Robert Rafal - US grants

DESCRIPTION (ADAPTED FROM THE APPLICANT'S ABSTRACT): This project would continue ongoing investigations of the neurobiology of visual attention in normal subjects and neurologic patients. These investigators' previous work has identified the neural regions associated with three elementary operations for allocating visual attention: the parietal lobe disengages, the midbrain moves, and the thalamus engages attention. A continuing focus of this project has been the role of midbrain extra-geniculate visual pathways in controlling visually guided behavior. Chronometric measures of detection reaction time and saccade latency are employed to obtain converging evidence about collicular function from three subject groups: (a) in progressive supranuclear palsy patients, the effects of collicular lesions are examined on orienting behavior; (b) in hemianopic patients, experiments determine what orienting behaviors are preserved when the only available visual input is from the retinotectal pathway; and (c) in normal human subjects, an asymmetry in retinotectal projections from nasal and temporal hemiretinae is exploited to compare the efficiency of orienting attention and eye movements into temporal and nasal hemifields. These studies have established that the retinotectal pathway is critical for moving attention and for favoring novelty in visual scanning by inhibiting reorienting to recently attended locations. The studies proposed would further examine the interplay between reflexive and controlled neural processes in the allocation of visual attention. The goals are: (1) to specify the role of human extra-geniculate pathways in orienting attention to visual signals; and (2) to determine how these subcortical mechanisms for reflex orienting are regulated by higher centers which govern voluntary, goal-directed behavior. The proposed experiments would test the hypothesis that midbrain visual pathways have a special role in orienting attention to exogenous signals and in integrating attention with eye movement control. Other experiments would investigate the role of prefrontal cortex and the basal ganglia in orienting attention under endogenous control. These studies would attempt to determine how midbrain mechanisms for reflex orienting are regulated by these higher centers, and whether the prefrontal cortex or basal ganglia have a special role in orienting under delayed response conditions and, if so, whether the mechanisms involved reflect spatial memory capacity, sustained attention to a location, or control of oculomotor set.

We will investigate the neurobiology of preparatory set in order to isolate the cognitive components, and their neural substrates, of those brain switching mechanisms which enable humans to respond flexibly and efficiently to their environment. Reaction time (RT) experiments will be conducted in normal humans and neurological patients to separate the cortical and subcortical components of perceptual and motor preparatory set. The tasks are similar to those which have been employed in unit recordings in animal experiments for identifying selective enhancement related to preparatory set, so that the two strands of research may begin to converge. The perceptual set tasks involve a simple RT manual response on detecting a luminance changes in the visual field; the motor set tasks involve choice RT manual movements. For both tasks, preparatory set is induced by a preliminary visual cue which instructs the subject where to expect the target or which movement to prepare. Preparatory set is inferred, and its time course measured, on the basis of facilitation or inhibition in RT performance depending upon whether the cue correctly prepares the subject for the subsequent target. We will measure convert orienting in patients with progressive supranuclear palsy, and compare orienting into temporal and nasal hemifields in normal subjects, to test the hypotheses that midbrain centers are involved both in moving attention to exogenous signals, and in coordinating attention with eye movements. Experiments in patients with frontal and caudate lesions will test the hypothesis that these structures are involved in moving attention under endogenous control. Experiments in patients with thalamic lesions will test the hypothesis that the pulvinar is involved in engaging attention at a new location. Experiments in patients with Parkinson's disease, frontal lobe and cerebellar lesions will investigate the role of cortical and subcortical centers in mediating motor set. While the primary importance of this research lies in its potential for elucidating a fundamental problem in neurobiology, it also has potential clinical relevance as well. It may lead to more rational approaches to the rehabilitation of patients with attention and motor planning disorders due to neurological diseases.

This project will define the role of the basal ganglia in selective attention, and is motivated by a consideration of an emerging understanding of fronto-striatal circuits. Although Parkinson patients have motor problems, consideration of neuroanatomy suggests a more general description of the computation formed by the basal ganglia. One neural circuit begins in dorsolateral prefrontal cortex, an area often thought to subserve working memory for the separate domains of color, form, and space. The circuit courses through the basal ganglia in a manner not unlike that for circuits coming from motoric frontal regions, suggesting that the basal ganglia performs the same computation for each circuit. We propose an attentional computation in which the basal ganglia are involved in establishing, maintaining, and switching set. A decisive test of the theory would come from a demonstration that Parkinson patients and frontal stroke patients have impairment in establishing and switching sets involving color and form. Previous studies of Parkinson patients in our laboratories and others have not provided evidence for a role of the basal ganglia in shifting spatial attention, or shifting between movement sequences. We therefore draw a distinction between biasing functions of attention and selective functions, and suggest that the failure of earlier studies to identify attentional functions for basal ganglia was due to their use of biasing paradigms. These paradigms cue for one stimulus feature or dimension, leaving others as still relevant should they unexpectedly occur. Selection, on the other hand, requires that irrelevant dimensions be actively blocked to prevent their activation of a response in a given task context. Since the basal ganglia contain both inhibitory and net excitatory subcircuits, this dual characteristic fits with our proposal that the basal ganglia involves both selection of relevant dimensions and inhibition of irrelevant ones. The theory of basal ganglia attention switching within fronto-striatal circuits will be tested in Parkinson patients by manipulations of medication state, and in patients with infarcts of dorsolateral prefrontal cortex in a series of experiments on attention to color and form.

The project will test the hypothesis that there are two separate attention processes mediated by posterior association cortex: One which conjoins visual features in the process of object recognition, an a second which selects objects for action. In addition the studies will investigate whether these two processes are independent and, if so, identify the neural substrate underlying each. Most of the research will involve experiments that test the attentional abilities of patients with lesions of posterior association cortex. One series of experiments will investigate patients with clinical extinction to determine the degree to which simple visual features are processed in the unattended field in comparison to the ipsilesional field. It is predicted that processing of simple features in the contralesional field will be comparable to that for features in the ipsilesional field, and that the deficit in extinction will reflect primarily a failure to transfer the percept to the action system. A second series of studies will test patients without clinical extinction in a task to examine illusory conjunctions, a phenomenon in which information from different objects is erroneously combined. It is predicted that these patients will show a deficit in feature integration in the contralesional field.