Alvaro Pascual-Leone, Jesus Pujol, Joan Deus, Antonio Capdevila, Jose Maria Tormos, Josep Valls-Sole
Tuesday April 15 3:00 pm / Exhibit Hall A

OBJECTIVE:
Evaluate the effects of rTMS on cortical activity as measured by fMRI in order to enhance our understanding about the mechanisms of action of rTMS.

BACKGROUND:
Several neurophysiologic studies suggest that rTMS can modulate the level of cortical activity beyond the duration of the rTMS trains. This raises the possibility of applying rTMS in the therapy of various neuropsychiatric conditions in which alterations of cortical excitability have been documented. Beneficial effects of left prefrontal rTMS in depression have been suggested to rely on such a modulation of cortical excitability.

DESIGN/METHODS:
We have studied 10 normal, right-handed subjects. Each subject was studied on two separate days with an fMRI measuring activation of bilateral primary motor cortex (M1), premotor cortex and supplementary motor area (SMA), while the subjects performed a paced (1 Hz) fist opening and closing movement with the left hand. The fMRI studies were performed with a 1.5 Tesla Signa (General Electric Medical) using a gradient echo with long TE times, and overlaid on a T1 weighted image for anatomical localization. The subject laid on a stretcher that could be wheeled out of the MRI suite with the head inmobilized and markers for accurate repositioning. A first fMRI was obtained and the subjects moved just outside the MRI suite where rTMS or no rTMS were applied. Real rTMS consisted of 20 trains of rTMS (30 s intertrain interval) at 10 Hz and 90% of the subject"s motor threshold intensity focally to the right motor cortex. We used a Dantec Magpro equipped with an 8-shaped coil. The no rTMS experiments were performed as control condition on a different day randomly before or after the rTMS experimental day. After the rTMS, the subjects were moved back into the fMRI suite, a T1 weighted image was obtained to document correct repositioning, and the fMRI study during left fist movements was repeated. Therefore, this second fMRI study was obtained approximately 5 min after completion of the rTMS trains. The degree of cortical activation before and following rTMS versus no rTMS was calculated. RESULTS: When no rTMS was applied, the pattern of activation of right (contralateral) M1 and dorsal SMA remained stable in the two fMRI studies. However, high frequency rTMS resulted in a significant change of this pattern with an increase in M1 activity and an associated decrease in dorsal SMA activity. These changes in cortical activation were not related to changes in the motor performance which remained constant as documented by video and neurophysiologic monitoring.

CONCLUSION:
Our results document the feasibility of combining fMRI and rTMS in order to improve our understanding of the mechanisms of action of rTMS. Furthermore, the results illustrate that rTMS effects on cortical excitability, extend beyond the stimulation trains themselves and are not limited to the site of stimulation, but rather, can also affect cortical regions connected with the stimulated site, presumably by trans-synaptic effects. Finally, these results suggest that rTMS effects in neuropsychiatric conditions might indeed be related to the effects of rTMS on cortical activity.

Sponsored by: Generalitat Valenciana, Spanish Ministerio de Educacion y Ciencia (DGICYT).