Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of the brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators need to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.

Goals of the study are to 1) establish a detailed mechanistic understanding of the brain changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain and clinical changes.

Inclusion criteria

• Men and women, ages 18 to 65
• Medication-refractory epilepsy requiring phase II monitoring
• Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent
• No current or history of major neurological disorders other than epilepsy

Exclusion criteria

• Those with a contraindication for MRIs (e.g. implanted metal)
• Any unstable medical condition
• Neurological or uncontrolled medical disease
• Active substance abuse
• Currently pregnant or breastfeeding