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Brain, Vol. 123, No. 1, 51-64, January 2000
© 2000 Oxford University Press

Functional corticospinal projections are established prenatally in the human foetus permitting involvement in the development of spinal motor centres

J. A. Eyre, S. Miller, G. J. Clowry, E. A. Conway and C. Watts

Developmental Neuroscience Group, Department of Child Health, University of Newcastle upon Tyne, UK

Correspondence to: Professor J. A. Eyre, Professor of Paediatric Neuroscience, Department of Child Health, The Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE2 4LP, UK E-mail: J.A.Eyre{at}newcastle.ac.uk

From studies of subhuman primates it has been assumed that functional corticospinal innervation occurs post-natally in man. We report a post-mortem morphological study of human spinal cord, and neurophysiological and behavioural studies in preterm and term neonates and infants. From morphological studies it was demonstrated that corticospinal axons reach the lower cervical spinal cord by 24 weeks post-conceptional age (PCA) at the latest. Following a waiting period of up to a few weeks, it appears they progressively innervate the grey matter such that there is extensive innervation of spinal neurons, including motor neurons, prior to birth. Functional monosynaptic corticomotoneuronal projections were demonstrated neurophysiologically from term, but are also likely to be present from as early as 26 weeks PCA. At term, direct corticospinal projections to Group Ia inhibitory interneurons were also confirmed. Independent finger movements developed much later, between 6 and 12 months post-natally. These data do not support the proposal that in man, establishment of functional corticomotoneuronal projections occurs immediately prior to and provides the capacity for the expression of fine finger movement control. We propose instead that such early corticospinal innervation occurs to permit cortical involvement in activity dependent maturation of spinal motor centres during a critical period of perinatal development. Spastic cerebral palsy from perinatal damage to the corticospinal pathway secondarily involves disrupted development of spinal motor centres. Corticospinal axons retain a high degree of plasticity during axon growth and synaptic development. The possibility therefore exists to promote regeneration of disrupted corticospinal projections during the perinatal period with the double benefit of restoring corticospinal connectivity and normal development of spinal motor centres.

corticospinal tract; development; human; spinal cord; {alpha}-motor neuron; Group Ia inhibitory interneuron

ADM = abductor digiti minimi; biceps = biceps brachii; CMCD = central motor conduction delay; CV = conduction velocity; EPSP = excitatory post-synaptic potential; GAP43 = growth associated protein 43; NMDA = N-methyl-D-aspartate; PCA = post-conceptional age; PMCD = peripheral motor conduction delay; PVL = periventricular leucomalacia; stretch reflex = homonymous phasic stretch reflex; TMCD = total motor conduction delay; TMS = transcranial magnetic stimulation; triceps = triceps brachii


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