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Abstract

Introduction

CASL (continuous arterial spin labeling) offers the possibility of simultaneously measuring absolute rCBF (regional cerebral blood flow) and the BOLD effect. The aim of this project is to demonstrate the technical feasibility of combining TMS with multi slice CASL imaging and to investigate the effect of different TMS protocols on rCBF.
Methods

Interleaved TMS/CASL was performed on 8 subjects (3T Siemens TIM Trio). Inside the scanner, the TMS coil was positioned over the motor cortex representation of a particular finger muscle using a method previously described (Moisa et al 2009) and the motor threshold (MT) was determined.

Each subject underwent 16 experimental runs in a block design in two different sessions: Six with 2Hz continuous rTMS (3 different intensities: 100%, 110% and 120% MT; 2 runs per intensity; Fig. 1a), six with short 10Hz rTMS trains at 110% MT intensity (8 pulses per train; 3 different number of trains per block with 2, 4 and 12 sec gaps between trains; Fig. 1b) and 4 runs volitional movement (acoustically triggered by 50% MT stimuli). Each run consisted of 8 blocks (24 seconds of rTMS followed by 52 seconds of rest). An in-house written CASL sequence with separate RF coils for labeling the inflowing blood (Zaharchuk et al 1999) was used for assessing rCBF.
Results

The group rCBF activation map due to rTMS stimulation, pooled over all conditions, shows significant rCBF increases in brain areas related to the motor and premotor system: ipsilateral M1/S1, contralateral S1, CMA, SMA, ipsi- and contralateral PMv and PMd (Fig. 2a). The activation pattern is similar to that elicited by volitional movement (data not shown). Fig. 2b shows the brain regions exhibiting increasing rCBF with increasing stimulation intensity for the 2Hz stimulation and with increasing number of trains for the 10Hz stimulation. Figure 3 shows the relative rCBF time courses in two representative regions (ipsilateral M1/S1 and SMA).
Conclusions

We found robust rCBF changes in response to TMS stimulation measured by simultaneous ASL imaging, thereby demonstrating the feasibility of this new combination. The observed spatial activation patterns are in concordance with previous TMS motor cortex studies (Bestmann et al 2004, Bohning et al 2003). For 2Hz stimulation, the linear increase in rCBF with increasing intensity observed in stimulated M1/S1 area as well as in co-activated areas is in concordance with previous TMS/PET studies (e.g., Speer et al 2003). However, for stimulation with short 10Hz trains, the linear increases with increasing number of trains contradicts the PET data reported by Paus and colleagues (1998). This might stem from the fact that we used supra- rather than sub-MT stimulation, as originally used in (Paus et al, 1998). Interestingly, however, the rCBF time courses consistently show a clear-cut peak at the beginning of the stimulation period when using 10Hz trains, while this behavior is absent for 2Hz stimulation. This might indicate that an inhibitory component starts to build up in the second half of the stimulation period when using 10Hz trains (see also de Labra et al 2006).