Evidence of activity-dependent withdrawal of corticospinal projections during human development

Objective: To characterize the development of ipsilateral corticospinal pro jections from birth and compare to 1) development of contralateral projecti ons in the same subjects and 2) ipsilateral corticospinal projections in su bjects with unilateral lesions of the corticospinal system acquired perinat ally or in adulthood. Methods: Transcranial magnetic stimulation excited th e motor cortex, and responses were recorded bilaterally in pectoralis major , biceps brachii, and the first dorsal interosseus muscles. Subjects studie d included 9 neonates recruited at birth, studied longitudinally for 2 year s; 85 healthy subjects aged from birth to adulthood; 10 subjects with hemip legic cerebral palsy; and 8 with hemiplegia after stroke. Results: In neona tes, ipsilateral responses had significantly shorter onsets than contralate ral responses but similar thresholds and amplitudes. Thresholds within both pathways increased in the first 3 months. Differential development was pre sent from 3 months so that by 18 months ipsilateral responses were signific antly smaller and had significantly higher thresholds and longer onset late ncies than contralateral responses. A similar pattern of smaller and later ipsilateral responses was observed after transcranial magnetic stimulation of the intact cortex in subjects with stroke. In contrast, subjects with he miplegic cerebral palsy had ipsilateral responses with onsets, thresholds a nd amplitudes similar to those of contralateral responses. Significant bran ching of contralateral corticospinal axons from the intact motor cortex was excluded by cross-correlation analysis. Conclusions: These data, together with previously published anatomic and radiologic studies, are consistent w ith activity-dependent corticospinal axonal withdrawal during development a nd maintenance of increased corticomotoneuronal projections from the intact hemisphere after unilateral perinatal lesions.