NemoImage 13, Number 6, 2001, Part 2 of 2 Parts 10E@w PHYSIOLOGY

Transcranial Magnetic Stimulation (TMS) Intensity Dependent Alterations in Regional Cerebral Blood Flow.

Nitin Tandon*t, Shalini Narayanat, Frank Zamarripat, Jack Lancaster?, Peter Fox? *Division of Neurosurgery University of Texas Health Science Center - San Antonio, Texas, USA TResearch Imaging Center University of Texas Health Science Center San Antonio, Texas, USA

The intensity of stimulation is a variable intrinsic to all TMS experiments. Stimulus intensity is a measure of the strength of the induced electrical field, a factor crucial in determining the extent of neuronal reactivity. We seek to evaluate the effect of varying TMS intensity on induced cortical neuronal responses in a direct and accurately quantifiable manner using [O-15]H20 PET.

Methods Eight right handed volunteers underwent concurrent TMS-PET. TMS of the right supplementary motor area (SMA) was carried out at 3 Hz, at intensity levels of 75%, 100% and 125% of motor threshold (mt). A neurosurgical robot NeumMate@, was used to position and to hold the B shaped TMS coil. Scans were acquired during TMS, during sham TMS and during volitional left hand movement. Following spatial normalization, statistical parametric images of z scores (SPI{z)) were generated by contrasting real vs sham TMS for the entire group at each intensity level as well as per individual. Positive extrema in the right SMA were obvious in all SPI( z} images. Defining characteristics of extrema (z> 1.96) from the groupwise contrasts per intensity level - peak z score and cluster size were computed. SPI( z) generated per subject was used to localize the peak voxel in the SMA. Individualized regions of interest (ROIs) were then used to sample each value normalized (VN) PET injection and SPI[ z} per subject, per intensity level. Fig 1 - Locations of peak voxels in the ex-

trema within SMA from SPI[ z) of the group (n=8) contrasting different intensities of TMS stimulation and hand movement with sham TMS (p<O.OOl).

ReSultS The SPI[ z) for the group data shows that the SMA was accurately and consistently targeted. There was a systematic caudal progression of the location of the extrema in the SPI{z) with rising intensity levels (Figure 1). Cluster sizes of extrema in contrasts generated for the group per intensity level increased monotonically as a function of stimulation intensity, while peak z scores increased between the 75% mt and the 100% mt conditions and then plateaued (Figure 2). Analysis of VN counts per injection in the ROB, revealed a strong effect of TMS intensity (p<O.OOOl, F= 24.04) on resting blood flow. Analysis of ROI data from condi- tional contrast images per intensity level per individual also a revealed strong intensity effect (p= 0.03).

Discussion The increase in activated cortical volume with increasing intensity suggests that the enhancing effect of suprathreshold TMS stimulation is due to increasing numbers of activated neurons and not to progressive elevation of activity in the same neuronal pool. Interestingly, all TMS induced activations, in the grouped as well as individual data sets sites were deep seated and not closest to the inner table of the skull where the induced electric field was highest. We explain this obser- vation by proposing that cortical areas may vary in their degree of excitability by

pzfz== --*.l”.lblE Figure 2 - Grouped data for each intensity of TMS. Peak z score does not rise with suprathreshold stimulation while the size of the cluster that reaches significance (z> 1.96) does.

TMS, presumably as a consequence of intercortical inhibitory circuits. This hypothesis can also explain the caudal progression of the location of extrema with rising intensity levels.

Knowledge of cortical intensity-response function will allow the modulation of response strength in a predictable manner, bringing response magnitude to detectable levels for imaging studies and for varying local response systematically, maximizing the power of inter-regional connectivity studies.

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