Lynn C. Robertson - US grants

The proposed work will extend the PI's recent findings that recovering alcoholics differ from controls on specific components of visuospatial processing. Certain visuospatial functions are impaired while others are spared. Moreover, a similar pattern emerges when intoxicated non-alcoholics are tested even at a relatively low dose of alcohol (0.6 ml EtOH/kg). The proposed studies use new procedures developed for investigating normal cognitive functioning. These techniques are applied to explore specific effects of alcohol use and aubse on cognitive components of visuospatial functioning. A comprehensive series of experiments is proposed which examine alterations produced in perception of spatial relationships by acute and chronic alcohol intake. These procedures will allow a careful examination of alcohol's acute and long-term effects on l) orientation and form perception, 2) spatial analysis of stimuli presented over time, 3) memory for different properties of a form and 4) processing visual material associated with hemisphere specialization. The results of these experiments have implications for outcome studies, assignment of patients to treatment, and for suggesting biological markers of alcoholism.

The performance of any cognitive task invariabley depends on the adequacy of more than one cognitive process. Recent investigations from many laboratories (including the PI's) reveal that acute and chronic alcohol use affects some specific processes in visuospatial analysis relative to control subjects but not others. In addition, the subjects under the influence of alcohol and alcoholics exhibit a pattern of performance deficits which resemble, at least superficially, those seen in patients with right hemisphere lesions but not in those with left hemispere lesions. The proposed studies will employ relatively new methods to permit an evaluation of the specific processes of visuospatial analysis that are affected in alcohol and brain damaged subjects. We can then determine if the same specific cognitive processes are affected in the different populations whose overall performance in visuospatial tasks is similar. The findings from the proposed studies will be relevant to four general questions: 1) What specific processes of visuospatial analysis are affected by long term alcohol use? 2) What specific processes of visuospatial analysis are affected in intoxicated non- alcoholic subjects? 3) What specific processes of visuospatial analysis are affected in selected brain damaged patients and are they similar to or different from those affected by alcohol? 4) To what extent, if any, can visuospatial processing deficits found with alcohol (both acute and chronic) be attributed to visuospatial functioning of specified neural systems, and are any of these associated with mechanisms of perceptual organization? The results of these experiments have implications for outcome studies, assignment of patients to treatment and for suggesting biological markers for alcoholism.

The goals of this project are to isolate cognitive and neurological operations involved in perception of more local objects within other more global objects (e.g., a door knob as part of a door, a drawer as part of a desk) to understand the neural basis of why alcoholics are more likely to miss global visual information than local. The proposed studies will test alcoholics, patients with focal lesions in association cortex, patients with callosal commissurotomy and normals to assess the functional significance of 4 mechanisms involved in analysis of local and global levels of visual patterns. Our work indicates that one mechanism responds to local before global forms and is disrupted by lesions in left temporal-parietal (T-P) junction; one responds to global before local forms and is disrupted by lesions in right T-P junction; one is responsible for interdependency effects between the two levels and appears to be associated with interhemispheric transfer between posterior regions; and one controls the allocation of attention to global and local levels associated with inferior parietal lobe (PAR). By using reaction time measures, the proposed studies will test the following hypotheses: 1) Global and local form identification is weighted differently by the left and right T-P junction with differences in the fundamental spatial frequencies at the global and local levels contributing to this asymmetry. 2) Spatial organization processes are responsible for the influence of one level on the other (usually called interference) and are due to callosal connectivity between posterior cortex. 3) Alcohol affects both global processing and interference effects. Because the non-human primate literature has isolated one visual area in monkey posterior temporal lobe that responds to relative motion (MT) and another that responds to relative frequency and relative wavelength (V4) the effects of T-P damage on global and local motion will also be explored. By examining motion and spatial frequency deficits in alcoholics and groups with focal cortical lesions we will assess whether or not human temporal-parietal junction is involved in early comparative visual judgments over multiple visual domains and the degree to which alcoholics conform to the performance shown by selected posterior groups.

DESCRIPTION (Adapted from applicant's abstract): Large advances have been made in techniques to study human cortical function and its relationship to cognition. However, to know whether a certain area of the brain is not only sufficient but necessary to support particular cognitive operations, lesion studies are still required. The study of humans with lesions in targeted areas has the added importance of directly testing the cognitive sequela of brain damage, an increasingly frequent occurrence in an aging American population. Many studies that combine cognitive theory and methods with studies of neurological patients have demonstrated that the posterior cortex is extensively involved in object perception and visual spatial attention. Damage in these areas can cause severe problems in perceiving such features as shape, color, motion, location, etc. However, little is known about links between attention, object perception and memory and the neural mechanisms that support these links. The investigator recently found evidence for attentional and perceptual contributions to memory from spatial feature traces even when explicit memory was not required. These traces were altered in stable patients with focal lesions in the posterior cortex. In normals, features of attended objects seem to be automatically encoded and leave a trace for at least several seconds. These traces affect subsequent performance, but their duration is unknown. They are absent in groups of patients with left parietal lobe lesions. These traces could represent the elementary building blocks of memory that contributes to our knowledge of what features are critical in a selective task and how they are accessed. The proposed studies will extend investigation of these feature traces to issues in neuropsychology and cognitive neuropsychology. Studies are proposed to determine what features of unattended objects remain in memory, for how long, and under what conditions. The studies will help to determine the impact of cortical damage on these feature representations and the long-term functional consequences.

Several studies that combine behavioral methods with anatomical data in neurological patients have complimented evidence for two very general processing streams through the cortex, one involved in spatial processing (occipital-parietal) and the other in the perception and recognition of objects and their features (occipital-temporal). However, our preliminary work using chronometric measures reveals that despite the nearly complete loss of spatial abilities with relatively large bilateral dorsal lesions, spatial maps existed intact below the level of spatial awareness. These findings evolved from other preliminary work showing that bilateral occipital-parietal damage in humans affects how features are bound (presumably through ventral /dorsal interactions), suggesting a larger role for dorsal spatial functioning in object perception than previously recognized. When extensive loss of spatial awareness occurs, as with bilateral damage to the dorsal stream, shape perception remains but binding shape to surface features such as color, size or motion is severely disrupted. The proper binding of features appears to require explicit spatial knowledge that relies on dorsal systems. Although implicit spatial information remains intact, proper binding appears to require explicit awareness. The evidence is consistent with multiple spatial maps. Two sets of proposed studies are designed to explore targeted regions that may disrupt implicit spatial information and to determine the relationship of bilateral dorsal damage to unilateral damage that often produce other spatial deficits such as seen with unilateral inattention or hemineglect. Other sets of studies are designed to begin to explore the cognitive operations that contribute to implicit spatial effects observed in neuropsychological syndromes. The studies should help to determine the impact of cortical damage and underlying mechanisms that remain intact, potentially aiding in rehabilitation efforts and patient management. The translational potential of the work adds to the proposal's strength.

DESCRIPTION (Provided by applicant): The cognitive neuroscience program at UC, Berkeley (UCB) has experienced an abrupt growth in areas focused on human research with the appointments of two behavioral neurologists as Full Professors in the Department of Psychology (Mark D?Esposito, Director of the Wills Brain Imaging Center and Robert Knight) and by the appointment of senior cognitive neuropsychologist (Lynn Robertson). As a result there are 3 fully functioning new laboratories run by senior investigators on campus that focus on human cognitive neuroscience in addition to several preexisting laboratories across campus with a focus in this area. The development of a cognitive neuroscience graduate training program at UCB has been swift, and the demand for training in this area has multiplied greatly. To help meet the demand, we are requesting support for 8 graduate students per year. Trainees will engage in training activities at both the UCB campus and the Office of Veterans Affairs medical facility in Martinez (VA) where 12 active laboratories continue to focus on cognitive neuroscience research. The link between the two institutions is exceptionally strong in this area. One of the strengths of the program is the interdisciplinary background of its faculty and the interdisciplinary nature of training. Another strength is the access the program affords to observe a wide range of cognitive deficits associated with neural abnormalities, both structural and neurochemical in nature. The investigation of neurologically intact and neurologically impaired individuals with behavioral, electrophysiological and neuroimaging measurers gives students an appreciation of the breadth of the field and necessity for integration and converging evidence. Applicants to graduate programs at UCB have some of the highest qualifications in the country, and selection of trainees from among the accepted students will emphasize the potential for professional and scientific success. UCB has made a substantial commitment to health and neuroscience in the coming decade, and there is every reason to believe that the demand for translational training like that discussed in this application, will only grow.

DESCRIPTION (provided by applicant): The prevalence of facial recognition problems appears to have been underestimated in the normal population. Prosopagnosia or "face blindness" (whether congenital or acquired) causes untold embarrassment and often leads to social isolation. Recent imaging studies in normals have suggested that an area within the fusiform gyrus of the human cortex is active when faces are present, and non-invasive electrophysiological studies have now demonstrated that this activation begins around 140 ms over posterior cortex after presentation of a face (N170 component of the scalp ERP). The amplitude of the N170 is usually larger over the right than left hemisphere for normal upright faces and has been argued to reflect configural processing of faces. There has been some evidence that the response to faces can be modulated by attention. Attention to the configural properties produces more modulation in the right fusiform while attention to parts produces more modulation in the left, reminiscent of the evidence for other global/local hemispheric differences. The studies proposed here concern attention and face perception, including the role of awareness and automaticity (i.e., testing our hypothesis for mandatory priority of faces), some which address questions concerning the level of processing at which faces enter awareness (i.e., testing our hypothesis that all else being equal, attention is drawn to faces reflexively), and others that address the role of executive or top down mechanisms in processing faces under divided and focused conditions. These issues are addressed by combining neuropsychological, cognitive and electrophysiological methods to examine face processing in normal participants, in individuals who suffer from congenital prosopagnosia and in patients with attentional deficits that affect awareness (i.e., hemi-inattention). There are several unique strengths to this proposal: 1) collaboration between the PI and Co-PI with their respective expertise in cognitive neuropsychology of attention and electrophysiology of face perception; 2) the relatively large cohort of congenital prosopagnosic subjects (2 in Israel & 6 in California), some who have already been tested with the same paradigms across our two laboratories; 3) the opportunity for translational training for graduate and post doctoral students who will work on the proposed projects.

attention; neural information processing; visual perception; space perception; visual cortex; parietal lobe /cortex; clinical research; human subject;

DESCRIPTION (provided by applicant): Face discrimination is an outstanding example of human perceptual expertise, as it requires discrimination at the individual exemplar level within a highly homogeneous category of stimuli with similar global organization. Yet the ability to recognize a face seems effortless and is normally very efficient. To achieve this level of efficiency, specially-tuned perceptual processes are triggered when physiognomic qualities signal the existence of a face in the visual field. These processes include the analysis of characteristic face features (e.g. shape of the eyes, arc of the nose, etc.) as well as the computation of precise spatial metrics between the features themselves as well as their spatial relations to the outer contour of a face. Combining results reported in the literature with those found during our previous funding period, we propose that in the absence of quick and efficient basic-level categorization of visual stimuli as faces, the additional computations that allow discrimination among individual faces are either not elicited or are elicited disproportionately by face compared to objects. The consequence of such a state is impaired or inefficient face identification and, in extreme cases, face blindness, as can be observed in some individuals who never learn to identify faces (often referred to as congenital prosopagnosia or CP). One goal of the proposed experiments is to further explore individual variations in face processing among participants with normal face identification abilities as well as face identification deficits in CP and other face deficient populations. We also propose studies of face perception in selected patients with right hemisphere damage due to stroke for whom local processing can be relatively spared while global organization is impaired. We will continue to collect EEG and behavioral to study the perceptual and neural mechanisms underlying successful face perception. The studies proposed are expected to increase our understanding of the extraordinary human ability of face identification. Importantly, the results also will be useful for the development of training programs that would help to improve this socially important skill (see an example from our own research described in the preliminary studies section of this proposal). PUBLIC HEALTH RELEVANCE Prosopagnosia is a perceptual condition in which a face can be recognized as a face but cannot be discriminated from other faces despite intact visual, cognitive and other perceptual abilities. It can occur as a result of damage to certain areas of the human brain (acquired prosopagnosia) or as a developmental deficit (congenital prosopagnosia). Given the importance of face recognition skills in normal social discourse, understanding the cognitive and neural mechanisms associated with this ability will lead to greater understanding of how the brain performs this complex perceptual act as well as guide the direction of rehabilitation measures designed to enhance face recognition functions.