Area:
frontal lobe functions, decision-making
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High-probability grants
According to our matching algorithm, Lesley K. Fellows is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2003 — 2004 |
Fellows, Lesley K |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Mapping the Anatomy of Decision Making @ University of Pennsylvania
DESCRIPTION (provided by applicant): Decision-making, the process of choosing between options, is a fundamental human behavior. Despite its ubiquity and importance, little is known about the neural substrates of this cognitive process. Impaired decision-making is an important symptom of a variety of neurological and psychiatric disorders, ranging from frontotemporal dementia to drug addiction. Focal injury to the ventral part of the frontal lobes, such as follows aneurysm rupture or closed head injury, seems to lead to selective impairment in decision making. This proposal describes work designed to break new ground in the cognitive neuroscience of decision-making. A series of exploratory studies based on classical decision-making theory will identify the neural substrates of this fundamental aspect of human cognition. The specific goals of this work are to (a) develop novel tasks that operationalize the core cognitive processes of human decision making by adapting experimental paradigms from psychology and economics, (b) use these tasks to identify the neural substrates of these fundamental elements of decision making: at the neuroanatomical level by evaluating patients with fixed lesions of the frontal lobes, and at the neurochemical level by studying patients with Parkinson's disease, (c) determine how impairments in basic reinforcement processing and learning in these patient populations may contribute to poor decision making both on the gambling task and in life, and (d) apply these decision making tasks to better characterize the frontal dysfunction of patients with frontotemporal dementia. Innovative behavioral methods adapted from decision-making research across multiple disciplines will be employed to study decision making in patients with fixed lesions of ventral or dorsal prefrontal cortex, Parkinson's disease, or normal subjects administered drugs that manipulate relevant neurochemical systems. This work will serve the long-term aim of establishing a framework to study the component processes of decision-making in the human brain, in both health and disease. This approach has the potential to provide insights into the basis for a wide range of pathological human behavior.
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0.961 |
2006 — 2009 |
Fellows, Lesley K |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Orbitofrontal and Striatal Mechanisms in Stress and Addiction
[unreadable] DESCRIPTION (provided by applicant): Significant progress has been made in understanding the brain mechanisms that underlie addiction in animal models. However, addiction in humans arises through a complex interplay between individual vulnerabilities and experiences, in turn modulated by social and cultural factors. Relating the basic neurobiology of addiction to the clinical complexity of this condition in the real world remains a challenge. Doing so is an important step in translating basic scientific advances to improve prevention, diagnosis, and treatment of addiction. This work will pursue this over-arching goal by exploring the neural mechanisms that mediate social influences in nicotine addiction, using a combination of behavioral, neuroimaging, and computational modelling techniques. Social stress is a common trigger of smoking behavior, and of relapse in smokers trying to quit. We have recently shown that in vulnerable individuals, even mild social stress can lead to measurable increases in dopamine release. We hypothesize that such a mechanism is also important in vulnerability to addiction, and will test that hypothesis with both behavioral and PET imaging studies in addicted and non-addicted smokers. The proposed work will focus on two regions of the brain that seem to play key roles in addiction: striatum and orbitofrontal cortex, and examine how behaviors mediated by these brain regions are influenced by the dopamine changes induced by a standardized social stressor. Orbitofrontal cortex may be a crucial mediator of maladaptive responses to social stress: this region appears to be important in inhibiting the compulsive behavior at the core of addiction, but it is also involved in the interpretation of subtle social-emotional information, and in the regulation of the stress response. As such, dysfunction of orbitofrontal cortex could be a common factor underlying several aspects of addiction vulnerability. This work will explore how common mechanisms may underlie both the social and reinforcement-learning functions of orbitofrontal cortex, through a combination of computational modeling and behavioral methods. This proposal arises from a new collaboration between investigators with complementary theoretical, methodological, and clinical expertise. It aims to develop a solid theoretical and experimental foundation for applying neurobiological findings to understand the real-life complexity of addictive behavior in humans. [unreadable] [unreadable] [unreadable]
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