Role of the insula in rTMS response for depression

J Affect Disord. 2025 Feb 1:370:538-546. doi: 10.1016/j.jad.2024.11.043. Epub 2024 Nov 13.

Abstract

Background: The insula has a significant impact on interoception and depression. This study aims to explore the role of the insula in mediating treatment responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC).

Methods: Twenty-five patients with either bipolar disorder (BD, n = 15) or major depressive disorder (MDD, n = 10) were recruited. All subjects were aged between 20 and 70, with a minimum score of 18 on the 24-item Hamilton Rating Scale for Depression (HDRS-24). Each patient received 12 sessions of rTMS treatment using a figure-eight-shaped coil at 10 Hz high-frequency stimulation intensity, targeted to the left DLPFC. Resting-state functional magnetic resonance imaging was conducted before and after the rTMS treatment to assess changes in insula-seeded functional connectivity.

Results: Both BD and MDD patients experienced significant reductions in depressive symptoms following rTMS therapy. The respective response rates at weeks 4, 8 and 12 were 64.0 %, 64.0 % and 68.0 % and remission rates were 40.0 %, 36.0 % and 44.0 %. Decreases in functional connectivity between the right anterior insula and right calcarine were significantly larger in the remitters than in the non-remitters (p = 0.013). Additionally, a higher baseline functional connectivity between the right anterior insula and right superior temporal gyrus correlated with better treatment outcome.

Limitations: The small sample size of 25 participants is small.

Conclusion: Our findings highlight the potential role of the insula in depression and suggest that insula-seeded functional connectivity could serve as a predictive biomarker for rTMS efficacy.

Keywords: Bipolar disorder; Depression; Functional connectivity; Insula; Predictive biomarker; Repetitive transcranial magnetic stimulation.

MeSH terms

  • Adult
  • Aged
  • Bipolar Disorder* / diagnostic imaging
  • Bipolar Disorder* / physiopathology
  • Bipolar Disorder* / therapy
  • Depressive Disorder, Major* / diagnostic imaging
  • Depressive Disorder, Major* / physiopathology
  • Depressive Disorder, Major* / therapy
  • Dorsolateral Prefrontal Cortex
  • Female
  • Humans
  • Insular Cortex* / diagnostic imaging
  • Insular Cortex* / physiopathology
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Transcranial Magnetic Stimulation* / methods
  • Treatment Outcome
  • Young Adult