Effects of tDCS-enhanced Cognitive Control Training on Depression

Study Overview
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Brief Summary
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Deficient cognitive control (CC) is one of the central characteristics of major depression (MD). Hypoactivation of the dorsolateral prefrontal cortex (dlPFC) has been linked with this deficit. Antidepressants and cognitive-behavioral therapies modify CC most-likely as a common mechanism of treatment. Transcranial direct current stimulation (tDCS) is a safe, simple and effective non-invasive method to modulate the cortical excitability. It has been shown, that the activity of the dlPFC can be modulated by transcranial direct current stimulation (tDCS) with polarity-dependent learning-phase specific effects on performance that, when combined with training, can outlast the stimulation. The goal of this randomized, sham-controlled, rater blind clinical trial is to investigate the effect of a tDCS-enhanced CC Training (CCT) on depressive symptom severity and compare the stimulation intensities 1mA, 2mA and sham tDCS. Overall, the study will include 57 participants (n = 19 per group). Each participant will complete 12 training sessions with online sham/ anodal tDCS. As a training task we will use an adaptive version of the paced auditory serial addition task (PASAT). In the PASAT, digits are presented auditive and participants have to add the current digit to the digit they heard before. In the adaptive version the interstimulus-intervals decrease (increase) when four consecutive trials are correct (incorrect). The PASAT is known to elicit frustration. Participants have to exert cognitive control over these emotions to complete the task successfully. Before, during and after the training symptom severity will be assessed. Baseline and post-training performance in the PASAT and in a transfer task (delayed working memory task, DWM) will be measured. To further explore variables that influence the effect of tDCS on depressive symptom severity we will measure brain activity (EEG, NIRS), heart rate, global functioning (GAF), emotion regulation strategies, self-esteem, mood ratings and subjective performance ratings before and after the training and collect genetic factors. Sustainability of the training effects will be measured at a follow-up visit (3 months later).

Official Title
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Effects of tDCS-enhanced Cognitive Control Training on Depression

Conditions
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Depression Unipolar

Intervention / Treatment
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* Other: 1mA tDCS
* Other: 2mA tDCS
* Behavioral: Cognitive control training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: current Major Depressive Episode right handedness Exclusion Criteria: history of seizures Intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed pregnancy use of mood stabilizers diagnosed bipolar disorder current substance abuse (nicotine excluded) current substance addiction (nicotine excluded) diagnosed psychotic diseases diagnosed anorexia nervosa diagnosed personality disorders: cluster A, antisocial personality disorder, borderline personality disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1mA anodal tDCS + cognitive control training<br>1 mA anodal tDCS will be administered to the left dlPFC (F3) for 23 mins during the performance of a cognitive control training. | Other: 1mA tDCS<br>* transcranial direct current stimulation with the intensity of 1mA<br>Behavioral: Cognitive control training<br>* cognitive control training with the PASAT<br>|
| Active Comparator: 2mA tDCS + cognitive control training<br>2 mA anodal tDCS will be administered to the left dlPFC (F3) for 23 mins during the performance of a cognitive control training. | Other: 2mA tDCS<br>* transcranial direct current stimulation with the intensity of 2mA<br>Behavioral: Cognitive control training<br>* cognitive control training with the PASAT<br>|
| Placebo Comparator: sham tDCS + cognitive control training<br>Sham tDCS (30 secs of tDCS) will be administered to the left dlPFC (F3) with 2mA at the beginning of a cognitive control training. | Behavioral: Cognitive control training<br>* cognitive control training with the PASAT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of MADRS scores | Change in Depressive Symptom severity will be measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) from Baseline session to the last stimulation session, scale range from 0 to 60 points, higher scores indicate a more severe depression | Assessment one week before training start (week -1, day -5 on average) and in the last training session (week 4, day 26) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BDI scores | Beck Depression Inventory | Assessment one week before training start (week -1, day -5 on average), in the post training session (week 5, day 31 on average) and at follow-up (week 17, day 110 on average) | 
| Number of correct trials in the PASAT | Performance in the PASAT. Number of correct trials. | Assessment one week before training start (week -1, day -5 on average), in the post training session (week 5, day 31 on average) and at follow-up (week 17, day 110 on average) | 
| RT in the DWM | Reaction time in the transfer task, a delayed working memory task (DWM) | Assessment one week before training start (week -1, day -5 on average), in the post training session (week 5, day 31 on average) and at follow-up (week 17, day 110 on average) | 
| Number of correct trials in the DWM | Number of correct trials in the transfer task, a delayed working memory task (DWM) | Assessment one week before training start (week -1, day -5 on average), in the post training session (week 5, day 31 on average) and at follow-up (week 17, day 110 on average) | 
| GAF score | Global Assessment of Functioning | Assessment one week before training start (week -1, day -5 on average) and in the post training session (week 5, day 31 on average) | 
| Delta Mood ratings | Mood changes (PANAS delta) through the PASAT performance: the positive and negative affective schedule (PANAS) will be conducted immediately before and after the PASAT performance. The change in mood ratings (PANAS delta = PANAS pre PASAT - PANAS post PASAT) will be the outcome measure. | Assessment one week before training start (week -1, day -5 on average), in the post training session (week 5, day 31 on average) and at follow-up (week 17, day 110 on average) | 
| Subjective performance ratings | Participants will be asked to rate their performance and overall cognitive abilities on a likert scale. | Assessment one week before training start (week -1, day -5 on average), in the post training session (week 5, day 31 on average) and at follow-up (week 17, day 110 on average) | 
| Electroencephalography (EEG) measures | EEG will be conducted to measure resting state oscillations and event related potentials stimulus locked to the presented feedback in the PASAT | Assessment one week before training start (week -1, day -5 on average) and in the post training session (week 5, day 31 on average) | 
| Prefrontal Brain activity (NIRS) | Functional Near Infrared Spectroscopy will be used to measure frontal brain activity: resting state and during task performance. | Assessment one week before training start (week -1, day -5 on average) and in the post training session (week 5, day 31 on average) | 
| Course of MADRS scores | Depressive Symptom severity will be measured with the Montgomery-Åsberg Depression Rating Scale | Assessment once a week during training (week 1, 2 and 3 at day 5, 12 and 19 respectively on average) and at the follow up visits (week 5 and 17, day 31 and 110 on average) | 
| Prefrontal Brain activity (NIRS) as a predictor | The investigators will analyze if frontal brain activity measured with NIRS during resting state and task performance can contribute to the prediction of the effectiveness of the tDCS training. | Assessment one week before training start (week -1, day -5 on average) | 
| Electroencephalography (EEG) measures as a predictor | The investigators will analyze if resting state oscillations and event related potentials stimulus locked to the presented feedback in the PASAT can contribute to the prediction of the effectiveness of the tDCS training. | Assessment one week before training start (week -1, day -5 on average) | 
| Genetic factors as predictors | The investigators will analyze if genetic factors involved in neuroplasticity (5-HTTLPR, BDNF, COMT) can contribute to the prediction of the effectiveness of the tDCS training. | Assessment one week before training start (week -1, day -5 on average) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, transcranial direct current stimulation (tDCS)