Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex

Abstract

We describe a new technique permitting the mapping of neural connections in the living human brain. The method combines two well established tools of brain research: transcranial magnetic stimulation (TMS) and positron emission tomography (PET). We use TMS to stimulate directly a selected cortical area while simultaneously measuring changes in brain activity, indexed by cerebral blood flow (CBF), with PET. The exact location of the stimulation site is achieved by means of frameless stereotaxy. In the first study using this technique, we found significant positive correlations between CBF and the number of TMS pulse trains at the stimulation site, namely the left frontal eye field (FEF) and, most importantly, in the visual cortex of the superior parietal and medial parieto-occipital regions. The pattern of these distal effects was consistent with the known anatomic connectivity of the monkey FEF. We suggest that the combined TMS/PET technique offers an objective tool for assessing the state of functional connectivity without requiring the subject to engage in any specific behavior.

Fig. 1.

The top of the figure shows a coronal (left) and a sagittal (right) section through a transmission scan obtained in one subject, superimposed on an MR image of the same subject. The TMS coil can be seen in the inset. Note the figure-eight shape of the coil. The bottom of the figure contains three-dimensional plots of the crystal identification matrix obtained in the absence of magnetic field (A), during magnetic stimulation (B), and during the same magnetic stimulation but with metal shields placed between the coil and the photo multipliers (C). Note a serious distortion of the matrix during unshielded exposure to the pulse magnetic field (B).

Fig. 2.

The top of the figure shows the process of registering the subject’s head with the corresponding MR image. A computer-linked probe is touching the bridge of the nose (right); the matching location is highlighted by a cross hair on the MR image (left). The bottomof the figure shows a location targeted by TMS in this study, i.e., the left frontal eye field, FEF (left), and the probe–coil interface used to position the coil over this location (right). 1, Arm of the frameless-stereotaxy unit; 2, probe inside the interface; 3, coil inside the interface.

Fig. 3.

Brain regions that showed significant (t > 3.5) correlations between CBF and the number of TMS pulse trains. The top of the figure shows a significant correlation in the vicinity of the frontal eye field (FEF), i.e., in the stimulated area. Thebottom of the figure shows one of the cortical regions that most likely was activated through the spread of electrical stimulation from the FEF, namely the parieto-occipital (PO) cortex of the ipsilateral hemisphere. A similar region is known to be connected anatomically with the FEF in the monkey (Schall et al., 1995).