The purpose of this study is to examine whether cerebellar stimulation can be used to improve cognitive deficits and mood in patients with schizophrenia, autism, bipolar disorder, Parkinson's disease, and major depression.
Our recent work found that patients with Parkinson's disease and schizophrenia have impaired frontal EEG rhythms in the theta and delta range (1-8 Hz).We have been using transcranial direct current stimulation to recover these rhythms as patients perform elementary cognitive tasks. We found that although we are able to modulate cerebellar and frontal activity with tDCS, this effect is minimal as the depth of the current is not great enough to modulate all cerebellar activity. Here we use transcranial magnetic stimulation (TMS) to modulate neural activity in the frontal cortex and recover cognitive function in patients with autism, schizophrenia, bipolar disorder and Parkinson's disease. The purpose of the study is to explore cerebellar stimulation as a potential new treatment to restore frontal activity and cognitive function in autism, schizophrenia, bipolar disorder and Parkinson's disease.Subjects will be brought in for 5 to 6 separate visits, with cerebellar or sham TMS stimulation twice per day for 5 days, as well as 3 follow-up visits.During these visits the patient will have cognitive, disease-specific and emotional testing, including EEG testing and MRI imaging. For those participants that received sham stimulation we will again use EEG to record how single pulses of magnetic or electrical stimulation influences other regions of the cerebellum and downstream brain regions. These data will provide insight into how the cerebellum may influence downstream brain regions and play a role in cognitive and motor performance. All data will be analyzed offline to determine if performance on the interval timing task and/or frontal brain rhythms change following transcranial magnetic stimulation as compared to the pre-stimulation blocks of trials. Additionally, we will analyze changes in their cognitive function, symptom ratings, functional and structural MRI, and mood following stimulation. Controls will receive both active and sham treatment for comparison.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
200
Subjects with neuropsychiatric diagnoses and matched-controls will be receive theta frequency stimulation of the cerebellum. We will target the cerebellar vermis.
Subjects with neuropsychiatric diagnoses and matched-controls will be receive sham stimulation of the cerebellum. We will target the cerebellar vermis.
University of Iowa
Iowa City, Iowa, United States
RECRUITINGChange in disease-specific symptom rating scale, one scale identified for each group (MADRS for bipolar group; PANSS for schizophrenia group; UPDRS in Parkinson's patient group).
Change between pre- and post-assessments.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Change in brain rhythms
Change from baseline EEG activity in participants receiving stimulation during a timing task.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Change in cognitive function
Improvement in cognitive function following cerebellar stimulation as compared to controls as measure by higher scores on an NIH Toolbox cognitive battery.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Changes in functional MRI
Changes in resting-state functional connectivity.
Time frame: During the 1 week of treatment comparing pre- and post-stimulation scans.
Change in NIH Toolbox emotion battery
Improvement in emotion T-scores following cerebellar stimulation as compared to controls
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Change in motor function
Improvement in motor function as measured by the Abnormal Involuntary Movement Scale for schizophrenia patients.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
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Schizophrenia group: Change in Calgary depression scale.
Improvement in Calgary depression scale from pre- to post-treatment assessments.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Bipolar group: Change in Young Mania Rating Scale.
Improvement in YMRS scale from pre- to post-treatment.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Bipolar group: Change in Columbia Suicide Severity Rating Scale.
Improvement in C-SSRS from pre- to post-treatment.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Change in PHQ9 score.
Improvement in PHQ9 score from pre- to post-treatment.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Change in CGI.
Improvement as measured on CGI from pre- to post-treatment.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Change in cognitive function.
Improvements as measured by a neuropsychological battery pre and post-treatment.
Time frame: During the 1 week of treatment, with follow up 1 week, 3 weeks, and 2 months post-stimulation.
Changes in structural MRI.
Changes in volumetrics in the active treatment group as compared to sham.
Time frame: During the 1 week of treatment comparing pre- and post-stimulation scans.
Changes in MRI-based timing task.
More accurate evaluation of a passage of time in the MRI scanner in the active treatment group as compared to the control group.
Time frame: During the 1 week of treatment comparing pre- and post-stimulation scans.
Changes in DTI.
Greater changes in the white matter tracts of the active treatment group as compared to the control group.
Time frame: During the 1 week of treatment comparing pre- and post-stimulation scans.
Changes in T1 rho MRI signal.
Normalization of T1 rho abnormalities greater in the active treatment group compared to the control group.
Time frame: During the 1 week of treatment comparing pre- and post-stimulation scans.