White Matter Connectivity and iTBS Response in Depression: Insights from a 2025 Study
This content is intended for healthcare professionals and is provided for educational purposes only.
Intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS), has been shown to produce antidepressant effects in patients with major depressive disorder. However, clinical response to iTBS varies across individuals, and the biological factors underlying this variability remain an area of active investigation.
A 2025 open access study by Wilkening and Goya Maldonado, published in Molecular Psychiatry, examined whether structural brain connectivity influences response to iTBS in patients with major depressive disorder. In addition to assessing symptom changes, the study evaluated heart rate deceleration during stimulation as a physiological marker of parasympathetic nervous system activation.
The findings indicate that patients with stronger white matter connectivity between the prefrontal cortex, cingulate cortex, and limbic regions showed greater physiological engagement during iTBS, reflected by increased heart rate deceleration. These patients also experienced greater clinical improvement in depressive symptoms. In contrast, weaker structural connectivity was associated with reduced physiological response and less symptom improvement.
These observations support a network-level mechanism of action, suggesting that the effects of iTBS may depend on the ability of stimulation to propagate through intact neural circuits linking cognitive, emotional, and autonomic systems.
The study provides insight into how individual differences in brain structure may influence neuromodulation outcomes, highlighting the potential relevance of white matter integrity when interpreting variability in treatment response.
As an observational study, these findings describe associations between brain connectivity, physiological response, and clinical outcomes. Further research is needed to determine how these factors may be integrated into clinical decision-making or personalized neuromodulation strategies.
Access the full peer-reviewed study:
