Apathy is a common set of symptoms seen in many people following a stroke. Apathy occurs when a person has lost motivation, becomes withdrawn, and stops doing things that used to be important to them. Apathy has a large negative impact on a person's quality of life, and can also have a large impact the people who take care of them. There are currently no FDA-approved treatments to help with apathy, and other services like therapy may be difficult to access for people who have had a stroke. To address this problem, investigators are conducting a study to find out if a form of treatment called repetitive transcranial magnetic stimulation (rTMS) can be safe and helpful for people struggling with apathy after a stroke. This study will apply a new form of rTMS which can be delivered quickly to a part of the brain called the medial prefrontal cortex (mPFC). This study will help establish whether this treatment is safe, comfortable, and effective for people with apathy after a stroke, and will help researchers develop new forms of treatment.
40 years old or greater
Right- or left-hemisphere ischemic or hemorrhagic stroke with at least 6 months chronicity
Symptomatic apathy as confirmed by (A) total score on the Apathy Evaluation Scale by the participant or the caregiver/co-participant (AES) of ≥39
Ability to participate in psychometric testing and cognitive tasks
Primary extra-axial hemorrhage (subdural or subarachnoid) without ischemic stroke or intraparenchymal hemorrhage
Concomitant neurological disorders affecting motor or cognitive function (e.g. dementia)
Moderate or severe global aphasia
Visual impairment precluding completion of cognitive tasks
Parallel
MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System (Active)
DeviceActive treatment will consist of high-dose iTBS-rTMS to left dmPFC delivered in runs of 600 pulses at an intensity of 120% resting motor threshold (rMT). iTBS triplets at 50 Hz will be delivered for 2 seconds, repeated every 10 seconds for a total of 190 seconds. Each session will be separated by at least 10-15 minutes and a total of 12 sessions will be given on each treatment day (3-4 hours per study day). A total of 43,200 pulses will be delivered over the entire six days of treatment.
MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System (Sham)
DeviceFor the sham stimulation group, a focal electric sham will be used which is indistinguishable from active TMS including a pretreatment individualized sham titration, sham outputs noises synchronized to pulse delivery, and an individualized level of sham stimulation throughout the treatment. Technicians administering active vs sham TMS will be masked by using a random code generated by the statistician that will indicate whether to use the active or sham side of the coil. Treatments will appear identical to the technician regardless of whether active or sham TMS is administered.
Brainsight Neuronavigation System
Other interventionA brainsight neuronavigation system will be used during TMS treatments to target treatment location using individual MRI data
Change in apathy symptoms, as measured by the Lille Apathy Rating Scale (LARS) compared to baseline
The Lille Apathy Rating Scale (LARS) is a clinically validated 33-item structured interview assessing clinical symptoms of apathy. The structured interview is broken into 9 sub-scales including everyday productivity, interests, taking the initiative, novelty seeking, motivation, emotional responsiveness, concern, and social life. Total scores can range from -36 to +36 and are further stratified by factorial sub-scores including intellectual curiosity, emotion, action initiation, and self-awareness.
Change in apathy symptoms as measured by the Apathy Evaluation Scale (AES) - Self and Informant Versions
The Apathy Evaluation Scale (AES) clinically validated rating scale assessing symptoms of apathy. The AES is comprised of 18 items rated on a four-point Likert-Scale assessing and quantifying emotional, behavioural and cognitive aspects of apathy. Total scores on the AES range from 18 to 72 with high scores correlating with greater severity of apathy.
Incidence of Treatment-Emergent Adverse Events and Side Effects as assessed by change in the Review of Systems Criteria compared to baseline
A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).
Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery compared to baseline
Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance.
Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Short Form
Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Short Form The Patient-Reported Outcomes Measurement Information System (PROMIS) is a clinically validated adaptive clinical assessment tool designed under the NIH to capture patient-reported symptoms in several psychiatric symptom domains for use in clinical research.
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