Abstract
Attention-deficit hyperactivity disorder (ADHD) is a complex brain development disorder characterized by hyperactivity/impulsivity and inattention. A major hypothesis of ADHD is a lag of maturation, which is supported mainly by anatomical studies evaluating cortical thickness. Here, we analyzed changes of topological characteristics of whole-brain metabolic connectivity in twelve SHR rats selected as ADHD-model rats by confirming behavior abnormalities using the marble burying test, open field test, and delay discounting task and 12 Wistar Kyoto rats as the control group, across development from 4 weeks old (childhood) and 6 weeks old (entry of puberty). A topological approach based on graph filtrations revealed a lag in the strengthening of limbic-cortical/subcortical connections in ADHD-model rats. This in turn related to impaired modularization of memory and reward-motivation associated regions. Using mathematical network analysis techniques such as single linkage hierarchical clustering and volume entropy, we observed left-lateralized connectivity in the ADHD-model rats at 6 weeks old. Our findings supported the maturational delay of metabolic connectivity in the SHR model of ADHD, and also suggested the possibility of impaired and compensative reconfiguration of information flow over the brain network.
Highlights
Attention-deficit hyperactivity disorder (ADHD) is one of the most common brain developmental disorder characterized by typical symptoms of inattention, hyperactivity, and impulsivity
We examined the developmental changes of whole-brain network longitudinally by acquiring brain F-18 fluorodeoxyglucose (FDG) positron-emission-tomography (PET) from ages of childhood (4 weeks old) to the period of ‘entry of puberty’ (6 weeks old) in a spontaneous hypertensive rat (SHR) model of ADHD and in its control that Wistar Kyoto rat (WKY)
The ADHD-model rats moved more than the control rats in the open field test (OFT) at 8–9 weeks old with a borderline significance (5.0 m ± 1.5 m vs. 3.6 m ± 1.3 m; P = 0.079) (Fig. 2B)
Summary
Attention-deficit hyperactivity disorder (ADHD) is one of the most common brain developmental disorder characterized by typical symptoms of inattention, hyperactivity, and impulsivity. Considering the difficulty of repeated imaging in ADHD children, a preclinical longitudinal study in rats might help corroborate this ‘delayed maturation’ hypothesis or to discover more elaborate findings to be translated to explain the changes of brain networks in ADHD children. In this investigation, we examined the developmental changes of whole-brain network longitudinally by acquiring brain F-18 fluorodeoxyglucose (FDG) positron-emission-tomography (PET) from ages of childhood (4 weeks old) to the period of ‘entry of puberty’ (6 weeks old) in a spontaneous hypertensive rat (SHR) model of ADHD and in its control that Wistar Kyoto rat (WKY). The graph filtration was successfully applied to brain network analysis[19,20,21]
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