Noninvasive neuromodulation for Parkinson’s disease: clinical perspectives

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to motor deficits and non-motor symptoms. While current pharmacotherapies provide symptomatic relief, they fail to halt disease progression and often lead to complications like levodopa-induced dyskinesia (LID). Non-invasive brain stimulation offers a promising adjunct by modulating neural excitability. Repetitive transcranial magnetic stimulation (rTMS) improves motor function and gait when applied at high frequencies to the motor cortex, while low-frequency stimulation targets the supplementary motor area to alleviate LID. Transcranial direct current stimulation (tDCS) utilizes weak currents to enhance motor performance and cognition, though larger trials are needed to confirm its efficacy. The most advanced modality, low-intensity focused ultrasound (LIFU), provides millimeter-scale precision to target deep subcortical structures. It shows potential for neuroprotection and targeted drug delivery via transient blood-brain barrier opening. This review evaluates the mechanisms and clinical evidence for rTMS, tDCS, and LIFU, focusing on optimizing stimulation parameters for standardized clinical use in PD. Overcoming the limitations of traditional medicine, these technological advancements represent a significant frontier in restorative neurology.