| Author: | Qin, Ping |
| Title: | Elucidating the therapeutic potential of transcranial pulse stimulation in depression |
| Advisors: | Kranz, Georg (RS) |
| Degree: | Ph.D. |
| Year: | 2026 |
| Department: | Department of Rehabilitation Sciences |
| Pages: | 238 pages : color illustrations |
| Language: | English |
| Abstract: | Background: Transcranial pulse stimulation (TPS) is a novel, non-invasive brain stimulation technique that uses shock waves to modulate brain function. Preliminary evidence suggests its potential for alleviating depressive symptoms, but no randomized, double-blind, sham-controlled trials have yet confirmed its antidepressive efficacy in major depressive disorder (MDD). Furthermore, the potential of TPS as a combined therapy and its capability to effectively target deeper brain regions associated with depression, such as the dorsal anterior cingulate cortex (dACC) and anterior insula cortex (AIC), remain unexplored. Methods: This thesis comprises four studies. Study 1 was a systematic review investigating the efficacy and safety of low-intensity transcranial ultrasound stimulation (LITUS). Study 2 was a randomized, double-blind, sham-controlled trial evaluating the clinical and neural effects of TPS in 80 patients with MDD. Study 3 was a randomized, single-blind, crossover pilot trial in 34 healthy individuals examining the behavioral aftereffects of a single TPS session. Study 4 was a randomized, single-blind, sham-controlled pilot trial in 60 healthy individuals testing the feasibility and modulation effects of TPS targeting the dACC and AIC. Main findings: The systematic review (Study 1) found LITUS to be therapeutically effective for various conditions with a favorable safety profile. In patients with MDD (Study 2), active TPS produced a significantly greater reduction in depression severity compared to sham (p = 0.048) and significantly increased resting-state functional connectivity (rsFC) within the left dorsolateral prefrontal cortex (lDLPFC), as well as between lDLPFC and the left orbitofrontal, superior medial prefrontal, pregenual anterior cingulate, posterior cingulate cortices, and bilateral precuneus and calcarine cortex. Study 3 showed that a single session of TPS of the primary motor cortex did not yield superior behavioral effects compared with a control TPS session of the vertex in healthy individuals. Study 4 demonstrated the feasibility and efficacy of TPS application to dACC and AIC over 2 weeks. Results showed that dACC-TPS reduced risk-taking behavior, whereas AIC-TPS increased it, as measured by the balloon analog risk task. Target-specific TPS-induced rsFC changes were observed following both dACC and AIC stimulation compared to sham. Specifically, dACC stimulation enhanced dACC-seeded rsFC with the bilateral ventrolateral prefrontal, right dorsolateral prefrontal, and right dorsomedial prefrontal cortices. In contrast, AIC stimulation resulted in decreased AIC-seeded rsFC with the right middle and inferior frontal (opercular and triangular parts), right precentral gyrus, right supramarginal, right posterior superior temporal, the left posterior middle temporal, left superior and middle occipital cortices, left middle cingulate cortex, and left cuneus. Discussions and Conclusions: This research establishes TPS as a safe, well-tolerated, and effective intervention for MDD, with demonstrable neuromodulation effects on depression-relevant brain circuits. However, a single TPS session did not demonstrate sufficient utility in modulating behavior. Conversely, multiple TPS sessions targeting the dACC and AIC were feasible and safe in healthy adults, modulating risk-taking behaviors and producing target-specific neuromodulatory effects. These findings provide a strong foundation for future studies to optimize TPS protocols, explore the dACC and AIC as novel therapeutic targets, and further investigate the underlying neural mechanisms of depression treatment. |
| Rights: | All rights reserved |
| Access: | open access |
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