Increasing striatal dopamine release through repeated bouts of theta burst transcranial magnetic stimulation of the left dorsolateral prefrontal cortex. A 18F-desmethoxyfallypride positron emission tomography study

Usman Jawed Shaikh*, Antonello Pellicano, Andre Schueppen, Alexander Heinzel, Oliver H. Winz, Hans Herzog, Felix M. Mottaghy, Ferdinand Binkofski*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Transcranial Magnetic Stimulation (TMS) can modulate fronto-striatal connectivity in the human brain. Here Positron Emission Tomography (PET) and neuro-navigated TMS were combined to investigate the dynamics of the fronto-striatal connectivity in the human brain. Employing 18F-DesmethoxyFallypride (DMFP) - a Dopamine receptor-antagonist - the release of endogenous dopamine in the striatum in response to time-spaced repeated bouts of excitatory, intermittent theta burst stimulation (iTBS) of the Left-Dorsolateral Prefrontal Cortex (L-DLPFC) was measured.Methods: 23 healthy participants underwent two PET sessions, each one with four blocks of iTBS separated by 30 minutes: sham (control) and verum (90% of individual resting motor threshold). Receptor Binding Ratios were collected for sham and verum sessions across 37 time frames (about 130 minutes) in striatal sub-regions (Caudate nucleus and Putamen).Results: Verum iTBS increased the dopamine release in striatal sub-regions, relative to sham iTBS. Dopamine levels in the verum session increased progressively across the time frames until frame number 28 (approximately 85 minutes after the start of the session and after three iTBS bouts) and then essentially remained unchanged until the end of the session.Conclusion: Results suggest that the short-timed iTBS protocol performed in time-spaced blocks can effectively induce a dynamic dose dependent increase in dopaminergic fronto-striatal connectivity. This scheme could provide an alternative to unpleasant and distressing, long stimulation protocols in experimental and therapeutic settings. Specifically, it was demonstrated that three repeated bouts of iTBS, spaced by short intervals, achieve larger effects than one single stimulation. This finding has implications for the planning of therapeutic interventions, for example, treatment of major depression.
Original languageEnglish
Article number1295151
Number of pages11
JournalFrontiers in Neuroscience
Volume17
DOIs
Publication statusPublished - 18 Jan 2024

Keywords

  • positron emission tomography (PET)
  • transcranial magnetic stimulation (TMS)
  • intermittent theta burst stimulation (iTBS)
  • prefrontal cortex (PFC)
  • dorso-lateral prefrontal cortex (DLPFC)
  • resting motor threshold (rMT)
  • ANOVA
  • repeated-measure analysis of variance
  • MAJOR DEPRESSION
  • CORTICAL EXCITABILITY
  • ENDOGENOUS DOPAMINE
  • PARKINSONS-DISEASE
  • C-11 RACLOPRIDE
  • FRONTAL-CORTEX
  • HUMAN BRAIN
  • CONNECTIVITY
  • RTMS
  • TMS

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