The Utility of Concurrent TBS/fNIRS for Antidepressant Treatment Optimization

Summary

Repetitive transcranial magnetic stimulation (rTMS) with theta bursts (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive disorder (MDD). Indeed, the U. S. Food and Drug Administration (FDA) has only recently approved TBS (in August 2018). However, fewer than 50% of patients show sufficient response to this treatment; markers for response prediction are urgently needed. Moreover, there is a lack of knowledge of the mechanism of action of TBS of the DLPFC. This is due to difficulties of directly measuring prefrontal stimulation effects, as compared to the stimulation of motor cortex and utilizing motor evoked potentials as direct readout. However, knowledge of immediate DLPFC modulation by TBS is necessary to extrapolate downstream effects on the neural and symptoms level.

Thus, there is a need for research that aims to quantify the direct and immediate after-effects of TBS on DLPFC function. Most importantly, with regard to precision medicine, there is a need for research that explores the utility of immediate DLPFC reactivity to TBS for the prediction of antidepressant treatment response. There is common agreement that certain forms of rTMS inhibit or excite brain activity, respectively. However, evidence indicates that there is considerable individual variability in the brain responses to rTMS. Whether differences in individual DLPFC modulation by rTMS can be utilized as a predictive marker for treatment response remains to be investigated.

This research program will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent TBS/fNIRS measurements will allow us to systematically investigate TBS-induced modulation of blood oxygenation as a proxy for induced brain activity changes. The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory TBS on prefrontal activity in TBS treatment-naïve patients with MDD and (2) validate the potential utility of TBS-induced brain modulation at baseline for the prediction of antidepressant response to four weeks of daily TBS treatment.

Major depression is a severe mental disorder and is associated with considerable economic costs but adequate treatments are poorly explored. This research program will pave the way towards an affordable and easy-to-implement method for response prediction before treatment commencement. Thus, our research proposal has high potential to inform tailored treatment strategies, as envisaged in precision medicine.

Conditions

• Major Depressive Disorder

Interventions

DEVICE

Theta-burst stimulation (TBS)

TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz) as described previously (Huang, Edwards et al. 2005). iTBS consists of 2-second trains with an inter-train-interval of 8 seconds. We will repeat trains (30 pulses; 10 bursts) for 20 times to reach a total number of 600 pulses (3x10x20). cTBS will comprise uninterrupted bursts to reach a total number of 600 pulses, as done routinely by others. Concurrent TBS/fNIRS stimulation will be applied over the left (iTBS) and right (cTBS) DLPFC at an intensity of 70-120%\* resting motor threshold (RMT) (The ideal %RMT will be determined first in a pilot study). In part two, stimulation intensity for patients will be 120% RMT (titration to full therapeutic dose over the first three days), as approved by the FDA in the U.S. (Blumbeger et al. 2018). The stimulation site will be the same as in the concurrent TBS/fNIRS stimulation (see above).

Sponsors & Collaborators

• Chinese University of Hong Kong

  collaborator OTHER

• Prince of Wales Hospital, Shatin, Hong Kong

  collaborator OTHER

• Kowloon Hospital, Hong Kong

  collaborator OTHER

• Dr Georg Kranz

  lead OTHER

Principal Investigators

• Georg S Kranz, PhD · The Hong Kong Polytechnic University

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-03-01

Primary Completion

2024-05-15

Completion

2024-05-15

Countries

• Hong Kong

Study Locations