4D-EEG: Uncovering the neurological mechanisms behind upper limb functional recovery after stroke

Rationale:

Stroke is a major cause of disability in the developed world. Up to 80% of the stroke patients suffer an upper limb paresis. Only one one-third of those patients regain some dexterity, leaving the majority with disabilities in activities of daily living. (Dobkin et al. 2005; Kwakkel 2003). Little is known of the mechanisms behind functional recovery. Much of our knowledge on neuroplasticity and its mechanisms is derived from animal studies. Ways to assess neuroplasticity in humans are in an early developmental phase. In order to make true progress, the next step is to assess the dynamics of cortical activity in a larger cohort of patients, covering the entire possible phenotype from patients with an initial good to poor prognosis and longitudinal in time. In order to develop additional evidence based therapies, a better understanding of underlying brain dynamics is essential. To this end, accurate mapping of brain network connectivity and localization is needed.



Objective:

The 4D-EEG study aims to elucidate the underlying mechanisms of upper limb functional recovery using portable EEG (electroencephalography) methodology as well as clinical measures of motor function. The following questions are asked: How do true neurological restitution and substitution contribute to upper limb recovery? What changes occur in the brain when patients show recovery of upper limb capacity? Do these changes contribute to better function or do they result from decreased cortical inhibition? Does early EEG provide additional value in prediction algorithms of functional outcome of upper limb dexterity? And finally, how does the cortical spinal tract integrity affect the functional outcome?



Study design:

Projects:

A. Cross-sectional study: Relate our EEG methodology to fMRI (functional magnetic resonance imaging).

B. Prospective cohort study: Repeated application of our EEG method in the first six month post stroke.

C. Cross-sectional study: Cortical spinal tract (CST) integrity and its relation with functional recovery. Using trans cranial magnetic stimulation (TMS) & diffusion tensor imaging (DTI) measurements



Study population:

A. Chronic stroke patients (i.e. > six months post stroke), age ≥18 years old
+ Age matched control subjects. (N*=21, C*=10).

B. First ever stroke patients, 1-3 weeks post stroke, age ≥18 years old. (N=50).

C. Sub-acute stroke patients (i.e. five-six months post stroke), age ≥18 years old
+ Age matched control subjects. (N=21, C=10).

*C = Number of control subjects, *N = Number of Patients

Intervention

Not applicable, all three projects are observatory hence all subjects will receive normal rehabilitation care according to the guidelines.



Main study parameters/endpoints:

The main endpoint of project A is the validation of the source localization of EEG cortical activity in relation to the local oxygen metabolism as measured with fMRI. The corresponding parameter is the displacement in millimeters MRI space. The first application of our protocol in project A to stroke patients will be used to compile a feasible experimental paradigm for the prospective cohort study. Although the repeatability of the experiments has already been verified in pilot-experiments, the sensitivity of the novel outcome parameters to stroke pathophysiology needs to be established prior to the prospective cohort.
The main endpoint of the prospective cohort study (B) is the longitudinal relationship, between, on the one hand dexterity and feedback properties of the upper limb motor system and on the other hand, observed changes in cortical dynamics related to movement. The main study outcome of project C is the correlation between CST integrity and functional outcome.

The dynamics of motor task related cortical electrical activity will be related to the outcome of upper limb function after stroke

Project A & C are cross-sectional with one time point.

Prospective cohort project B:
weeks 1-5, 8, 12 & 26 post stroke

Not applicable: The study does not interfere with patients’ normal care according to the guidelines. The healthy control subjects will not receive treatment.