PROJECT SUMMARY/ABSTRACT
Unilateral cerebral palsy (UCP) is a leading cause of childhood disability. An early brain injury impairs
the upper extremity function, bimanual coordination, and impacts the child's independence. The effectiveness of
existing rehabilitation approaches to improve the paretic arm function is limited due to higher training doses,
modest effect sizes, and poor retention of training effects. Thus, there is a critical need to find an effective priming
agent that, when paired with motor (bimanual) skill training, will facilitate neurobiological processes to enhance
the magnitude of training effects and improve functional capabilities of children with UCP. This proposal aims to
determine the effects of a novel priming agent, remote ischemic conditioning (RIC), when paired with bimanual
skill training to enhance bimanual skill learning and to augment skill dependent plasticity in children with UCP.
Ischemic conditioning (IC) is a phenomenon of protecting the target organ from ischemia by directly
exposing it to brief episodes of sublethal ischemia. RIC is a clinically feasible way of performing IC where
episodes of ischemia and reperfusion are delivered with cyclic inflation and deflation of a blood pressure cuff on
the arm or leg. Pre-clinical and preliminary clinical trials in humans show neuroprotective effects of RIC. Our
prior work has shown that when paired with motor training, RIC enhances motor learning in healthy individuals.
Based on these diversified benefits of RIC, our central hypothesis is that the multifactorial mechanisms of RIC
can be harnessed as a priming agent to enhance motor learning and augment neuroplasticity in children with
UCP. Our Specific Aims are: 1) to determine the effects of RIC + training on bimanual skill performance, and 2)
to determine the effects of RIC + training on corticospinal
randomized controlled trial, 30 children with UCP will first
upper
conditioning
excitability
undergo bimanual speed stack performance, functional
extremity, and Transcranial Magnetic Stimulation assessments. Children will then undergo RIC/Sham
plus training.
in children with UCP. In this triple blind,
We will deliver RIC/sham conditioning via cyclic inflation and deflation of a pressure
cuff on the paretic arm using a standard protocol. Training will involve 5 days (15 trials/day) of bimanual speed
stack training. Thechildren will perform the same baseline assessmentspost-intervention. We hypothesize that
compared to sham conditioning + training, RIC + training will significantly enhance: 1) bimanual skill performance
(decrease in movement time (sec) to complete bimanual speed stack task), 2) bimanual function (increase in the
Assisting Hand Assessment scores), 3) cortical excitability in the ipsilesional primary motor cortex (M1) (larger
amplitude of motor evoked potentials and lower resting or active motor thresholds), and 4) reduce motor cortex
inhibition (reduced short-interval intracortical inhibition and increase in intracortical facilitation in ipsilesional M1).
Our long-term goal is to develop effective interventions to improve function of children with UCP. Outcomes of
this project will provide critical ingredients for designing Phase II trials that will determine the effects of RIC
combined with intensive behavioral interventions to improve functional outcomes in children with UCP.
