Prefrontal repetitive transcranial magnetic stimulation (rTMS) changes relative perfusion locally and remotely

Mark S. George, Laurie E. Stallings, Andrew M. Speer, Ziad Nahas, Kenneth M. Spicer, Diana J. Vincent, Daryl E. Bohning, Kenneth T. Cheng, Monica Molloy, Charlotte C. Teneback, S. Craig Risch

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Although transcranial magnetic stimulation has been used as a stand-alone brain mapping tool, relatively few studies have attempted to couple TMS with functional brain imaging to understand the neurobiological effects of TMS. Technical problems of placing a TMS coil in a PET or MRI scanner have hampered previous efforts at imaging the immediate effects of TMS. Perfusion SPECT offers the advantage of tracer injection away from the camera, with later image development. We wondered if perfusion SPECT could be used to visualize brain changes during rTMS over the left prefrontal cortex - a region where rTMS has been shown to cause changes in mood or working memory. Eight healthy adult subjects were scanned with brain SPECT scintigraphy using 30 mCi (1110 MBq) Neurolite® (DuPont Pharma) on a triple-headed Picker camera. Each subject had three scans: (1) baseline, (2) bolus tracer injection during seconds 10-20 of a train of 2 min of left prefrontal rTMS (10 Hz; 60% motor threshold (MT); 10 s on/off, 600 stimuli) (2MIN), and (3) exactly as in the 2MIN, but immediately after subjects had received 18 min of high frequency stimulation (20 Hz; 80% MT; 2 s on/28 s off, 1440 + 600 = 2040 total stimuli) (20MIN). Scans were linearly transformed into Talairach space using SPM96b and compared across conditions (p < 0.05 for display). Contrary to our prestudy hypothesis, there was no relative increase at the coil site during the 2 min or the 20 min scan compared to baseline. In fact, at the 20 min comparison perfusion was relatively decreased in the right prefrontal cortex, bilateral anterior cingulate, and anterior temporal cortex. Also, relative perfusion was significantly increased in the orbitofrontal cortex (L > R) and hypothalamus at 20 min and at 2 min, with thalamic increases occurring at the 30 min scan compared to baseline. There was an apparent TMS dose effect with twice as many decreases at 20 min than 2 min. Directly comparing the 20 min to the 2 min scans demonstrated opposite hemisphere decreases and relative increases in the ipsilateral (left) hemisphere as a function of more TMS stimuli. Full interpretation of these results is hampered by incomplete knowledge of the effect of the relative amount of stimulation to rest during tracer uptake, pharmacokinetics of tracer uptake, and depth and intensity of the magnetic field. Nevertheless, coupling rTMS with split-dose perfusion SPECT appears to be a promising method for understanding the brain changes associated with rTMS, and for directly visualizing neural circuits. We have demonstrated that prefrontal rTMS at high frequencies has both local and remote effects. These imaging results may help explain the cognitive and behavioural effects demonstrated in other prefrontal rTMS studies involving mood and working memory.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalHuman Psychopharmacology
Issue number3
StatePublished - Apr 1 1999


  • Blood flow
  • Cingulate
  • Imaging
  • Prefrontal cortex
  • Transcranial magnetic stimulation


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