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The rules that govern many aspects of skeletal muscle structure and function are very different for the extraocular muscle allotype. The myoblast lineages present in the extraocular muscle primordia are permissive for generation of an unusually wide range of fiber types. The balance that is struck between genetic specification and activity dependent factors in shaping fiber phenotype to suit the demands of complex visuomotor systems is not yet well defined. Because skeletal muscle has high energy demands, diversity in fiber types is needed to maximize efficiency; greater diversity in fiber composition then indicates a more diverse functional repertoire. Together, the characteristics of small motor unit size, precise dependence of muscle force upon motor neuron discharge rate, high contractile speed but low tension development, and contractile protein heterogeneity contribute toward the high precision and diversity that is required for eye movements. Finally, the structural and functional characteristics and plasticity of the individual extraocular muscle fiber types play an important role in determining their response to disease or manipulation. The lack of uniform responses across the muscle allotypes in disease, or in response to pharmaceutical or surgical interventions, requires that we obtain a better understanding of the fundamental differences that exist between muscle groups.

Individual-based models provide modularity and structural flexibility necessary for modeling of infectious diseases at the within-host and population levels, but are challenging to implement. Levels of complexity can exceed the capacity and timescales for students and trainees in most academic institutions. Here we describe the process and advantages of a multi-disease framework approach developed with formal software support. The epidemiological modeling software, EMOD, has undergone a decade of software development. It is structured so that a majority of code is shared across disease modeling including malaria, HIV, tuberculosis, dengue, polio and typhoid. In additional to implementation efficiency, the sharing increases code usage and testing. The freely available codebase also includes hundreds of regression tests, scientific feature tests and component tests to help verify functionality and avoid inadvertent changes to functionality during future development. Here we describe the levels of detail, flexible configurability and modularity enabled by EMOD and the role of software development principles and processes in its development.

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OBJECTIVE To identify blinking-induced functional magnetic resonance imaging (fMRI) activation patterns in five benign essential blepharospasm (BEB) patients and five age-matched control subjects. METHODS fMRI brain activation maps were obtained during repeated conditions of spontaneous and voluntary blinking in BEB and control groups. Blood oxygen level-dependent intensity images were collected from two separate runs as 16 axial and 16 coronal, 8 mm thick slices using a T2-star weighted gradient echo EPI sequence, coregistered with anatomic images. Spatially normalized and isotropically blurred activation maps for each subject were combined within groups of BEB patients and control subjects to generate maps of the intersubject mean fractional signal change.RESULTS Substantially greater activation during spontaneous and voluntary blinking was seen in BEB patients compared with control subjects in the anterior visual cortex, anterior cingulate cortex, primary motor cortex, central region of the thalamus, and superior cerebellum. In both groups, activations were generally greater for voluntary than for spontaneous blinking. CONCLUSIONS The activations observed might represent a hyperactive cortical circuit linking visual cortex, limbic system, supplementary motor cortex, cerebellum, and supranuclear motor pathways innervating the periorbital muscles.

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A macaque monkey with a preexisting facial nerve injury showed a synkinesis of perioral muscles with blinking and thus provided a serendipitous model for a multiphasic analysis of this common neurologic syndrome. The amplitude of the paretic eyelid in spontaneous and air-puff-induced blinks was about one-third that of the normal eyelid. Despite the blink hypometria, induced blink durations remained matched for the two lids. EMG confirmed co-contraction of the zygomaticus and orbicularis oculi muscles on the affected side during blinking, with silence of the zygomaticus on the normal side. Neuroanatomic investigation showed that, on the affected side, some zygomaticus motoneurons were in the somatotopically correct nuclear subdivisions but that the majority were in the dorsal subdivision, which normally innervates the orbicularis oculi. This study supports the contention that some orbicularis oculi motoneurons are incorrectly rerouted to supply the perioral musculature following recovery from a peripheral seventh-nerve injury. This same pattern of relative weakness in eyelid muscles and the stereotyped co-contraction of lid and perioral muscles with blinking occurs in humans, suggesting that aberrant reinnervation may be the mechanism for this clinical phenomenon.