Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and l-DOPA Administration
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Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n = 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (l-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n = 22) and compared the results between both studies. We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS- and l-DOPA-induced activation, and >100 neuronal receptor gene expression maps based on transcriptional data from the Allen Institute for Brain Science. In line with a specific activation of the dopaminergic system, we found that both interventions predominantly activated regions with high expression levels of the dopamine receptors D2 and D3. SIGNIFICANCE STATEMENT Studies in animals and humans provide evidence that transcranial direct current stimulation (tDCS) allows a manipulation of the dopaminergic system. Based on these findings, we used fMRI to assess changes in spontaneous neural activity strength in the human dopaminergic system after prefrontal tDCS compared with the administration of the dopamine precursor and standard anti-Parkinson drug levodopa (l-DOPA). We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. Using whole-brain transcriptional data of >100 neuronal receptor genes, we found that both interventions specifically activated regions with high expression levels of the dopamine receptors D2 and D3.
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There is evidence that transcranial direct current stimulation also indirectly modulates dopamine activity in the basal ganglia.
“there is evidence it also indirectly modulates dopamine activity in BG (Fonteneau et al., 2018; Meyer et al., 2019; Tanaka et al., 2013).”
From Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating (2020) · cites this paper as Meyer et al., 2019
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Desikan, R. S., Ségonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., Buckner, R. L., Dale, A. M., Maguire, R. P., Hyman, B. T., et al. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.01.021 · Cited by 13,324 · see citing works
Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.10.018 · Cited by 7,429 · see citing works
The organization of the human cerebellum estimated by intrinsic functional connectivity
Buckner, R. L., Krienen, F. M., Castellanos, A., Diaz, J. C., & Yeo, B. T. T. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00339.2011 · Cited by 7,304 · see citing works
Nitsche, M. A., & Paulus, W. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00633.x · Cited by 5,656 · see citing works
Consistent resting-state networks across healthy subjects
Damoiseaux, J. S., Rombouts, S. A. R. B., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., & Beckmann, C. F. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601417103 · Cited by 4,326 · see citing works
The reward circuit: linking primate anatomy and human imaging
Haber, S. N., & Knutson, B. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.129 · Cited by 3,718 · see citing works
Large-scale automated synthesis of human functional neuroimaging data.
Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C., & Wager, T. D. (2011) · Nature Methods · doi:10.1038/nmeth.1635 · Cited by 3,686 · cited 1× · see citing works
“Averaged and smoothed (6 mm hard sphere) AIB gene expression maps were available from the Neurosynth database (Yarkoni et al., 2011).”
MethodAn anatomically comprehensive atlas of the adult human brain transcriptome
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., et al. (2012) · Nature · doi:10.1038/nature11405 · Cited by 3,083 · see citing works
The Neural Basis of Addiction: A Pathology of Motivation and Choice
Kalivas, P. W., & Volkow, N. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.8.1403 · Cited by 2,757 · see citing works
Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI
Yu-Feng, Z., Yong, H., Chao-Zhe, Z., Qing-Jiu, C., Man-Qiu, S., Meng, L., Li-Xia, T., Tian-Zi, J., & Yu-Feng, W. (2007) · Brain and Development · doi:10.1016/j.braindev.2006.07.002 · Cited by 2,660 · see citing works
Zou, Q., Zhu, C.-Z., Yang, Y., Zuo, X., Long, X., Cao, Q., Wang, Y., & Zang, Y. (2008) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.04.012 · Cited by 2,169 · see citing works
Brunoni, A. R., Nitsche, M. A., Bolognini, N., Bikson, M., Wagner, T., Merabet, L., Edwards, D. J., Valero-Cabre, A., Rotenberg, A., Pascual-Leone, A., et al. (2012) · Brain stimulation · doi:10.1016/j.brs.2011.03.002 · Cited by 1,445 · see citing works
Thielscher, A., Antunes, A., & Saturnino, G. B. (2015) · 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2015.7318340 · Cited by 942 · see citing works
Frazier, J. A., Chiu, S., Breeze, J. L., Makris, N., LANGE, N. D., Kennedy, D. N., Herbert, M. R., Bent, E. K., Koneru, V. K., Dieterich, M., et al. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.7.1256 · Cited by 795 · see citing works
The organization of the human striatum estimated by intrinsic functional connectivity
Choi, E. Y., Yeo, B. T. T., & Buckner, R. L. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00270.2012 · Cited by 746 · see citing works
Decreased volume of left and total anterior insular lobule in schizophrenia
Makris, N., Goldstein, J. M., Kennedy, D. N., Hodge, S. M., Caviness, V. S., Faraone, S. V., Tsuang, M. T., & Seidman, L. J. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2005.11.020 · Cited by 743 · see citing works
Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects
Rahman, A., Reato, D., Arlotti, M., Gasca, F., Datta, A., Parra, L. C., & Bikson, M. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2012.247171 · Cited by 560 · see citing works
Pathophysiology of Parkinsonism
Galván, A., & Wichmann, T. (2008) · Clinical Neurophysiology · doi:10.1016/j.clinph.2008.03.017 · Cited by 551 · see citing works
Hypothalamic Abnormalities in Schizophrenia: Sex Effects and Genetic Vulnerability
Goldstein, J. M., Seidman, L. J., Makris, N., Ahern, T., O’Brien, L. M., Caviness, V. S., Kennedy, D. N., Faraone, S. V., & Tsuang, M. T. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.027 · Cited by 542 · see citing works
Absolute Coding of Stimulus Novelty in the Human Substantia Nigra/VTA
Bunzeck, N., & Düzel, E. (2006) · Neuron · doi:10.1016/j.neuron.2006.06.021 · Cited by 503 · see citing works
Polanía, R., Paulus, W., & Nitsche, M. A. (2012) · Human Brain Mapping · doi:10.1002/hbm.21380 · Cited by 423 · see citing works
Transcranial direct current stimulation in the treatment of major depression: a meta-analysis
Kalu, U. G., Sexton, C. E., Loo, C. K. A., & Ebmeier, K. P. (2012) · Psychological Medicine · doi:10.1017/s0033291711003059 · Cited by 298 · see citing works
Appleby, B. S., Duggan, P. S., Regenberg, A. C., & Rabins, P. V. (2007) · Movement Disorders · doi:10.1002/mds.21551 · Cited by 290 · see citing works
On the importance of electrode parameters for shaping electric field patterns generated by tDCS
Saturnino, G. B., Antunes, A., & Thielscher, A. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.06.067 · Cited by 263 · see citing works
Valdes-Hernandez, P. A. (2011) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2011.00026 · Cited by 257 · see citing works
PET evaluation of the dopamine system of the human brain.
Volkow, N. D., Fowler, J., Sj, G., Logan, J., Wang, G., Ding, Y., & Dewey, S. L. (1996) · PubMed · Cited by 250 · see citing works
Organization of striatopallidal, striatonigral, and nigrostriatal projections in the macaque
Hedreen, J. C., & Delong, M. R. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903040406 · Cited by 245 · see citing works
Functional imaging of the human dopaminergic midbrain
Düzel, E., Bunzeck, N., Guitart-Masip, M., Wittmann, B., Schott, B. H., & Tobler, P. N. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.02.005 · Cited by 216 · see citing works
Bikson, M., Brunoni, A. R., Charvet, L. E., Clark, V. P., Cohen, L. G., Deng, Z., Dmochowski, J., Edwards, D. J., Frӧhlich, F., Kappenman, E. S., et al. (2017) · Brain stimulation · doi:10.1016/j.brs.2017.12.008 · Cited by 215 · see citing works
Treatment of Parkinson's disease: levodopa as the first choice
Katzenschlager, R., & Lees, A. J. (2002) · Journal of Neurology · doi:10.1007/s00415-002-1204-4 · Cited by 209 · see citing works
Fonteneau, C., Redoute, J., Haesebaert, F., Le Bars, D., Costes, N., Suaud-Chagny, M.-F., & Brunelin, J. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy093 · Cited by 198 · see citing works
Haaker, J., Gaburro, S., Sah, A., Gartmann, N., Lonsdorf, T. B., Meier, K., Singewald, N., Pape, H.-C., Morellini, F., & Kalisch, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303061110 · Cited by 166 · see citing works
Self-citationDopamine-Dependent Architecture of Cortico-Subcortical Network Connectivity
Cole, D. M., Oei, N. Y. L., Soeter, R. P., Both, S., van Gerven, J., Rombouts, S. A. R. B., & Beckmann, C. F. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs136 · Cited by 164 · see citing works
Prefrontal Cortical Projections to the Midbrain in Primates: Evidence for a Sparse Connection
Frankle, W., Laruelle, M., & Haber, S. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300990 · Cited by 141 · see citing works
Energetics of neuronal signaling and fMRI activity
Maandag, N. J. G., Coman, D., Sanganahalli, B. G., Hermán, P., Smith, A. J., Blumenfeld, H., Shulman, R. G., & Hyder, F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709515104 · Cited by 131 · see citing works
Altered Spontaneous Brain Activity in Schizophrenia: A Meta-Analysis and a Large-Sample Study
Xu, Y., Zhuo, C., Qin, W., Zhu, J., & Yu, C. (2015) · BioMed Research International · doi:10.1155/2015/204628 · Cited by 128 · see citing works
Chib, V. S., Yun, K., Takahashi, H., & Shimojo, S. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.44 · Cited by 128 · see citing works
Hone-Blanchet, A., Edden, R. A., & Fecteau, S. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.11.008 · Cited by 110 · see citing works
Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves
Schwalm, M., Schmid, F., Wachsmuth, L., Backhaus, H., Kronfeld, A., Aedo-Jury, F., Prouvot, P.-H., Fois, C., Albers, F., van Alst, T. M., et al. (2017) · eLife · doi:10.7554/elife.27602 · Cited by 101 · see citing works
Self-citationYan, C., Rincón‐Cortés, M., Raineki, C., Sarro, E. C., Colcombe, S. J., Guilfoyle, D. N., Yang, Z., Gerum, S. V., Biswal, B. B., Milham, M. P., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.276 · Cited by 96 · see citing works
The Dopamine System and the Pathophysiology of Schizophrenia: A Basic Science Perspective
Goto, Y., & Grace, A. A. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(06)78002-3 · Cited by 94 · see citing works
Striatal Dopamine Metabolism in Monoamine Oxidase B‐Deficient Mice : A Brain Dialysis Study
Fornai, F., Chen, K., Giorgi, F. S., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0732434.x · Cited by 82 · see citing works
A rat model for measuring the effectiveness of transcranial direct current stimulation using fMRI
Takano, Y., Yokawa, T., Masuda, A., Niimi, J., Tanaka, S., & Hironaka, N. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.01.004 · Cited by 79 · see citing works
Zhou, Y., Yu, F. F., Duong, T. Q., & Initiative, A. D. N. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24550 · Cited by 76 · see citing works
Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia
Fryer, S. L., Roach, B. J., Ford, J. M., Turner, J. A., van Erp, T. G. M., Voyvodic, J. T., Preda, A., Belger, A., Bustillo, J., OʼLeary, D. S., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.119 · Cited by 72 · see citing works
Frequency-specific alternations in the amplitude of low-frequency fluctuations in chronic tinnitus
Chen, Y., Xia, W., Luo, B., Muthaiah, V. P. K., Xiong, Z., Zhang, J., Wang, J., Salvi, R., & Teng, G. (2015) · Frontiers in Neural Circuits · doi:10.3389/fncir.2015.00067 · Cited by 56 · see citing works
Liu, C., Liu, C., Zhang, J., Yuan, Z., Tang, L., Tie, C.-L., Fan, J., & Liu, Q. (2016) · Brain Research · doi:10.1016/j.brainres.2016.07.024 · Cited by 55 · see citing works
Lu, C., Wei, Y., Hu, R., Wang, Y., Li, K., & Xiaoli Li, A. (2015) · Neuromodulation Technology at the Neural Interface · doi:10.1111/ner.12302 · Cited by 53 · see citing works
Leffa, D. T., de Souza, A., Scarabelot, V. L., Medeiros, L. F., de Oliveira, C., Grevet, E. H., Caumo, W., de Souza, D. O., Rohde, L. A. P., & Torres, I. L. S. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.11.012 · Cited by 50 · see citing works
Resting state signatures of domain and demand-specific working memory performance
van Dam, W. O., Decker, S. L., Durbin, J. S., Vendemia, J. M. C., & Desai, R. H. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.05.017 · Cited by 34 · see citing works
Foster, H. D., & Hoffer, A. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00318-9 · Cited by 33 · see citing works
Jongkees, B. J. (2020) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-020-00783-8 · Cited by 29 · see citing works
LEVODOPA AND 3-O-METHYLDOPA IN CEREBROSPINAL FLUID AFTER LEVODOPA-CARBIDOPA ASSOCIATION
Benetello, P., Furlanut, M., Fortunato, M. G., et al. (1997) · Pharmacological Research · doi:10.1006/phrs.1997.0145 · Cited by 29 · see citing works
Flodin, P., Gospic, K. A. M., Petrović, P., & Fransson, P. (2012) · Brain Connectivity · doi:10.1089/brain.2012.0081 · Cited by 22 · see citing works
Sanchez, M. G. D. B., Morissette, M., & Paolo, T. D. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.06.012 · Cited by 21 · see citing works
Austin, A., Jiga‐Boy, G. M., Rea, S., Newstead, S., Roderick, S., Davis, N. J., Clement, R. M., & Boy, F. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2016.00315 · Cited by 21 · see citing works
Cha, J., Kim, S. T., Jung, W. B., et al. (2016) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2016.04.004 · Cited by 21 · see citing works
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- Hilal-Dandan R, Brunton L (2014) Goodman and Gilman manual of phar- macology and therapeutics, Vol 2. Auflage. New York: McGraw-Hill.
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Jongkees, B. J. (2020) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-020-00783-8 · Cited by 29 · see citing works
- Authors
- Meyer, B., Mann, C., Götz, M., Gerlicher, A., Saase, V., Yuen, K. S. L., Aedo-Jury, F., Gonzalez-Escamilla, G., Stroh, A., & Kalisch, R.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Goethe University Frankfurt (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-05-01
- Volume
- 39
- Issue
- 27
- Pages
- 5326-5335
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6607760
- OpenAlex
- W2943278155
- Cited by
- 43
- References
- 57
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (subproject C01, CRC--1193)
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- transcranial direct current stimulation, levodopa, dopaminergic dysfunction, prefrontal cortex, spontaneous neuronal activity, fractional amplitude of low-frequency fluctuations, Parkinson's disease
- MeSH terms
- Adult, Animals, Brain Mapping, Corpus Striatum, Dopamine, Female, Humans, Levodopa, Magnetic Resonance Imaging, Male, Neurons, Rats, Inbred Lew, Single-Blind Method, Prefrontal Cortex, Receptors, Dopamine D1, Receptors, Dopamine D2, Young Adult, Transcranial Direct Current Stimulation
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