Myelination in Development

The human brain is not a finished organ at birth -- in fact, another 10 or 12 years are needed before even a general development is completed. Structural maturation of individual brain regions and their connecting pathways is required for the successful development of cognitive, motor, and sensory functions. This maturation eventually provides for a smooth flow of neural impulses throughout the brain, which allows for information to be integrated across the many spatially segregated brain regions involved in these functions. The speed of neural transmission is an important factor, and this depends not only on the junctions between nerve cells (synapses), but also on the structural properties of the connecting fibers (axons). Critical axon structural properties include their diameters and the thickness of the special insulation (myelin) around many fibers. Large groups of myelinated axons, which connect various regions in the brain, appear visibly as "white matter". Axons of the major pathways in the human brain, such as those of the corpus callosum (which connects the two halves of the brain) or the corticospinal tract (which connects the brain to the spinal cord and the rest of the body), continue to develop throughout childhood and adolescence. Postmortem studies suggest that axon diameters and myelin sheaths undergo conspicuous growth during the first two years of life, but may not be fully mature before adolescence or even late adulthood. The scarcity of human brain specimens for postmortem analysis has made it difficult to draw definite conclusions about the timetable of myelinization during childhood and adolescence.

Our understanding of the propagation of nerve impulses represents an interesting convergence of physics and biology. The nerve impulse is a rapid propagating wave (approximately 1 millisecond in duration) of depolarization followed by repolarization. In the language of physics, the neuron axon behaves as an electrical transmission line with a transverse time-variant and voltage-dependent negative conductance element in parallel with a high capacitance. In fact, the equations describing the propagation of neuron action potentials derive from the classical equations for wave propagation along electrical transmission lines developed by Maxwell and Kelvin. As expected from these equations, the cross- sectional diameter of an axon is an important determinant of impulse propagation velocity: the larger the diameter, the greater the velocity of propagation. The myelin sheath that surrounds certain types of axons is a periodically interrupted electrical insulation, and on physical grounds it can be demonstrated that the effect of this type of insulation, considering the known electrical properties of the axon, is a substantial increase in pulse propagation velocity over that of a bare axon of the same diameter. Myelinization is thus a major aspect of the workings of neural circuits.

T. Paus et al. (2000) report a computational analysis of structural magnetic resonance images (see note below) obtained in 111 living children and adolescents. The authors report the analysis reveals age-related increases in white-matter density in fiber tracts constituting apparent corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, but that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. The authors suggest these findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions. The authors also suggest their finding may provide guidance for further investigations of neurodevelopmental disorders such as schizophrenia: "the abnormal rate of myelinization during childhood or adolescence may very well underlie the emergence of psychotic symptomatology." Finally, the authors suggest that the demonstrated possibility of detecting subtle structural variations in white matter in the living human brain opens up new avenues of research on normal and abnormal cognitive development and in the evaluation of the long-term effects of various treatment strategies.

T. Paus et al: Structural maturation of neural pathways in children and adolescents: In vivo study. Science 283 (19 Mar 99): 1908) Contact: Tomas Paus <tomas@bic.mni.mcgill.ca>.

Source: Science Week, 15 December 2000.

Magnetic resonance imaging (MRI) is a technique for examining morphology (as opposed to functional magnetic resonance imaging, or fMRI, which is a technique for examining anatomical correlates of function). In general, MRI involves magnetic coils producing a static magnetic field parallel to the long axis of the patient or subject, combined with inner concentric magnetic coils producing a static magnetic field perpendicular to the long axis. A radio-frequency coil specifically designed for the head perturbs the static fields to generate a magnetic resonance image. The interaction physics in this technique is that between the magnetic fields and atomic nuclei in brain tissue. "Sliced" views can be obtained from any angle, and the resolution is quite high and on the order of millimeters for magnetic field strengths of 1.5 tesla.

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