Low-intensity transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique offering high spatial precision and depth penetrance. Theta burst TUS (tbTUS), featuring a temporal theta burst stimulation pattern, has been reported to facilitate corticomotor excitability, when applied to the human primary motor hand area (M1-HAND). However, replication outcomes have varied, pointing to unresolved dependencies in execution and protocol design.
Fifteen healthy human participants underwent neuronavigated tbTUS targeting the left M1- HAND in the anterior wall of the precentral sulcus, as well as anterior and posterior active control sites. The three tbTUS conditions were applied in counterbalanced order on separate days. Corticospinal excitability was assessed via motor evoked potentials (MEPs) recorded before and 5, 15, 30, and 60 min after tbTUS, and analyzed using an rmANOVA and a linear mixed model.
None of the tbTUS conditions produced consistent group-level changes in MEP amplitude at any time point. Both intra- and inter-subject variability were high, and individual MEP changes following precentral tbTUS did not meaningfully correlate with changes after control-site stimulation. We found no evidence that tbTUS targeting the anterior wall of the central sulcus reliably facilitated corticospinal excitability under the specific experimental conditions employed in the present study.
Methodological and hardware differences may account for discrepancies across studies. To reliably modulate cortical excitability, future tbTUS research requires individualized acoustic modeling, harmonized protocols, and adequately powered designs. The authors would like to thank Kim Lara Kürzel for her assistance during data collection and Dr.
Xavier Corominas-Teruel for his assistance in free field acoustic measurements, simula- tions and reporting of intensity parameters. This project was funded by the project “Adaptive and Precise Targeting of cortex-basal ganglia circuits in Parkinson´s Disease—ADAPT-PD” from the Lundbeck Foundation (collaborative project grant, PI Hartwig Roman Siebner, grant nr. Hartwig Roman Siebner has received funding as principal investigator for the project “Precision Brain-Circuit Therapy—Precision-BCT” from Innovation Fund Denmark (grant nr. 9068- 00025B).
Lasse Christiansen has received funding as principal investigator for the project "Individualized targeting of Cerebellar Output Nuclei with Transcranial Ultrasound" from the Lundbeck Foundation (Experiment grant, grant nr. Axel Thielscher was supported by the Lundbeck foundation (grant R313-2019-622), the Ger- man Research Foundation (project grants TH 1330/6–1, TH 1330/7–1 of Research Unit 5429/1 (467,143,400)) and the European Union’s Horizon Europe research and innovation programme under grant agreement No 101071008 (“CITRUS”). Bertino contributed equally to this work.
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