Imaging Post-Stroke Recovery: Using MEG to Evaluate Cognition

Imaging the Network: Using MEG to Determine the Pathophysiology Underlying Post-Stroke Cognitive Impairment

This is a study using magnetoencephalography (MEG) to look at recovery in those with minor stroke. The investigators know that these individuals report difficulties in attention, concentration, multi-tasking, energy level, and processing speed that appear to be independent of lesion size or location. The underlying pathophysiology is unclear; however, anecdotally, many individuals are significantly improved by 6 months post-stroke. One hypothesis is that a single lesion, regardless of size, may disrupt the classic neural networks required for cognitive function. The investigators are currently collecting data to better characterize these difficulties and stroke patients' recovery as part of a previously approved recovery study. In this sub-study, the investigators propose to add MEG at 1 and 6 months in a subset of individuals with small: 1) subcortical, and 2) cortical lesions. The investigators will partner with colleagues at the University of Maryland (College Park), who are well experienced with MEG to conduct this research. In addition a control population of age-similar individuals will be recruited for comparison. Cerebral activation patterns of individuals with stroke versus controls will be compared, both across patients with stroke at a given time point, and within subjects from 1 to 6 months to determine the association of abnormal activation with cognitive dysfunction and recovery.

**The investigators have recently extended follow-up by adding an additional assessment at 12 months and will enroll additional participants (up to 40 patients with minor stroke, 15 age-similar controls).

This is a prospective longitudinal study of patients with minor stroke versus age-similar controls that will make use of the following protocol:

• Patients are admitted to the hospital for acute stroke and undergo work-up including MRI; they are entered into a clinical outcomes database (routine clinical care)
• All patients are scheduled for an appointment in the Bayview Stroke Intervention Clinic approximately 4-6 weeks +/- 4 weeks post-stroke
• Seen at 4-6 weeks (routine care)- consented and tested if enrolled (per research protocol, as part of a prior approved study on stroke recovery)
• Those meeting inclusion criteria for MEG testing will be consented and undergo the following additional procedures: 1 month MEG visit at the University of Maryland- brain activity will be measured at rest and during cognitive tasks evaluating domains such as: executive function, attention, and multi-tasking including a visual naming test Repeat MEG at approximately 6 months +/- 4 weeks post-stroke

University of Maryland's MEG Protocol:

The head shape will be measured using a 3D tracking system. This involves using a plastic stylus to mark a series of points around the head that will map the entire surface of the head. In addition, each of three "fiducial" points; one in front of each ear and one above and between the eyes will be marked. The purpose of the head shape measurement is to be able to co-localize brain activity recorded with the MEG with the subject's MRI.

Magnetic fields will be recorded using a 275-channel whole-head MEG system. A third-order gradient will be used for noise cancellation.

The MEG system non- invasively measures the magnetoencephalographic (MEG) signals (and, optionally, electroencephalographic EEG signals) produced by electrically active tissue of the brain. These signals are recorded by a computerized data acquisition system, displayed, and may then be interpreted by trained physicians to help localize these active areas. The location may then be correlated with anatomical information of the brain. MEG is routinely used to identify the locations of visual, auditory, somatosensory, and motor cortex in the brain. MEG is also used to non-invasively locate regions of epileptic activity within the brain. The localization information provided by MEG may be used, in conjunction with other diagnostic data, in neurosurgical planning.

The total length of the MEG recordings will depend on the length of the tasks (an estimate of 30-45 min has been used). There will be a 2-5 -minute break between each run. For all runs magnetic fields will be recorded in 42 consecutive 10-second trials. In this way if there are artifacts during the session, such as the subject moving his or her head, the 10-second trial during which this occurs can be eliminated from analysis.

Patients will return for their 6 month and 12 month post-stroke follow-up appointments (routine care) and testing (if part of the recovery study).

Inclusion Criteria:

1. Adults (≥18 years) admitted to Bayview Medical Center Neurology.
2. Evidence of acute ischemic stroke (CT or MRI)- lacunar stroke or branch occlusion (M3/A3/P3 or smaller) OR NIHSS ≤ 8 on admission.
3. Competent speaker of English (by self or family report) prior to stroke.
4. Return for follow-up 4-6 weeks post event (+/- 4 wks).
5. Cognitive deficits present on initial testing.** unique to MEG study
6. Willing to travel to the University of Maryland twice for MEG.** unique to MEG study
7. Fully independent functionally and able to travel to the University of Maryland unassisted.** unique to MEG study

Exclusion Criteria:

1. Primary intracerebral hemorrhage- as evidenced by blood on head CT or MRI.
2. Previous neurological disease (e.g., dementia, multiple sclerosis, prior symptomatic stroke). Incidental asymptomatic lacunar strokes found on imaging will not be excluded as prior disease.
3. Uncorrected hearing or visual loss.
4. Large vessel occlusion.
5. Presence of any of the following that would lead to significant artifact on MEG: cardiac pacemaker, intracranial clips, metal implants, or external clips within 10mm of the head, metal in the eyes.** unique to MEG study
6. Claustrophobia, obesity, and/or any other reason leading to difficulty staying in the MEG for up to 1 hour.** unique to MEG study
7. For controls- clinical history of stroke or other neurological dysfunction (seizure, multiple sclerosis, etc.); psychiatric disease