Teen and Adult Tic TMS Study

For Aims 1 and 2, the investigators propose to test a protocol of accelerated inhibitory continuous theta burst stimulation (cTBS) targeting areas of tic-related hyperactivity as identified by functional MRI. Participants will be randomized by computerized list to either receive rTMS directed at the SMA or rTMS directed toward the M1. The investigators will examine data on tolerability, adverse events and early efficacy signals that could inform future, larger scale controlled trials for this indication in adolescents and young adults.

TMS: Our protocol consists of five treatments of inhibitory continuous TBS (cTBS) with the target intensity less than 100% to the SMA or M1 Thumb (as determined by random assignment) lasting five minutes delivered over the course of 10 days (2 weeks) for a total of 50 treatments.

For Aim 3, the investigators will utilize repeated brain MRI imaging pre- and post-TMS treatment within persons with CTD to gauge direction of effects. The investigators plan to observe functional network activity in presumed tic-related neural circuits in youth with CTD pre- and post-treatment. A within-person design also highlights a personalized approach to circuit-based therapeutics that can be explored for individual differences in neural and clinical responses.

MR Imaging Protocol: MRI scanning including T1-weighted anatomical and rs-fMRI will take place on a GE Discovery MR750 3 Tesla scanner. For the rs-fMRI scan, patients will be asked to undergo at least 2x 7 minute scans with eyes open and were observed by an MR technician to ensure wakefulness. All T1 and fMRI scans will be preprocessed using the fMRIprep, a standardized preprocessing pipeline which utilizes tools from the widely-used MRI processing software packages AFNI, ANTs, FreeSurfer, and FSL. T1 scans will be corrected for intensity nonuniformity, skull-stripped, and segmented for registration purposes, then resampled into MNI space. fMRI scans will be slice-time corrected and resampled back to their native space with headmotion correction, then registered and resampled to both T1 space and MNI space. Data analysis will be performed in AFNI, including denoising of fMRI data using nuisance regressors generated by fMRIprep including 12 motion parameters as well as CSF and white matter signals. The resulting residual signal will then be utilized to generate RSFC matrices from the Fisher transformed correlation to generate normalized Z statistics.

Inclusion criteria

• Outpatients
• Ages 15 - 35 years old
• Meets DSM-5 criteria for persistent (chronic) vocal/motor tic disorder or Tourette's syndrome with screening YGTSS score ≥ 20 (moderate or greater severity).
• Moderate severity or intolerable side effects with at least one prior trial of an evidence-based anti-tic medication.
• Stable on chronic psychotropic medications and/or therapy for 6 weeks prior to the study and agreeable to continue current treatments without change throughout the study.
• Participants may continue to take medications and record daily usage throughout the study.
• Capacity to provide informed assent or consent and parent or legal guardian able to provide consent for minors.
• Ability to tolerate clinical study procedures.
• Successfully complete the screening forms without any contraindications.

Exclusion criteria

• Psychiatric: history of schizophrenia, bipolar disorder, substance /alcohol abuse disorder, current elevated suicide risk, prior psychosurgery.
• Neurologic: severe neurocognitive disorder, seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, TBI, hydrocephalus, sequelae of meningitis, frank brain injury).
• TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics.
• Subjects with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension; malnutrition).
• Females who are pregnant or nursing (as determined by a questionnaire and urine pregnancy test).
• Inability to complete the research protocol as determined by the Principal Investigator.