Sex-specific interhemispheric brain oscillation asymmetries in an ADHD rat model

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by hyperactivity, impulsivity, and inattention, with notable differences between sexes. Brain oscillation patterns recorded on electroencephalogram (EEG) are suggested as potential contributors to the diagnosis of psychiatric disorders, including ADHD. However, interhemispheric analysis of brain oscillations considering sex differences requires further investigation. We evaluated the correlation of the hemispheric brain oscillation asymmetries with behavioral and neurochemical parameters in male and female adolescent spontaneously hypertensive rats (SHR, ADHD model) and Wistar Kyoto rats (WKY, control strain). Subdural electrodes were implanted, open field task was used for behavioral analyses, and immunocontent of dopamine (DAT) and norepinephrine (NET) transporters known to be impaired in ADHD were analyzed. In the open field task, the ADHD model exhibited hyperactivity, evidenced by increased distance traveled, mean speed, number of stops, and rearing. In the frontal cortex, females from the ADHD model demonstrated asymmetries with higher power of alpha, beta, and gamma bands in the right hemisphere compared to the left. However, NET immunocontent showed a rightward pattern in the frontal cortex only in the control strain (WKY). The interhemispheric asymmetries in brain oscillations observed in females from the ADHD model were not associated with NET and DAT levels. Given that brain oscillations asymmetries described here resemble those found in mood disorders such as depression and anxiety, our data suggest that these sex differences may be relevant to the neurobiology of ADHD and its emotional comorbidities.