Transcranial magneto-acoustic stimulation modulates M1-PPN spike-LFP coupling and improves motor dysfunction in parkinsonian rats.

OBJECTIVE

This study aimed to investigate whether transcranial magneto-acoustic stimulation (TMAS) improves motor dysfunction in Parkinson's disease (PD) model rats and whether its effects are associated with modulation of bidirectional spike-local field potential (LFP) coupling between the primary motor cortex (M1) and the pedunculopontine nucleus (PPN).

METHODS

Two primary cohorts (n = 24 each) comprised WT + Sham, PD + Sham, and PD + TMAS groups (n = 8/group). An independent supplementary healthy-control experiment included newly allocated WT + Sham and WT + TMAS groups (n = 8/group; 16 rats total), both of which followed the Experiment 1 workflow. Pre-treatment APO rotation counts were compared between the two PD groups as a functional index of lesion severity. Motor performance, TH and c-Fos immunofluorescence, and in vivo M1-PPN electrophysiology were evaluated. Spike-LFP coherence and phase-locking value (PLV) were compared among the three primary groups separately within each putative neuronal class, behavioral state, and frequency band.

RESULTS

APO rotation counts did not differ between PD + Sham and PD + TMAS rats before treatment in either experiment. TMAS-treated PD rats showed improved behavioral performance, and the pattern of differences in M1-PPN spike-LFP coherence and PLV relative to PD + Sham rats varied across frequency bands, behavioral states, and putative neuronal classes. At the terminal histological assessment, PD + TMAS rats showed a higher proportion of TH-positive cells in the SNc than PD + Sham rats. In the independent healthy-control experiment, WT + TMAS did not significantly differ from WT + Sham in most behavioral indices or TH-positive cell proportion, but it showed a shorter pole-test turning time and a higher c-Fos-positive cell proportion.

CONCLUSION

TMAS ameliorated motor deficits in PD model rats and was associated with frequency band, behavioral-state, and putative-class-dependent changes in M1-PPN spike-LFP coupling. These findings provide preliminary evidence supporting TMAS as a potential noninvasive neuromodulation strategy for PD-related motor dysfunction, while the disease specificity of the electrophysiological effects remains to be established.