Temporal Interference and Depression

Summary

Major Depressive Disorder (MDD) has a high prevalence, is the leading cause of disability, and currently available interventions are associated with side effects and high treatment resistance. There is an urgent need for the development of novel interventions for MDD with alternate mechanisms of action. Temporal Interference (TI) stimulation is a newly emerging form of transcranial alternating current stimulation (tACS) that involves the application of two high-frequency currents at slightly different kHz frequencies. Since neurons, due to their intrinsic low-pass filtering, do not respond to high frequencies (i.e. \> 100 Hz), TI relies on the 'beat' interaction leading to neuromodulation at any given location, resulting in a much smaller focus and allowing for better targeting. The subgenual cingulate cortex (SCC) appears to be critical in the pathophysiology of depression and treatment response, especially in treatment-resistant cases. Non-invasive treatments, however, are not able to accurately target SCC due to its deep location within the brain. In this trial, 30 participants meeting the diagnostic criteria for MDD will be randomized to receive 10 sessions of 130 Hz TI delivered daily for 30 minutes, or 10 sessions of sham stimulation. During the stimulation, participants will be watching emotional film clips to enhance target engagement. The investigators will collect metrics of SCC target engagement using the resting-state fMRI and EEG technologies, and determine feasibility, tolerability, safety, and therapeutic efficacy of TI stimulation in MDD. The results of this trial will inform the TI technology as a therapeutic tool for network-based psychiatric disorders, including MDD, and be vital for the design and development of a large-scale randomized-controlled trial.

Conditions

• Major Depressive Disorder

Interventions

DEVICE

Temporal Interference stimulation

TI involves simultaneous delivery of independent currents to the brain at slightly different kHz frequencies, which are individually too high to recruit neural firing. However, the difference ('beat') frequency where the currents overlap (i.e., temporally interfered) is low enough to drive neural activity. The interferometrically derived low frequencies have been demonstrated to activate neurons at a selected focus without activation of surrounding regions in awake mice. The safety of the TI paradigm has been demonstrated in over 60 healthy human volunteers, and finite element modeling of simulations of TI fields in human anatomical models suggests that large subcortical structures such as the hippocampus or SCC could be selectively targeted. However, the precise TI parameters for selective engagement of SCC in healthy participants and in MDD is currently unknown.

DEVICE

Sham stimulation

Electrodes will be placed in the same location on the head as that for the TI intervention; 0 mA of electrical current will be delivered to the brain (compared to 2 mA in the active intervention arm), therefore it is expected to elicit no changes in neural activity.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center

  collaborator OTHER

• Northeastern University

  collaborator OTHER

• Centre for Addiction and Mental Health

  collaborator OTHER

• Charite University, Berlin, Germany

  collaborator OTHER

• Toronto Metropolitan University

  collaborator OTHER

• Unity Health Toronto

  lead OTHER

Principal Investigators

• Venkat Bhat, MD MSc · Unity Health Toronto

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-15

Primary Completion

2027-12-31

Completion

2027-12-31

Countries

• Canada

Study Locations