Structural differences among children, adolescents, and adults with attention-deficit/hyperactivity disorder and abnormal Granger causality of the right pallidum and whole-brain

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a childhood mental health disorder that often persists to adulthood and is characterized by inattentive, hyperactive, or impulsive behaviors. This study investigated structural and effective connectivity differences through voxel-based morphometry (VBM) and Granger causality analysis (GCA) across child, adolescent, and adult ADHD patients. Structural and functional MRI data consisting of 35 children (8.64 ± 0.81 years), 40 adolescents (14.11 ± 1.83 years), and 39 adults (31.59 ± 10.13 years) was obtained from New York University Child Study Center for the ADHD-200 and UCLA dataset. Structural differences in the bilateral pallidum, bilateral thalamus, bilateral insula, superior temporal cortex, and the right cerebellum were observed among the three ADHD groups. The right pallidum was positively correlated with disease severity. The right pallidum as a seed precedes and granger causes the right middle occipital cortex, bilateral fusiform, left postcentral gyrus, left paracentral lobule, left amygdala, and right cerebellum. Also, the anterior cingulate cortex, prefrontal cortex, left cerebellum, left putamen, left caudate, bilateral superior temporal pole, middle cingulate cortex, right precentral gyrus, and the left supplementary motor area demonstrated causal effects on the seed region. In general, this study showed the structural differences and the effective connectivity of the right pallidum amongst the three ADHD age groups. Our work also highlights the evidence of the frontal-striatal-cerebellar circuits in ADHD and provides new insights into the effective connectivity of the right pallidum and the pathophysiology of ADHD. Our results further demonstrated that GCA could effectively explore the interregional causal relationship between abnormal regions in ADHD.

Corticostriatal causality analysis in children and adolescents with attention‐deficit/hyperactivity disorder

“…This study investigated possible patterns of directional influence between the cortex and striatum in children and adolescents with ADHD by using the GCA, a commonly used causal method. Agoalikum and colleagues found a mutual influence between the striatum and cortex in ADHD 36 . To further refine this influence pattern, we employed a detailed striatum VII‐subregions segmentation atlas in the current study.…”

“…Agoalikum and colleagues found a mutual influence between the striatum and cortex in ADHD. 36 To further refine this influence pattern, we employed a detailed striatum VII-subregions segmentation atlas in the current study. We found altered GCA connectivity in the VIS-striatum-DMN pathway exhibited the interaction effects between diagnosis and age and the closed relationships with clinical symptoms.…”

Abnormal and Changing Information Interaction in Adults with Attention-Deficit/Hyperactivity Disorder Based on Network Motifs

“…We found that some brain regions in ADHD patients have changed in the way information interacts. Specifically, the function of the bilateral thalamus to receive information was decreased, which may be caused by changes in the volume of the thalamus in ADHD patients [ 23 , 75 ]. The thalamus is a key subcortical structure of the cortico-stria-to-thalamo-cortical loop (CSTC) [ 76 ], mostly involved in attention and cognitive behavioral processes, and is considered a mediator connecting the basal ganglia, cerebral cortex, and cerebellum [ 47 , 77 , 78 ].…”

“…Comparing this to undirected functional networks, direction increases our understanding of the association between brain function and behavior [ 20 ]. Some studies have confirmed the abnormal effective connectivity of certain brain regions and the directional causal relationships among ROIs in ADHD patients, which could differentiate patients with ADHD from NC [ 21 , 22 , 23 , 24 ]. However, the majority of these studies have described macro- and micro-scale network properties in functional networks in these individuals, and the underlying meso-scale characteristics of brain function networks in ADHD patients are not well known.…”