Single pulse TMS to the DLPFC, compared to a matched sham control, induces a direct, causal increase in caudate, cingulate, and thalamic BOLD signal

Logan T. Dowdle, Truman R. Brown, Mark S. George, Colleen A. Hanlon

Research output: Contribution to journalArticlepeer-review


Background: In the 20 years since our group established the feasibility of performing interleaved TMS/fMRI, no studies have reported direct comparisons of active prefrontal stimulation with a matched sham. Thus, for all studies there is concern about what is truly the TMS effect on cortical neurons. Objective: After developing a sham control for use within the MRI scanner, we used fMRI to test the hypothesis of greater regional BOLD responses for active versus control stimulation. Methods: We delivered 4 runs of interleaved TMS/fMRI with a limited field of view (16 slices, centered at AC-PC) to the left DLPFC (2 active, 2 control; counterbalanced) of 20 healthy individuals (F3; 20 pulses/run, interpulse interval:10–15sec, TR:1sec). In the control condition, 3 cm of foam was placed between the TMS coil and the scalp. This ensured magnetic field decay, but preserved the sensory aspects of each pulse (empirically evaluated in a subset of 10 individuals). Results: BOLD increases in the cingulate, thalamus, insulae, and middle frontal gyri (p < 0.05, FWE corrected) were found during both active and control stimulation. However, relative to control, active stimulation caused elevated BOLD signal in the anterior cingulate, caudate and thalamus. No significant difference was found in auditory regions. Conclusion(s): This TMS/fMRI study evaluated a control condition that preserved many of the sensory features of TMS while reducing magnetic field entry. These findings support a relationship between single pulses of TMS and activity in anatomically connected regions, but also underscore the importance of using a sham condition in future TMS/fMRI studies.

Original languageEnglish (US)
Pages (from-to)789-796
Number of pages8
JournalBrain Stimulation
Issue number4
StatePublished - Jul 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health ( T32 DA007288 , R01 DA036617 , R21 DA041610 , P20 GM109040 , UL1 TR001450 , F31 DA043330 and P2 CHD086844 ). The authors declare no conflicts of interest associated with this manuscript. Financial support was exclusively provided by NIH , and the NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The authors also thank James Purl for his invaluable assistance and expertise as an MRI technician, Jayce Doose for his help with technical and engineering concerns. Additionally, the authors would like to thank Oliver Mithoefer and Sarah Hamilton for their help with executing this project and Dr. Jeffrey Borckardt for his statistical advice and expertise.

Publisher Copyright:
© 2018 Elsevier Inc.


  • Brain stimulation
  • Connectivity
  • Frontostriatal
  • Neuroimaging


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