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Updated: Jul 2, 2026
Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses
Published on: September 28, 2018
Continuous theta burst stimulation to the frontal pole durably decreases medial frontoamygdala connectivity
Kevin C Bickart1,2, Alice Hsu1,2, Daniel M McCalley3
1Department of Neurology, University of California Los Angeles, Los Angeles, California, USA.
Abstract:
The frontal pole is a transdiagnostic target for affective disorders, perhaps through its connectivity with affective regions like the amygdala. Recent work shows that single-pulse or single-session transcranial magnetic stimulation (TMS) to the frontal pole (FP) modulates amygdala activity and frontoamygdala connectivity. In a secondary analysis of a double-blind, Sham-controlled clinical trial, 17 participants with alcohol use disorder (10 Real, 7 Sham; 24% Female; age 46 ± 13 years) received 10 sessions of continuous theta burst stimulation (cTBS) to the left frontal pole (FP1). Resting-state fMRI was acquired pre-treatment, post-treatment (within one week of treatment completion), and 1 month after treatment. Voxelwise mixed-effects modeling revealed that Real cTBS, compared to Sham, selectively decreased connectivity between the frontal pole and the medial amygdala. Using an ANCOVA approach to account for regression to the mean, this reduction was confirmed to be durable over the 1-month follow-up and was most pronounced in participants exhibiting the highest baseline connectivity. These results extend knowledge on amygdala modulation and set the stage for future work to access the amygdala through the frontal pole for affective disorders marked by amygdala dysregulation.
Insights
Continuous theta burst stimulation (cTBS) to the frontal pole selectively reduced medial amygdala connectivity in alcohol use disorder. This effect was durable and most pronounced in individuals with high baseline connectivity.
Area of Science:
- Neuroscience
- Psychiatry
- Medical Imaging
Background:
- The frontal pole (FP) is a key target for treating affective disorders due to its connections with regions like the amygdala.
- Transcranial magnetic stimulation (TMS) to the FP can modulate amygdala activity and frontoamygdala connectivity.
Purpose of the Study:
- To investigate the effects of continuous theta burst stimulation (cTBS) to the left frontal pole (FP1) on frontoamygdala connectivity in individuals with alcohol use disorder (AUD).
- To determine the durability of these effects over a 1-month follow-up period.
Main Methods:
- A secondary analysis of a double-blind, Sham-controlled trial involving 17 participants with AUD.
- 10 sessions of cTBS applied to the left FP1.
- Resting-state functional magnetic resonance imaging (fMRI) acquired at baseline, post-treatment, and 1-month follow-up.
- Voxelwise mixed-effects modeling and ANCOVA were used to analyze connectivity changes.
Main Results:
- Real cTBS, compared to Sham, significantly decreased connectivity between the frontal pole and the medial amygdala.
- This reduction in connectivity was durable, persisting at the 1-month follow-up.
- The effect was most pronounced in participants with higher baseline frontoamygdala connectivity.
Conclusions:
- cTBS applied to the left frontal pole can selectively modulate frontoamygdala connectivity in individuals with AUD.
- This modulation, specifically the reduction in medial amygdala connectivity, is durable and may be a mechanism for treating affective dysregulation.
- Targeting the frontal pole offers a potential pathway for neuromodulation interventions in affective disorders.
