Assessing an electroencephalography (EEG) biomarker of response to transcranial magnetic stimulation for major depression

NIH RePORTER · VA · I01 · · view on reporter.nih.gov ↗

Abstract

Major Depressive Disorder (MDD) is highly prevalent among Veterans and associated with significant cost, disability and mortality. Although evidence-based medications and psychotherapies are available to treat MDD, full and sustained remission is uncommon. Transcranial magnetic stimulation (TMS) is an FDA-cleared intervention that offers a novel strategy for treating patients with treatment-resistant depression (TRD). TMS is available within the VA through the VA Clinical TMS Pilot Program. TMS is based in a neural circuit paradigm of MDD positing that stimulation at a key node (e.g., dorsolateral prefrontal cortex) can restore function within a network of brain regions involved in mood regulation. Although a substantial number of TRD patients respond well to TMS, many do not. This suggests some patients have a form of neural network dysfunction that is more amenable to TMS. Resting electroencephalography (EEG) provides a safe, convenient and reliable way to measure focal brain electrical activity and neural network function. Prior studies have identified EEG markers associated with response to antidepressant medications, but limited research has been conducted to identify EEG markers predictive of an antidepressant response with TMS. This is a critical gap, since TMS likely operates via direct modulation of neural network activity, such that baseline differences in neural network function should help identify which patients are more or less likely to respond to TMS. Investigators in our group have identified putative predictive EEG-based biomarkers for response to TMS for TRD. One of these (differential patterns of gamma oscillations) may specifically predict response to 10 Hz TMS applied to the left dorsolateral prefrontal cortex, the type of TMS received by >80% of Veterans receiving TMS in the TMS Pilot Program. Another (changes in theta cordance early in the course of treatment) may predict eventual response to TMS; this potential biomarker was identified by Dr. Andrew Leuchter (a consultant on this grant) and has been shown to also predict response to antidepressant medications and deep brain stimulation for TRD. By adding baseline (pretreatment) and weekly resting EEG assessment to the VA National Clinical TMS Pilot Program, the goals of this study are to: (1) test a potential response biomarker measured at baseline in a large sample of Veterans receiving TMS to treat depression (N=400); (2) assess whether a second putative biomarker (early changes in theta cordance during treatment) predict eventual response to TMS; (3) leverage this large sample to identify other potential biomarkers (such as markers of early versus late response to TMS, markers of response to other TMS parameters (e.g., 5 Hz, 1 Hz or theta burst TMS), and markers of change with treatment that may speak to mechanism); and (3) create an infrastructure to rapidly identify and test additional EEG-based biomarkers of treatment response in patients with depression and other p...

Key facts

NIH application ID
9933192
Project number
1I01CX002088-01
Recipient
WHITE RIVER JUNCTION VA MEDICAL CENTER
Principal Investigator
Amit Etkin
Activity code
I01
Funding institute
VA
Fiscal year
2021
Award amount
Award type
1
Project period
2020-10-01 → 2024-09-30