Brief Report

Transcranial magnetic stimulation andneuroimaging

Similar to neuroimaging, transcranial magneticstimulation (TMS) is a localizing technique. Byits very nature though, TMS is two-dimensionalgiving a resolution by cautious displacement of thecoil, of at best a few millimetres along the surface

of the scull. If a three-dimensional understandingof TMS-effects is sought, imaging methods, such ascomputed tomography (CT, SPECT, PET) ormagnetic resonance imaging (MRI) are required.What functional neuroimaging lacks, on the other

Ebmeier KP. Transcranial magnetic stimulation and neuroimaging.Bipolar Disord 2002: 4(Suppl. 1): 96–97. � Blackwell Munksgaard, 2002

KP Ebmeier

Department of Psychiatry, University of Edinburgh,

Kennedy Tower, Morningside Park, Edinburgh

EH10 5HF, UK

Table 1. Studies combining TMS and neuroimaging

Ref Imaging mode TMS method Results

Healthy volunteer studies1 BOLD fMRI 3D maps of the magnetic field

created by TMS coils in humanvolunteers

5 PET TMS pulse trains at the left frontaleye field

Positive correlations between CBF at frontal eye field (FEF)and in the visual cortex of the superior parietal and medialparieto-occipital regions and the number of TMS pulsetrains

6 PET in six controls Brief 10-Hz trains were deliveredto left primary sensorimotorcortex, at subthreshold intensity

In the left primary sensorimotor cortex, CBF covariedsignificantly and negatively with the number of stimulustrains

1 BOLD fMRI in five controls Single TMS pulse over the motorcortex at 120% MT

Response to a single TMS pulse over the motor cortex at120% MT similar to auditory cortex response

11 BOLD fMRI 23 bursts, 1 s duration, 10 Hz Neither subthreshold rTMS of the motor cortex norsuprathreshold rTMS of the lateral premotor cortexinduced a detectable BOLD response

12 BOLD fMRI in five controls 1 Hz at 80,100,120% MT 80% auditory cortex; 100% contralateral prefrontal;120% bilateral prefrontal activation

9 PET; functional connectivityof modulation of LDPLFcortex

rTMS to the left MDLPFC The results showed a strong rTMS-related modulationof brain activity in the fronto-cingulate circuit

Clinical depression studies13 ECD SPECT in 23

depressedFifth day of treatment, 5 or 20 Hz Increased under coil 20 Hz > 5 Hz, decreased inanterior

cingulate, temporal poles14 SPECT and PET Before and after 10 days rTMS Increases in rCBF and rCMRGlu patterns were found in the

upper frontal regions bilaterally i and decreases in the leftorbitofrontal cortex

15 SPECT in 22 depressed 2 weeks of left prefrontal TMS TMS-responders, compared with non-responders, showedincreased inferior frontal lobe activity. Followingtreatment, the effect was greater

10 SPECT in 15 depressed Pre and post first treatment day,5,10, 20 Hz over LDLPFC.

Anterior cingulate activation, increased connectivity inlimbic loop bilaterally and dorsolateral loop left

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hand, is the ability to analyse brain–behaviourassociations in a causal fashion: If, for example, amental task is associated with an increase in localbrain activity, this could mean that brain activa-tion is necessary to generate the task relatedbehaviour. However, brain activation could alsobe equivalent to perception or monitoring ofbehaviour, as is postcentral brain activation duringmovements. A possible further cause of local brainactivation may be associated, but not necessary,mental events, such as task-related anxiety, arousalor compensatory changes. Similarly, functionalconnectivity data do not allow for the directionof influence to be determined, unless the anatom-ical connections unambiguously favour one direc-tion, or the time course of the spread of activationcan be clearly observed (using electro-encephalo-graphic mapping). This is where TMS can usefullyadd information. Dorsolateral-prefrontal TMS canonly directly affect underlying cortex, so thatchanges remote from the stimulation site, such asin anterior cingulate cortex, are clearly secondarywith few notable exceptions, such as auditorycortex. It is thus the combination of TMS withother neuroimaging methods that is likely togenerate new and important results.

Because of the strong magnetic field changesgenerated by TMS coils, the safest imagingmethods are those where the image can be gener-ated away from the electronically sensitive scanners.Examples are Perfusion-SPECT and PET with 18F-fluoro-deoxyglucose. In both methods, the radiotr-acer is injected and incorporated into brain cellswell before scanning. More challenging is thecombination of TMS with imaging methods thatrequire stimulation in the scanner, such as PET withshort half-life radio-ligands, such as 15O andfunctional MRI (fMRI). The development of suchprotocols counts amongst the major new methodo-logical achievements of neuroscience (1–7).

Because of the use of TMS in the treatment ofdepression (8) imaging studies of TMS have inparticular been conducted in depressed patientsduring treatment, as well as in healthy volunteers(see Table 1). Evidence is accumulating that sug-gests remote effects in anterior cingulate andincreased connectivity in limbic loop structuresafter TMS (9, 10). If such changes can be shown tooccur in association with treatment response, thismay allow some plausible explanations of themode of action of TMS in the future.

References

1. Bohning DE, Pecheny AP, Epstein CM et al. Mappingtranscranial magnetic stimulation (TMS) fields in vivo withMRI. Neuroreport 1997; 8: 2535–2538.

2. Bohning DE, Shastri A, McConnell KA et al. A combinedTMS ⁄ fMRI study of intensity-dependent TMS over motorcortex. Biol Psychiatry 1999; 45: 385–394.

3. Bohning DE, Shastri A, Wassermann EM et al. BOLD-fMRI response to single-pulse transcranial magneticstimulation (TMS). J Magn Reson Imaging 2000; 11: 569–574.

4. Paus T. Imaging the brain before, during, and aftertranscranial magnetic stimulation. Neuropsychologia 1999;37: 219–224.

5. Paus T, Jech R, Thompson CJ, Comeau R, Peters T,Evans AC. Transcranial magnetic stimulation duringpositron emission tomography. A new method for studyingconnectivity of the human cerebral cortex. J Neurosci.Official J Soc Neurosci 1997; 17: 3178–3184.

6. Paus T, Jech R, Thompson CJ, Comeau R, Peters T,Evans AC. Dose-dependent reduction of cerebral bloodflow during rapid-rate transcranial magnetic stimulation ofthe human sensorimotor cortex. J Neurophysiol 1998; 79:1102–1107.

7. Paus T, Wolforth M. Transcranial magnetic stimulationduring PET: reaching and verifying the target site. HumanBrain Mapping 1998; 6: 399–402.

8. Ebmeier KP, Lappin JM. Electromagnetic stimulation inpsychiatry. Adv Psychiatr Treat 2001; 7: 181–188.

9. Paus T, Castro-Alamancos MA, Petrides M. Cortico-cortical connectivity of the human mid-dorsolateral frontalcortex and its modulation by repetitive transcranial mag-netic stimulation. Eur J Neurosci 2001; 14: 1405–1411.

10. Shajahan PM, Glabus MF, Steele JD et al. Left dorso-lateral repetitive transcranial magnetic stimulation affectscortical excitability and functional connectivity, but doesnot impair cognition in major depression. Prog Neuro-psychopharmacol Biol Psychiatry 2002 in press.

11. Baudewig J, Siebner HR, Bestmann S et al. FunctionalMRI of cortical activations induced by transcranialmagnetic stimulation (TMS). Neuroreport 2001; 12:3543–3548.

12. Nahas Z, Lomarev M, Roberts DR et al. Unilateral leftprefrontal transcranial magnetic stimulation (TMS) pro-duces intensity-dependent bilateral effects as measuredby interleaved BOLD fMRI. Biol Psychiatry 2001; 50:712–720.

13. Nahas Z, Teneback CC, Kozel A et al. Brain effects ofTMS delivered over prefrontal cortex in depressed adults:role of stimulation frequency and coil-cortex distance.J Neuropsychiatry Clin Neurosci 2001; 13: 459–470.

14. Conca A, Peschina W, Konig P, Fritzsche H, Hausmann A.Effect of chronic repetitive transcranial magnetic stimula-tion on regional cerebral blood flow and regional cerebralglucose uptake in drug treatment-resistant depressives. Abrief report. Neuropsychobiology 2002; 45: 27–31.

15. Teneback CC, Nahas Z, Speer AM et al. Changes inprefrontal cortex and paralimbic activity in depressionfollowing two weeks of daily left prefrontal TMS. TheJ Neuropsychiatry Clin Neurosci 1999; 11: 426–435.

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