Dystonia Treatment With Injections Supplemented By Transcranial Magnetic Stimulation (D-TWIST)

We will apply 16 sessions of rTMS over 4 consecutive days for adult patients suffering from cervical dystonia who receive botox on a regular basis. The TMS protocol will take place 9 weeks following their last botox injection. The primary outcome measure will be improvement in cervical dystonia as measured by the TWSTRS scale. The secondary outcome measures include mood, cognition, gait, TMS measures, and high-density EEG measures.

This is a crossover study design in which patients will be randomized to active or sham stimulation during session 1 (S1) and then crossover to the condition they were not randomized to at first during session 2 (S1). Patients who are receiving botox for cervical dystonia on a regular basis but having benefit from botox for 9 weeks or less will be eligible to participate. The total study protocol will take place over 24 weeks. During week 1, patients will have their regularly scheduled botox injections. During week 9, patients will undergo either active or sham rTMS, as detailed below. They will have outcome measures obtained at week 9 (S1:T0; baseline/pre-TMS), week 10 (S1:T1; post-TMS), and week 12 (S1:T2; 2 weeks post-TMS). At week 12, they will undergo their regularly scheduled botox injections. During week 21, patients will undergo either active or sham rTMS, whichever condition they were not randomized into during the first session. They will have outcome measures obtained at week 21 (S2:T0; baseline/pre-TMS), week 22 (S2:T1; post-TMS), and week 24 (S2:T2; 2 weeks post-TMS). The neurostimulation protocol will be as follows: The dPMC target will be defined as 1 cm medial and 2 cm anterior to the site of RMT acquisition. The rTMS protocol will be as follows: each session will consist of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. Patients will receive 4 sessions per day for 4 consecutive days with a 10-minute break between each session. Daily duration of the rTMS protocol, including breaks, will last approximately 160 minutes

Patients will be randomized to one of two conditions during session 1: active or sham rTMS. During session 2, patients will undergo whichever condition they did not undergo in session 1.

A sham coil will be used for sham rTMS. Both conditions will undergo the exact same study procedures except the sham coil will not deliver pulses; it will deliver a sound and tapping sensation meant to mimic the real rTMS coil, but no real stimulation will be provided in this condition. Patients and outcomes assessors will not be made aware of the condition that the participant is currently partaking in.

Active rTMS will use a figure of eight TMS coil that will deliver real neurostimulation pulses to the patients.

Sham rTMS will use a sham figure of eight TMS coil that sounds and looks like a real rTMS coil, except no neurostimulation is being delivered to the patient.

repetitive transcranial magnetic stimulation is a painless, noninvasive form of neurostimulation. This study uses an accelerated protocol in which the neurostimulation pulses are delivered in 4 sessions per day over 4 consecutive days (16 total sessions). Active or sham rTMS will be provided at 9 weeks following botox injections.

This is an objective scale evaluating patients on a variety of features including maximal excursion, duration, effects of sensory trick, shoulder elevation, range of motion, and time. Scores range from 0 to 85 where a higher score indicates more severity.

This is a 21-question survey evaluating depression in patients on a 0 to 3 scale, with a minimum score of 0 and maximum score 63, and higher score indicating a higher level of depression.

Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 78 seconds to complete Part A is considered impaired).

Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 273 seconds to complete Part B is considered impaired).

Patients will be asked to walk across the Zeno walkways system for dynamic stability index (ratio between single and double support time).

The patient's electrical activity of the brain will be recorded with maximal range of motion/excursion in six directions: up, down, left, right, left shoulder, right shoulder

In a paired-pulse TMS paradigm, a subthreshold pulse will be provided followed by an interstimulus interval and then subsequent delivery of a suprathreshold pulse. When the interstimulus interval is short (1-4 msec), the ratio of MEP amplitudes produced by these two pulses is known as short interval intracortical inhibition (SICI).

A single-pulse of TMS will be targeted over the motor cortex to generate a motor evoked potential (MEP), which can be captured on EMG.

A single-pulse of TMS will be targeted over the motor cortex and the rest of the EMG will be analyzed to assess the amount of time muscle activity remains silent following the MEP (also known as the cortical silent period).

Inclusion Criteria: patients 18-85 years of age who receive regular botulinum toxin (BoNT) scheduled every 12 weeks, on stable optimized doses but with reported benefits lasting ≤ 9 weeks for 2 consecutive cycles. Patents followed at our center routinely fill out a self-reported form to document the duration of benefits perceived with BoNT therapy. Participants will be allowed to continue oral medications that they are taking for dystonia concurrently but will not be allowed to change their concurrent medication regimen throughout the duration of the study. Exclusion Criteria: Presence of metallic objects or neurostimulators in the brain Pregnancy History of active seizures or epilepsy Patients with severe scoliosis or other gait impairment that will preclude them from participating in gait evaluation.