Activity-dependent competition drives development of the corticospinal (CS) system during early postnatal life. Animal studies have demonstrated that imbalance of activity between the motor cortex (Ml) in the two hemispheres causes aberrant CS circuit formation and motor impairments. Rebalancing Ml activity on the two sides later in development restores normal CS connections and motor function. In human hemiplegic CP, a neurological disorder characterized by poor motor control, motor areas become damaged during perinatal development. The damage tends to have a unilateral predominance. Decreased CS system activity on the affected side is thought to be crucial to development of hemiplegic CP. It is hypothesized that restoring balance between the activity of Ml on each side is essential for restitution of normal CS circuitry and motor skill. One treatment effective in improving motor function in children with hemiplegic CP is training of the affected side with concurrent restraint of the unaffected limb. During treatment, children engage in skilled, repetitive movements with the affective side, while the unaffected side is restrained with a sling. This behavioral treatment balances Ml activity by increasing activity of the affected side through training while decreasing activity of the unaffected side through restraint. The proposed work will also examine how different intensities of skill training influence recovery. The important issue of whether training of movements focusing on precise distal control and shaping of increasing skill difficulty is more effective than repetitive task performance without increasing skill difficulty has not been addressed. Understanding the mechanisms underlying behavioral improvements is an important step towards developing new therapies that can be applied to a broader population of children with hemiplegia, especially those with more debilitating impairments who have the greatest need for an effective treatment. This proposal takes a translational approach to the study of CP rehabilitation, built upon an understanding of the development of the cat motor system. The applicant will obtain training in TMS, human motor skill assessment and analysis, and translating hypotheses between the animal and the human. By understanding the mechanisms of recovery, particularly the interplay between training and CS system plasticity in recovery, the applicant will be in the unique position to translate these mechanisms to improve CP treatment.

Agency
National Institute of Health (NIH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01NS062116-05
Application #
8322089
Study Section
Neurological Sciences Training Initial Review Group (NST)
Program Officer
Chen, Daofen
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Friel, Kathleen M; Chakrabarty, Samit; Martin, John H (2013) Pathophysiological mechanisms of impaired limb use and repair strategies for motor systems after unilateral injury of the developing brain. Dev Med Child Neurol 55 Suppl 4:27-31
Martin, John H; Chakrabarty, Samit; Friel, Kathleen M (2011) Harnessing activity-dependent plasticity to repair the damaged corticospinal tract in an animal model of cerebral palsy. Dev Med Child Neurol 53 Suppl 4:9-13