Non-invasive Neuromodulation Unit (NNU)

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

Work was conducted under clinical protocols NCT03065335, NCT03289923, NCT04798274, NCT03351764, NCT02363296, and NCT05172271. NCT03065335: Mechanisms of Rapid Antidepressant Action, a collaboration with Dr. Zarate This project develops biomarkers of rapid antidepressant response by adding TMS-EMG and TMS-EEG neuroplasticity measures to the existing intramural research program examining ketamine’s antidepressant effects. NCT05172271: A Feasibility Study of Transcranial Electric Stimulation Therapy (TEST) for treatment resistant depression (TRD). This project examines ECT dosing by lowering the dose below seizure threshold to determine whether adverse cognitive effects are minimized and whether stimulation can be reliably and safely administered below seizure threshold. TEST is compared to sham in a randomized, double-blind fashion for the first six treatments of a treatment course. Antidepressant response and neuroimaging and blood-based biomarkers will also be assessed as secondary outcomes. NCT03289923: Concurrent fMRI-guided rTMS and cognitive therapy for the treatment of major depressive episodes. This project uses fMRI-guided TMS paired with a form of cognitive behavioral therapy for the treatment of depression (in collaboration with Dr. Strauman). NCT02363296: Closed-loop paired associative stimulation. The effects of noninvasive brain stimulation can be extremely variable across individuals. One source of this variability is known to be the state of the brain at the time of stimulation. One way of addressing this source of variability is to trigger the TMS when the brain is in an up-state or a down-state. To accomplish this, in collaboration with Christoph Zrenner of the University of Toronto, real-time signal processing is used to analyze the EEG and predict where the brain oscillations will be milliseconds in advance. The TMS trigger is controlled by real-time hardware. Also under this study, we examine closed-loop stimulation to brain networks beyond motor cortex. In September 2022, the NIH Center for Compulsive Behaviors awarded a fellowship (successfully renewed twice and in the final year) to Dr. Sunday Francis for a study building upon closed-loop paired associative stimulation. The study uses the EEG-triggered TMS technique to study EEG phase synchronization and functional connectivity among brain regions in a network associated with the neurocognitive endophenotype compulsivity in a sample of the general population assessed for subclinical levels (dimensional) of compulsivity and impulsivity. This project is in collaboration with Drs. Audrey Thurm (co-mentor) and Christoph Zrenner (EEG-triggered expert). A long-term goal of this research is a transdiagnostic approach to optimize TMS to treat individuals with impairments driven by these neurocognitive endophenotypes. NCT04798274: Role of GABAergic transmission in auditory processing in Autism Spectrum Disorder (DECIBELS). This project uses MEG and fMRI to measure brain network engagement and neurochemical changes following an acute session of rTMS in healthy volunteers and adolescents with autism spectrum disorder (in collaboration with Lindsay Oberman (OCD/NNU), Audrey Thurm (OCD), and Allison Nugent (MEG Core)). NCT03351764: Development of Non-Invasive Brain Stimulation Techniques. This healthy volunteer protocol addresses fundamental challenges impacting the efficacy of TMS. Ongoing projects include: 1. Individualized fMRI-based TMS targeting to affect performance of a numerical Stroop task. The objective of this study was to ascertain whether we could produce a reliable TMS enhancement of numerical Stroop task performance with participants in a well-practiced state. Our results highlight the necessity of controlling for the state of learning in the brain, from naïve to over-learned. Moreover, we demonstrated that more subtle brain-behavior relationships may be uncovered by applying more sophisticated behavioral analyses to TMS-derived data beyond simpler measures of central tendency. 2. Using real-time fMRI neurofeedback to control brain state during TMS. This study seeks to assess whether controlling brain states using neurofeedback results in greater intra- and inter-individual variability in response to rTMS. The aim of this study is to explore whether the use of real-time fMRI neurofeedback to control brain state can constrain rTMS effects to only the stimulated network.