Laurel J. Buxbaum - US grants

DESCRIPTION: (Adapted From The Investigator's Abstract): An extensive literature suggests that speed and accuracy of detection of a target object in an array of other objects (distractors) is a function of the locations of target and distractor objects and the visual and semantic characteristics of these objects. Recent evidence for control subjects and patients with frontal and parietal lesions suggests that response factors (such as whether the task requires a button press or target-touch response) may also critically influence performance on such tasks. On the basis of such data, as well as findings from physiological studies, we have developed a provisional model of the role of distinct fronto-parietal processing modules in location coding and "selection for action". This model predicts differing roles for spatial, object, and response factors in selection as a function of the integrity of each of the proposed processing modules. A major goal of this research program is to test whether the predictions of the model are borne out in the performance of patients with perceptual neglect, directional hypokinesic neglect, and optic ataxia, whose lesions are hypothesized to affect different modules. The proposed experimental program will center upon selective reaching tasks, and will culminate in a series of studies of real-object detection and prehension designed to have greater relevance to naturalistic action than do most traditional laboratory studies of visual attention. In addition to contributing to the understanding of normal and disordered percept-motor processing, data from these studies are expected to provide evidence bearing on the real-life action performance of patients with such disorders, and thus, to have clinical implications for assessment and treatment.

DESCRIPTION (provided by applicant): An emerging movement within cognitive neuroscience posits that many cognitive processes are a product of goal-directed interactions between actors and environments. A complementary view is the theory of "motor facilitation", which maintains that viewing an object activates the appropriate movements for interacting with it. Thus hypothesized is a strong bi-directional link between conceptual representations of objects and goal- directed actions. Due in part to the novelty of this area of investigation, relevant theories are for the most part highly unconstrained. This proposal makes use of our conceptual model of object-related actions, the 2 Action System model, to frame a theoretically- driven set of predictions that will be tested in an interdigitated series of studies with patients with stroke and cortico-basal ganglionic degeneration syndrome, both of whom exhibit high-level action disorders, healthy subjects, detailed neuroimaging analyses, and transcranial magnetic stimulation. One of the critical hypotheses to be tested is that different types of action representations may be activated under different task demands, with differing predicted time courses, and based upon distinct neuroanatomic substrates. Also to be tested are predictions related to a hypothesized set of constraints on the relationship of motor competence and conceptual organization. Finally, several experiments will relate individual differences in the current status of the motor system, and underlying integrity of brain structures involved in motor planning and execution, to a) activation of previously-existing, natural conceptual representations and b) the ability to develop artificial conceptual object and action representations. These studies will test the hypothesis that the competence of the motor system has highly circumscribed and predicted relevance for both natural concept retrieval as well as artificial concept learning. The proposed work is expected to have broad significance for theories of "selection for action" and "embodied cognition", as well as for accounts of higher-level disorders of motor control. Specifically, the proposed work will 1) provide critical constraints on the contexts in which bidirectional links are observed at the conceptual- motor interface, 2) elucidate the precise representational structure and time-course of activation of object and action representations, 3) anchor relevant constructs in a detailed cognitive-neuroanatomic model, and 4) clarify the nature of conceptual-motor impairments of patients with high-level (cognitive) action disorders. PUBLIC HEALTH RELEVANCE: The proposal describes a series of studies with neurological patients and transcranial magnetic stimulation (TMS) having broad significance for our understanding of clinical disorders of object-related action (apraxias). These disorders are extremely common and disabling in both stroke and degenerative dementia, yet have been the subject of comparatively little research. The proposed experiments will focus on clarifying the mechanisms and interactions of neural systems responsible for coding different types of object-related action, and are a critical missing step in the design of theoretically and empirically informed approaches to treatment.

Project Summary Limb loss due to amputation is a common problem, occurring in nearly 2 million people in the US. Approximately 90% of individuals with limb amputation experience the persistent sensation of the missing extremity, known as a phantom limb, and up to 85% experience persistent and debilitating pain in the missing limb, termed phantom limb pain (hereafter PLP). We previously demonstrated that Virtual Reality (VR) with active leg movements and vision of a virtual limb significantly reduce phantom limb pain in subjects with below the knee amputations. The work proposed here has several objectives. In Specific Aim 1 we will randomize 40 subjects with PLP to treatment with our Active VR or a commercially available VR pain treatment (Cool!). In Specific Aim 2 we propose to develop a home intervention for PLP using the intervention (Active VR or Cool!) that in Specific Aim 1 proved to be most efficacious. In specific Aim 3 we will obtain multimodal ultra-high resolution (7T) MRI imaging in subjects with PLP before and after treatment, and normal subjects without amputation; we will also attempt to develop imaging biomarkers that predict efficacy of treatment. Imaging studies will address a number of controversies regarding the neural basis of PLP and explore human neuroplasticity more generally. Finally, in Specific Aim 4 we propose to determine factors that could be used in a clinical biomarker-based algorithm to predict response to home-based VR treatment. Using classification and regression tree (CART) analysis with the data from Aim 2, we will identify behavioral and neuroanatomic factors that predict treatment response. By the end of the grant period, we will have determined the relative efficacy of two VR treatments for PLP, assessed the feasibility and efficacy of a low-cost home-based treatment, determined the neuroanatomic changes associated with treatment response using advanced methods, and explored the behavioral and neuroimaging biomarkers predicting treatment response. These data will provide a critical step toward clinical implementation of a VR treatment protocol for PLP and will advance theoretical understanding of the mechanisms and functional neuroanatomy of PLP.