Though the pathophysiology of dystonia remains uncertain, two primary factors implicated in the development of dystonic symptoms are excessive cortical excitability and impaired sensorimotor processing. The aim of this study was to determine the functional efficacy of an intervention combining repetitive transcranial magnetic stimulation (rTMS) and sensorimotor retraining. A randomized, single-subject, multiple baseline design with crossover was used to examine participants with focal hand dystonia (FHD) (n = 9). Intervention: 5 days rTMS + sensorimotor retraining (SMR) vs. Five days rTMS + control therapy (CTL) (which included stretching and massage). The rTMS was applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed. Each session in both groups consisted of rTMS followed immediately by 30 min of the therapy intervention (SMR or CTL). Contrary to our hypothesis, group analyses revealed no additional benefit from the SMR training vs. CTL. When analyzed across group however, there was significant improvement from the first baseline assessment in several measures, including tests of sensory ability and self-rated changes. The patient rated improvements were accompanied by a moderate effect size suggesting clinical meaningfulness. These results provide encouragement for further investigation of rTMS in FHD with a need to optimize a secondary intervention and determine likely responders vs. non-responders.

Background The pathophysiology of adductor spasmodic dysphonia (AdSD), like other focal dystonias, is largely unknown. Objective The purposes of this study were to determine 1) cortical excitability differences between AdSD, muscle tension dysphonia (MTD) and healthy controls 2) distribution of potential differences in cranial or skeletal muscle, and 3) if cortical excitability measures assist in the differential diagnosis of AdSD and MTD. Methods 10 participants with adductor spasmodic dysphonia, 8 with muscle tension dysphonia and 10 healthy controls received single and paired pulse transcranial magnetic stimulation (TMS) to the primary motor cortex contralateral to tested muscles, first dorsal interosseus (FDI) and masseter. We tested the hypothesis that cortical excitability measures in AdSD would be significantly different than in MTD and healthy. In addition, we hypothesized there would be a correlation between cortical excitability measures and clinical voice severity in AdSD. Results Cortical silent period (CSP) duration in masseter and FDI was significantly shorter in AdSD than MTD and healthy controls. Other measures failed to demonstrate differences. Conclusion There are differences in cortical excitability between AdSD, MTD and healthy controls. These differences in the cortical measure of both the FDI and masseter muscles in AdSD suggest widespread dysfunction of the GABAB mechanism may be a pathophysiologic feature of AdSD, similar to other forms of focal dystonia. Further exploration of the use of TMS to assist in the differential diagnosis of AdSD and MTD is warranted.

The purpose of this study was to compare cortical inhibition in the hand region of the primary motor cortex between subjects with focal hand dystonia (FHD), adductor spasmodic dysphonia (AdSD), and healthy controls. Data from 28 subjects were analyzed (FHD n=11, 53.25 ± 8.74 y; AdSD: n=8, 56.38 ± 7.5 y; and healthy controls: n=941.67 ± 10.85 y). All subjects received single pulse TMS to the left motor cortex to measure cortical silent period (CSP) in the right first dorsal interosseus (FDI) muscle. Duration of the CSP was measured and compared across groups. A one-way ANCOVA with age as a covariate revealed a significant group effect (p<0.001). Post hoc analysis revealed significantly longer CSP duration in the healthy group vs. AdSD group (p<0.001) and FHD group (p<0.001). These results suggest impaired intracortical inhibition is a neurophysiologic characteristic of FHD and AdSD. In addition, the shortened CSP in AdSD provides evidence to support a widespread decrease in cortical inhibition in areas of the motor cortex that represent an asymptomatic region of the body. These findings may inform future investigations of differential diagnosis as well as alternative treatments for focal dystonias.

Objectives The excitability of primary motor cortex (M1) can be modulated by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) over M1 or premotor cortex (PMC). A comparison of inhibitory effect between the two locations has been reported with inconsistent results. This study compared the response secondary to rTMS applied over M1, PMC and a combined PMC+M1 stimulation approach which first targets stimulation over PMC then M1. Materials and Methods Ten healthy participants were recruited for a randomized, cross-over design with a 1-week wash-out between visits. Each visit consisted of a pre-test, an rTMS intervention and a post-test. Outcome measures included short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Participants received one of the three interventions in random order at each visit including: 1-Hz rTMS at 90% of resting motor threshold to: M1 (1200 pulses), PMC (1200 pulses) and PMC+M1 (600 pulses each, 1200 total). Results PMC+M1 stimulation resulted in significantly greater inhibition than the other locations for ICF (P = 0.005) and CSP (P < 0.001); for SICI, increased inhibition (group effect) was not observed after any of the three interventions and there was no significant difference between the three interventions. Conclusion The results indicate that PMC+M1 stimulation may modulate brain excitability differently from PMC or M1 alone. CSP was the assessment measure most sensitive to changes in inhibition and was able to distinguish between different inhibitory protocols. This work presents a novel procedure that may have positive implications for therapeutic interventions.

Objective Examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); present method for determining the optimal stimulation to increase inhibition in a given patient; and examine individual responses to prolonged intervention. Design A single-subject design to determine optimal parameters to increase inhibition for a given subject and to employ the selected parameters 1/wk for 6 weeks, with 1 wk follow up, to determine response. Setting Clinical research laboratory Participants A volunteer sample of 2 subjects with FHD. One participant had TMS responses indicating impaired inhibition, the other had responses within normal limits. Interventions 1200 pulses of 1 Hz rTMS delivered using 4 different stimulation site/intensity combinations: primary motor cortex (M1) at 90% or 110% resting motor threshold (RMT); dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as intervention. Main outcome measures Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short-latency intracortical inhibition and facilitation. Results The individual with baseline TMS responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, increase in CSP and subjective report of “moderate” symptom improvement at 1-wk follow-up. The individual with normal baseline responses failed to respond to the intervention. In both subjects, 90% RMT to PMd produced greatest lengthening of CSP and was used as intervention. Conclusions An individualized understanding of neurophysiologic measures may be indicators of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine 3 likely responders vs. non-responders.