Transcranial Magnetic Stimulation to Augment Behavior Therapy for Tics

All participants will receive 10 daily sessions of CBIT, a well-established behavioral treatment that is considered by the American Academy of Neurology to be the first-line intervention for tics. Immediately prior to each CBIT session, participants will undergo TMS targeting the SMA. The specific type of TMS procedure will be randomly assigned between subjects and be either: 1 Hz repetitive TMS (rTMS), continuous theta burst stimulation (cTBS), or sham stimulation.

• Comprehensive Behavioral Intervention for Tics (CBIT) (Behavioral): CBIT is a manualized treatment program focused on tic management skills
• Repetitive Transcranial Magnetic Stimulation (rTMS) (Device): During repetitive transcranial magnetic stimulation (rTMS), a electromagnetic coil is placed against the scalp while an electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the target brain region
• Continuous Theta Burst Stimulation (cTBS) (Device): During continuous theta burst stimulation (cTBS), a electromagnetic coil is placed against the while an electromagnet painlessly delivers magnetic bursts that stimulate nerve cells in the target brain region

Primary outcomes

• Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits [baseline to post-treatment; approximately 10 days]: For each participant, signal intensity (unitless measure) will be measured using fMRI in the supplementary motor area (SMA) during a finger tapping task. An ANOVA will be conducted to compare change in signal intensity within SMA from pre- to post-treatment across the groups. The outcome will be reported as an effect size value (Cohen's d).
• Change in SMA Activation [baseline to post-treatment; approximately 10 days]: For each participant, signal intensity (unitless measure) will be measured using fMRI in the supplementary motor area (SMA) during a finger tapping task. An ANOVA will be conducted to compare change in signal intensity within SMA from pre- to post-treatment across the groups. The outcome will be reported as an effect size value (Cohen's d).

Secondary outcomes

• Safety: Measured as Rate of Adverse Events Related to Study Treatment [approximately 3-4 months]: The number of adverse events judged to be treatment related will be totaled and reported for each group.
• Change in Tic Suppression Task [baseline to 3 months post-treatment]: The Tic Suppression Task is a clinician-rated tool for assessing tic frequency. A video recording of participant is rated and yields a score in units of tics per minute. Outcome reported as change from baseline to post treatment; change from baseline to 1 month post treatment; change from baseline to 3 months post treatment; change from post treatment to 1 month post treatment; and change from post treatment to 3 months post treatment.
• Feasibility: Measured as Participant Treatment Completion [approximately 3-4 months]: For each group, the number of participants who completed at least 80% of treatment sessions will be totaled and reported for each group.

Sex: All, ages: 12 Years to 21 Years

Inclusion Criteria:

* Current chronic motor and/or vocal tics, defined as tics for at least 1 year without a tic-free period of more than 3 consecutive months. Tics must not be due to a medical condition or the direct physiological effects of a substance.
* At least moderate tic severity, defined as a Yale Global Tic Severity Scale total score ≥14 (≥9 for those with motor or vocal tics only).
* Full scale IQ greater than or equal to 70
* English fluency to ensure comprehension of study measures and instructions.
* Right-handed

Exclusion Criteria:

* Medical conditions contraindicated or associated with altered TMS risk profile, including history of intracranial pathology, epilepsy or seizure disorders, traumatic brain injury, brain tumor, stroke, implanted medical devices or metallic objects in the head, current pregnancy or participants of childbearing age not using effective contraception, or any other medical condition deemed serious or contraindicated by a study physician
* Inability to undergo MRI.
* Left handedness.
* Active suicidality.
* Previous diagnosis of psychosis or cognitive disability.
* Substance abuse or dependence within the past year.
* Concurrent psychotherapy focused on tics.
* Neuroleptic/antipsychotic medications.
* Taking a medication that has not reached stability criterion (same medication and dose for 6 weeks with no planned changes over the intervention period)

Participant flow

Outcome results

• Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits (Primary), Mean, eta squared: CBIT + rTMS 0.0312 +/- 0.05; CBIT + cTBS 0.261 +/- 0.05; CBIT + Sham 0.158 +/- 0.03
• Change in SMA Activation (Primary), Mean, eta squared: CBIT + rTMS 0.45 +/- 1.25; CBIT + cTBS 0.01 +/- 1.25; CBIT + Sham 0.27 +/- 1.3
• Safety: Measured as Rate of Adverse Events Related to Study Treatment (Secondary), Number, events: CBIT + rTMS 46; CBIT + cTBS 22; CBIT + Sham 18
• Change in Tic Suppression Task (Secondary), Mean, tics per minute: CBIT + rTMS 0.58 +/- 9.47; CBIT + cTBS -3.83 +/- 23.92; CBIT + Sham -8.24 +/- 15.71
• Feasibility: Measured as Participant Treatment Completion (Secondary), Number, participants: CBIT + rTMS 17; CBIT + cTBS 15; CBIT + Sham 16

Adverse events

Time frame: 4 months

Other adverse events by term

• Results publication: Conelea CA, Kretsch S, Greene DJ, Mueller BA, Breitenfeldt C, Houlihan K, Wellen B, Hendrickson T, Alexander J, Fiecas M, Cui E, Duffy K, Schneck D, Chen M, Lewis CP, Roediger D, Opitz A, Jacob S, Lim K. 1Hz vs. cTBS Transcranial Magnetic Stimulation to Augment Behavior Therapy for Tics: A Randomized Clinical Trial. medRxiv [Preprint]. 2026 Oct 1:2026.09.29.26364036. doi: 10.64898/2026.09.29.26364036. PMID 42856611
• Results publication: Conelea C, Greene DJ, Alexander J, Houlihan K, Hodapp S, Wellen B, Francis S, Mueller B, Hendrickson T, Tseng A, Chen M, Fiecas M, Lim K, Opitz A, Jacob S. The CBIT + TMS trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics. Trials. 2023 Jul 3;24(1):439. doi: 10.1186/s13063-023-07455-1. PMID 37400828
• Results publication: Conelea C, Greene D, Alexander J, Houlihan K, Hodapp S, Wellen B, Francis S, Mueller B, Hendrickson T, Tseng A, Chen M, Fiecas M, Lim K, Opitz A, Jacob S. The CBIT+TMS Trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics. Res Sq [Preprint]. 2023 Jun 13:rs.3.rs-2949388. doi: 10.21203/rs.3.rs-2949388/v1. PMID 37398344

• Study Protocol and Statistical Analysis Plan (PDF, 2022-02-24)
• Informed Consent Form (PDF, 2023-07-19)

• Christine Conelea, PhD, Principal investigator, University of Minnesota