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1.  Do brainstem omnipause neurons terminate saccades? 
Saccade-generating burst neurons (BN) are inhibited by omnipause neurons (OPN), except during saccades. OPN activity pauses before saccade onset and resumes at the saccade end. Microstimulation of OPN stops saccades in mid-flight, which shows that OPN can end saccades. However, OPN pause duration does not correlate well with saccade duration, and saccades are normometric after OPN lesions. We tested whether OPN were responsible for stopping saccades both in late-onset Tay–Sachs, which causes premature saccadic termination, and in individuals with cerebellar hypermetria. We studied gaze shifts between two targets at different distances aligned on one eye, which consist of a disjunctive saccade followed by vergence. High-frequency conjugate oscillations during the vergence movements that followed saccades were present in all subjects studied, indicating OPN silence. Thus, mechanisms other than OPN discharge (e.g., cerebellar caudal fastigial nucleus–promoting inhibitory BN discharge) must contribute to saccade termination.
PMCID: PMC3438674  PMID: 21950975
Tay–Sachs disease; saccades; omnipause neurons; fastigial nucleus; Müller paradigm
2.  The nonlinearity of passive extraocular muscles 
Passive extraocular muscles (EOMs), like most biological tissues, are hyper-elastic, i.e., their stiffness increases as they are stretched. It has always been assumed, and in a few occasions argued, that this is their only nonlinearity and that it can be ignored in central gaze. However, using novel measurement techniques in anesthetized paralyzed monkeys, we have recently demonstrated that EOMs are characterized by another prominent nonlinearity: the forces induced by sequences of stretches do not sum. Thus, superposition, a central tenet of linear and quasi-linear models, does not hold in passive EOMs. Here, we outline the implications of this finding, especially in light of the common assumption that it is easier for the brain to control a linear than a nonlinear plant. We argue against this common belief: the specific nonlinearity of passive EOMs may actually make it easier for the brain to control the plant than if muscles were linear.
PMCID: PMC3187914  PMID: 21950971
viscoelasticity; model; control; quasilinear; superposition
3.  Pharmacological tests of hypotheses for acquired pendular nystagmus 
Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for the pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus.
PMCID: PMC3187918  PMID: 21951011
cerebellum; inferior olive; plasticity; learning; Guillain–Mollaret triangle; multiple sclerosis
4.  The effects of ion channel blockers validate the conductance-based model of saccadic oscillations 
Conductance-based models of reciprocally inhibiting burst neurons suggest that intrinsic membrane properties and postinhibitory rebound (PIR) determine the amplitude and frequency of saccadic oscillations. Reduction of the low-threshold calcium currents (IT) in the model decreased the amplitude but increased the frequency of the simulated oscillations. Combined reduction of hyperpolarization-activated cation current (Ih) and IT in the model abolished the simulated oscillations. We measured the effects of a selective blocker of IT (ethosuximide) in healthy subjects on the amplitude and frequency of saccadic oscillations evoked by eye closure and of a nonselective blocker of Ih and IT (propronolol) in a patient with microsaccadic oscillation and limb tremor syndrome (mSOLT). Ethosuximide significantly reduced the amplitude but increased the frequency of the saccadic oscillations during eye closure in healthy subjects. Propranolol abolished saccadic oscillations in the mSOLT patient. These results support the hypothetical role of postinhibitory rebound, Ih, and IT, in generation of saccadic oscillations and determining their kinematic properties.
PMCID: PMC3431800  PMID: 21950976
burst neurons; hyperpolarization-activated cation current; low-threshold calcium current; reciprocal innervations

Results 1-4 (4)