Repetitive TMS & Cognitive Training in Adults With Schizophrenia

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.

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