Stroke is a leading cause of disability, with deficits encompassing multiple functional domains. The heterogeneity underlying stroke poses significant challenges in the prediction of post-stroke recovery, prompting the development of neuroimaging-based biomarkers. Structural neuroimaging measurements, particularly those reflecting corticospinal tract injury, are well-documented in the literature as potential biomarker candidates of post-stroke motor recovery. Consistent with the view of stroke as a ‘circuitopathy’, functional neuroimaging measures probing functional connectivity may also prove informative in post-stroke recovery. An important step in the development of biomarkers based on functional neural network connectivity is the establishment of causality between connectivity and post-stroke recovery. Current evidence predominantly involves statistical correlations between connectivity measures and post-stroke behavioral status, either cross-sectionally or serially over time. However, the advancement of functional connectivity application in stroke depends on devising experiments that infer causality. In 1965, Sir Austin Bradford Hill introduced nine viewpoints to consider when determining the causality of an association: [1] Strength, [2] Consistency [3] Specificity, [4] Temporality, [5] Biological gradient, [6] Plausibility, [7] Coherence, [8] Experiment, and [9] Analogy. Collectively referred to as the Bradford Hill Criteria, these points have been widely adopted in epidemiology. In this review, we assert the value of implementing Bradford Hill’s framework to stroke rehabilitation and neuroimaging. We focus on the role of neural network connectivity measurements acquired from task-oriented and resting-state functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and functional near-infrared spectroscopy in describing and predicting post-stroke behavioral status and recovery. We also identify research opportunities within each Bradford Hill tenet to shift the experimental paradigm from correlation to causation.

Aerobic exercise and action observation are two clinic-ready modes of neural priming that have the potential to enhance subsequent motor learning. Prior work using transcranial magnetic stimulation to assess priming effects have shown changes in corticospinal excitability involving intra- and interhemispheric circuitry. The objective of this study was to determine outcomes exclusive to priming- how aerobic exercise and action observation priming influence functional connectivity within a sensorimotor neural network using electroencephalography. We hypothesized that both action observation and aerobic exercise priming would alter resting-state coherence measures between dominant primary motor cortex and motor-related areas in alpha (7–12 Hz) and beta (13–30 Hz) frequency bands with effects most apparent in the high beta (20–30 Hz) band. Nine unimpaired individuals (24.8 ± 3 years) completed a repeated-measures cross-over study where they received a single five-minute bout of action observation or moderate-intensity aerobic exercise priming in random order with a one-week washout period. Serial resting-state electroencephalography recordings acquired from 0 to 30 minutes following aerobic and action observation priming revealed increased alpha and beta coherence between leads overlying dominant primary motor cortex and supplementary motor area relative to pre- and immediate post-priming timepoints. Aerobic exercise priming also resulted in enhanced high beta coherence between leads overlying dominant primary motor and parietal cortices. These findings indicate that a brief bout of aerobic- or action observation-based priming modulates functional connectivity with effects most pronounced with aerobic priming. The gradual increases in coherence observed over a 10 to 30-minute post-priming window may guide the pairing of aerobic- or action observation-based priming with subsequent training to optimize learning-related outcomes.

Introduction: Recent changes in reimbursement policies for inpatient rehabilitation facility (IRF) providers prompted the adoption of Quality Indicators (QI) on the IRF Patient Assessment Instrument leading to the discontinuation of the Functional Independence Measure (FIM). Given that the FIM has shown associations with motor assessments and self-efficacy measures during early stroke recovery, the purpose of this study was to confirm if similar associations exist with QI. Methods: Participants with acute ischemic and hemorrhagic stroke completed a battery of assessments at the time of IRF admission and discharge: Total QI (summation of self-care and mobility items), Upper Extremity Fugl-Meyer (UEFM), Action Research Arm Test (ARAT), and Stroke Self-Efficacy Questionnaire (SSEQ). We determined associations between QI and these measures by computing correlation coefficients with an alpha value=.01 denoting significance following a Bonferroni correction. Results: Fourteen individuals (7 females, age=65.9±9.0 years, 8.1±3.5 days post-stroke) with moderate-severe motor deficit completed study procedures. Table 1 summarizes admission and discharge scores and associations with QI. Conclusions: Significant associations between motor assessments and QI from this ongoing study parallel similar associations involving the FIM. The implementation of QI in IRFs necessitates additional work to validate our findings and to determine psychometric properties of QI to enhance clinical research in stroke rehabilitation.