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Effects of unilateral tDCS over left prefrontal cortex on emotion regulation in depression: Evidence from concurrent functional magnetic resonance imaging.

ABSTRACT: Major depressive disorder (MDD) is the most common mood disorder and a primary cause of disability worldwide. MDD symptomatology entails disturbances in emotion regulation, namely one's ability to modify the intensity and duration of emotional reactions towards affective events. Transcranial direct current stimulation (tDCS) has emerged as a promising treatment for MDD. Yet, positive tDCS outcomes vary across studies, while the precise effects of the procedure for cortical excitability in MDD during emotion regulation remain largely unexplored. Here, we leveraged functional magnetic resonance imaging (fMRI)-compatible tDCS technology to examine the functional consequences of a unilateral anodal tDCS montage at 1.5 mA over left PFC (area F3; with the reference electrode over an extracephalic location) for brain activity during an emotion-regulation task in MDD patients and age-matched healthy control subjects. Our results revealed down-regulation of negative emotions in the right amygdala and visual cortex of healthy controls but not MDD patients prior to stimulation, the degree of which correlated with the magnitude of the participants' reappraisal scores. TDCS did not elicit significant changes in neural activation patterns for either group. These findings contribute to the literature on the pathophysiology of MDD by showing that a key disturbance in the disorder entails the ineffective down-regulation of activity not only within the amygdala, but also within visual cortical areas in response to negative information. Further, these results suggest that relative to bifrontal tDCS montages, unilateral stimulation of moderate intensity over left PFC may not be sufficient to elicit therapeutic effects for MDD.

SUBMITTER: van Dam WO

PROVIDER: S-EPMC8572372 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Anodal transcranial direct current stimulation (tDCS), applied over the left dorsolateral prefrontal cortex (lDLPFC), can produce significant effects on working memory (WM) performance and associated neurophysiological activity. However, results from previous studies are inconsistent and occasionally contradictory. This inconsistency may be attributed to methodological and individual differences during experiments. This study therefore investigated two hypotheses: (1) A multichannel-optimized montage was expected to be more effective than a classical bipolar montage, because of increased focality. (2) The subjects were expected to benefit differently from the stimulation depending on their initial task performance. In a sham-controlled crossover study, 24 healthy participants received bipolar, multichannel, and sham stimulation for 20 min in randomized order, targeting the lDLPFC while performing a 2-back WM task. After stimulation, electroencephalography (EEG) was recorded at rest and during 2-back and nontarget continuous performance task (CPT) performance. Bipolar and multichannel stimulations were both well tolerated and effectively blinded. We found no effect of stimulation on behavioral performance or neuronal oscillations comparing the classical bipolar or multichannel montage with sham stimulation. We did, however, find an interaction between stimulation and initial task performance. For multichannel stimulation, initially low-performing participants tended to improve their WM performance while initially high-performing participants tended to worsen their performance compared to sham stimulation. Both tDCS montages induced changes in neural oscillatory power, which correlated with baseline performance. The worse the participants' initial WM performance was, the more task-related theta power was induced by multichannel and bipolar stimulation. The same effect was observed for alpha power in the nontarget task following multichannel stimulation. Notably, we were not able to show a superiority of multichannel stimulation compared to bipolar stimulation. Still, comparing both montages with sham stimulation, multichannel stimulation led to stronger effects than bipolar stimulation. The current study highlights the importance of investigating different parameters with potential influence on tDCS effects in combination. Our results demonstrate how individual differences in cognitive performance and electrode montages influence effects of tDCS on neuropsychological performance. These findings support the idea of an individualized and optimized stimulation setting, potentially leading to increased tDCS effects.

Project description:Emotion regulation is critically disrupted in depression, and the use of paradigms that tap into these processes may uncover essential changes in neurobiology during treatment. In addition, because neuroimaging outcome studies of depression commonly use only baseline and end-point data-which are more prone to week-to-week noise in symptomatology-we sought to use all data points over the course of a 6-month trial.To examine changes in neurobiology resulting from successful treatment.Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from 1 of 2 antidepressant treatments during a 6-month trial. Twenty-one patients with major depressive disorder and without other Axis I or Axis II diagnoses were scanned before treatment and 2 and 6 months into treatment at the university's functional magnetic resonance imaging facility.Venlafaxine hydrochloride extended release (with doses of up to 300 mg) or fluoxetine hydrochloride (with doses of up to 80 mg).Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm, as well as regular assessments of symptom severity using the Hamilton Depression Rating Scale. For use of all data points, slope trajectories were calculated for rate of change in depression severity and for rate of change in neural engagement.The depressed individuals who showed the steepest decrease in depression severity over the 6-month period were the same individuals who showed the most rapid increases in activity in Brodmann area 10 and the right dorsolateral prefrontal cortex activity when regulating negative affect over the same time frame. This relationship was more robust when using only the baseline and end-point data.Changes in prefrontal cortex engagement when regulating negative affect correlate with changes in depression severity over 6 months. These results are buttressed by calculating these statistics, which are more reliable and robust to week-to-week variation than are difference scores.

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Effects of unilateral tDCS over left prefrontal cortex on emotion regulation in depression: Evidence from concurrent functional magnetic resonance imaging.

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