Visual Neurophysiological Biomarkers for Patient Stratification and Treatment Development Across Neuropsychiatric Disorders

The human visual system begins in the retina and projects to cortex through both the thalamocortical and retinotectal visual pathways. The thalamocortical system is divided into separate magnocellular and parvocellular divisions, which engage separate layers of the lateral geniculate nucleus (LGN) and project preferentially to the dorsal and ventral visual streams, respectively. The retinotectal system, in contrast, projects to the superior colliculus, pulvinar nucleus of the thalamus and amygdala. The pulvinar nucleus also plays a critical role in the integration of information processing across early visual regions.The functions of the visual system can be assessed using convergent EEG- and functional brain imaging approaches, increasingly supplemented by simultaneously collected eye-tracking information. These approaches may be used for tracing the flow of information from retina through early visual regions, as well as the contribution of these regions to higher-order cognitive processing. A pathway of increasing interest in relationship to neuropsychiatric disorders is the primate-specific "third visual pathway" that relies extensively on motion-related input and contributes preferentially to social information processing. Thus, disturbances in the brain's responsiveness to motion stimuli may be especially useful as biomarkers for early visual dysfunction related to impaired social cognition.Visual event-related potentials (ERPs) can be collected with high-fidelity and have proven effective for the study of neuropsychiatric disorders such as schizophrenia and Alzheimer's disease, in which alterations in visual processing may occur early in the disorder, andautism-spectrum disorder (ASD), in which abnormal persistence of early childhood patterns may persist into adulthood, leading to impaired functioning of visual social pathways. The utility of visual ERPs as biomarkers for larger clinical studies is limited at present by the need for standardization of visual stimuli across laboratories, which requires specialized protocols and equipment. The development of optimized stimulation protocols as well as newer headset-based systems may increase the clinical utility of present stimulation approaches.