Deficits in fronto-parietal neuronal activity in a preclinical animal model of attention deficit hyperactivity disorder (ADHD)

ADHD is the most common childhood disorder. It persists into adulthood and recently identified sub-types present a particular therapeutic challenge. There is urgent need to understand ADHD sub-type pathophysiology and develop improved treatment strategies. A major step in achieving this goal was the development of a new model system in the rat by Professor Jo Neill’s group. This separates rats into sub-types relating to those identified in humans using the translational 5-choice continuous performance test (5C-CPT). As this test assesses the constructs of sustained attention, impulsive action and behavioural disinhibition, it translates extremely well to the clinic, providing a validated animal model for the core symptoms of adult ADHD.

Ritalin is the most widely prescribed ADHD medication. We have identified an unique electrophysiological signature of Ritalin in the brains of anaesthetised rats (Gigg & Neill labs); it appears to increase fronto-parietal network EEG activity, supporting a potential mechanism of action in improving attention. A major problem with Ritalin, however, is the pronounced abuse liability; validating novel compounds without such addictive properties is a priority. Our hypothesis is that the efficacy of Ritalin in low-attentive rats in the 5C-CPT is mediated by augmented coherence in alpha, beta and gamma EEG bands in the awake state. We further predict that improvement in these behavioural and EEG markers for ADHD will require increased dopaminergic neurotransmission. To investigate these assertions the student will be trained to separate rats by their 5C-CPT performance at test and then implant electrodes into frontal and parietal cortices. Recordings of EEG and single unit activity will be made from these regions in the presence of conventional and novel ADHD compounds during behavioural challenge. Overall, the project will reveal the underlying brain changes in ADHD and how conventional and novel medications play a role in reversing these deficits.

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