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The impact of targeted cathodal transcranial direct current stimulation on reward circuitry and affect in Bipolar Disorder


Bipolar Disorder is costly and debilitating, and many treatments have side effects. Transcranial Direct Current Stimulation (tDCS) is a well-tolerated neuromodulation technique that may be a useful treatment for Bipolar Disorder if targeted to neural regions implicated in the disorder. One potential region is the left ventrolateral prefrontal cortex (vlPFC), which shows abnormally elevated activity during reward expectancy in individuals with Bipolar Disorder. We used a counterbalanced repeated measures design to assess the impact of cathodal (inhibitory) tDCS over the left vlPFC on reward circuitry activity, functional connectivity, and affect in adults with Bipolar Disorder, as a step toward developing novel interventions for individuals with the disorder. −1mA cathodal tDCS was administered over the left vlPFC versus a control region, left somatosensory cortex, concurrently with neuroimaging. Affect was assessed pre and post scan in remitted Bipolar Disorder (n = 27) and age/gender-matched healthy (n = 31) adults. Relative to cathodal tDCS over the left somatosensory cortex, cathodal tDCS over the left vlPFC lowered reward expectancy-related left ventral striatal activity (F(1,51) = 9.61, p = 0.003), and was associated with lower negative affect post scan, controlling for pre-scan negative affect, (F(1,49) = 5.57, p = 0.02) in all participants. Acute cathodal tDCS over the left vlPFC relative to the left somatosensory cortex reduces reward expectancy-related activity and negative affect post tDCS. Build on these findings, future studies can determine whether chronic cathodal tDCS over the left vlPFC has sustained effects on mood in individuals with Bipolar Disorder, to guide new treatment developments for the disorder.

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Data availability

Individual data along with a data dictionary defining each field are available at the NIMH data archive repository, updates made every 6 months to study end, Following data use certification scientists can access these data.


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We would like to acknowledge the participants for their contributions to this study.


National Institute of Mental Health (MLP, HWC, R21MH108421), Pittsburgh Foundation (MLP). This work was supported by the National Institute of Mental Health (MLP and HWC, grant number R21 MH108421) and the Pittsburgh Foundation (MLP).

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MAB, HWC, and MLP completed the literature search; MAB, BAC, EKE, and MLP created the figures; HWC, BDG, and MLP designed the study; HWC, SG, RS collected the data; MAB, HWC, and RS performed data analysis; MAB, HWC, BAC, BDG, and MLP data interpretation; MAB, HWC, BAC, BDG, and MLP writing the manuscript.

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Correspondence to M. A. Bertocci.

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The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

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Bertocci, M.A., Chase, H.W., Graur, S. et al. The impact of targeted cathodal transcranial direct current stimulation on reward circuitry and affect in Bipolar Disorder. Mol Psychiatry 26, 4137–4145 (2021).

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