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Research Interests:

I have been exploring the differential effects of normal aging and Alzheimer's disease (AD) on sensory integration and attention. AD produces a unique disconnection syndrome in which corticocortical projections connecting distinct but functionally related cortical regions are systematically disrupted. A major consequence of this distribution of pathology should be the loss of effective interaction between otherwise relatively intact cortical areas. One phenomenon that should be particularly sensitive to this disruption is the ability to bind sensory features processed in different cortical regions into a coherent representation, since such sensory integration is thought to be dependent upon coordinated activity across different cortical regions.

As an initial test of this hypothesis, we examined the ability of AD patients to integrate visual features processed in separate cortical regions using a global motion coherence task in which subjects are asked to detect the direction of motion for a subset of signal dots moving coherently across a circular aperture while embedded within a larger number of randomly moving noise dots. Previous studies in normal subjects have found that the ability to detect this motion can be enhanced either by segmenting the signal and noise on the basis of luminance contrast (i.e., black vs. white) or by segmenting the signal on the basis of isoluminant chromatic structure (i.e., red vs. green): While the enhancement from luminance segmentation reflects the integration of motion and luminance information solely within the dorsal visual stream, the enhancement from color segmentation must reflect integration of motion and color information across the dorsal and ventral streams, respectively. We found that patients with AD were able to effectively use the luminance cues to bind two visual features processed within the same cortical stream, but were unable to use the color cues to bind two visual features processed in separate cortical streams. In contrast, neurologically intact individuals and patients with a subcortical neurodegenerative disease (i.e., Huntington's disease) were able to effectively bind sensory information both within and across the cortical streams. This cross-cortical binding deficit not only provides psychophysical confirmation of the neocortical disconnectivity in AD, but also suggests that this disorder can serve as an excellent "model system" for delineating the cognitive and neural substrates mediating sensory integration in humans.

This novel finding has led to the development of several other sensory integration projects. First, since tests of sensory integration may provide direct neurocognitive probes of the functional disconnectivity that is pathognomonic to AD, we are currently examining the feasibility and utility of sensory integration as a novel marker for early detection and tracking the progression of AD. In particular, we are assessing the ability of normal elderly subjects, patients with mild cognitive impairment (MCI), and AD patients to integrate sensory information at three different levels of cortical information processing: (1) Unimodal integration of visual featural information; (2) Cross-modal integration of lower-level visual and auditory information; and (3) Cross-modal integration of higher-level visual and auditory information. Second, we have recently begun to employ both electrophysiological event-related potential (ERP) measures and functional imaging (fMRI) techniques to investigate whether normal elderly participants and patients with MCI or AD show similar patterns of activation across the different brain regions while performing these sensory integration tasks. The use of ERP and fMRI in conjunction with the behavioral assessment of sensory integration has great potential for identifying patients in the earliest prodromal phase of AD. The development of such a marker would have substantial implications for more effective application of pharmacologic and neuroprotective therapies for AD, as well as for longitudinal tracking of the efficacy of these treatments throughout the course of the disease.

Another line of research is concerned with understanding the effects of normal aging and Alzheimer's disease on different attentional systems. In an initial study, we examined the interaction of phasic alerting and spatial orienting in AD patients using a spatial pre-cuing task in which a cue indicating the probable location of the target is presented just prior to the presentation of that target. The difference between response speeds to invalidly cued and validly cued targets, referred to as the orienting effect, reflects how efficiently observers engage, move, and disengage attention from one location to another. While some studies have found an increased orienting effect in AD patients similar to that observed in patients with parietal lobe damage, several other studies have found AD patients to demonstrate normal or even anomalous orienting effects. One explanation for these discrepant results that has not previously been considered is that the performance of AD patients on spatial pre-cuing tasks does not solely reflect changes in spatial orienting processes in these patients, but rather reflects the interaction between changes in orienting and phasic alerting. Phasic alerting refers to non-selective, stimulus-driven processes that enhance performance on sensory processing tasks and that are elicited within the orienting task whenever a cue is presented prior to the target. Although not typically examined within spatial pre-cuing paradigms, phasic alerting can be assessed by directly comparing response times for neutrally cued targets with those for targets not preceded by any cue.

We found a marked deficit of phasic alerting in AD patients suggestive of a disruption within the ascending noradrenergic projection system previously implicated in the modulation of phasic arousal. Although AD patients also demonstrated an increased orienting effect in our task, this effect was due to an apparent increase in the benefit of validly cued targets associated with a decrease in the non-selective alerting benefit provided by these cues rather than to an actual change in orienting per se. These results suggest that performance within the spatial pre-cuing task reflects an interaction between non-selective phasic alerting processes and spatially selective orienting processes. These findings not only serve to increase our understanding of the nature of attentional deficits in AD patients, but also suggest that the simultaneous assessment of alerting and orienting processes within the same task may be a particularly powerful approach for investigating the neural and cognitive architecture of attention in neurologically intact individuals. To further explore the nature of this interaction, we have recently completed a follow-up study with young normal adults in which we systematically manipulated the level of phasic alerting elicited within this task by presenting non-spatial auditory cues simultaneously with visual cues on half of the trials. Consistent with our conclusion from our initial study that alerting specifically facilitates sensory processing of targets, we found that increased phasic alerting selectively enhanced performance on validly but not invalidly cued targets.

Finally, I have been involved in a series of studies designed to systematically assess the status of different attention systems in AD patients cross-sectionally as well as longitudinally, and to then examine how changes to these attention systems contribute to changes in actual driving ability. To this end, we have developed a set of computerized cognitive tests that assess a number of distinct aspects of attention (i.e., vigilance, arousal, selective and divided attention, and working memory), and that can be performed both in isolation or embedded within a computerized driving task in order to simulate the high cognitive demands associated with real-world driving. These studies should not only provide a better understanding of the neurocognitive substrates underlying different attentional processes, but should ultimately lead to more effective diagnostic measures for predicting on-road driving performance.