Spatial Frequency Dependent Deficits in Anisometropic Amblyopia

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Two primary features of visual coding—spatial frequency and contrast perception—are abnormal in neurophysiological and behavioral measures of amblyopia. Mounting evidence indicates that interocular inhibition may drive amblyopic deficits, and this has led to the employment of varying gain control models to explain abnormal binocular interaction amblyopia. Psychophysical measures of contrast perception are commonly used to validate these models; however, a single gain control model has been unsuccessful in explaining amblyopic performance. This 5-year mentored training award seeks to address this problem by using novel neuroimaging and visual psychophysics to investigate whether spatial frequency and contrast deficits in anisometropic amblyopia are indeed secondary to interocular inhibition. Each aim of the study corresponds to specific training goals, which will map to competency in four main areas: (1) fMRI experimental design and model-based analyses; (2) computational modeling of both neuroimaging and psychophysical data; (3) clinical research design incorporating the use of fMRI, psychophysics, and computational modeling in clinical populations; and (4) career development. Such training will transform the applicant into an independent translational clinical scientist who can utilize both neuroimaging and psychophysics to examine underlying deficits in pediatric vision disorders. Training will be implemented at the reputable environments of Boston Children’s Hospital, Boston University, and Harvard Medical School with the expert guidance of Dr. Sam Ling (primary mentor), Dr. David Hunter (co-mentor), and Dr. MiYoung (advisor). Specifically, the mentor team will train the applicant to design, implement, and analyze measures of population spatial frequency tuning and contrast response in participants with anisometropic amblyopia. This work will enhance our understanding of interocular inhibition and spatial frequency and contrast-dependent deficits in amblyopia. Our data will guide and constrain models of binocular interaction in amblyopia. Furthermore, this additional neural characterization of the response of the amblyopic visual system to unbalanced dichoptic stimuli will explain variability in the efficacy of alternative therapies and identify new treatments that specifically target deficits in spatial frequency and contrast coding of the amblyopic eye. Through this training, the candidate will gain considerable mentorship and training in advanced neuroimaging techniques to quantify binocular visual function in amblyopia, providing a foundation to build a career as an independent clinician-scientist.