Attention-deficit hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric disorders affecting 5-10% of children worldwide (7\~8% in Taiwan) characterized by a persistent pattern of inattention and/or hyperactivity/impulsivity. Recent survey estimated that around 57% of children with ADHD will continue to have persistent symptoms into adolescents and adulthood. Due to the dynamic neurocognitive development process, and the transition and formation of educational and social relationship, adolescents (13-17 years) represent critical periods in the phase of life. Emerging literature has proposed the main conditions of ADHD are related to cognitive function impairments such as inhibitory control, working memory and cognitive planning. These deficits disrupt educational process, harm academic and social functions, and seriously reduce quality of life for adolescents with ADHD.

Recently, noninvasive brain stimulation techniques are considered for investigating the neural mechanism of neurodevelopmental disorders including ADHD. Previous studies using transcranial magnetic stimulation (TMS) in combination with motor-evoked potentials (MEPs; muscle contraction in response to TMS) have reported deficits in specific inhibitory functions of the motor loop in ADHD. In line with this, our previous study found decreased intracortical inhibition and enhanced intracortical facilitation in ADHD subjects compared to healthy control (under review). These findings implied that ADHD causes stem from disturbances in large-scale brain networks Therefore, it is essential to understand the neurophysiological mechanism in ADHD, and furthermore develop effective interventions based on this foundation.

Aerobic exercise has been suggested as a safe and low-cost adjunctive therapy for ADHD and is known to have beneficial effects on cognition and behavioral performance in children and adolescents. The underlying mechanism depends at least partially on mechanisms of neuroplasticity. Animal data suggest that neuronal excitability is enhanced by aerobic exercise via suppressing gamma-aminobutyric acid (GABA)-ergic inhibition and facilitating the activation of N-methyl-D-aspartate (NMDA) receptors. Furthermore, aerobic exercise enhanced the induction of long-term potentiation (LTP) which is thought to play a key role in the cellular mechanisms of learning and memory. These findings align with human data. Our and other studies have shown that aerobic exercise can enhance cortical excitability via increasing intracortical facilitation and reducing inhibition in healthy subjects by TMS. At the cognitive domain, animal models have shown that aerobic exercise prominently affects diverse cognitive functions, including learning and memory. Similarly, in the human study, a single bout of light-intensity aerobic exercise promotes performance of a visuomotor accuracy-tracking task and verbal memory. Meta-analytic research has shown beneficial effects of moderate to vigorous-intensity aerobic exercise on cognitive performance in humans. Specific for ADHD population, previous results showed significant improvement in inhibitory control, speed of processing, and attention after acute aerobic exercise (30 mins cycling: a 5 min warm up, 20 min of core exercise, and a 5 min cool-down) at moderate intensity. Taken together, these studies suggest that impact of aerobic exercise might not restricted to motor domain. Additionally, the positive effects of aerobic exercise on cognitive processes and clinical outcomes might be caused by its mediating effects on neural mechanisms.

According to our research experienced, we are interested in the neurophysiological foundation of the impact of the acute effects of controlled aerobic exercise intensities in adolescents with ADHD, its involvement in cognitive processes, and clinical outcomes. Combined application of neurophysiological recording tools, including non-invasive brain stimulation, are suited to explore the impact of aerobic exercise on cortical physiology of motor and prefrontal cortex, and the functional association of cognition and clinical performance in humans. We will apply TMS to obtain evoked potentials recorded either with electromyography (EMG) or EEG to cortical excitability, also with regard to the contributions of specific transmitters and neuromodulators, such as glutamate and GABA, over task-relevant target areas such as motor and prefrontal cortex. Furthermore, we will combine cognitive task (e.g., inhibitory control, working memory and cognitive planning tasks) to explore the association between the neurophysiological effects of aerobic exercise and respective cognitive and clinical alterations. The study will be critically important in setting a conceptual framework for developing alternative treatment in ADHD, especially for aerobic exercise intervention. In addition, results of the study contribute to lay the ground work for both scientific and clinical application in adolescents with ADHD.