Neural synchrony, axonal path lengths, and general anesthesia: a hypothesis.

Despite decades of research, the mechanism by which general anesthetics produce loss of consciousness remains mysterious. A clue may be provided by the evidence that synchronous firing of cortical neurons underlies higher forms of neural processing. In order for these synchrony codes to be precise, transmission time must be independent of path length over all the connected sites between any two cortical areas. Because path lengths vary, developmental mechanisms must compensate for the resulting delay variations. Delay variations could be detected by spike-timing-dependent cues and compensation implemented by systematic changes in axon diameter, myelin thickness, or internodal distance. Anesthetics have been shown to increase conduction velocity in myelinated fibers and may therefore disrupt path-length compensation by changing velocities by different amounts in different types of axon. This simple and testable theory explains why anesthetics interfere selectively with higher cognitive functions but leave those dominated by rate-based firing relatively intact.