Transcranial Direct Current Stimulation and Effects on Early Auditory Processing in Schizophrenia

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.