The human motor cortex microcircuit: insights for neurodegenerative disease

The human motor cortex comprises a microcircuit of five interconnected layers with different cell types. In this Review, we use a layer-specific and cell-specific approach to integrate physiological accounts of this motor cortex microcircuit with the pathophysiology of neurodegenerative diseases affecting motor functions. In doing so we can begin to link motor microcircuit pathology to specific disease stages and clinical phenotypes. Based on microcircuit physiology, we can make future predictions of axonal loss and microcircuit dysfunction. With recent advances in high-resolution neuroimaging we can then test these predictions in humans in vivo, providing mechanistic insights into neurodegenerative disease. The human motor cortex is selectively vulnerable in numerous neurodegenerative diseases. In this Review, McColgan et al. integrate layer-specific physiology with pathobiology in the motor cortex, thereby generating hypotheses that can be tested in humans using ultra-high-resolution neuroimaging techniques.