Neural substrates of low-frequency repetitive transcranial magnetic stimulation during movement in healthy subjects and acute stroke patients. A PET study

Abstract

The aim of the study was to investigate, with an rTMS/PET protocol, the after-effects induced by 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the regional cerebral blood flow (rCBF) of the primary motor cortex (M1) contralateral to that stimulated during a movement. Eighteen healthy subjects underwent a baseline PET scan followed, in randomized order, by a session of Real/Sham low-frequency (1 Hz) subthreshold rTMS over the right M1 for 23 min. The site of stimulation was fMRI-guided. After each rTMS session (real or sham), subjects underwent behavioral hand motor tests and four PET scans. During the first two scans, ten subjects (RH group) moved the right hand ipsilateral to the stimulated site and eight subjects (LH group) moved the left contralateral hand. All remained still during the last two scans (rest). Two stroke patients underwent the same protocol with rTMS applied on contralesional M1. Compared with Sham-rTMS, Real-rTMS over the right M1 was followed by a significant increase of rCBF during right hand movement in left S1M1, without any significant change in motor performance. The effect lasted less than 1 h. The same rTMS-induced S1M1 overactivation was observed in the two stroke patients. Commissural connectivity between right dorsal premotor cortex and left M1 after real-rTMS was observed with a psychophysiological interaction analysis in healthy subjects. No major changes were found for the left hand. These results give further arguments in favor of a plastic commissural connectivity between M1 both in healthy subjects and in stroke patients, and reinforce the potential for therapeutic benefit of low-frequency rTMS in stroke rehabilitation.

(c) 2008 Wiley-Liss, Inc.

Figures

Figure 1

Experimental design for the rTMS/PET/motor behavior protocol.

Figure 2

Areas of increased normalized regional cerebral blood flow (rCBF) during movement of the right hand (RH Group) or the left (LH Group) hand after sham‐rTMS. Statistical parametric maps are rendered on the SPM template and statistical threshold of P < 0.05, corrected FDR. The gray flash symbolizes the sham‐rTMS site.

Figure 3

Areas of increased normalized regional cerebral blood flow (rCBF) after real‐rTMS (Effect of real‐rTMS vs. sham‐rTMS on movement‐related activation) during movement of the right hand (RH Group). Same comparison is shown for the subgroup having real‐rTMS first and sham‐rTMS afterward. Statistical parametric maps are rendered on the SPM template and statistical threshold of P < 0.01. The red flash symbolizes the real‐rTMS site.

Figure 4

Areas showing a change in connectivity (P = 0.046, FDR corrected). White cross indicates the index area in left M1. Red flash indicates the site of 1‐Hz rTMS. Real‐rTMS induced a coupling between left M1 and right dorsal PMC, whereas no coupling existed after sham‐rTMS. Regression lines have been fitted (real‐rTMS: r = 0.54, P = 0.0005; sham‐rTMS: r = 0.15, P = 0.11, NS).

Figure 5

Lesion of Patient No. 1, activation related to the movement of the paretic hand, and rTMS effect during movement at P < 0.001. Statistical parametric maps are rendered on the T1 images of the patient. The red and gray flashes symbolize the real‐ and sham‐rTMS site respectively.

Figure 6

Lesion of Patient No. 2, activation related to the movement of the paretic hand, and rTMS effect during movement at P < 0.001. Statistical parametric maps are rendered on the T1 images of the patient. The red and gray flashes symbolize the real‐ and sham‐rTMS site respectively.