National Eye Institute (NEI)

Mechanisms of perception and cognition 
Section on Perception, Cognition, and Action, Laboratory of Sensorimotor Research (NEI/NIMH)

Students would have the option to work on any project in the lab, and to take it in new directions. Current projects in the lab aim to understand the normal brain processes by which physical signals that impinge on the sensory apparatus (eyes, ears) are transformed into perceptions, thoughts, and actions. Work in the lab has been especially invested in developing color as a model system. The advantage of color is that its physical basis (wavelength) is well characterized, yet these chromatic signals support not only low-level visual abilities such as color matching but also high-level cognitive processes such as categorization, memory, social cognition, and emotion. This variety of phenomena provides a rich opportunity for investigating the full scope of perceptual and cognitive computations that make human vision such an important source of information about the world. The lab uses many research techniques, including psychophysics and non-invasive brain imaging (MRI, MEG) in humans, along with fMRI-guided microelectrode recording, fMRI-guided pharmacological blockade, microstimulation, tract-tracing, and computational modeling in non-human primates (NHPs). Work in the lab is organized around Four broad approaches:

First, the use of MRI in humans and NHPs to investigate homologies of brain anatomy and function between these species, to support the applicability of neurophysiology from NHPs to the human case, and to test hypotheses about the fundamental organizational plan of the cerebral cortex in the primate.

Second, the use of well-controlled psychophysics (including longitudinal experiments) combined with microelectrode recording in NHPs to show on a mechanistic level how populations of neurons drive behaviors such as perceptual decisions, categorization, and concept formation and memory.

Third, comparative psychophysical studies in humans and NHPs, as part of a program of neuroethology to understand the relative computational goals of perception/cognition in different primate species. In addition to studies of vision, the lab conducts experiments using auditory and combined audio-visual stimuli, to understand common principles of sensory-cognitive information processing, and to determine how signals across the senses are integrated into a coherent experience.

Fourth, large-scale neurophysiological experiments combined with cutting-edge analysis methods including machine learning, to determine the mechanisms of high-acuity visual perception at the center of gaze. We have developed several eye-trackers that afford photo-receptor resolution, providing an unprecedented look at fine-scale spatial and chromatic processing of the foveal representation in primary visual cortex. 
 

The laboratory of Prof. Bridge in Oxford uses multi-modal MRI to understand the pathways in the human visual system, and how they are affected by vision loss early or late in life.

The laboratory of Dr. Nienborg at the NIH combines behavior, neurophysiology, and videography in mammalian animal models to better understand how the visual system processes information depending on the animal’s behavioral and cognitive state. 

Visual processing during natural behavior requires subjects to distinguish between changes in visual information caused by a subject’s own body movements (e.g. by walking along a street), and those caused by changes in the external world (e.g. a car driving by). How the brain achieves this is fundamental to understanding visual perception. Moreover, the degree to which their own body movements affect processing in visual cortex in normally sighted and blind subjects has direct implications for the development of neural prostheses targeting the visual cortex.

The project will have two objectives:

1. Identify how spontaneous body movements affect processing in the visual cortex in a mammalian animal model during head-free, naturalistic behavior.
2. Compare the modulations in the visual cortex by a subject’s own body movements in sighted and blind human participants.

This project will allow students to learn wireless electrophysiological recordings in mammalian animal models (e.g. non-human primates or a highly visual rodent species) combined with videography during naturalistic behavior. Students will also be able to learn how to leverage recent machine learning approaches for the analysis of the video and neural data. Additionally, students will have the opportunity to learn how to acquire and analyze functional MRI data in sighted and blind human subjects, using a variety of tools.  

Hibernation confers extraordinary protection against various forms of stress and insults that would be life-threatening to non-hibernators. However, the mechanisms of such promising protection remain elusive, hindering potential therapeutic applications. One of the hallmarks of hibernation is metabolic regulation, exemplified by modifications in mitochondrial respiration throughout the different stages of hibernation. Nonetheless, the possible link between metabolic regulation and cellular protection is unclear.  This project aims to study the mitochondrial regulations and their roles in metabolic adaptation during hibernation, in the context of neuroprotection.

Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly affecting over 30 million individuals world-wide. AMD initiates in the back of the eye because of dysfunctions in the retinal pigment epithelium (RPE), a monolayer of cells that maintains vision through maintenance of photoreceptor healthy and integrity. AMD can lead to severe vision loss and blindness in advanced stages – “dry” and “wet” forms. In the dry stage, the death of RPE cells triggers photoreceptor cell death and atrophy of the choroidal blood supply causing vision loss. It is thought that RPE cell death in AMD is triggered by the formation of sub-RPE protein/lipid deposits called drusen. Our recent work shows that drusen formation is initiated by reduced autophagic flux in RPE cells resulting in reduced ability of RPE cells to process intracellular “debris” that eventually gets secreted as drusen deposits. TFEB, a member of MiT family of transcription factors is a known master regulator of autophagy. Here, we propose to investigate the activity of transcription factor TEFB in our AMD cellular models of iPSC-derived RPE cells. We hypothesize that autophagy downregulation is triggered by post-translational changes in TFEB that affect its sub-cellular localization and reduce its transcriptional activity. Here, we propose to identify those changes in TEFB and discover signaling pathways that lead to its altered activity. Lastly, we will test the ability of our recently discovered FDA-approved drugs that stimulate TEFB activity to reduce drusen formation by increasing autophagy in iPSC-RPE AMD models. This work will lead to a better understanding of AMD pathogenesis and potentially retool existing  drugs to treat AMD patients.