Objective: To investigate repetitive transcranial magnetic stimulation (rTMS) in parkinsonian rats as a non-invasive, malleable superficial brain stimulation (SBS) alternative to DBS.

Background: DBS is highly efficacious, but because of its invasiveness, it is generally restricted to advanced patients. Also in distinction from DBS, rTMS is curative in select patients with intractable depression, with a course of treatment providing enduring amelioration in up to 30% of cases. In a number of investigations in patients with PD, rTMS targeting the supplementary motor area (SMA) or primary motor cortex has shown promising benefits. These studies however were limited by current relatively crude TMS technology and by utilizing stimulation protocols designed without due consideration of the underlying pathophysiology. In our laboratory, we are defining the cortical pathophysiology in parkinsonian and dystonic rats and have localized PD principally to SMA and dystonia to primary motor basal ganglia thalamocortical subcircuits.

Method: I. The dorsomedial striatum was briefly mapped with microelectrodes and injected with 6-OHDA to induce parkinsonism. The previously defined M2 parkinsonian territory (purported SMA) was localized via intracortical microstimulation (ICMS), injected with optogenetic vectors, and implanted with optical fibers. II. In separate rats, the M2 parkinsonian territory was initially localized via brief mapping of motor responses to single pulse TMS prior to initiating rTMS. Our engineering/neurophysiology team has manufactured and affirmed the effectiveness of an advanced, highly focal small animal TMS system.

Results: I. 20 Hz & burst optogenetic activation of M2 layer 5 neurons (based on the healthy M2 pyramidal mixed patterned discharge activity) induced prominent benefits on objective parkinsonian akinesia measures compared to continuous inhibition or no stimulation. II. Tonic and burst rTMS induced sustained improvement (n=3 rats), up to 11 days post-stimulation in the longest permitted survival rat to date. None of the control rats (n=5 to date) showed interval recovery.

Conclusion: These results suggest the therapeutic potential of SBS for patients with PD and other movement disorders, based on defining the cortical neuropathophysiology and neuronal effects of stimulation in rodent models.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigation-of-superficial-brain-stimulation-sbs-in-parkinsonian-rats-as-a-non-invasive-alternative-treatment-for-patients-with-movement-disorders/