What this trial measures

• Change in Cortical excitability measured as presence/absence of motor evoked potentials (MEP)3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

  Motor evoked potentials (MEPs) are the electrical signals recorded from the descending motor pathways or from muscles following stimulation of motor pathways within the brain. Responses from TMS pulses will be measured by recording muscle activity, referred to as motor evoked potentials (MEP).

• Change in Cortical excitability measured by intensity of motor threshold (MT)3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

  The MT is the minimum stimulation intensity that will elicit a consistent MEP of a pre-determined amplitude. MT and MEP are the common measures of TMS-induced excitability. Together, these measures provide information about the brain's excitability, associated with synaptic activity.

• Change in Mean Fractional Anisotropy (FA) within the CST1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

  Mean Fractional Anisotropy (FA) within the CST will be used to study structural connectivity. It is a dimensionless index between 0 and 1. (0 equals no anisotropy; greater anisotropy is indicated by higher FA values approaching the maximum of 1). N=10 infants aged 0-2 months (first timepoint) will participate in MRI scans

• Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale1 ±1 month

  The General Movements Assessment is used to identify absent or abnormal general movements. GMA requires 5-10 minutes video taping when infants are placed in spine position for scoring. "Absence or abnormal movements" will be reported as "Y".

• Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale3 ±1 months

  The General Movements Assessment is used to identify absent or abnormal general movements. GMA requires 5-10 minutes video taping when infants are placed in spine position for scoring. "Absence or abnormal movements" will be reported as "Y".

• Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score1 ±1 month

  The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are \<57 at 3 months and \<73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

• Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score3-6 months (one visit in this time frame)

  The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are \<57 at 3 months and \<73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

• Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score12±1 months

  The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are \<57 at 3 months and \<73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

• Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score18±1 months

  The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are \<57 at 3 months and \<73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

• Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score24±1 months

  The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are \<57 at 3 months and \<73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

• Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) Asymmetry Scoresdata collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

  An asymmetry can also be recorded for each item, with one point maximum allotted per item, with a total score ranging from 0-26. Based on the literature regarding asymmetries, the cutoff score of \>3 asymmetries will be used for recommendation of referral to early intervention service. See article by Fehlings, 2024 for additional context.

• Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score3-6 months (one visit in this time frame)

  Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

• Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score12±1 months

  Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

• Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-IV) score18±1 months

  Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

• Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score24±1 months

  Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

• Baby Observation of Selective Control AppRaisal (Baby OSCAR)1±1 month

  Baby OSCAR assessments are scored from video recordings of infant movement. Each limb is scored separately, with scores ranging 0-7 per lower limb, and 0-9 per upper limb for a total score of 0-32. Higher scores indicate better selective motor control.

• Baby Observation of Selective Control AppRaisal (Baby OSCAR)3-6 months (one visit in this time frame)

  Baby OSCAR assessments are scored from video recordings of infant movement. Each limb is scored separately, with scores ranging 0-7 per lower limb, and 0-9 per upper limb for a total score of 0-32. Higher scores indicate better selective motor control.

• Change in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

  Patient/caregiver-reported outcome measure of functional abilities and performance in children with disabilities. Scores are displayed instantly after completion of an assessment. A Detailed Score Report and a Summary Score Report are available. Normative scores are provided as age percentiles and T scores are based on a child's chronological age and intended for use by clinicians so that they may interpret a particular child's functioning relative to others of the same age. Scaled scores provide a way to look at a child's current functional skills and progress in these skills over time. Scaled scores are especially helpful in documenting improvements in functional skills for children not expected to exhibit or regain normative levels of functioning.