Why brains behave differently: Insights from eye movement disorders

The variability in the evolution, phenomenology, and response to treatment of diseases, even among patients with the same genetic mutation or identical structural or metabolic insults, is a common challenge in contemporary neurology and neuroscience. Why does the human brain react so differently to the same disease or treatment? Genetic variability among individuals might be part of the answer. Epigenetics, how the activity of genes changes with changes in the environment also contributes to the variability. Genes determine the expression profile of molecules within and on the surface of neurons, such as ion channels. This profile influences membrane physiology, which in turn affects the behavior (or misbehavior) of neural circuits and thus the disease phenomenology. The physiology of circuit behavior is extremely complex. In this context, studying eye movements is valuable because normal ocular motor physiology is better understood, the structural correlates of ocular motor disorders are clearer, and the behavioral outcomes of these disorders can be precisely measured and interpreted with mathematical models. Here, we review three disorders characterized by unwanted oscillations of the eyes. While their structural correlates are relatively well defined, the phenomenology and response to treatment of these disorders are surprisingly variable. Mathematical models suggest that the mechanisms for the diverse phenomenology of these three diseases are centered on genetically determined variability in the physiology of neuronal membranes and the internal connections of neural circuits.