Transcranial Direct Current Stimulation and Effects on Early Auditory Processing in Schizophrenia
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, the investigators propose
      to examine the benefit of combining auditory training exercises with transcranial direct
      current stimulation (tDCS). tDCS is a new tool that is being developed as a safe and
      noninvasive 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 added to auditory training
      exercises can improve how schizophrenia patients process sound.
    

Detailed description: 
      Neuroplasticity is the capacity of the brain to adapt and change in response to stimuli. In
      schizophrenia, structural and synaptic neuroplastic impairments potentially contribute to
      early perceptual processing deficits that in turn contribute to downstream higher cognitive
      dysfunction. The N-methyl-D-aspartate receptor (NMDA-R) hypofunction hypothesis of
      schizophrenia potentially explains the synaptic neuroplastic impairments as the NMDA receptor
      is a key component of synaptic plasticity. A rational treatment strategy involves targeting
      the underlying synaptic neuroplastic and perceptual processing deficits. That is, modulating
      the capacity for synaptic plasticity and remediating the processing deficits could then
      cascade into improved perceptual processing and eventually lead to better cognitive
      functioning.

      Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation technique
      that has been shown to modulate synaptic plasticity. tDCS is promising because the technology
      is low cost and the treatment is well-tolerated and has a good safety profile. Both human and
      animal studies have implicated an essential role of the NMDA receptor in tDCS induced
      neuroplastic changes. Recent animal studies demonstrated that tDCS increased levels of an
      NMDA-R agonist and induced neuroplastic changes.

      Cognitive training has been shown to induce both synaptic and structural neuroplastic changes
      in control and psychiatric patient populations. This approach targets specific neural systems
      with directed exercises that employ a combination of repetition, reward, and motivation to
      induce adaptive neuroplastic changes.

      While both tDCS and cognitive training can induce synaptic plasticity changes, each approach
      has specific strengths that could converge in a cooperative manner. tDCS modulates NMDA-R
      activity and creates an environment that enhances the likelihood of synaptic changes to
      occur. However, tDCS alone has no inherent mechanism that drives change with specificity or
      directionality. Cognitive training employs targeted and repeated exercises, which confers
      specificity and directionality to synaptic changes. However, the extent of change that occurs
      is limited by the impaired state of neuroplasticity in schizophrenia. Conceivably, employing
      cognitive training in an environment enriched for plasticity could lead to enhanced and
      adaptive synaptic neuroplastic change.

      Subjects who have a psychiatric illness and may be cognitively impaired will be included in
      the study. Persons with schizophrenia commonly have cognitive impairments that affect
      attention, memory, and executive functioning. There is considerable evidence that these
      deficits are linked to impairments in social and occupational functioning that are
      characteristic of the disorder.

      The cognitive deficits and functional impairments of the illness are the target of interest
      in the study and therefore this patient population will be the specific targets for subject
      recruitment.

      Objectives and Aims

      The purpose of this proposal is to determine the effect of adding adjunctive cognitive
      training to tDCS in improving early auditory processing in schizophrenia patients.

      Specific Aims

        1. Determine if adding a cognitive auditory training exercise concurrently to cathodal tDCS
           offers an advantage to improving early auditory processing over tDCS alone in
           schizophrenia patients.

        2. Determine if adding cathodal tDCS to a cognitive auditory training exercise offers an
           advantage to improving early auditory processing over auditory training alone in
           schizophrenia patients.

      Study Protocol

      30 individuals with schizophrenia will be randomly divided into 3 groups.

      Group 1- Cathodal tDCS + auditory training exercise

      Group 2- Cathodal tDCS + control condition

      Group 3- Sham tDCS + auditory training exercise

      Subjects in Group 1 and 2 will receive cathodal stimulation while Group 3 will receive Sham
      stimulation. The training component for Groups 1 and 3 will be an active auditory training
      program while Group 2 will engage in a control condition. On day 1, subjects will receive a
      baseline Tone Matching Task (TMT) and Mismatch Negativity (MMN) assessment followed by 2
      sessions of tDCS. Subjects will received tDCS + training for 20 min followed by a 20 min rest
      period, and then a second 20 min tDCS + training session. Subjects will return the following
      day (approximately 21 hrs later) where they will undergo tDCS + training, a 20 min rest, and
      a final tDCS + training session. The post-stimulation TMT and MMN assessment will be
      conducted immediately following the final tDCS + training session. Each of these sessions
      will take approximately 3 hrs hours to complete.
    

Intervention name(s): Active tDCS + Auditory Training; Active tDCS + Control Condition; Sham tDCS + Auditory Training
Intervention type(s): Combination Product; Combination Product; Combination Product
Intervention description(s): Active tDCS will be cathodal tDCS applied bilaterally over the auditory cortex for 20 min. The auditory training exercise will 20 min of computerized auditory training using the Sound Sweeps module of the Posit Science Brain HQ; Active tDCS will be cathodal tDCS applied bilaterally over the auditory cortex for 20 min. The control condition will be subjects watching a silent movie for 20 min during active tDCS stimulation.; Sham tDCS will be cathodal tDCS applied bilaterally over the auditory cortex for 1 min with the current then slowly ramped down to 0 amps over the course of another minute. The auditory training exercise will 20 min of computerized auditory training using the Sound Sweeps module of the Posit Science Brain HQ
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Transcranial Direct Current Stimulation; tDCS; Auditory Processing; tone matching