Maturational delay and asymmetric information flow of brain connectivity in SHR model of ADHD revealed by topological analysis of metabolic networks

Sci Rep. 2020 Feb 21;10(1):3197. doi: 10.1038/s41598-020-59921-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Behavior, Animal
  • Brain / diagnostic imaging*
  • Brain / growth & development*
  • Brain Mapping*
  • Cerebral Cortex / physiopathology
  • Cluster Analysis
  • Fluorodeoxyglucose F18
  • Image Processing, Computer-Assisted
  • Limbic System
  • Models, Biological
  • Nerve Net
  • Neural Pathways
  • Phenotype
  • Positron-Emission Tomography
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

Substances

  • Fluorodeoxyglucose F18