A pilot study of basal ganglia and thalamus structure by high dimensional mapping in children with Tourette syndrome

Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).  A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. Objective: Pilot the HDBM-LD method in children and estimate effect sizes. Methods: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age.  The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. Results: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry.  Effect sizes were greater for shape analysis than for volume. Conclusion: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences

Differential engagement of anterior cingulate corte subdivisions for cognitive and emotional function.

Abstract Functional differentiation of dorsal (dACC) and rostral (rACC) anterior cingulate cortex for cognitive and emotional function has received considerable indirect support. Using fMRI, parallel tasks, and within-subject analysis, the present study directly tested the proposed specialization of ACC subdivisions. A Task  Region interaction confirmed more dACC activation during color-word distractors and more rACC activation during emotion-word distractors. Activity in ACC subdivisions differentially predicted behavioral performance. Connectivity with prefrontal and limbic regions also supported distinct dACC and rACC roles. Findings provide direct evidence for differential engagement of ACC subdivisions in cognitive and emotional processing and for differential functional connectivity in the implementation of cognitive control and emotion regulation. Results point to an anatomical and functional continuum rather than segregated operations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Both reactive and proactive control are deficient in children with ADHD and predictive of clinical symptoms.

Cognitive control deficits are a hallmark of attention deficit hyperactivity disorder (ADHD) in children. Theoretical models posit that cognitive control involves reactive and proactive control processes but their distinct roles and inter-relations in ADHD are not known, and the contributions of proactive control remain vastly understudied. Here, we investigate the dynamic dual cognitive control mechanisms associated with both proactive and reactive control in 50 children with ADHD (16F/34M) and 30 typically developing (TD) children (14F/16M) aged 9-12 years across two different cognitive controls tasks using a within-subject design. We found that while TD children were capable of proactively adapting their response strategies, children with ADHD demonstrated significant deficits in implementing proactive control strategies associated with error monitoring and trial history. Children with ADHD also showed weaker reactive control than TD children, and this finding was replicated across tasks. Furthermore, while proactive and reactive control functions were correlated in TD children, such coordination between the cognitive control mechanisms was not present in children with ADHD. Finally, both reactive and proactive control functions were associated with behavioral problems in ADHD, and multi-dimensional features derived from the dynamic dual cognitive control framework predicted inattention and hyperactivity/impulsivity clinical symptoms. Our findings demonstrate that ADHD in children is characterized by deficits in both proactive and reactive control, and suggest that multi-componential cognitive control measures can serve as robust predictors of clinical symptoms

Both reactive and proactive control are deficient in children with ADHD and predictive of clinical symptoms

Cognitive control deficits are a hallmark of attention deficit hyperactivity disorder (ADHD) in children. Theoretical models posit that cognitive control involves reactive and proactive control processes but their distinct roles and inter-relations in ADHD are not known, and the contributions of proactive control remain vastly understudied. Here, we investigate the dynamic dual cognitive control mechanisms associated with both proactive and reactive control in 50 children with ADHD (16F/34M) and 30 typically developing (TD) children (14F/16M) aged 9-12 years across two different cognitive controls tasks using a within-subject design. We found that while TD children were capable of proactively adapting their response strategies, children with ADHD demonstrated significant deficits in implementing proactive control strategies associated with error monitoring and trial history. Children with ADHD also showed weaker reactive control than TD children, and this finding was replicated across tasks. Furthermore, while proactive and reactive control functions were correlated in TD children, such coordination between the cognitive control mechanisms was not present in children with ADHD. Finally, both reactive and proactive control functions were associated with behavioral problems in ADHD, and multi-dimensional features derived from the dynamic dual cognitive control framework predicted inattention and hyperactivity/impulsivity clinical symptoms. Our findings demonstrate that ADHD in children is characterized by deficits in both proactive and reactive control, and suggest that multi-componential cognitive control measures can serve as robust predictors of clinical symptoms

Latent brain state dynamics distinguish behavioral variability, impaired decision-making, and inattention.

Children with Attention Deficit Hyperactivity Disorder (ADHD) have prominent deficits in sustained attention that manifest as elevated intra-individual response variability and poor decision-making. Influential neurocognitive models have linked attentional fluctuations to aberrant brain dynamics, but these models have not been tested with computationally rigorous procedures. Here we use a Research Domain Criteria approach, drift-diffusion modeling of behavior, and a novel Bayesian Switching Dynamic System unsupervised learning algorithm, with ultrafast temporal resolution (490 ms) whole-brain task-fMRI data, to investigate latent brain state dynamics of salience, frontoparietal, and default mode networks and their relation to response variability, latent decision-making processes, and inattention. Our analyses revealed that occurrence of a task-optimal latent brain state predicted decreased intra-individual response variability and increased evidence accumulation related to decision-making. In contrast, occurrence and dwell time of a non-optimal latent brain state predicted inattention symptoms and furthermore, in a categorical analysis, distinguished children with ADHD from controls. Importantly, functional connectivity between salience and frontoparietal networks predicted rate of evidence accumulation to a decision threshold, whereas functional connectivity between salience and default mode networks predicted inattention. Taken together, our computational modeling reveals dissociable latent brain state features underlying response variability, impaired decision-making, and inattentional symptoms common to ADHD. Our findings provide novel insights into the neurobiology of attention deficits in children

Cortical organization of inhibition-related functions and modulation by psychopathology

Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology

Relationships among cognition, emotion, and motivation : implications for intervention and neuroplasticity in psychopathology

Emotion-cognition and motivation-cognition relationships and related brain mechanisms are receiving increasing attention in the clinical research literature as a means of understanding diverse types of psychopathology and improving biological and psychological treatments. This paper reviews and integrates some of the growing evidence for cognitive biases and deficits in depression and anxiety, how these disruptions interact with emotional and motivational processes, and what brain mechanisms appear to be involved. This integration sets the stage for understanding the role of neuroplasticity in implementing change in cognitive, emotional, and motivational processes in psychopathology as a function of intervention.publishe

Cortical organization of inhibition-related functions and modulation by psychopathology

Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.publishe