Does rTMS affect motor performance

Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability with the effects partly depending on the frequency of stimulation. The possible therapeutical potential of rTMS attracts interest and is currently evaluated in several neuropsychiatric disorders such as Parkinson`s disease (PD). Recently, it was suggested that 1 Hz rTMS may have an effect on preparatory movement activity in normal controls (Rossi et al., 2000). In addition, it has been shown that 5 Hz rTMS may cause a clinical improvement in PD patients (Siebner et al., 1999, 2000). However, rTMS mechanisms of action remain largely unknown and still it is not clear whether rTMS has any functional relevant effect at all. Studies in PD have yielded divergent results so far and have often suffered from a lack of standardization. Event-related potentials (ERPs) such as the Bereitschaftspotential (BP) and the contingent-negative variation (CNV) have been widely used to investigate preparatory motor related activity of the cerebral cortex and provide an objective tool to assess changes in motor control in normal controls and PD patients, respectively. The present proposal elaborates upon previous research on ERPs and on rTMS and aims to gain further insight into the mechanisms underlying rTMS in normal controls and PD patients. Four different experiments will be performed to answer the following questions which stem from preliminary observations: Experiment I and II (in normal controls) (1) Does low frequency subtreshold rTMS (1 Hz) applied over the primary motor cortex have an effect on preparatory motor activity and on motor performance in normal controls as measured with the BP and CNV, respectively? Experiment III and IV (will be carried out in PD patients) (1) Does high frequency subthreshold rTMS (5 Hz) applied over the motor cortex affect motor symptoms in PD patients, as evidenced by the UPDRS? Does 5 Hz rTMS has an effect on motor performance and motor preparation in PD patients as evidenced by the BP and CNV, respectively? (3) Are changes in the amplitude of the BP and CNV correlated to clinical changes? In each experiment 15 participants will be tested on separate days in a counterbalanced order involving either effective rTMS or ineffective "sham" stimulation.

Repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex (Ml) can modulate corticospinal excitability. High-frequency rTMS (e.g. 5 Hz) increases corticospinal excitability, whereas low- frequency rTMS (1 Hz) results in a decrease. rTMS has attracted interest for therapeutic applications in disorders associated with abnormal corticospinal excitability such as Parkinson`s disease (PD). Recent studies suggested that rTMS might improve motor symptoms, such as tremor and bradykinesia, in PD patients. We sought to investigate effects of 1 Hz rTMS, applied over the M1, on cognitive processing in normal controls.. Cognitive processing was assessed by the contingent negative variation (CNV). The CNV is a slow negative brain potential occuring between a warning stimulus and an imperative stimulus and reflects cognitive activity associated with planning and anticipation to the imperative stimulus. In an other experiment we investigated effects of 5 Hz rTMS, applied over the M1, on motor symptoms and the CNV in PD patients. In 10 healthy subjects 1500 stimuli 1 Hz rTMS over M1 increased CNV`s amplitudes ipsilateral to the site of stimulation significantly, whereas a control condition involving "sham-stimulation" did not result in changes of the CNV. Overall, this is the first study showing effects of rTMS on cognitive processessing in healthy subjects by using the CNV, an electrophysiological, quantitative index of mental chronometry and basal ganglia- thalamocortical functioning. In 8 PD patients 2250 stimuli 5 Hz rTMS over M1 did not improve motor symptoms and did not result in any change of CNV`s amplitudes. As opposed to previous reports, we employed blinded raters to assess PD patients` motor symptoms. We conclude that 5 Hz rTMS is not efficacious in improving control of motor symptoms and in improving cognitive processing in PD patients.