Activation of frontal premotor areas during suprathreshold transcranial magnetic stimulation of the left primary sensorimotor cortex: a glucose metabolic PET study

Abstract

We employed cerebral (18)Fluoro-deoxyglucose positron emission tomography ([(18)F]FDG-PET) to visualize neuronal activation of the frontal motor and premotor cortex during suprathreshold repetitive transcranial magnetic stimulation (rTMS) applied to the left primary sensorimotor hand area (SM1(HAND)). Twelve right-handed normal subjects underwent two [(18)F]FDG-PET measurements at baseline without rTMS and during suprathreshold 2 Hz rTMS of the left SM1(HAND). In the rTMS condition, 1,800 magnetic stimuli at an intensity of 140% of motor-resting threshold were delivered immediately after intravenous injection of [(18)F]FDG. Relative differences in the normalized regional cerebral metabolic rate for glucose (rCMRglc) between the rTMS condition and baseline were determined using a voxel-by-voxel Student's t-test and a volume-of-interest analysis. Data analysis was a priori restricted to primary motor and premotor areas in the frontal cortex, namely the SM1, the supplementary motor area (SMA), the lateral premotor cortex (PMC), and the caudal anterior cingulate cortex (ACC) of either hemisphere. In addition to a relative increase in normalized rCMRglc in the stimulated SM1(HAND), suprathreshold rTMS was associated with well-localized increases in normalized rCMRglc in the caudal SMA and ACC on the medial wall of the frontal cortex and in the right precentral gyrus in the lateral PMC rostrally to the SM1. These data demonstrate that a selective activation of the SM1(HAND) is paralleled by an activation of a distinct set of remote premotor areas, suggesting a functional interaction between the primary motor and premotor cortex in humans.

Figure 1

Graphic representation of the experimental procedures during the “rTMS condition.” Immediately after the intravenous injection of the radioisotope, rTMS was delivered over the left SM1_HAND at an average frequency of 2 Hz and at an intensity of 140% of motor resting threshold. One rTMS session consisted of a total number of fifteen 1‐min trains separated by an intertrain interval of 10 sec, corresponding to a total number of 1,800 magnetic stimuli. Data acquisition started 30 min after tracer injection.

Figure 2

Twelve axial sections of color‐coded statistical Z‐score maps showing regions of significant relative increases in normalized rCMRglc at the level of the primary sensorimotor area representing the hand (SM1_HAND), the supplementary motor area (SMA) and the anterior cingulate cortex (ACC). The number at the top of each axial section denotes the axial position relative to the intercommissural line in millimeters. For illustrative purposes, the statistical parametric maps are superimposed onto corresponding axial sections of stereotactically normalized T1‐weighted MRI images and thresholded at an uncorrected P value of 0.01. Right side of the axial sections corresponds to the left hemisphere. White arrows delineate the stimulated left SM1_HAND. In addition to a relative increase in normalized rCMRglc in the stimulated left SM1_HAND, suprathreshold rTMS at a mean frequency of 2 Hz resulted in relative rCMRglc increases in the caudal parts of the SMA and the ACC on the medial wall of the hemispheres as well as in the right precentral gyrus on the hemispheric surface.