Imaging Post-Stroke Recovery: Using MEG to Evaluate Cognition

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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).

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

Conditions
-----------------
Stroke, Stroke Sequelae, Stroke/Brain Attack

Intervention / Treatment
-----------------
* Diagnostic Test: Magnetoencephalography (MEG)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (≥18 years) admitted to Bayview Medical Center Neurology. Evidence of acute ischemic stroke (CT or MRI)- lacunar stroke or branch occlusion (M3/A3/P3 or smaller) OR NIHSS ≤ 8 on admission. Competent speaker of English (by self or family report) prior to stroke. Return for follow-up 4-6 weeks post event (+/- 4 wks). Cognitive deficits present on initial testing.** unique to MEG study Willing to travel to the University of Maryland twice for MEG.** unique to MEG study Fully independent functionally and able to travel to the University of Maryland unassisted.** unique to MEG study Exclusion Criteria: Primary intracerebral hemorrhage- as evidenced by blood on head CT or MRI. 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. Uncorrected hearing or visual loss. Large vessel occlusion. 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 Claustrophobia, obesity, and/or any other reason leading to difficulty staying in the MEG for up to 1 hour.** unique to MEG study For controls- clinical history of stroke or other neurological dysfunction (seizure, multiple sclerosis, etc.); psychiatric disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Minor Stroke<br>We will enroll a cohort of 15 adult patients previously admitted to Johns Hopkins Bayview Medical Center with small/minor acute ischemic stroke visible on neuroimaging. Patients will follow-up in clinic 4-6 weeks following hospital discharge. To be eligible for the study, patients must have a minor stroke, defined as NIH Stroke Scale score at follow-up of less than or equal to 8, modified Rankin score of 0-2, be competent speakers of English, and have no prior history of stroke, dementia, or untreated psychiatric disease. Those with proximal large vessel (M1) or branch (M2) occlusions will be excluded. *Based on preliminary results we have expanded our trial and will continue to recruit up to 40 patients with minor stroke. | Diagnostic Test: Magnetoencephalography (MEG)<br>* Participants will undergo MEG at the University of Maryland (College Park) to measure cerebral activity while performing a visual naming task. The Montreal Cognitive Assessment (MOCA) will also be administered.<br>* Other names: Cognitive Testing;|
| Controls<br>For comparison, we will recruit a group of age-similar controls (n=15) without neurologic disease or prior clinical history of stroke. | Diagnostic Test: Magnetoencephalography (MEG)<br>* Participants will undergo MEG at the University of Maryland (College Park) to measure cerebral activity while performing a visual naming task. The Montreal Cognitive Assessment (MOCA) will also be administered.<br>* Other names: Cognitive Testing;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Activity Measured Using Magnetoencephalography (MEG) | Global patterns of cerebral activity as well as individual brain areas important for cognitive processing will be analyzed for differences with respect to amplitude, latency, and frequency. | Up to 10 weeks | 
| Cerebral Activity Measured Using Magnetoencephalography (MEG) | Global patterns of cerebral activity as well as individual brain areas important for cognitive processing will be analyzed for differences with respect to amplitude, latency, and frequency. | Up to 6 months | 
| Cerebral Activity Measured Using Magnetoencephalography (MEG) | Global patterns of cerebral activity as well as individual brain areas important for cognitive processing will be analyzed for differences with respect to amplitude, latency, and frequency. | Up to 12 months | 
| Reaction Time | Reaction times will be recorded and compared during the visual naming task | Up to 10 weeks | 
| Reaction Time | Reaction times will be recorded and compared during the visual naming task | Up to 6 months | 
| Reaction Time | Reaction times will be recorded and compared during the visual naming task | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MOCA | Scores on the MOCA will be compared between those with minor stroke and controls | Up to 10 weeks | 
| MOCA | Scores on the MOCA will be compared between those with minor stroke and controls | Up to 6 months | 
| MOCA | Scores on the MOCA will be compared between those with minor stroke and controls | Up to 12 months |