A prospective, multi-center, randomized, sham-controlled, blinded study combining active Nexstim NBS-guided 1Hz rTMS or sham-rTMS targeting the healthy hemisphere with standardized task oriented rehabilitation will be conducted in patients with post-stroke motor impairment of the upper limb. The therapy will be provided for 6 weeks and primary outcome assessed 6 months later.

Inclusion Criteria:

• ≥ 18 years of age
• An ischemic stroke suffered 3-12 months prior to the study
• No other known brain abnormalities by history;
• A one-sided stroke resulting in upper extremity paresis
• A Chedoke-McMaster Stroke Assessment arm stage and hand stage of 3-6 for the affected limb

Exclusion Criteria:

• Implanted metallic parts of implanted electronic devices, including pacemakers, defibrillators, or implant medication pump;

• Pregnant or trying to become pregnant; Lack of pregnancy established in females of child-bearing potential by a negative urine pregnancy test at screening.

• Active alcohol abuse, illicit drug use or drug abuse or significant mental illness

• Patients suffering from depression as measured by a score of >10 on the Patient Health Questionnaire (PHQ9). For clarity, patients diagnosed with depression which is controlled with stable anti-depressive medication and in whom PHQ9 is <10 are eligible to participate in the trial.

• History of epilepsy, defined as at least two unprovoked seizures occurring greater than 24 hours apart or diagnosis of an epilepsy syndrome, OR a seizure within the last 12 months.

• Any condition that would prevent the subject from giving voluntary informed consent;

• An implanted brain stimulator;

• Any metal in head with the exception of dental work or any ferromagnetic metal -elsewhere in the body;

• Enrolled or plans to enroll in an interventional trial during this study;

• Scalp wounds or infections;

  • Claustrophobia precluding MRI;

• A fixed contraction deformity in the affected limb that would prevent normal dexterity if patient were neurologically intact;

• Excessive spasticity as indicated by the Modified Ashworth Spasticity (MAS) Scale >2/4 in either elbow flexors, wrist flexors or finger flexors of the affected limb;

• Previous stroke with residual deficits (TIAs not a reason for exclusion);

• Premorbid (retrospective) modified Rankin Scale (mRS) score ≥2 of any aetiology;

• A concurrent progressive neurologic disorder, acute coronary syndrome, severe heart disease (NYHA Classification > 3), or other major medical condition,

• Confirmed or suspected lower-limb fracture preventing mobilization, patients requiring palliative care

• Patients planning to undergo any other occupational therapy during the 6 week active treatment period of the trial (see section 5.2 for study schedule) than what is provided in the study

• A recent injection of botulinium toxin to the affected upper limb in the last 3 months, or the need of an injection of botulinum toxin anytime during the study period and follow up.

• A recent injection of phenol to the affected upper limb in the last 6 months, or the need of an injection of phenol anytime during the study period and follow up.

• Ataxia as measured by a score > 1 on item 7 (limb ataxia) of the NIH stroke scale.

• Severe sensory deficits as measured by a score of 2 on item 8 of the NIH stroke scale.

• Severe aphasia as measured by a score of > 2 on item 9 (best language) of the NIH stroke scale.

• Severe neglect as measured by a score of 2 on item 11 (extinction and inattention) of the NIH stroke scale.

• Patients unable to comprehend or follow verbal commands

• Based on PI's or local physician's assessment patient unable to tolerate the trial procedure due to medical condition

• A Mini mental status exam (MMSE) <25.

From baseline until 6 months after end of treatment.