Detecting the subtle shape differences in hemodynamic responses at the group level

The nature of the hemodynamic response (HDR) is still not fully understood due to the multifaceted processes involved. Aside from the overall amplitude, the response may vary across cognitive states, tasks, brain regions, and subjects with respect to characteristics such as rise and fall speed, peak duration, undershoot shape, and overall duration. Here we demonstrate that the fixed-shape or adjusted-shape methods may fail to detect some shape subtleties. In contrast, the estimated-shape method (ESM) through multiple basis functions can provide the opportunity to identify some subtle shape differences and achieve higher statistical power at both individual and group levels. Previously, some dimension reduction approaches focused on the peak magnitude, or made inferences based on the area under the curve or interaction, which can lead to potential misidentifications. By adopting a generic framework of multivariate modeling (MVM), we showcase a hybrid approach that is validated by simulations and real data. Unlike the few analyses that were limited to main effect, two- or three-way interactions, we extend the approach to an inclusive platform that is more adaptable than the conventional GLM, achieving a practical equipoise among representation, false positive control, statistical power, and modeling flexibility

Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder

AbstractA major controversy in child psychiatry is whether bipolar disorder (BD) presents in children as severe, non-episodic irritability (operationalized here as severe mood dysregulation, SMD), rather than with manic episodes as in adults. Both classic, episodic BD and SMD are severe mood disorders characterized by deficits in processing emotional stimuli. Neuroimaging techniques can be used to test whether the pathophysiology mediating these deficits are similar across the two phenotypes. Amygdala dysfunction during face emotion processing is well-documented in BD, but little is known about amygdala dysfunction in chronically irritable youth. We compared neural activation in SMD (n=19), BD (n=19), and healthy volunteer (HV; n=15) youths during an implicit face-emotion processing task with angry, fearful and neutral expressions. In the right amygdala, both SMD and BD exhibited greater activity across all expressions than HV. However, SMD and BD differed from each other and HV in posterior cingulate cortex, posterior insula, and inferior parietal lobe. In these regions, only SMD showed deactivation in response to fearful expressions, whereas only BD showed deactivation in response to angry expressions. Thus, during implicit face emotion processing, youth with BD and those with SMD exhibit similar amygdala dysfunction but different abnormalities in regions involved in information monitoring and integration

Increased intrasubject variability in response time in unaffected preschoolers at familial risk for bipolar disorder

Increased intrasubject variability in response time (ISVRT) is evident in healthy preschoolers at familial risk for bipolar disorder, suggesting it may be an endophenotype

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

Comparing brain morphometry across multiple childhood psychiatric disorders

Objective: In both children and adults, psychiatric illness is associated with structural brain alterations, particularly in the prefrontal cortex (PFC). However, most studies compare gray matter volume (GMV) in healthy volunteers (HVs) to one psychiatric group. We compared GMV among youth with anxiety disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), and HVs. Method: 3-Tesla T1-weighted magnetic resonance imaging scans were acquired in 184 youths (39 anxious, 20 BD, 52 DMDD, 20 ADHD, and 53 HV). Voxel-based morphometry analyses were conducted. One-way analysis of variance tested GMV differences with whole-brain familywise error (p = 200 voxels. Given recent frameworks advocating dimensional approaches in psychopathology research, we also tested GMV associations with continuous anxiety, irritability, and inattention symptoms. Results: Specificity emerged in the left dorsolateral PFC (d1PFC), which differed among youth with BD, anxiety, and HVs; GMV was increased in youth with anxiety, but decreased in BD, relative to HVs. Secondary analyses revealed BD-specific GMV decreases in the right lateral PFC, right d1PFC, and dorsomedial PFC, and also anxiety specific GMV increases in the left d1PFC, right ventrolateral PFC, frontal pole, and right parahippocampal gyrus/lingual gyrus. Both BD and DMDD showed decreased GMV relative to HVs in the right d1PFC/superior frontal gyrus. GMV was not associated with dimensional measures of anxiety, irritability, or ADHD symptoms. Conclusion: Both disorder-specific and shared GMV differences manifest in pediatric psychopathology. Some differences were specific to anxiety disorders, others specific to BD, and others shared between BD and DMDD. Further developmental research might map commonalities and differences of structure and function in diverse pediatric psychopathologies