Rationale: 75% of all stroke survivors suffer from cognitive deficits in the acute phase, with serious implications for their long-term quality of life and societal participation. A promising novel therapy is repetitive transcranial magnetic stimulation (rTMS). Only a handful of studies have attempted to promote cognitive functioning after stroke with rTMS. These studies exclusively used a one-size-fits-all approach, which had limited success, as post-stroke cognitive deficits are highly variable. We propose a two-step personalized treatment strategy to identify targets for therapeutic TMS for cognitive rehabilitation after stroke. Step one consits of identification of personalized TMS targets by measuring fMRI activity during a representative cognitive task. In step two, TMS disruption is used to temporarily disrupt activity in the targeted brain region to investigate causal involvement of a brain area in cognitive task performance.

Objective: To validate a proof-of-concept to identify personalized targets for therapeutic TMS for cognitive rehabilitation after stroke.

Study design: A prospective mechanistic intervention study.

Study population: 10 healthy individuals and 15 stroke patients with cognitive impairment

Intervention: Active and sham TMS disruption of personalized targets

Main study endpoints: The n-back test

Inclusion Criteria:

1. Age ≥ 18 years;
2. First-ever ischemic stroke or intracerebral haemorrhage in a cerebral hemisphere or the brainstem;
3. Cognitive impairment based on assessment by the treating rehabilitation physician.
4. Able to perform n-back task at inclusion.
5. Inclusion possible within 10 weeks after stroke onset;
6. Signed informed consent.

Exclusion Criteria:

1. Known cognitive impairment prior to stroke onset;
2. Absolute contra-indication to TMS: Magnetic sensitive objects implanted in the head or neck area (e.g. cochlear implants, implanted neurostimulator, pacemaker or defibrillator, metal splinters, metal fragments or metal clips), history of epilepsy, pregnancy or other contra-indications that may potentially be harmful as determined by the treating rehabilitation physician;
3. Incompetence or severe impairments that can impede study participation as determined by the treating rehabilitation physician (i.e. extreme fatigue, severe communication deficits);
4. Life expectancy shorter than one year.

Anonymized patient data can be made available on request