Cerebellar Stimulation and Cognitive Control

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.

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.

Change 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).

Improvement in cognitive function following cerebellar stimulation as compared to controls as measure by higher scores on an NIH Toolbox cognitive battery.

Improvement in motor function as measured by the Abnormal Involuntary Movement Scale for schizophrenia patients.

More accurate evaluation of a passage of time in the MRI scanner in the active treatment group as compared to the control group.

Greater changes in the white matter tracts of the active treatment group as compared to the control group.

Normalization of T1 rho abnormalities greater in the active treatment group compared to the control group.

Inclusion Criteria: A clinical diagnosis consistent with enrollment Exclusion Criteria: History of recurrent seizures or epilepsy Any other neurological or psychiatric diagnosis outside the diagnosis for which the participant is enrolled. Active substance use disorder in the past 6 months other than tobacco use disorder. Inability to consent for study. Pacemaker Coronary Stent Defibrillator Neurostimulation Claustrophobia Uncontrolled high blood pressure Atrial fibrillation Significant heart disease Hemodynamic instability Kidney disease Pregnant, trying to become pregnant, or breast feeding