PROJECT SUMMARY
Walking and balance impairment resulting from stroke significantly reduces functional walking independence,
increases fall risk, and is a rising public health issue. The time window to have the greatest impact after a stroke
is within the first six months, yet there is limited knowledge of the drivers of balance and walking recovery in this
period. In addition, the lack of mechanistic grounding regarding anatomical correlates of walking and balance
recovery after stroke limits the ability for customized and targeted non-invasive neuromodulation protocols.
Hence, there is an urgent need to identify reliable physiologic and neuroanatomic correlates in the earlier stages
of recovery (<6 months) to enable timely and targeted rehabilitation interventions. This developmental research
proposal aims to longitudinally track the development of post-stroke sensory reweighting (PSR) in the first six
months after stroke, identify associated structural neuroanatomical correlates, and investigate their relationship
to walking and fall outcomes. The central hypothesis is that PSR development is critical for walking and balance
recovery and is related to the extent of injury to critical sensorimotor integration networks and descending motor
tracts. The rationale for the proposed research is its expectation to yield relevant information on the mechanisms
of walking and balance recovery and establish a framework to develop targeted strategies for rehabilitation in
stroke and related disorders. Dr. Oluwole Awosika, an early-stage clinical investigator with expertise in post-
stroke walking recovery and non-invasive neuromodulation, will lead this proposal. He has assembled an
excellent team of collaborating investigators with expertise in longitudinal clinical trial recruitment and retention
in the acute hospital setting (Dr. Stacie Demel), post-stroke multimodal neuroimaging (Dr. Brady Williamson),
human biomechanics (Dr. Amit Bhattacharya), and biostatistics (Dr. Heidi Sucharew). The study hypotheses will
be tested by pursuing two specific aims: 1) Serially investigate the development of PSR (1a) and determine its
relationship to walking speed (1b) and falls (1c) at 2-, 4-, and 6-months post-stroke and 2) Exploring the
relationship between the degree of structural injury to the parieto-insular vestibular cortical network (PIVC-N),
corticospinal (CST), and corticoreticulospinal (CRT) tracts. Under the first aim, static posturography will be used
to determine PSR status and will be correlated to walking speed and interval fall incidence. The second aim will
explore the relationship between the mean fractional anisotropy of the PIVC-N, CST, and CRT on diffusion tensor
imaging and PSR status at six months. This proposed research is innovative because it is mechanistically driven,
methodologically rigorous, and uses cutting-edge technology to investigate the early determinants of post-stroke
walking and balance recovery. The project is significant because it will shed light on potential mechanisms and
neuroanatomical correlates of walking and balance recovery early after stroke, help to optimize post-acute
rehabilitation strategies, and provide key considerations in designing future walking rehabilitation trials.
