Placebo-controlled study of rTMS for the treatment of Parkinson's disease.

The objective of this study is to assess the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for gait and bradykinesia in patients with Parkinson's disease (PD). In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz rTMS in 18 PD patients. Eight rTMS sessions were performed over a 4-week period. Four cortical targets (left and right motor and dorsolateral prefrontal cortex) were stimulated in each session, with 300 pulses each, 100% of motor threshold intensity. Left motor cortex (MC) excitability was assessed using motor evoked potentials (MEPs) from the abductor pollicis brevis. During the 4 weeks, times for executing walking and complex hand movements tests gradually decreased. The therapeutic rTMS effect lasted for at least 1 month after treatment ended. Right-hand bradykinesia improvement correlated with increased MEP amplitude evoked by left MC rTMS after individual sessions, but improvement overall did not correlate with MC excitability. rTMS sessions appear to have a cumulative benefit for improving gait, as well as reducing upper limb bradykinesia in PD patients. Although short-term benefit may be due to MC excitability enhancement, the mechanism of cumulative benefit must have another explanation.

An increased precision comparison of TMS-induced motor cortex BOLD fMRI response for image-guided versus function-guided coil placement.

OBJECTIVE: To examine with high precision the differences between function-guided and image-guided transcranial magnetic stimulation (TMS). METHOD: Using a calibrated TMS coil holder/positioner, interleaved TMS/functional magnetic resonance imaging (fMRI), and individualized anatomy-based regional normalization, we conducted a two-phase study of TMS coil positioning guided by either function (elicited thumb motion) or image-based targeting of the "hand knob," the anatomy associated with fMRI activation during thumb motion. RESULTS: In every case, image-guided TMS coil placement produced a thumb movement response at thresholds similar to those found under function guidance. Unexpectedly, function-guided coil locations clustered bimodally over central and precentral sulci. Image-guided locations clustered as anticipated toward the targeted gyral crown. Despite these differences, blood oxygenation level-dependent (BOLD) activation locations and magnitude for the two methods displayed no consistent differences in mean or variance between or within subjects. Image guidance produced more consistent coil placement from subject to subject relative to targeted anatomy. Surprisingly, BOLD time courses from image-guided experiments showed significantly slower return to baseline after TMS than was observed under function guidance. CONCLUSIONS: The results demonstrate the effectiveness and precision of image-guided positioning of TMS coils combined with a precisely adjustable holder/positioner and regional normalization. Image guidance provides an accurate TMS placement relative to individual anatomy when no external sign is available.

BOLD-fMRI response vs. transcranial magnetic stimulation (TMS) pulse-train length: testing for linearity.

PURPOSE: To measure motor and auditory cortex blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) response to impulse-like transcranial magnetic stimulation (TMS) pulses as a function of train length. MATERIALS AND METHODS: Interleaved with fMRI at 1.5 T, TMS pulses 0.3-msec long were applied at 1 Hz to the motor cortex area for thumb. Six subjects were studied in a TR = 1 second session administering trains of 1, 2, 4, 8, and 16 pulses, and a TR = 3 seconds session administering trains of 1, 2, 4, 8, 16, and 24 pulses. A simple hemodynamic model with finite recovery and saturation was used to quantitatively characterize the BOLD-fMRI response as a function of train length. RESULTS: In both the activations directly induced in motor cortex by TMS and the indirect activations in auditory cortex caused by the sound of the TMS coil firing, the BOLD-fMRI responses to multiple pulses were well described by a summation of single-pulse impulse functions. CONCLUSION: Up to 24 discrete pulses, BOLD-fMRI response to 1 Hz TMS in both motor cortex and auditory cortex were consistent with a linear increase in amplitude and length with train length, possibly suggesting that stimuli of 1 to 2 seconds may be too long to represent impulses.