The epileptic network is characterized by pathologic, seizure-generating ‘foci’ embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci—a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices.

Both eye position and head orientation are influenced by the macular (otolith) organs, via the tilt maculo-ocular reflex (tiltMOR) and the vestibulo-collic reflexes, respectively. The mechanisms that control head position also influence the rest position of the eye, because head orientation influences eye position through the tiltMOR. Despite the increasing popularity of mice for studies of vestibular and ocular motor functions, relatively little is known in this species about tiltMOR, spontaneous orientation of the head, and their interrelationship. We used 2D video oculography to determine in C57BL/6 mice the absolute horizontal and vertical positions of the eyes over body orientations spanning 360° about the pitch and roll axes. We also determined head pitch during ambulation in the same animals. Eye elevation varied approximately sinusoidally as functions of pitch or roll angle. Over the central ±30° of pitch, sensitivity and gain in the light were 31.7°/g and 0.53, respectively. The corresponding values for roll were 31.5°/g and 0.52. Absolute positions adopted in light and darkness differed only slightly. During ambulation, mice carried the lambda-bregma plane at a downward pitch of 29°, corresponding to a horizontal eye position of 64° and a vertical eye position of 22°. The vertical position is near the center of the range of eye movements produced by the pitch tiltMOR. The results indicate the tiltMOR is robust in this species, and favor standardizing pitch orientation across laboratories. The robust tiltMOR also has significant methodological implications for the practice of pupil-tracking video oculography in this species.

Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains.