Effects of tDCS-enhanced Cognitive Control Training on Depression

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).

Study Overview

• Status: Unknown
• Conditions: Depression Unipolar
• Intervention / Treatment: Other: 1mA tDCS; Behavioral: Cognitive control training; Other: 2mA tDCS

• Study Type: Interventional
• Enrollment (Anticipated): 57
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Tubingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • University Hospital Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: German Federal Ministry of Education and Research; Universität Tübingen

Publications and helpful links

General Publications

• Sommer A, Fallgatter AJ, Plewnia C. Investigating mechanisms of cognitive control training: neural signatures of PASAT performance in depressed patients. J Neural Transm (Vienna). 2022 Jun;129(5-6):649-659. doi: 10.1007/s00702-021-02444-7. Epub 2021 Nov 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: May 7, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 15, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Depression; transcranial direct current stimulation (tDCS)
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 01EE1403D-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No