Intermittent Theta-burst Transcranial Temporal Interference Stimulation focusing on the Putamen improves Symptom Severity in Parkinson’s Disease – A randomized controlled Trial

Abstract Transcranial temporal interference stimulation (tTIS) is a non-invasive approach for targeting deep brain regions such as the basal ganglia. This randomized, double-blind, crossover study examined whether intermittent theta-burst tTIS (iTBS-tTIS) applied to the right putamen reduces symptom severity in Parkinson’s disease (PD) and enhances motor learning and performance. Nineteen PD patients and 19 matched healthy controls underwent structural MRI and individualized electric field simulations. Primary outcome was the motor score of the left-sided MDS-UPDRS III; secondary outcomes included motor performance (alternating tapping task) and motor learning (sequential finger tapping task). iTBS-tTIS significantly reduced MDS-UPDRS scores in PD patients, and improvement correlated with simulated electric field strength in the right putamen. However, no significant effects were observed for motor performance or motor learning in either group. These results suggest that iTBS-tTIS may offer a promising non-invasive strategy to modulate deep brain structures and alleviate motor symptoms in PD.