Augmentation of Working Memory Training With Transcranial Direct Current Stimulation in Patients With Schizophrenia
Condition: Schizophrenia; Cognitive Deficits
MeSH terms: Schizophrenia; Cognition Disorders; Cognitive Dysfunction
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): active tDCS; sham tDCS; Adaptive working memory training
Intervention type(s): Device; Device; Behavioral
Intervention description(s): Using the NeuroConn Plus tDCS device, 2 mA anodal tDCS will be applied to the right dorsolateral prefrontal cortex (F4). 15 s fade in and fade out. Total stimulation time of 1365 s. Cathode over contralateral deltoid muscle.; Sham mode of the NeuroConn Plus tDCS device with 2 mA stimulation for 45 s at the beginning. Anode over right dorsolateral prefrontal cortex (F4), Cathode over contralateral deltoid muscle. After that, only continuous impedance checking is performed.; Adaptive spatial n-back training.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: transcranial direct current stimulation; schizophrenia; cognitive deficits; working memory training