance. There was not evidence for treatment effects on hyperactivity or teacher ratings of symptoms. Results suggest training IC alone has potential to positively impact symptoms of ADHD and provide evidence for neural underpinnings of this impact (change in theta power; change in N200 latency). This shows promising initial results for the use of computerized training of IC in children with ADHD as a potential adjunct treatment option for children with ADHD.

Examining cognitive control and reward interactions in adolescent externalizing symptoms.

During adolescence, rapid development and reorganization of the dopaminergic system supports increasingly sophisticated reward learning and the ability to exert behavioral control. Disruptions in the ability to exert control over previously rewarded behavior may underlie some forms of adolescent psychopathology. Specifically, symptoms of externalizing psychopathology may be associated with difficulties in flexibly adapting behavior in the context of reward. However, the direct interaction of cognitive control and reward learning in adolescent psychopathology symptoms has not yet been investigated. The present study used a Research Domain Criteria framework to investigate whether behavioral and neuronal indices of inhibition to previously rewarded stimuli underlie individual differences in externalizing symptoms in N = 61 typically developing adolescents. Using a task that integrates the Monetary Incentive Delay and Go-No-Go paradigms, we observed a positive association between externalizing symptoms and activation of the left middle frontal gyrus during response inhibition to cues with a history of reward. These associations were robust to controls for internalizing symptoms and neural recruitment during inhibition of cues with no reward history. Our findings suggest that inhibitory control over stimuli with a history of reward may be a useful marker for future inquiry into the development of externalizing psychopathology in adolescence.

Registration-free analysis of diffusion MRI tractography data across subjects through the human lifespan.

Diffusion MRI tractography produces massive sets of streamlines that need to be clustered into anatomically meaningful white-matter bundles. Conventional clustering techniques group streamlines based on their proximity in Euclidean space. We have developed AnatomiCuts, an unsupervised method for clustering tractography streamlines based on their neighboring anatomical structures, rather than their coordinates in Euclidean space. In this work, we show that the anatomical similarity metric used in AnatomiCuts can be extended to find corresponding clusters across subjects and across hemispheres, without inter-subject or inter-hemispheric registration. Our proposed approach enables group-wise tract cluster analysis, as well as studies of hemispheric asymmetry. We evaluate our approach on data from the pilot MGH-Harvard-USC Lifespan Human Connectome project, showing improved correspondence in tract clusters across 184 subjects aged 8-90. Our method shows up to 38% improvement in the overlap of corresponding clusters when comparing subjects with large age differences. The techniques presented here do not require registration to a template and can thus be applied to populations with large inter-subject variability, e.g., due to brain development, aging, or neurological disorders.

Development of Prefrontal Cortical Connectivity and the Enduring Effect of Learned Value on Cognitive Control.

Inhibitory control, the capacity to suppress an inappropriate response, is a process employed for guiding action selection in the service of goal-directed behavior. Under neutral circumstances, inhibitory control success improves from childhood to adulthood and has been associated with developmental shifts in functional activation and connectivity of the PFC. However, the ability to exercise inhibitory control is challenged in certain contexts by including appetitive cues, a phenomenon that may be particularly pronounced in youths. Here, we examine the magnitude and temporal persistence of learned value's influence on inhibitory control in a cross-sectional sample of 8- to 25-year-olds. Participants first underwent conditioning of a motor approach response to two initially neutral cues, with one cue reinforced with monetary reward and the other with no monetary outcome. Subsequently, during fMRI, participants reencountered these cues as no-go targets in a nonreinforced go/no-go paradigm. Although the influence of learned value increasingly disrupted inhibitory control with increasing age, in young adults this pattern remitted over the course of the task, whereas during adolescence the impairing effect of reward history persisted. Successful no-go performance to the previously rewarded target was related to greater recruitment of the right inferior frontal gyrus and age-related increase in functional connectivity between the inferior frontal gyrus and the ventromedial PFC for the previously rewarded no-go target over the control target. Together, results indicate the complex influence of value on goals over development relies upon the increased coordination of distinct higher-order regions in the PFC.

Spanish Linguistic Validation of the Velopharyngeal Insufficiency Effects on Life Outcomes: VELO-Spanish.

BACKGROUND: Quality of life (QOL) assessments are useful tools that measure a patient's health status and monitor patient-reported outcome measures. This study highlights the process of linguistic validation of a QOL assessment to serve Spanish-speaking families and ultimately help decrease language barriers in the treatment of velopharyngeal insufficiency (VPI). METHODS: The standardized linguistic validation process included forward and backward translation, reconciliation, and cognitive interviews with patients and families. Preliminary instrument test-retest measurement was assessed. Eligibility for cognitive interviews included families with familiarity of velopharyngeal insufficiency. Exclusion criteria included illiteracy and parent and child respondents who do not speak Spanish. Reliability was tested by intraclass correlation (ICC) on VPI Effects on Life Outcomes (VELO)-Spanish instruments completion on 2 measurements from the medical record. RESULTS: The instrument was optimized through a standardized forward and backward translation process. Further problematic language was identified during cognitive interviews with families and their children. In the second interview, only minimal changes were needed. Twenty-one patients (8 males and 13 females) were included. Mean (SD) age was 8.0 (5.3) years (range, 3-21 years). The mean (SD) Velo-Spanish score was 65 (22.1); range 32.7-100. The VELO-Spanish instrument demonstrated excellent test-retest reliability [ICC = 0.91; n = 21 and internal consistency (α = 0.96)]. CONCLUSIONS: The Spanish VELO has been developed and refined for use in Spanish-speaking populations as a VPI-specific QOL instrument. The linguistic validation process including cognitive interviews and initial reliability testing. The instrument may improve the understanding of patient-reported outcomes and potential disparities from linguistic and cultural barriers in VPI treatment.

MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography.