Repetitive TMS & Cognitive Training in Adults With Schizophrenia (CrTMS)

Repetitive Transcranial Magnetic Stimulation and Cognitive Training for Treatment of Cognitive Problems in Adults With Schizophrenia: A Pilot Randomized Trial

The proposed project aims to establish the feasibility and tolerability of delivering repetitive transcranial magnetic stimulant (rTMS) combined with computerized cognitive training in patients with Schizophrenia or Schizoaffective Disorder and cognitive difficulties. The investigators will conduct a 2 week randomized controlled trial study evaluating computerized cognitive training combined with either active or sham rTMS on cognitive and functional outcomes in adults with Schizophrenia or Schizoaffective Disorder.

Schizophrenia affects approximately 1.1% of U.S adults per year and is among the most disabling psychiatric illnesses, due primarily to poor functioning related to cognitive dysfunction. Negative (e.g. flattened affect, limited speech output, lack of motivation) and cognitive symptoms (e.g. poor executive functioning, attention and working memory) are by far the leading cause of social, occupational and educational disability and functional impairment in patients with schizophrenia. Since the advent of antipsychotic medications, Schizophrenia treatment has improved significantly with respect to positive symptom control. However, there are limited resources for improving cognitive symptoms in Schizophrenia, which remain disabling for most with the diagnosis. Cognitive remediation and cognitive training programs have shown promise in improving these symptoms. Specifically, adults with Schizophrenia show significant improvements in cognition after participating in 2 weeks of computer based cognitive training. Functional capacity has also been shown to improve with longer periods of computer-based cognitive training. However, the effects of cognitive training alone may be most effective in the short-term. Longer term effectiveness of cognitive training has yet to be shown. There has been emergent interest in using neuromodulation for treatment of cognitive decline in people with various illnesses including children with ADHD, adults with schizophrenia and older adults with late life depression. Specifically, high frequency (20Hz) rTMS applied to the dorsolateral prefrontal cortex (DLPFC) bilaterally has been shown to improve working memory in patients with schizophrenia. By improving neuroplasticity and working memory, rTMS could significantly improve effects of cognitive training in patients with schizophrenia. Combination cognitive training and rTMS treatment has been used in patients with depression with promising results. Previously, the implementation of cognitive training programs in clinical settings was challenged by the intensity of required patient engagement. However, our group and others have applied computerized training programming that is accessible remotely, improving accessibility and engagement. Thus, computerized training offers a feasible and scalable combination with neuromodulation treatment. Here, we propose to test rTMS, in combination with a computerized cognitive training program, to remediate cognitive dysfunction in Schizophrenia and Schizoaffective Disorder in a pilot randomized clinical trial. Aim: Conduct a randomized pilot and feasibility study of active versus sham rTMS combined with computerized cognitive training program in adults with Schizophrenia or Schizophreniform Disorders, comparing neurocognitive and functional outcomes between groups. 1a) the investigators hypothesize favorable differences between groups in acute improvement on neuropsychological executive functioning, as measured by the Screen for Cognitive Impairment in Psychiatry (SCIP). 1b) The investigators hypothesize favorable differences between groups in daily functioning as measured by the Canadian Objective Assessment of Life Skills (COALS) and the WHO Disability Assessment Schedule (WHODAS) in participants receiving CrTMS compared to controls.

participants will be masked to the TMS versus sham treatment. Sham treatment will be very similar to active TMS without the active magnetic stimulation

Participants will receive 6 sessions of active rTMS followed by a computerized cognitive training session over 2 weeks.

Participants will receive 6 sessions of sham rTMS followed by a computerized cognitive training session over 2 weeks.

Participants will receive either active or sham bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) for 12.5 min per side.

Evaluate differences in neuropsychological functioning between active and sham rTMS groups using the Screen for Cognitive Impairment in Psychiatry (SCIP).

Evaluate differences in daily functioning between active and sham rTMS groups using the Canadian Objective Assessment of Life Skills (COALS).

Evaluate differences in daily functioning between active and sham rTMS groups using the WHO Disability Assessment Schedule (WHODAS).

Inclusion Criteria: Age 18-65 Diagnosis of schizophrenia or schizoaffective disorder Psychotic symptoms are stable Exclusion Criteria: Active substance use History of seizures or seizure disorder Active psychosis or recent psychiatric hospitalization Use of medications that could impair cognitive functioning

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