Augmentation of Working Memory Training With Transcranial Direct Current Stimulation in Patients With Schizophrenia

Cognitive impairment is a core symptom of schizophrenia and is in a large part responsible for the poor psychosocial outcome of the disorder. The use of non-invasive brain stimulation techniques as a therapeutic option is just commencing for neuropsychiatric patients. Concerning healthy subjects the investigators have previously shown that anodal tDCS to the right dorsolateral prefrontal cortex (DLPFC) parallel to working memory training can sustainingly enhance performance in a spatial n-back task. Additionally, first translational experiments regarding the use of anodal tDCS to improve working memory (WM) in patients with schizophrenia rendered promising results.

On those grounds, the investigators now test the hypothesis that anodal tDCS to the right DLPFC can augment working memory training in patients with schizophrenia.

Cognitive impairments are a core and debilitating feature of schizophrenia, but effective treatment options are scarce. These deficits develop early in the progression of the disorder, frequently persist throughout lifespan and are considered a possible endophenotype of the disorder. Everyday functioning, work ability and social integration are substantially affected. A proper treatment of cognitive symptoms would probably reduce individual consequences like unemployment or early retirement and alleviate the resulting cost for our societies.

Working memory, the ability to temporally maintain and manipulate information, is critically relevant as interface between sensory input and the attainment of behavioral goals. It plays a pivotal role in executive functioning and shares overlapping cognitive processes with social cognition. The characteristic WM deficits in patients with schizophrenia are associated with aberrant dlPFC activation and connectivity, rendering this brain region a prime target for treatment interventions. Cognitive and specifically WM training have been proven effective to change prefrontal activation pattern resulting in improved performance. However, the effect sizes are moderate and the expenditure is high, so that training paradigms are not consistently implemented in regular treatment.

A possible way to increase the efficacy of WM training is the augmentation with non-invasive brain stimulation techniques. Transcranial direct current stimulation modulates neuronal membrane potentials and is regulating cortical excitability depending on polarity. Specifically, anodal stimulation can induce long-lasting cortical excitability elevations.

First translational studies exploring the effectiveness of tDCS to enhance cognition in patients with schizophrenia yielded promising results.To extend this knowledge, the investigators examine the effect of a tDCS augmented WM training (2 mA to the right dlPFC) in patients with schizophrenia. The WM training consists of two weeks (10 daily sessions) of 20 minute adaptive spatial n-back training, complemented by a Pre/Post session and two follow-up measurements after 4 and 12 weeks. In the two arms parallel study design, patients will be randomized either to the group receiving active anodal tDCS during the training or to the other group receiving sham stimulation during the training. The investigators hypothesize an enhancement of WM performance by anodal tDCS and investigate possible transfer effects in other cognitive tasks, psychopathology, quality of life and subjective cognitive capabilities. The investigators will further analyze the influence of the genetic make-up, neurophysiological signatures and other demographic and cognitive variables on the stimulation effect.

Eligibility Criteria:
Inclusion Criteria:

* diagnosis of schizophrenia or schizoaffective disorder
* age 18-60 years
* Ability to give informed consent
* right handedness
* stable antipsychotic medication one week prior to the experiment and during the training sessions

Exclusion Criteria:

* epilepsy
* metal implants near the head
* pregnancy
* use of antiepileptics
* use of benzodiazepines \> 1 mg lorazepam equivalent
* current substance abuse (excluding tabacco)
* missing consent of the legal representative, if existing