Dual-Site Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease

Abstract

Abnormal oscillatory activity in the subthalamic nucleus (STN) may be relevant for motor symptoms in Parkinson's disease (PD). Apart from deep brain stimulation, transcranial magnetic stimulation (TMS) may be suitable for altering these oscillations. We speculated that TMS to different cortical areas (primary motor cortex, M1, and dorsal premotor cortex, PMd) may activate neuronal subpopulations within the STN via corticofugal neurons projecting directly to the nucleus. We hypothesized that PD symptoms can be ameliorated by a lasting decoupling of STN neurons by associative dual-site repetitive TMS (rTMS). Associative dual-site rTMS (1 Hz) directed to PMd and M1 (“ADS-rTMS”) was employed in 20 PD patients treated in a blinded, placebo-controlled cross-over design. Results: No adverse events were noted. We found no significant improvement in clinical outcome parameters (videography of MDS-UPDRS-III, finger tapping, spectral tremor power). Variation of the premotor stimulation site did not induce beneficial effects either. A single session of ADS-rTMS was tolerated well, but did not produce a clinically meaningful benefit on Parkinsonian motor symptoms. Successful treatment using TMS targeting subcortical nuclei may require an intervention over several days or more detailed physiological information about the individual brain state and stimulation-induced subcortical effects.

A Scoping Review of Neuromodulation Techniques in Neurodegenerative Diseases: A Useful Tool for Clinical Practice?

“…Finally, Fricke and co-workers [75] hypothesised that PD symptoms could be ameliorated by a lasting decoupling of subthalamic nucleus neurons by associative dual-site rTMS (1 Hz) employed to the primary motor cortex and dorsal premotor cortex. To this aim, 20 PD patients were treated in a blinded, placebo-controlled cross-over design.…”

Motor recovery and antidepressant effects of repetitive transcranial magnetic stimulation on Parkinson disease

“…Supplementary Table 1 shows characteristics of 28 finally selected studies. Among these studies, 25 studies [ 10 – 14 , 18 – 37 ] investigated the therapeutic effect of rTMS on motor in PD (including 409 patients given rTMS and 378 patients given sham stimulation). In the 25 studies, 14 studies were with crossover design, 11 studies were with randomized controlled design.…”

Transcranial Magnetic Stimulation in Tremor Syndromes: Pathophysiologic Insights and Therapeutic Role

“…A novel protocol known as associative dual-site rTMS was implemented by Fricke et al, who hypothesized that simultaneous targeting of the dorsal premotor cortex and the M1 in a coordinated fashion might lead to decoupling of pathogenic oscillatory tremor activity (44). However, the study found no clinical improvements, suggesting that the optimal target site for PD tremor is still not clear (44). Based on the data from pathophysiological studies, it is reasonable to postulate that the rest and postural tremors are likely amenable to different stimulation sites.…”

“…There is high variability in the rTMS paradigms and study designs used to investigate tremor syndromes, including differences in sham application, washout periods in crossover designs, target location, number of pulses, number of stimulation sessions, and duration of the stimulation in total. Many studies implemented only a single stimulation session (26,28,36,37,39,43,44,51,52,64,73), whereas other studies included multiple sessions ranging anywhere from 5 consecutive days to 15 stimulation days (38, 40-42, 47, 49, 50), or more unique protocols in which 5 consecutive days of stimulation are followed with a weekly session of stimulation for 3 weeks (53). The number of stimulation sessions may play a role in the duration of benefit, and thus it is critical to not only assess benefit following stimulation but also to assess how long that benefit lasts.…”

“…However, there is variability in the TMS study designs within the same type of tremor syndrome as well. Some studies chose to randomize two separate groups of patients in an active and sham protocol (40,41,43,53,73), whereas others used a crossover design to evaluate benefit (36,37,39,42,44,47,51,64). There are a few limitations specific to crossover designs performed in rTMS studies.…”