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Deep TMS of the insula using the H-coil modulates dopamine release: a crossover [11C] PHNO-PET pilot trial in healthy humans


Modulating the function of the insular cortex could be a novel therapeutic strategy to treat addiction to a variety of drugs of abuse as this region has been implicated in mediating drug reward and addictive processes. The recent advent of the H-coil has permitted the targeting of deeper brain structures which was not previously feasible. The goal of this study was to bilaterally target the insular region using the H-coil with repetitive Transcranial Magnetic Stimulation (rTMS) and subsequently measure changes in dopamine levels using Positron Emission Tomography (PET) with [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO). This was a within-subject, crossover, blinded and sham-controlled pilot study. Eight healthy, right-handed subjects, aged 19–45, participated in the investigation. All subjects underwent 3 PHNO-PET scans preceded by rTMS (sham, 1 Hz or 10 Hz), on 3 separate days. Low frequency rTMS (1 Hz), targeting the insular cortex, significantly decreased dopamine levels in the substantia nigra, sensorimotor striatum and associative striatum. Replicating this study in tobacco smokers or alcoholics would be a logical follow-up to assess whether H-coil stimulation of the bilateral insula can be employed as a treatment option for addiction. Trial registration: NCT02212405

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Repeated Transcranial Magnetic Stimulation


Positron Emission Tomography




[11C]-(+)-PHNO specific binding


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The authors would like to thank Heather O’Leary and Annabel Fan for their assistance.


This work was funded by a research grant from the Campbell Family via the CAMH foundation fund (grant #200).

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Correspondence to Bernard Le Foll.

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Conflict of interest

Dr. Malik, Dr. Cho, Dr. Boileau, Dr. Strafella, Dr. Wilson, Dr. Heilig and Mark Jacobs reported no biomedical financial interests or potential conflicts of interest. Dr. Le Foll has received in-kind support from Brainsway that provided the equipment used in this study. In addition, Dr. Le Foll received in kind donation of drug supplies from Pfizer or GW-Pharma. He received grant and salary support for other unrelated studies from Pfizer Inc. and Bioprojet laboratory. Dr. Le Foll has been a consultant or has received honorariums for lectures from Richter Pharmaceuticals, Lundbeck, Mylan, Ethypharm, Metrum and Pfizer. Dr. Daskalakis has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc, and has also served on the advisory board for Sunovion, Hoffmann-La Roche Limited and Merck and received speaker support from Eli Lilly. Dr. Blumberger has received research support from the Canadian Institutes of Health Research (CIHR), National Institute of Health (NIH), Brain Canada and the Temerty Family through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Research Institute. He receives research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for an investigator-initiated study and receives medication supplies for an investigator-initiated trial from Invidior. Dr. Zangen is a co-inventor of the deep TMS H-coil system, serves as consultant for, and has financial interests in Brainsway.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Malik, S., Jacobs, M., Cho, SS. et al. Deep TMS of the insula using the H-coil modulates dopamine release: a crossover [11C] PHNO-PET pilot trial in healthy humans. Brain Imaging and Behavior 12, 1306–1317 (2018).

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  • Insula
  • PET
  • Dopamine
  • H-coil
  • Deep rTMS
  • PHNO