Target Engagement of the Early Auditory Processing Network by Transcranial Direct Current Stimulation (tDCS)
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      Individuals with schizophrenia have difficulties in functioning in the community. No one
      really knows what factors determine how well patients manage in the real world. The purpose
      of this pilot study is to try a new approach to improving a potential determinant of good
      community functioning, namely how we process sounds. Specifically, we propose to examine the
      benefit of transcranial direct current stimulation (tDCS), a new tool that is being developed
      as a safe and non-invasive neurostimulation method, for improving processing of sounds.
      Transcranial direct current stimulation involves placing a wet sponge electrode on the head
      and one on the arm. Electrical current from a device powered by a 9-volt battery will flow
      from one electrode to the other. A small portion of the current will pass through the skull
      and stimulate the brain. This procedure is non-invasive and painless and it results in
      increase or decrease of spontaneous neuronal firing in the brain. Neurons are brain cells
      that send electrochemical messages to each other. Its safety and beneficial effect on mental
      functions has been demonstrated in healthy individuals and several clinical populations.

      The purpose of this study is to determine if transcranial direct current stimulation can
      effect how we process sounds.
    

Detailed description: 
      Neurocognitive and social cognitive deficits are increasingly recognized as core features of
      schizophrenia. The severity of these deficits closely correlate to functional impairment and
      patient outcomes in this population. Current pharmacological treatments do not address these
      illness domains and psychosocial interventions that do are not consistently available.
      Underlying these higher level cognitive domains are basic sensory processing deficits in the
      auditory and visual realm that contribute to higher order dysfunction. Evidence of these
      sensory defects are not readily apparent on clinical exam and are best appreciated using
      functional imaging and electrophysiological measures. Interventions that remediate these
      sensory deficits may lead to functional improvement as sensory level improvements may cascade
      up to higher cognitive domains.

      Deficits in auditory processing are evidenced using EEG based event related potentials (ERP).
      A robust measure of early auditory processing deficits in schizophrenia is the use of an
      auditory oddball paradigm to elicit Mismatch Negativity (MMN). The MMN ERP is generated when
      a rare deviant signal is detected in the context of a series of standards. The amplitude of
      the MMN in schizophrenia patients is decreased compared to healthy controls which reflects a
      deficit in detecting novel stimuli. This decreased auditory MMN has been shown to be closely
      correlated with deficits in auditory emotion recognition tasks in subjects with schizophrenia
      and patient functional outcomes.

      This deficit in early auditory processing is thought to be secondary to regions of cortical
      hypoactivity. Transcranial direct current stimulation (tDCS) is a non-invasive
      neuromodulation technique that targets cortical regions with direct current and can either
      increase or decrease cortical excitability depending on the polarity of the tDCS electrode.
      The MMN network is composed of several generators that serve to process the auditory signal,
      establish an auditory memory trace, and signal the appearance of the deviant signal. The
      initial aim of this proposed study will be to determine if tDCS stimulation over the auditory
      cortex can modulate early auditory processing as measured by the MMN response. Our second aim
      will be to determine the effect of tDCS stimulation over the auditory cortex on performance
      measures of auditory processing as assessed by a tone matching task.

      Aims and Hypotheses

      Aim 1 Determine whether the early auditory processing network can be engaged and modulated by
      tDCS of the superior temporal lobe, where the earliest generators of the network maybe
      located, as assessed by changes in the auditory mismatch negativity ERP.

      Hypothesis 1 Active tDCS stimulation of the superior temporal lobe will modulate the early
      auditory processing network resulting in an effect measurable by amplitude changes in the
      mismatch negativity ERP compared to control sham stimulation.

      Aim 2 Determine the effect of tDCS at the temporal generators on the early auditory
      processing network as assessed by the tone matching task performance measure

      Hypothesis 2 Active tDCS stimulation of the temporal generators will modulate the early
      auditory processing network resulting in a performance change on the tone-matching task
      compared to sham control stimulation.

      Study Protocol

      The study will be a within subject, cross over design counterbalanced for order of both
      stimulation condition and post-stimulation measurement. All patients will receive anodal,
      cathodal and sham stimulation targeted bilaterally to the superior temporal region
      (unipolarity, dual-site stimulation). We do not have a directional prediction for the active
      stimulations (anode and cathode) in terms of increasing or decreasing the amplitude of the
      MMN ERP, but we do expect active stimulation to change the MMN ERP amplitude. Patients with
      schizophrenia will be randomly assigned to one of six block stimulation sequences
      counterbalanced for order of stimulation condition. The goal will be to have complete and
      usable data from 12 subjects, and thus up to 30 subjects will be enrolled to account for
      screen failures and drop-outs. At the first visit, subjects will be screened, assessed, and
      consented if they meet selection criteria. They will then be randomized to one of the
      counterbalanced stimulation sequences and receive their first stimulation session followed by
      EEG assessment and tone matching task. Subjects will return in one week for visit 2 and the
      following week for visit 3. At visits 2 and 3, subjects will receive a tDCS session followed
      by EEG and tone matching task assessment. All visits will be separated by at least 1 week to
      washout the effect from the previous stimulation. Each patient will return for a total of 3
      stimulation visits.
    

Intervention name(s): tDCS Stimulation
Intervention type(s): Device
Intervention description(s): Subjects will receive tDCS stimulation over the auditory cortex for 20 min. For anodal stimulation the anode electrodes will be placed over the auditory cortex. For cathodal stimulation, the cathode electrodes will be placed over the auditory cortex. For sham stimulation, the anode electrodes will be placed over the auditory cortex and current turned on for 30 sec before being turned off to simulate the sensation of active stimulation.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Device Feasibility
Keywords: Mismatch Negativity; Transcranial Direct Current Stimulation; MMN; tDCS