Anjan Chatterjee - US grants

This proposal is based on the premise that complex cognitive disorders in brain-damaged subjects can be analyzed in an objective, quantitative manner. Such precision is necessary to get beyond qualitative descriptions and to probe for underlying mechanisms. In the syndrome of unilateral spatial neglect, patients fail to orient towards, respond to, or act on stimuli in space contralateral to their lesion. Neglect may reflect a disorder in the ability to direct attention into contralateral space. During his fellowship, the Candidate discovered that abnormal behavior of patients with neglect may be precisely captured by the simple mathematical formula, psi = K(phi)beta. This power function relates the quantity of stimuli of which these patients are aware (psi) to the quantity of stimuli presented to them (phi). The constant (K) and the exponent (beta) are empirically derived. The observation is of particular significance because the psychological experience of sensations in normal subjects is also related to objective measures of sensory magnitude by power functions. Power function analyses uncover specific quantitative ways in which neglect behavior is similar to and deviates from normal. The present investigation will extend preliminary observations by testing left and right brain damaged patients and normal subjects on line bisection, cancellation and reading tasks. Power function analyses will be applied to these tasks to examine 1) the relationship between the function and the anatomy of attentional networks, 2) develop a methodology to investigate patterns of recovery after acute brain damage, 3) assess disturbances of attentional capacity after damage to attentional networks, and 4) clarify the consequences of such damage to mental representations. It is anticipated that the Specific Aims proposed will establish power function analyses as a novel and precise method to investigate mechanisms underlying the syndrome of unilateral spatial neglect.

Patients with stroke often suffer chronic disability. This disability may be caused by damage to motor systems or damage to separate "intentional" systems. Intentional systems might be more successfully treated with rehabilitative therapy than the motor systems. A subset of chronic stroke patients show greater motor disability than would be expected from the degree if weakness they experience; these patients can improve function substantially following two weeks of a new type of rehabilitative treatment developed at UAB. In this study, we are characterizing by fMRI studies the patients most likely to benefit from this treatment, and investigating how intentional systems contribute to patient's deficits and their responses to treatment. Patients are asked to perform a simple motor task involving rotating or extending their hands while brain activity is imaged by functional MRI. The fMRI activation images are interpreted to determine which brain areas are involved in the motor task. Studies are performed just before the initial treatment and several weeks later. We are testing the basic repeatability of the functional imaging studies, to determine how variable activation patterns are in healthy volunteer subjects performing the same motor tasks in different experimental sessions several weeks apart. Thus far, we have performed studies on three patients and three normal subjects, and have demonstrated the ability to obtain useful activation images during the functional protocol, with the subject performing arm and hand motions. The repeatability testing now being undertaken will determine to what extent small changes in activation pattern occur normally, to establish a level at which changes observed in patients can be deemed significant.

DESCRIPTION: The goal of the proposed research is to investigate subtypes of unilateral spatial neglect theoretically, mathematically and neuroanatomically. Traditional accounts of neglect view space and spatial representations as a single homogeneous entity through which attention is directed. These accounts cannot explain a number of recent empiric observations. The central hypothesis driving this investigation is that the nervous system constructs multiple spatial representations, and neglect may occur within these different representations. These hypothesized representations are anchored to the viewer, the environment and the object. We will conduct three sets of experiments in brain damaged patients and normal control subjects. The first set of experiments which addresses viewer centered reference frames, examines the modulation of neglect by changes in the position of the head in relation to the trunk. The second set of experiments, which addresses environment centered reference frames, examines the modulation of neglect by changes in the position of the entire body in relation to the environment. The third set of experiments, which addresses object center neglect, examines modulation of neglect by changes in visual grain and texture in relation to nascent objects. Each set of experiments will focus on modulation by a different modality (proprioception, vestibular sensation and visual texture) to test the central hypothesis of multiple spatial representations. To precisely characterize neglect subtypes we will develop and apply mathematical analyses of data. The first two sets of experiments will use psychophysical power functions and the third experiment will introduce the use of logistic regression to derive sigmoid functions. From a detailed analysis of the anatomy of these patients' brain lesions, we will investigate lateralizing differences in disorders of spatial attention, the anatomic substrate mediating spatial attention in three dimensions, and the neural mediation of functional modularity. In short, the proposed investigations should provide important evidence to advance our understanding of: 1) how input from different sensory modalities contribute to multiple spatial representations, 2) precise mathematical analyses of neglect behavior, and 3) the neural substrates underlying neglect subtypes.

[unreadable] DESCRIPTION (provided by applicant): The goal of the proposed research is to understand the relationship between thought, perception and language. If we derive considerable knowledge of the world through our sensory and motor systems and this knowledge can be expressed in language, then the obvious question is how are sensory-motor systems linked to language? We will examine this question in the context of knowledge of events, which are described in language by verbs and thematic relations. The central hypothesis driving these studies is that simple spatial schemas can represent events 'pre-linguistically'. The following specific aims will test this general hypothesis and investigate the derivation and general utility of these schemas: [unreadable] [unreadable] 1) To establish that conceptual knowledge of events is distinct from linguistic knowledge of events. We will study patients with left and right hemisphere brain damage to test the hypotheses that patients may have deficits of knowledge of events at either a linguistic or a pre linguistic conceptual level. 2) To determine if conceptual knowledge of events is structured spatially and whether this structure derives from cultural habits or from properties of a lateralized brain. Normal US and Israeli subjects (including those that only read a right-to-left language) will be investigated on cognitive behavioral tasks, to ascertain if the spatial schemas that underlie event knowledge are derived from cultural habits or properties of a lateralized brain. 3) To determine if brain regions dedicated to visual-spatial processing in part mediate knowledge of events. Normal US subjects will be investigated in fMRI experiments on several tasks involving knowledge of events. This information in concert with lesion location data from patient investigations will help identify the neural substrate mediating this knowledge. 4) To determine whether spatial schemas used to represent events also serve other cognitive domains. Normal US and Israeli subjects will be investigated on memory tasks to help determine if directions of action influence recall and recognition of events. [unreadable] [unreadable] The proposed studies will advance our theoretical understanding of the functional architecture and neural mediation of simple spatial schemas and knowledge of events. These studies will have theoretical implications for models of conceptual development and reasoning and practical implications for the treatment of aphasic patients.

[unreadable] DESCRIPTION (provided by applicant): The central aim of this proposal is to characterize how humans conceptualize and label spatial events. Humans recognize events that occur in the world and use language to communicate information about these events. How does this world to word mapping occur? What are the links between perception, perceptual categories and linguistic spatial representations? In approaching these questions, we will test a set of nested hypotheses postulating that spatial events (for speaking) are decomposed into static and dynaimc as well as intrinsic and extrinsic spatial information. These kinds of spatial information are represented along a gradient, ranging from the concrete and perceptual to the abstract and conceptual. The system is also designed to both recognize specific spatial events and be able to generalize from specific instances to general categories. We will use a three-pronged strategy to test these hypotheses in our 3 specific aims. First, we will test the hypothesis that during development spatial events become decomposed into manner (intrinsic) and path (extrinsic) of motion. This decomposition occurs for both prelinguistic and linguistic categories and proceeds along a concrete/perceptual to an abstract/conceptual gradient. Second, we will test the hypothesis that the neural mediation of spatial events is decomposed into manner of motion (intrinsic) and path and locative (extrinsic) information. Perceptually, these two kinds of information are linked to human MT/MST and fronto- parietal networks respectively. Furthermore, each domain has a functional anatomic organization with a gradient ranging from perception to conception to linguistic expression. Finally, will test the hypothesis that intrinsic and extrinsic spatial information can be selectively disrupted by brain damage. These perceptual and cognitive systems will be selectively vulnerable to disruption depending on whether damage occurs within postero-lateral temporal or fronto-parietal networks. By using developmental, imaging and neurolinguistic studies, we hope to advance our understanding of spatial concepts for language. Our goal is to establish points of convergence in this aspect of spatial cognition across cognitive linguistics, developmental psychology, functional neuroimaging and neuropsychology. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The central aim of this proposal is to characterize how humans conceptualize and label spatial events. Humans recognize events that occur in the world and use language to communicate information about these events. How does this world to word mapping occur? What are the links between perception, perceptual categories and linguistic spatial representations? In approaching these questions, we will test a set of nested hypotheses postulating that spatial events (for speaking) are decomposed into static and dynamic as well as intrinsic and extrinsic spatial information. These kinds of spatial information are represented along a gradient, ranging from the concrete and perceptual to the abstract and conceptual. The system is also designed to both recognize specific spatial events and be able to generalize from specific instances to general categories. We will use a two-pronged strategy to test these hypotheses in our 2 specific aims. First, we will test the hypothesis that the neural mediation of spatial events is decomposed into manner of motion (intrinsic) and path and locative (extrinsic) information. Perceptually, these two kinds of information are linked to human MT/MST and fronto-parietal networks respectively. Furthermore, each domain has a functional anatomic organization with a gradient ranging from perception to conception to linguistic expression. Second, we will test the hypothesis that intrinsic and extrinsic spatial information can be selectively disrupted by brain damage. These perceptual and cognitive systems will be selectively vulnerable to disruption depending on whether damage occurs within postero-lateral temporal or fronto-parietal networks. These studies will further expand our knowledge of disabilities in relational thinking experienced by aphasic patients that are not traditionally investigated. Furthermore, we plan to advance voxel based lesion symptom analytic techniques in establishing the functional neuroanatomy in aphasic subjects. In summary, we plan to use imaging and neurolinguistic studies to advance our understanding of spatial concepts for language. Our goal is to establish points of convergence in this aspect of spatial cognition across cognitive linguistics, functional neuroimaging and neuropsychology, and to further our understanding of the deficits experienced by aphasic subjects.

DESCRIPTION (provided by applicant): There is widespread agreement that figurative language fundamentally organizes how humans think and communicate. Despite the importance of figurative language, we know little about its neural underpinnings and even less about the effects of brain damage on its use. Disorders of communication profoundly affect the lives of patients as seen with deficits in phonology, semantics, and even discourse. However, we do not know very much about the breakdown in comprehension of figurative language. We hypothesize that even when individuals make substantial recoveries in language deficits following brain damage they may continue to have profound problems with understanding non-literal language. We aim to examine metaphors, a critical form of figurative language, in functional neuroimaging and patient-based studies. To test hypothesis about the neural bases for figurative language, we will use contemporary theoretical accounts of metaphor processing to motivate our studies and design our approach to overcome previous methodological limitations in this research. We expect to uncover unappreciated communication deficits in patients with neurological damage. Given the ubiquity of metaphor use in structuring thought and communication, such deficits beg to be recognized. Our proposed studies will advance our understanding of the cognitive neuroscience of metaphor comprehension in health and disease and have implications for the rehabilitation of subjects with brain disorders such as stroke.