Preterm and term infants with brain injury frequently have delayed motor skills, and one hand and arm may become stronger than the other, which can signal early cerebral palsy. A new treatment, transcutaneous vagus nerve stimulation (taVNS), boosts specific brain circuits and may improve function when paired with intensive motor activities. This study will test taVNS-paired constraint induced movement therapy in infants who have greater weakness on one side and determine if a single pulse of transcranial brain stimulation over the motor area can cause a measurable movement of the hand or thumb, and indicate which infants can benefit from 40h taVNS-paired CIMT.

One of the most effective early therapies for improving motor skills in infants with unilateral motor weakness after perinatal brain injury, is constraint induced movement therapy (CIMT), in which a therapist engages a child in targeted play therapy with the more-affected arm/hand while the less-affected arm is immobilized in a mitt, reinforcing activity-dependent neuroplasticity. taVNS may accelerate functional gains and boost CIMT effects in young infants with hemiplegia over CIMT alone, based on pilot data. Before embarking on a larger scale trial, single pulse transcranial magnetic stimulation (sTMS) will be used to determine the connectivity and strength of the cortical spinal tract motor circuit with motor evoked potential of the hand or thumb.

The hypothesis is that the ability to respond to taVNS paired with intensive motor skill therapy in hemiplegic infants may be predicted by motor evoked potentials (MEP) elicited from sTMS over the motor cortex, as a quantifiable biomarker of CST circuit integrity, circuit response and cortical excitability.

Inclusion Criteria:

• Infants 8-24mo with hemiplegia or asymmetric weakness of one arm, with or without truncal and transitional motor delays
• Gross Motor function Classification system (GMFCS) I - IV
• Parents are able to make consecutive appointments for assessments and intervention over 2wks and complete the 3mo follow-up.
• Parents are willing to fill out developmental questionnaires and provide the study team feedback on tolerability and outcomes.

Exclusion Criteria:

• previous CIMT within 3 months
• GMFCS V or severe motor impairment/quadriplegia
• uncorrected blindness/deafness, cardiomyopathy
• poorly controlled seizure disorder

Videotapes of motor skills assessments are identifiable PHI and will not be shared. Extracted, de-identifed data may be shared on request.