Administration, patient recruitment, methods, informatics Funded Grant uri icon

description

  • DESCRIPTION (provided by applicant): Goal-directed behavior requires the ability to monitor and execute internal goals and intentions, maintain and manipulate information in working memory, select task-relevant information, and organize action plans to accomplish these goals. The proposed research program will employ a multidisciplinary approach directed toward investigations of the neural mechanisms underlying such "executive control" processes. Neurocognitive methods-particularly neuroimaging and neuropsychological techniques- have sharpened our understanding of such processes. Indeed, it is well established that the prefrontal cortex (PFC) is critically involved in the executive control of a variety of goal-directed behaviors. Yet, our understanding of how the PFC is itself organized and how it dynamically controls other cortical and subcortical regions is less well understood. We will develop and utilize a wide range of complementary methodologies to explore executive control processes. These methods include physiological techniques (e.g. single unit recording in monkeys, functional MRI in healthy subjects, electocorticography in epilepsy patients), neuropsychological methods (e.g. behavioral studies of patients with focal lesions due to stroke, transcranial magnetic stimulation of healthy subjects), pharmacological techniques (e.g. effects of dopaminergic agents in healthy subjects, behavioral studies of Parkinson's disease patients on and off their medication) and developmental methods (e.g., studies of healthy children). The Core of the Program Project will provide detailed neuropsychological and neuroanatomical assessment of neurological patients, state-of-the-art neuroimaging and electrophysiological facilities, and an integrative intellectual environment that will facilitate cross-fertilization of ideas and methods among investigators. Three proposed projects will address issues of executive control processes associated with goal-directed behavior. Project 1 will address the functional organization of regions within PFC and how they contribute to executive control. Project 2 will focus on mechanisms by which the PFC initiates top-down signals to posterior cortical regions in order execute control over bottom-up activations. Project 3 will focus 'on fronto-striatal circuits and how they contribute to decision-making and response plans. The knowledge gained from this work has the potential to be of central clinical significance, as many neurological disorders include impairment in executive control processes. Moreover, such knowledge may provide a foundation for developing cognitive and pharmacological therapies for treating the wide range of disorders characterized as deficits in executive control.
  • The Core of this Program Project consists of four components that represent services that are provided to each of the three research projects. In addition, each of these components will continue to be engaged in development of the infrastructure required for the implementation of the methods in the research plan. The four components of the core described below are: 1. Administrative services 2. Neurological patient and subject recruitment support and development 3. Neuroscientific method support and development 4. Informatics and datacenter support and development.
  • The broad goal of Project 1 is to advance understanding of the organization of lateral frontal cortex, both in terms of the regional distinctions that define its functional topography and the principles by which these regions interact to produce controlled behavior. The first set of experiments was designed to test the hypothesis that frontal cortex is hierarchically organized, with progressively more anterior regions processing higher-order representations. According to this hierarchical hypothesis, successive stages of processing lead to increased abstraction and complexity of representation along a posterior-anterior gradient across frontal cortex. This hypothesis will be tested with two paradigms and a variety of approaches: behavioral data from patients with focal PFC lesions, temporary lesions with transcranial magnetic stimulation, intracortical recordings in humans prior to epilepsy surgery, and fMRI studies in adults and children. The second set of experiments focuses on the most anterior part of lateral frontal cortex, a region implicated in higher cognition about which relatively little is known. Based on preliminary data, we have argued that this region is involved in the joint consideration of multiple relationships between mental representations - a general function that can be used to compare, evaluate, or integrate across concepts, or to coordinate several ongoing mental processes. A variety of complementary techniques will be used to test whether anterior lateral frontal cortex is sensitive to the need to consider multiple relations between items. Basic knowledge about the functional organization of frontal cortex gained from these proposed studies is of central clinical significance, and can provide substantial insights into the nature of a large number of neurological disorders associated with the frontal lobe dysfunction, such as stroke, traumatic brain injury, and degenerative brain diseases including Parkinson's, Alzheimer's Disease, and frontotemporal dementia.

date/time interval

  • 2002 - 2013