Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and l-DOPA Administration

Abstract

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 ϭ 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 ϭ 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-andL-DOPA-inducedactivation,andϾ100neuronalreceptorgeneexpressionmapsbasedontranscriptionaldatafromtheAllenInstitute forBrainScience.Inlinewithaspecificactivationofthedopaminergicsystem,wefoundthatbothinterventionspredominantlyactivatedregions with high expression levels of the dopamine receptors D2 and D3.

Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating

“…For example, there has been great interest in using techniques such as transcranial direct current stimulation (tDCS) to modulate WM in both healthy and clinical populations (Plewnia, Schroeder, & Wolkenstein, 2015). Although tDCS has relatively direct effects on cortical excitability (Nitsche et al, 2003;Nitsche & Paulus, 2000), there is evidence it also indirectly modulates dopamine activity in BG (Fonteneau et al, 2018;Meyer et al, 2019;Tanaka et al, 2013). The present study thus raises the question whether tDCS acts on WM via a modulation of more prefrontalbased updating/maintenance, BG-based gating efficiency, or both.…”

Neurotherapeutics for Attention Deficit/Hyperactivity Disorder (ADHD): A Review

“…In fact, several studies in healthy populations and patient groups have shown longer-term cognitive effects of up to 1 year after stimulation[124,125] (Ruf et al, 2017, Katz et al, 2017. With high relevance to ADHD, positron emission tomography (PET) studies have shown that anodal frontal tDCS can release neurotransmitters such as dopamine[126][127][128] (Fonteneau et al, 2018;Meyer et al, 2019Borwick et al, 2020, which furthermore correlated with better attention[129] (Fukai et al, 2019), with some indirect evidence for effects on noradrenaline[130,131] (Adelhöfer et al, 2019; Mishima et al, 2019). Similarly, rTMS over prefrontal regions in animals and humans has been shown to induce changes to neurotransmitter systems including alterations to serotonin, striatal dopamine release and metabolite levels, as well as to the release and concentrations of striatal glutamate [132,133] (Moretti et al, 2020; Poh et al, 2019).…”

Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating

“…For example, there has been great interest in using techniques such as transcranial direct current stimulation (tDCS) to modulate WM in both healthy and clinical populations (Plewnia, Schroeder, & Wolkenstein, 2015). Although tDCS has relatively direct effects on cortical excitability (Nitsche et al, 2003;Nitsche & Paulus, 2000), there is evidence it also indirectly modulates dopamine activity in BG (Fonteneau et al, 2018;Meyer et al, 2019;Tanaka et al, 2013).…”