Which functional magnetic resonance imaging sequence is most suited for neuronavigated transcranial magnetic stimulation?

Background: The accuracy of stereotaxic frameless neuronavigation for transcranial magnetic stimulation (TMS) may dependent on the spatial validity of functional magnetic resonance imaging (fMRI) sequences. Nearly all fMRI studies use a gradient echo (GRE) sequence which, in contrast to spin echo (SE) and arterial spin labeling (ASL), provides a better contrast-to-noise ratio but is prone to be shifted to veins. We tested the hypothesis (i) that the functional localisation of the motor area depends on the fMRI sequence used to detect neuronal activity and (ii) that TMS of the different peak voxels assessed by the different fMRI sequences impacts on the motor response at the respective peripheral muscle (motor evoked potential, MEP). Methods: 14 healthy right-handed subjects were scanned at 3T using standard GRE, SE and ASL sequences while performing repetitive thumb abductions. BOLD (blood oxygenation level-dependent) and perfusion data were acquired in a block design (20s movement; 40s rest; TR 2.2; 3×3x3 cmm; FWHM 4mm). Voxels with highest t-values at the hand knob (precentral gyrus) during thumb movements were stimulated at 120% resting motor threshold using a neuronavigated TMS device (Nexstim, Helsinki). MEPs were recorded from the contralateral abductor pollicis brevis. Results: The group analysis showed that GRE coordinates were located significantly more superior compared to peak voxels assessed by SE. When stimulating the respective local maxima, highest mean MEPs were recorded for GRE, lowest for SE. The electric field (EF) maximum at the stimulation target (calculated by means of computerized modelling) was significantly lower for SE than for GRE. ASL provided intermediate results more similar to GRE than to SE in all measures although the differences were not statistically significant. Discussion: Target definition for neuronavigated TMS was significantly influenced by the type of fMRI sequence. These differences were functionally relevant as TMS of the respective targets evoked significantly different response amplitudes at the respective peripheral muscle. Surprisingly, fMRI sequences less susceptible to venous shifts were not superior to the standard GRE sequence in terms of higher MEP amplitudes which might be at least partially attributed to the EF geometry built up by the TMS coil. The current study underpins the need for further investigation of the validity of functional MRI sequences used for neuronavigated TMS.