Transcranial Weak Current Stimulation Treatments for Working Memory Dysfunction in Schizophrenia
Condition: Schizophrenia; Schizo Affective Disorder
MeSH terms: Schizophrenia; Mood Disorders; Psychotic Disorders
Study type: Interventional

Summary: 
      For the present study, Investigators will examine the efficacy of active prefrontal anodal
      tDCS versus placebo (sham) interventions to treat WM dysfunction in schizophrenia.

      Investigators selected the prefrontal stimulation modality that proved most effective in
      enhancing high-load WM performance in single dose stimulation in healthy participants . The
      study employs a multi-stimulation approach, with 2 sessions per day for 5 consecutive days in
      the active treatment group (n=15) compared to a group that receives only sham stimulation
      (n=15). This preliminary approach is based upon findings of a recent study applying cathodal
      tDCS stimulation over left temporoparietal cortex (with left prefrontal anodal stimulation)
      for the treatment of persistent auditory hallucinations in schizophrenia. In a a recent study
      clinical benefits were maintained for at least 3 months following stimulation. In the present
      study, in addition to clinical outcome, researchers will evaluate whether similar improvement
      can be obtained with WM, EEG activity, and functional outcome (e.g., discharged from
      hospitalization following significant improvement or remission).
    

Detailed description: 
      In a recent tDCS study investigators conducted with 41 healthy participants, researchers
      administered a single blind tDCS protocol that included an active unilateral DLPFC condition
      (2 mA for 15 minutes, anode over the left DLPFC (midpoint between F3-AF3) and cathode over
      the dorsal area of the superior parietal cortex (at Cz) versus a sham condition to
      investigate changes in online working memory function. Our preliminary tDCS results indicated
      gender-dependent (left enhancement in males versus females) high-load WM enhancement during
      active prefrontal stimulation versus sham stimulation. The observed prefrontal tDCS enhancing
      effect on high-load WM function indicated that left DLPFC tDCS could be implemented with SZP
      who suffer from inefficient left DLPFC engagement during medium to high-load WM maintenance.

      Given the lack of effective treatments for attenuating WM impairments and the importance of
      these impairments to functional outcome in schizophrenia, tDCS based cognitive-enhancing
      approaches may become an important new treatment method, which will consequently improve
      treatment and functional outcome in schizophrenia patients.The innovative nature of the
      study's proposed research project is that it promotes non-invasive focal (left prefrontal
      cortex) neuromodulation to improve cognitive functioning as well as illness severity in SZP.
      Most importantly, unlike antipsychotic medication that affects the entire brain circuitry and
      produces undesired side effects (e.g., extrapyramidal effects, weight gain, hyperlipidemia,
      and sexual dysfunction), the current non-invasive focal intervention is aimed at reducing
      specific prefrontal dysfunctions in schizophrenia by specific targeting of prefrontal
      electrophysiological disturbances (e.g., frontal theta synchrony) within regions known to
      regulate behavior and the consolidation of goal-directed information.

      Hypothesis Essentially, currently proposed tDCS treatment is hypothesized to improve working
      memory functioning and reduce symptom severity in people diagnosed with schizophrenia versus
      sham prefrontal tDCS (placebo).The theoretical premise for our prediction implies that
      effective inhibition of excessive dopaminergic mesolimbic activity (impaired in
      schizophrenia), could result from excitatory left-prefrontal tDCS, which has been shown to
      increase executive regulation of behavior in healthy individuals and people diagnosed with
      schizophrenia .

      Research plan outline For the present study, investigators will examine the efficacy of
      active prefrontal anodal tDCS versus placebo (sham) interventions to treat WM dysfunction in
      schizophrenia. Investigatros selected the prefrontal stimulation modality that proved most
      effective in enhancing high-load WM performance in single dose stimulation in healthy
      participants. A multi-stimulation approach is implemnted, with 2 sessions per day for 5
      consecutive days in the active treatment group (n=15) compared to a group that receives only
      sham stimulation (n=15). This preliminary approach is based upon findings of a recent study
      applying cathodal tDCS stimulation over left temporoparietal cortex (with left prefrontal
      anodal stimulation) for the treatment of persistent auditory hallucinations in schizophrenia
      . In a recent study clinical benefits were maintained for at least 3 months following
      stimulation. In the present study, in addition to clinical outcome, we will evaluate whether
      similar improvement can be obtained with WM, EEG activity, and functional outcome (e.g.,
      discharged from hospitalization following significant improvement or remission).

      In regards to efficacy, since WM is considered a core cognitive deficit in schizophrenia,
      investigators will monitor working memory, psychosis severity and global outcome, at
      baseline, immediately following tDCS intervention, and at 1, 4, and 8, 12, and 16 week
      intervals, following the termination the five-day treatment. Importantly, in order to show
      external validity of our efficacy analysis we will examine functional outcome (level of
      independence), six months after the termination of the tDCS intervention.

      Finally, since DLPFC stimulation may contribute to long-term electroencephalography (EEG)
      theta- rhythm functional connectivity, associated with increased large-scale theta
      synchronization, WM function, and episodic memory formation, investigatros will examine
      effects of tDCS on prefrontal versus whole-brain EEG theta activity obtained during a WM task
      (see verbal n-Back task), using event-related potential (ERP) and event-related spectral
      power (ERSP) techniques similar to those in used in recent EEG studies in schizphrenia
      patients. Demonstrating significant functional-connectivity EEG differences in responders
      versus non-responders from baseline to post-intervention measurements will significantly
      increase the validity of our proposed prefrontal pathophysiological mechanism as
      significantly impacting psychosis severity and clinical outcome in schizophrenia.
    

Intervention name(s): transcranial direct current stimulation (tDCS)
Intervention type(s): Device
Intervention description(s): 10 sessions of Anodal tDCS of the dorsolateral prefrontal cortex over a period of 5 consecutive days (two session a day). Each session includes the placement of two tDCS electrodes (anodal at left prefrontal area and cathodal above the vertex) and 20 mins of anodal prefrontal stimulation. The tDCS session is received two time a day with a 3-5 hours interveal betwen sessions.
Other intervention name(s): Prefrontal tDCS
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Active tDCS versus Sham tDCS intervention
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Working memory; Schizophrenia symtom severity,; Prefrontal tDCS; Event related EEG