Age-related differences in the neural correlates of trial-to-trial variations of reaction time.

Intra-subject variation in reaction time (ISVRT) is a developmentally-important phenomenon that decreases from childhood through young adulthood in parallel with the development of executive functions and networks. Prior work has shown a significant association between trial-by-trial variations in reaction time (RT) and trial-by-trial variations in brain activity as measured by the blood-oxygenated level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI) studies. It remains unclear, however, whether such "RT-BOLD" relationships vary with age. Here, we determined whether such trial-by-trial relationships vary with age in a cross-sectional design. We observed an association between age and RT-BOLD relationships in 11 clusters located in visual/occipital regions, frontal and parietal association cortex, precentral/postcentral gyrus, and thalamus. Some of these relationships were negative, reflecting increased BOLD associated with decreased RT, manifesting around the time of stimulus presentation and positive several seconds later. Critically for present purposes, all RT-BOLD relationships increased with age. Thus, RT-BOLD relationships may reflect robust, measurable changes in the brain-behavior relationship across development.

Impaired fixation to eyes during facial emotion labelling in children with bipolar disorder or severe mood dysregulation.

BACKGROUND: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces. METHODS: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions. RESULTS: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls. LIMITATIONS: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns. CONCLUSION: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study.

Cross-sectional and longitudinal abnormalities in brain structure in children with severe mood dysregulation or bipolar disorder.

BACKGROUND: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time. Furthermore, the developmental trajectories of structural abnormalities in BD or SMD are unknown. This study provides such data in BD, SMD, and HV. METHODS: An optimized, modulated voxel-based morphometry (VBM) analysis was conducted on structural MRI scans from 201 children (78 SMD, 55 BD, and 68 HV). In addition, 92 children (31 SMD, 34 BD, and 27 HV) were rescanned after 2 years (mean interval 1.99 ± 0.94 years), to compare time-related changes among the three groups. RESULTS: Cross-sectionally, the groups differed in gray matter (GM) volume in presupplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), insula, and globus pallidus. The cortical differences were driven mainly by increased GM volume in HV compared with BD and SMD. In globus pallidus, there was increased GM in BD compared with HV and SMD. Longitudinally, group-by-time interactions were evident in two clusters in the superior/inferior parietal lobule (R SPL/IPL) and in the precuneus. In both clusters, the interactions were driven by an abnormal increase in volume in BD. CONCLUSIONS: Cross-sectionally, both BD and SMD are associated with structural abnormalities in frontal cortex, insula, and basal ganglia. Although some of these deficits overlap (insula and DLPFC), others differentiate SMD and BD (pre-SMA and globus pallidus). Abnormal developmental trajectories in lateral parietal cortex and precuneus are present in, and unique to, BD. Because of the high proportion of co-occurring ADHD in the SMD subjects, we could not separate effects of ADHD from those of SMD, and future research including a nonirritable ADHD group must address this issue.

The Affective Reactivity Index: a concise irritability scale for clinical and research settings.

BACKGROUND: Irritable mood has recently become a matter of intense scientific interest. Here, we present data from two samples, one from the United States and the other from the United Kingdom, demonstrating the clinical and research utility of the parent- and self-report forms of the Affective Reactivity Index (ARI), a concise dimensional measure of irritability. METHODS: The US sample (n = 218) consisted of children and adolescents recruited at the National Institute of Mental Health meeting criteria for bipolar disorder (BD, n = 39), severe mood dysregulation (SMD, n = 67), children at family risk for BD (n = 35), or were healthy volunteers (n = 77). The UK sample (n = 88) was comprised of children from a generic mental health setting and healthy volunteers from primary and secondary schools. RESULTS: Parent- and self-report scales of the ARI showed excellent internal consistencies and formed a single factor in the two samples. In the US sample, the ARI showed a gradation with irritability significantly increasing from healthy volunteers through to SMD. Irritability was significantly higher in SMD than in BD by parent-report, but this did not reach significance by self-report. In the UK sample, parent-rated irritability was differentially related to emotional problems. CONCLUSIONS: Irritability can be measured using a concise instrument both in a highly specialized US, as well as a general UK child mental health setting.