Transdiagnostic Investigation of Psychiatric Disorders with Transcranial Magnetic Stimulation

Abstract

Transcranial Magnetic Stimulation (TMS) is a non-invasive investigational tool that allows scientists to stimulate cortical areas of interest, which assists in studying the neurophysiology of the brain with temporal and spatial precision. Often TMS is administered to the human primary motor cortex as the activity in surface muscles like First Dorsal Interosseous can be used to quantify the response of intracortical and corticospinal response to magnetic pulses. Experiments with quantification of muscle response to different types of pulses as well as different combinations of magnetic pulse intensity and inter-pulse interval have yielded multiple TMS pulse paradigms that are dependent on excitatory and inhibitory mechanisms, modulated by different neurotransmitters such as Glutamate and Gamma-Aminobutyric Acid (GABA). We used three excitatory and two inhibitory paradigms to assess motor cortical response in patients suffering from various psychiatric disorders including Major Depressive Disorder (MDD), Schizophrenia, Bipolar Affective Disorder (BPAD) Mania, Obsessive-Compulsive Disorder (OCD) as well as Healthy Volunteers and First-degree relatives of BPAD Mania patients. Motor cortical excitability measures corresponding to GABAB are lower in patients with OCD and MDD, while they are higher in BPAD Mania patients. Patients with OCD and Depression also display enhanced motor cortical excitability when compared to patients with other disorders as well as healthy volunteers. Altogether, our findings indicate a deficiency in GABAergic mechanisms in OCD and MDD. The functioning of various neurotransmitter systems can be studied indirectly through TMS, which may help identify potential biomarkers for specific psychiatric conditions.