Charles J. Duffy - US grants

nervous system; eye; biomedical resource; Chordata;

An extensive study of the translational LVOR frequency response during interaural (horizontal) and dorsoventral (vertical) oscillation has been completed in squirrel monkeys. We have found that the now well-known influence of vergence on LVOR sensitivity is remarkably limited to frequencies above around 0.5 Hz. Further, phase angle displays an increasingly large lead as frequency declines from 4 to 0.5 Hz. These findings suggest that the translational LVOR behaves with high-pass filtering characteristics, as does the AVOR, but with a cut-off at a much higher frequency (0.5 in the LVOR as opposed to 0.01 in the AVOR). The LVOR was also shown to behave linearly with stimulus amplitude over the range, 0.1-0.7 g peak acceleration. This remarkable performance suggests that the LVOR operates in a bandwidth that is almost exclusively above the capabilities of vision. We have also completed a sub-project on eccentric rotation, which activates both the AVOR and LVOR simultaneously. When the subject is displaced eccentrically from the rotation axis (e.g., 40 cm), and with the nose facing out, the effect of vergence on response gain at 4 Hz increases dramatically. This reflects the addition of the LVOR to the AVOR. The LVOR is driven by interaural (with the head upright) or dorsoventral (with the head on its side) tangential acceleration induced by eccentric rotation. This component adds to the horizontal or vertical AVOR, respectively, stimulated by the rotatory motion (head yaw if upright or pitch if on side). When the subject is turned around to face in toward the rotation axis, the LVOR component of the response is reversed and subtracts from the AVOR. We then observe a decline in gain with decreasing viewing distance. At distances closer than the rotation axis, the overall ocular response reverses direction; this is so because the LVOR component overwhelms the smaller AVOR component under these viewing conditions. The frequency-dependent behavior of the VOR during eccentric rotation has been addressed in depth, and for both horizontal and vertical responses. In concert with our new understanding of the LVOR, we observe the same frequency limitations of its influence on combined AVOR-LVOR responses. That is, the LVOR component of respouses to eccentric rotation is limited to frequencies above around 0.5 Hz. Further, the AVOR and LVOR have been shown to interact linearly during complex motion, as vector additions.

Patients who have suffered strokes affecting the right postenor parietal cortex often exhibit the syndrome of hemispatial neglect, an attentional deficit causing the individual to ignore the opposite side of the body and extrapersonal space. A common part of this syndrome is double simultaneous stimulus extinction (DSSE), wherein awareness of an object in contralateral hemispace is blocked only when a second object is simultaneously presented in the ipsilateral hemispace. We are exploring the mechanisms of visuospatial perception by testing patients with hemispatial neglect in a DSSE paradigm which uses overlying optic flow stimuli to trigger perceptual reorientation towards the neglected hemifield. The goal is to explore the dynamics of spatial orientation in subjects with various impairments of orientation attributable to lesions located in different parts of posterior parietal cortex. This project is operating as a collaboration between members of different units within the the University of Rochester Department of Neurology at Strong Memorial Hospital (Dr. Duffy from the Neuro-ophthalmology Unit and Dr. Langfitt from the Neuropsychology Unit). We are currently developing a separate limb of this study in collaboration with Dr. John G. Schmidt of St. Mary's Hospital Neurorehabilitation Unit in Rochester.

Patients with Alzheimers often complain of an inability to find their way even in familiar surroundings. Many such patients suffer a deterioration of visual function by the loss of acuity, contrast sensitivity, and visual motion sensitivity. We are testing a large, community-based cohort of Alzheimer's patients in an attempt to determine whether their difficulties with spatial orientation might be the result of impaired visual motion processing. Our hypothesis is that focal cortical degeneration in extrastiate visual areas creates a specific incapacity to acces the orienting cues imbedded in the optic flow field.

In ongoing research Dr. Watson is assessing the impact of activity training on balance in a nursing home population of moderately impaired elderly subjects. Our experience with AMTI's posturography platform has been used to design a new direction for this research, now using AMTI's portable posture platform as a way of assessing the impact of activity training on postural stability. Dr. Duffy serves as a consultant to Dr. Watson on posturographic recording in the elderly as part of a new grant submission to the National Institutes of Health. This project will incorporate testing of a large number of subjects with the portable unit at a number of nursing homes where activity training programs vary in approach, intensity, and scheduling.

DESCRIPTION (provided by applicant): Navigational impairments force Alzheimer's disease (AD) patients to abandon driving and independent living. We hypothesize that navigational impairments in aging and AD reflect failures of the neural mechanisms supporting the spatial and temporal integration of visual cues. We suggest that specific navigational deficits reflect the reliance of particular navigational skills on different segments of the visual spatiotemporal spectrum. To test these ideas, we will characterize visual processing in aging and AD linked to three fundamental navigational behaviors: heading estimation, route perception, and path integration. We have previously linked optic flow perceptual deficits to navigational impairments in AD. These patients show combined impairments in the spatial and temporal integration of visual stimuli. We now propose a comprehensive test of optic flow's role in navigation by characterizing links between specific navigational skills and the spatiotemporal composition of optic flow stimuli. We will apply spatial and temporal filters to optic flow simulating self-movement as subjects engage in a series of two-alternative forced-choice tasks designed to measure their sensitivity to the direction, speed, and distance of simulated self-movement. These studies will be coupled with detailed navigational and neuropsychological tests. In three Specific Aims, we will study: 1) Heading estimation, as the ability to indicate the direction, speed, and distance of self-movement. 2) Route perception, as the ability to discriminate relative directions, speeds, and distances traveled on a two-segment route. 3) Path integration, as the ability to combine directions, speeds, and distances for an optimal route of return to the origin. In each aim, we will manipulate the spatiotemporal composition of the stimuli to probe the relationship between perception and navigation. This work will lead to a new understanding of the perceptual foundations of navigation. We will test the relationship between spatiotemporal integration and perceptual processing for different navigational tasks in the context of navigational impairments in aging and AD. This will contribute to approaches for monitoring the progression of AD, evaluating patients' safety for functional independence, and assessing new treatments.

DESCRIPTION (provided by applicant): Single neuron neurophysiology has identified mechanisms of optic flow analysis in macaque dorsal extrastriate cortex (Duffy 2004). We have shown that optic flow perceptual deficits are associated with navigational impairments in aging and Alzheimer's disease (AD) (O'Brien 2001) (Mapstone 2010). Recently, we linked these lines of research by recording human optic flow event related potentials (ERPs), finding that they are highly correlated with perceptual and navigational impairments in aging and AD (Kavcic 2006) (Fernandez 2007). We have now recorded optic flow ERPs in monkeys, creating an opportunity to relate ERPs to the growing understanding of the cellular neurophysiology underlying visual motion processing. These efforts will elucidate the cortical mechanisms of optic flow analysis and its decline in aging and AD. We hypothesize that components of optic flow ERPs are specifically linked to the effects of bottom-up dorsal stream visual motion processing, and top-down attention and task related mechanisms thought to originate in posterior parietal (PPC) and dorso-lateral prefrontal (DLPFC) cortices. We will test this hypothesis in studies of monkeys viewing sequential optic flow stimuli during a memory guided saccade task. These studies will integrate the recording of single neurons in cortical area MSTd with the recording of LFPs in STS (superior temporal sulcus), PPC, and DLPFC, and with the recording of ERPs in a full cranial array. We will take three parallel approaches to probing the cortico-cortical interactions that link optic flow analysis to behavioral task demands and ERPs. First, we will analyze the co-variation in the responses of single neurons, LFPs, and ERPs to understanding the neurophysiological foundations of ERP components. Second, we will use age-related variation in ERP components to test for correlated variation in single neuron and LFP responses. Third, we will use pharmacological reversible inactivation to establish relations between specific cortical areas, ERP components, and the underlying neurophysiological response mechanisms. Understanding the neural mechanisms of visual motion processing, and its relationship to age-related changes in behavior, will promote the detection and amelioration of navigational impairments in aging and AD.