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, 3 (6), e268

Noninvasive Remote Activation of the Ventral Midbrain by Transcranial Direct Current Stimulation of Prefrontal Cortex


Noninvasive Remote Activation of the Ventral Midbrain by Transcranial Direct Current Stimulation of Prefrontal Cortex

V S Chib et al. Transl Psychiatry.


The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson's disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.


Figure 1
Figure 1
Experimental setup and behavioral results. (a) The experiment can be divided into three sessions. During the first session (before stimulation), participants made facial attractiveness judgements. During the second session, participants were stimulated with transcranial direct current stimulation (tDCS) for 15 min. During the final session (after stimulation) participants again made facial attractiveness judgments. The main and active sham groups were scanned with functional magnetic resonance imaging during the before and after stimulation sessions and were removed from the scanner during stimulation. (b) At the beginning of each trial of the behavioral task, participants were shown a face and made a rating of how attractive they found the face on a scale from 0–7; 0 being not attractive at all and 7 being very attractive. (c) Anodal stimulation of the ventromedial prefrontal cortex (VMPFC) and cathodal stimulation of the right dorsolateral prefrontal cortex (DLPFC) (main stimulation group) resulted in a significant increase in mean attractiveness ratings (*P<0.05). We performed a number of control conditions on separate groups of participants, none of which resulted in a significant increase in attractiveness ratings (For a complete description of the control results, see Supplementary Figure S1). To allow for a more focal stimulation of VMPFC in the main group, we administered tDCS with a small electrode over VMPFC and a large electrode over DLPFC. Error bars denote s.e.m. a.u., arbitrary units.
Figure 2
Figure 2
Functional magnetic resonance imaging results. (a) A common region of the ventromedial prefrontal cortex (VMPFC) in which activity correlated with attractiveness ratings before and after stimulation, in both the main group and the active sham group. (b) The effect size in the VMPFC increased with attractiveness ratings (lower—lower tertile; medium—middle tertile; high—upper tertile). (c) An interaction contrast between attractiveness ratings and stimulation revealed a significant increase in ventral midbrain activity in the main group as compared with the active sham group. (d) For the interaction contrast, average effect sizes representing the correlation between ventral midbrain activity and rating values before and after stimulation in the main and active sham groups. Ventral midbrain activity was positively correlated with attractiveness ratings after administration of transcranial direct current stimulation. All contrasts are displayed at P<0.005 uncorrected, and significant at P<0.05, small volume corrected. a.u., arbitrary units.
Figure 3
Figure 3
Functional connectivity. (a) In the main group as compared with the active sham group, the ventromedial prefrontal cortex (VMPFC) showed positive stimulation-related functional connectivity with a region of ventral midbrain. (b) For the psychophysiological interaction (PPI) contrast, average effect sizes representing the functional connectivity between seed activity in the VMPFC and the ventral midbrain. (c) In the main group, the more enhanced a participants' functional connectivity between these regions following stimulation, the larger their increase in attractiveness ratings following stimulation. One participant in the main group was removed from this analysis because her PPI parameter estimate constituted a statistical outlier (outside two s.ds. of the mean). (d) Diagram summarizing the results of the PPI analyses and illustrating the path through which VMPFC stimulation might enhance activity in the ventral midbrain. All contrasts are displayed at P<0.005 uncorrected, and significant at P<0.05, small volume corrected. a.u., arbitrary units.

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