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.

Keywords: Granger causality analysis; age; attention deficit/hyperactivity disorder; resting-state fMRI; voxel-based morphometry.

Figure 1

Differences in Gray Matter Volume among the three ADHD patient groups. P < 0.05, FWE corrected. Differences were mainly found in the basal ganglia, cerebellum, insula, and left part of the superior temporal cortex.

Figure 2

Partial correlation between the right pallidum and overall disease severity with the right pallidum showing a positive relationship with overall disease severity.

Figure 3

Causal connectivity to and fro the right pallidum. (A) Causal effect from the right pallidum to significant whole-brain regions (Outflow). (B) Causal effect from the significant whole-brain regions to the right pallidum (Inflow). P < 0.05, FWE corrected. The arrows signify the direction of causality.

Figure 4

ROI-Wise GCA showing causal relationships among ROIs. (A) Causal relationships among outflow ROIs. (B) Causal relationships among inflow ROIs. The color bar indicates the connectivity strength. AMYG, Amygdala; PoCG, Postcentral gyrus; PCL, Paracentral lobule; CER45, Cerebellum_4_5; CER6, Cerebellum_6; FFG, Fusiform gyrus; MOG, Middle occipital gyrus; L, Left; ACC, Anterior cingulate cortex; MCC, Middle cingulate cortex; MFG, Middle frontal gyrus; TPOsup, Temporal pole: superior temporal gyrus; R, Right; PreCG, Precentral gyrus; SMA, Supplementary motor area; CAU, Caudate; PUT, Putamen; CERCRU2, Cerebellum_Crus2.