Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia--an fMRI-TMS study

Abstract

Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for noninvasive stimulation of the human cortex and can alter cortical excitability and associated behavior. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls. We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients with right-sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS-induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI). Before rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task-related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG. Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG-S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task.

Figure 1

Experimental design. Before the event-related fMRI sessions, participants practiced the sensory task with their right index finger during two training sessions (TS) outside the MRI scanner. After they reached a stable psychophysical performance, the rTMS coil was fixed over the S1 area. rTMS was applied, either using the real or the “sham” protocol. Within 7 minutes, participants were placed in the scanner. Event-related fMRI measurements were acquired during performance of the post-TMS sensory task.

Figure 2

Tactile discrimination in patients as compared to controls following real and sham TMS. Controls showed improved discrimination following real-rTMS as compared to sham stimulation. Dystonia patients performed worse than controls and failed to improve after rTMS.

Figure 3

Discrimination effects in patients vs controls during the sham condition. Dystonia patients show relative overactivity in the ventromedial pallidum bilaterally compared to healthy controls (left hemisphere (LH): −6,0,−12 xyz in mm, T=5.19, P= 6.27E−06; right hemisphere: 8,6,−12, T=5.24, P= 5.44E−06).

Figure 4

Effects of rTMS (real versus sham condition) on hemodynamic activation during sensory discrimination task in dystonia patients (A) and controls (B). C: Interaction (group x condition) during rTMS, dystonia patients compared to controls. (A) Dystonia patients show relative overactivity in the left premotor cortex (PMC) and the left sensorimotor cortex (S1) (thus, ipsilaterally to the TMS-stimulated hemisphere) after real-rTMS compared to sham stimulation. (B) Healthy controls show relative overactivity in the left premotor cortex (PMC) and the left sensorimotor cortex (S1) following real-rTMS compared to sham stimulation, similar to dystonia patients. In addition there is activation of the ventromedial pallidum bilaterally. (C) Compared to controls dystonia patients show reduced activity in the left oribtofrontal cortext (OFC) and the ventromedial pallidum bilaterally after real-rTMS compared to sham stimulation.

Figure 4

Effects of rTMS (real versus sham condition) on hemodynamic activation during sensory discrimination task in dystonia patients (A) and controls (B). C: Interaction (group x condition) during rTMS, dystonia patients compared to controls. (A) Dystonia patients show relative overactivity in the left premotor cortex (PMC) and the left sensorimotor cortex (S1) (thus, ipsilaterally to the TMS-stimulated hemisphere) after real-rTMS compared to sham stimulation. (B) Healthy controls show relative overactivity in the left premotor cortex (PMC) and the left sensorimotor cortex (S1) following real-rTMS compared to sham stimulation, similar to dystonia patients. In addition there is activation of the ventromedial pallidum bilaterally. (C) Compared to controls dystonia patients show reduced activity in the left oribtofrontal cortext (OFC) and the ventromedial pallidum bilaterally after real-rTMS compared to sham stimulation.

Figure 4

Effects of rTMS (real versus sham condition) on hemodynamic activation during sensory discrimination task in dystonia patients (A) and controls (B). C: Interaction (group x condition) during rTMS, dystonia patients compared to controls. (A) Dystonia patients show relative overactivity in the left premotor cortex (PMC) and the left sensorimotor cortex (S1) (thus, ipsilaterally to the TMS-stimulated hemisphere) after real-rTMS compared to sham stimulation. (B) Healthy controls show relative overactivity in the left premotor cortex (PMC) and the left sensorimotor cortex (S1) following real-rTMS compared to sham stimulation, similar to dystonia patients. In addition there is activation of the ventromedial pallidum bilaterally. (C) Compared to controls dystonia patients show reduced activity in the left oribtofrontal cortext (OFC) and the ventromedial pallidum bilaterally after real-rTMS compared to sham stimulation.