Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex
Open accessAbstract
Noninvasive neuromodulatory techniques such as transcranial direct current stimulation (tDCS) are attracting increasing interest as potential therapies for a wide range of neurological and psychiatric conditions. When targeted to the dorsolateral prefrontal cortex (DLPFC), anodal, facilitatory tDCS has been shown to improve symptoms in a range of domains including working memory, mood, and pain perception (Boggio et al., 2008a; Dockery et al., 2009; Kalu et al., 2012). However, the mechanisms underlying these promising behavioral effects are not well understood. Here, we investigated brain perfusion changes, as assessed using whole-brain arterial spin labeling (ASL), during tDCS applied to the left DLPFC in healthy humans. We demonstrated increased perfusion in regions closely anatomically connected to the DLPFC during anodal tDCS in conjunction with a decreased functional coupling between the left DLPFC and the thalami bilaterally. Despite highly similar effects on cortical excitability during and after stimulation (Nitsche and Paulus, 2000, 2001), cortical perfusion changes were markedly different during these two time periods, with widespread decreases in cortical perfusion being demonstrated after both anodal and cathodal tDCS compared to the period during stimulation. These findings may at least partially explain the different effects on behavior in these time periods described previously in the motor system (Stagg et al., 2011). In addition, the data presented here provide mechanistic explanations for the behavioral effects of anodal tDCS applied to the left DLPFC in terms of modulating functional connectivity between the DLPFC and thalami, as has been hypothesized previously (Lorenz et al., 2003).
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Changes in cortical excitability and improvements in behavior induced by tDCS have been reported to persist long after the stimulation period.
“Importantly, changes in cortical excitability and improvements in behavior induced by tDCS have been reported to persist long after the stimulation period [25–28].”
From Primary outcome from the augmenting cognitive training in older adults study (ACT): A tDCS and cognitive training randomized clinical trial (2023) · cites this paper as [26]
The Introduction reports behavioral aftereffects lasting at least three months, supporting the claim that behavioral effects can persist well beyond stimulation. The Discussion and “Brain perfusion changes after stimulation” section report cortical-excitability changes in the immediate poststimulation period, but do not establish that those changes persist long after stimulation. (LLM, conf=0.83)
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“Interestingly, Stagg et al. (2013) focused on brain perfusion changes during left DLPFC tDCS (using wholebrain arterial spin labeling) and found decreased functional connectivity between the left DLPFC and the bilateral thalami after tDCS, possibly offering a mechanistic explanation for the…”
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- Authors
- Stagg, C. J., Lin, R. L., Mezue, M., Segerdahl, A., Kong, Y., Xie, J., & Tracey, I.
- Affiliations
- John Radcliffe Hospital (GB)
- University of Oxford (GB)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-07-10
- Volume
- 33
- Issue
- 28
- Pages
- 11425-11431
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3724554
- OpenAlex
- W2077726842
- Cited by
- 279
- References
- 41
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 20 · 2022: 18 · 2021: 22 · 2020: 18 · 2019: 28 · 2018: 35 · 2017: 33 · 2016: 29 · 2015: 18 · 2014: 16 · 2013: 7
- FWCI
- 13.10
- 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)
- Funders
- Wellcome Trust (83259)
- Marshall Aid Commemoration Commission
- National Institute for Health and Care Research
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- transcranial direct current stimulation, dorsolateral prefrontal cortex, cerebral perfusion, arterial spin labeling, functional connectivity, thalamus, anodal stimulation, cathodal stimulation, cortical excitability, neuromodulation mechanisms
- MeSH terms
- Adult, Cerebrovascular Circulation, Electric Stimulation, Female, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Prefrontal Cortex, Transcranial Magnetic Stimulation, Young Adult
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