Epilepsy, Major Depressive Disorder
Conditions
Brief summary
Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. The goal of this proposal is to characterize the key markers of the brain's response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings. These markers will improve the understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.
Detailed description
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.
Interventions
DEVICEIntracranial electrodes
Intracranial electrodes will be used for the delivery of invasive brain stimulation.
DEVICETMS
TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.
Sponsors
Stanford University
University of Iowa
Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TMS-iEEG change after one TBS session | 45 minutes | Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ES-iEEG change after one TBS session | 45 minutes | Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG. |
| ES-iEEG change between two sequential TBS sessions | 45 minutes | Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG. |
| TMS-iEEG change between two sequential TBS sessions | 45 minutes | Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG. |
Countries
United States
Contacts
CONTACTJade Truong
Outcome results
None listed