Developing a Novel rTMS Intervention for Transdiagnostic Psychosocial Rehabilitation: ADose-finding Study

NIH RePORTER · VA · I21 · · view on reporter.nih.gov ↗

Abstract

High frequency repetitive transcranial magnetic stimulation (rTMS) to left dorsolateral prefrontal cortex (dlPFC) is FDA-approved for the treatment of major depression. The left dlPFC site typically targeted with rTMS is seated in an area of cortex integral to intact higher order cognition (i.e., executive function). The PI has demonstrated that this left dlPFC region is commonly hypoactivated during cognitive tasks across neuropsychiatric disorders. Accordingly, cognitive improvements have been reported as ancillary benefits to rTMS treatment and that rTMS improves cognition in mild to moderate cognitive impairment. We propose that because rTMS to dlPFC is targeting cognitive neurocircuitry integral to adaptive cognitive functioning, promoting neuroplasticity in this network with rTMS could be more precisely optimized to improve quality of life across psychosocial domains and across neuropsychiatric presentations. We postulate that through up-regulating cognitive control circuitry with rTMS that an individual would have 1) enhanced capacity for successfully contending with the shifting contingencies of daily life and 2) improved ability to regulate intrusive affect and impulses. As a function of these processes an individual is expected to experience reduced psychosocial impairment. Thus, we propose that rather than targeting specific symptom reductions in specific disorders, rTMS could be dosed for efficacy in enhancing psychosocial functioning. Such an approach has the potential to enhance rehabilitation for far more veterans suffering a range of neuropsychiatric conditions. A therapeutic course of rTMS typically consists of approximately 30-40 minutes of high-frequency (i.e., 10 Hz) treatment on each weekday, for 4 to 6 weeks. This schedule can be burdensome and reduce adherence. Recently, Co-investigator Mark George, M.D. and colleagues demonstrated that delivering multiple high-dose sessions to veterans on each of three consecutive days was safe, feasible, and suggestive of rapid antidepressant effects. These patients received in three days, the equivalent dose (i.e., total number of pulses) of a conventional 4- to 6-week course. We propose that establishing an efficacious accelerated protocol delivered within 1 week would greatly increase the likelihood of implementation in the VA healthcare system. Furthermore, an accelerated course of rTMS that enhances psychosocial functioning across disorders, would be a ready adjunct for other modalities of rehabilitation already utilized in the VA healthcare system including pharmacotherapy and cognitive-behavioral therapy as well as occupational and physical therapy. In light of the goal to utilize accelerated rTMS to reduce psychosocial functional impairment, it is essential to establish the associated dose-response curve as a first step in laying the foundation for this line of work. Prior rTMS investigations have relied upon rational decision trees in determining TMS dose, typically founded upon ...

Key facts

NIH application ID
9838092
Project number
5I21RX002886-02
Recipient
RALPH H JOHNSON VA MEDICAL CENTER
Principal Investigator
Lisa M McTeague
Activity code
I21
Funding institute
VA
Fiscal year
2020
Award amount
Award type
5
Project period
2019-01-01 → 2021-12-31