Manipulating Reward Sensitivity Using Reward Circuit–Targeted Transcranial Magnetic Stimulation

  • Jon Ryan
    Department of Biomedical Sciences, Florida State University, Tallahassee, Florida

    Department of Psychology, Florida State University, Tallahassee, Florida
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  • Jourdan J. Pouliot
    Department of Psychology, University of Florida, Gainesville, Florida
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  • Author Footnotes
    1 GH and DEN contributed equally to this work.
    Greg Hajcak
    1 GH and DEN contributed equally to this work.
    Department of Biomedical Sciences, Florida State University, Tallahassee, Florida

    Department of Psychology, Florida State University, Tallahassee, Florida
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  • Author Footnotes
    1 GH and DEN contributed equally to this work.
    Derek Evan Nee
    Address correspondence to Derek Evan Nee, Ph.D.
    1 GH and DEN contributed equally to this work.
    Department of Psychology, Florida State University, Tallahassee, Florida
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  • Author Footnotes
    1 GH and DEN contributed equally to this work.
Open AccessPublished:March 06, 2022DOI:



      The reward circuit is important for motivation and learning, and dysregulations of the reward circuit are prominent in anhedonic depression. Noninvasive interventions that can selectively target the reward circuit may hold promise for the treatment of anhedonia.


      We tested a novel transcranial magnetic stimulation intervention for modulating the reward circuit. A total of 35 healthy individuals participated in a crossover controlled study targeting the reward circuit or a control site with intermittent theta burst stimulation (iTBS), an excitatory form of transcranial magnetic stimulation. Individual reward circuit targets were defined based upon functional magnetic resonance imaging functional connectivity with the ventral striatum, yielding targets in the rostromedial prefrontal cortex (rmPFC). Reward circuit function was assessed at baseline using functional magnetic resonance imaging, and reward circuit modulation was assessed using an event-related potential referred to as the reward positivity, which has been shown to reliably track reward sensitivity, as well as individual differences in depression and risk for depression.


      Relative to control iTBS, rmPFC iTBS enhanced the reward positivity. This effect was moderated by reward function, suggesting greater enhancements in individuals with lower reward function. This effect was also moderated by rmPFC–ventral striatum connectivity insofar as iTBS reached the rmPFC, suggesting that efficacy relies jointly on the strength of the rmPFC–ventral striatum pathway and ability of transcranial magnetic stimulation to target the rmPFC.


      These data suggest that the reward circuit can be modulated by rmPFC iTBS, and amenability to such modulations is related to measures of reward circuit function. This provides the first step toward a novel noninvasive treatment of disorders of the reward circuit.


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