The long term goal of this project is elucidation of the pharmacological basis of decision making, a term which is often referred to in the psychological literature as """"""""executive functions,"""""""" and the application of the derived knowledge to the treatment and prevention of substance abuse. Both substance abusers and patients with ventromedial prefrontal frontal lobe lesions suffer from impairments in decision-making. Here we plan to study frontal patients and extend the findings to substance abusers. The proposal is guided by a theoretical framework designed to account for the defects in reasoning and decision-making that are so salient in frontal patients. The hypothesis posits that those decision-making defects, specifically those which involve personal and social behavior, are the results of defective activation of somatic markers that normally function as covert or overt signposts for helping with the process of making choices which are advantageous to the organism. In the past few years, we investigated the anatomical, physiological, and cognitive aspects of the neural network presumed to underlie decision-making and somatic marker activation. We found that the failure to enact somatic states results from dysfunction in a neural system in which the ventromedial (VM) prefrontal cortex is one critical region. However, other neural regions, including the amygdala and somatosensory cortices (SI, SII, and insula) are also hypothesized to be components of that same neural system. The operation of this system is thought to be influenced by non-specific neurotransmitter systems through direct or indirect anatomical connections. However, the nature of these neurotransmitter systems, has not been elucidated. Using experimental strategies which we perfected in the study of these patients, here we propose to carry out specific neurotransmitter manipulations and investigate their effects on decision-making in normals and in patients with frontal lobe lesions. In addition, we plan to investigate how another frontal lobe function, namely working memory, is affected by the same manipulations, relative to decision-making. Recent evidence has established that substance abusers suffer from decision-making impairments as revealed by the same laboratory tests which we used to study frontal patients. Ongoing investigations are probing further the link between decision-making, the frontal lobe, and substance abuse. Therefore, the results from this project will help the development of pharmacological therapies that assist in the rehabilitation of 1) substance abusers; and 2) many patients who suffer from disturbances of executive function caused by head injury, stroke, and surgical ablation of tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA012487-01
Application #
2840418
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Grant, Steven J
Project Start
1999-07-01
Project End
2003-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Iowa
Department
Neurology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Xue, Gui; Lu, Zhonglin; Levin, Irwin P et al. (2011) An fMRI study of risk-taking following wins and losses: implications for the gambler's fallacy. Hum Brain Mapp 32:271-81
Fineberg, Naomi A; Potenza, Marc N; Chamberlain, Samuel R et al. (2010) Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology 35:591-604
Xue, Gui; Lu, Zhonglin; Levin, Irwin P et al. (2010) The impact of prior risk experiences on subsequent risky decision-making: the role of the insula. Neuroimage 50:709-16
Xue, Gui; Lu, Zhonglin; Levin, Irwin P et al. (2009) Functional dissociations of risk and reward processing in the medial prefrontal cortex. Cereb Cortex 19:1019-27
Verdejo-GarcĂ­a, Antonio; Bechara, Antoine (2009) A somatic marker theory of addiction. Neuropharmacology 56 Suppl 1:48-62
D'Argembeau, Arnaud; Xue, Gui; Lu, Zhong-Lin et al. (2008) Neural correlates of envisioning emotional events in the near and far future. Neuroimage 40:398-407
Brand, Matthias; Recknor, Emily C; Grabenhorst, Fabian et al. (2007) Decisions under ambiguity and decisions under risk: correlations with executive functions and comparisons of two different gambling tasks with implicit and explicit rules. J Clin Exp Neuropsychol 29:86-99
Burns, Kelly; Bechara, Antoine (2007) Decision making and free will: a neuroscience perspective. Behav Sci Law 25:263-80
Lamers, C T J; Bechara, A; Rizzo, M et al. (2006) Cognitive function and mood in MDMA/THC users, THC users and non-drug using controls. J Psychopharmacol 20:302-11
Shiv, Baba; Loewenstein, George; Bechara, Antoine (2005) The dark side of emotion in decision-making: when individuals with decreased emotional reactions make more advantageous decisions. Brain Res Cogn Brain Res 23:85-92

Showing the most recent 10 out of 16 publications