The perturbational map of low frequency repetitive transcranial magnetic stimulation of primary motor cortex in movement disorders

Abstract

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is applied to the primary motor cortex (M1) for the treatment of different movement disorders like Writer's Cramp (WC), Essential tremor (ET), and Spinocerebellar ataxia (SCA). However, the benefits vary, ranging from no effect to significant improvement in tremor. The variation in the benefits obtained from rTMS might be due to the difference in the spread of the stimuli across the brain areas associated with tremor. The spread of stimuli can be evaluated by combining rTMS with resting state functional magnetic resonance imaging (rsfMRI). AimTo determine the spread of low frequency rTMS for WC, ET and SCA after stimulation of M1. MethodThe rsfMRI was collected from the participants with WC (n = 27), ET (n = 30) and SCA (n = 28) at two time points, i.e., before and after the delivery of 1 Hz rTMS. Two measures from dynamic systems theory were calculated to understand how the system interacts with exogenously applied input (rTMS), namely entropy and frustration. While entropy measures the disorder from the rsfMRI time series, frustration quantifies it by assessing the change in sign (positive to negative, and vice-versa) of the functional connections. The two quantities outlined the spread of perturbation due to rTMS. ResultFor WC, a dense architecture of functional connections facilitated the spread across the bilateral areas of the five regions namely- the frontal cortex (frontal-Mid and Sup), motor cortex (supplemental motor area, precentral- and postcentral gyrus), parietal cortex (precuneus), subcortical regions (caudate, thalamus, posterior and mid-cingulate cortex) and the cerebellum (Crus-I and II, Cerebellum III and VI, and Vermis VI). For ET, though the areas belong to the above-mentioned 5 regions, the spread was narrower (i.e., lesser areas in the region). For SCA, the sparse connection between the areas led to minimal spread with no propagation of rTMS perturbation to the cerebellar regions. Interestingly for the three disorders, rTMS reduced the disorderliness (frustration and entropy) of the neural circuit (motor, subcortical and cerebellar regions) but increased the disorderliness in the default mode network (frontal and parietal regions). ConclusionThe spread of perturbation (due to TMS on M1) in the functional circuit varies in the three movement disorders. The current rTMS protocol achieves a wider spread for WC but not for ET and SCA. Findings from the present study suggest that pathology-specific stimulation protocols are required in movement disorders.