Automatic versus evaluative components of cue reactivity: The protocol is aimed at studying psychological, physiological and brain responses to drug-associated cues, and at dissociating aspects of cue reactivity that occur automatically without cognitive elaboration, and those that require cognitive processing resources to unfold.? ? The Neural Basis of Cue-elicited Cigarette Craving and its Control: The main goal of this investigation is to ascertain the neural basis of cue-elicited cigarette craving and its control in smokers. This protocol employs new technologies such as fMRI-compatible EEG and real-time feedback fMRI while participants see smoking-related cues or neutral cues, and complete cognitive tasks (e.g. to report or regulate their craving, etc).? ? Effect of Functional Genetic Polymorphisms on Brain Morphology and Function: This protocol aims to integrate genotyping with both structural and functional brain imaging to investigate the impact of specific functional polymorphisms on morphology and function of the amygdala and the hippocampus and on behavior mediated by these brain regions elaboration, and those that require cognitive processing resources to unfold.? ? Effects of Nicotine on Cognitive Task Performance and Brain Activity as Measured by fMRI.
The aim of this study is to use fMRI to ascertain the changes in neural function associated with reward processing following acute administration of nicotine in dependent smokers. ? Dopamine Function and Reward Processing in Schizophrenia:
Our aim i s to examine brain activity related to reinforcement processing in schizophrenia (SZ) and the contributions of dopamine system dysfunction to symptoms in SZ. Behavioral paradigms involving reward processing are administered to SZ patients and controls in an MRI scanner to elicit brain responses to reinforcement, stimuli predictive of reinforcement, or the surprising omission of reinforcement.? ? Neuroimaging Studies of Neurophysiological Phenotypes in Schizophrenia: In this NIDA/MPRC collaborative protocol we designed several fMRI experiments to examine the perceptual and cognitive contributions to cortical mechanisms controlling eye movement outputs. We expect that fMRI will provide a safe, non-invasive approach to carefully examine the neurophysiological process leading to pursuit eye movement dysfunction in schizophrenia in this multi-year project.? fMRI Study of Nicotinic Effect on Neurophysiology of Schizophrenia: This NIDA/MPRC collaborative protocol aims to study nicotine effects on neurophysiological functions in eye movement and attention in schizophrenia patients by comparing behavioral performance and fMRI activation in schizophrenia patients and healthy controls in a double blind, placebo controlled fMRI study. Converging lines of evidence suggest that high rates of smoking and nicotine addiction among schizophrenic patients is influenced by the presence of disease-related abnormalities in brain function. Pharmacological studies show that nicotine temporally improves performance in several cognitive tasks including sensory gating, long-term memory, and eye tracking.? ? Prenatal Drug Exposure: Effects on the Adolescent Brain and Behavior Development: This collaborative study looks at the effects of intrauterine drug exposure on cognitive and reward system function in adolescents. Subjects perform a visuospatial working memory task and a gambling task with wins and losses while undergoing fMRI. Resting data and DTI are also obtained.? Effects of nicotine on brain activity aim to employ fMRI to define nicotines neural pharmacokinetic and pharmacodynamic properties and neurochemical sites and mechanisms of action in adults who are experienced smokers. A better understanding of these processes may lead to better behavioral and/or pharmacological therapeutic interventions for nicotine abuse and recidivism and identify a likely cognitive profile resulting from prolonged abuse.? ? Morphological Changes in Primate Brain due to Early Life Stress? Traumatic experiences in early childhood have been consistently associated with increased risk for developing mood and anxiety disorders later in life, which have been linked to structural brain abnormalities in adults and children. Morphological changes in the brain of juvenile Rhesus monkeys exposed to significant early life stress have been assessed using MRI. Compared to controls, we found an increased volume of cerebellar vermis, the medial prefrontal and dorsal anterior cingulate cortex. We suggest that increased ACC volume may be a structural phenotype for an increased risk of developing stress-related neuropsychiatric disorders. ? ? Functional MRI with Administration of Nicotine in Rats? While rapid tolerance is found to many of nicotines behavioral and autonomic effects, the central sites of nicotine tolerance are less well studied. We addressed this question by mapping regional cerebral blood volume (rCBV) change in adult rats after administering two consecutive doses (I.V., 25 min interval) of either 0.1 or 0.3 mg/kg nicotine under -chloralose. In most activated areas, rCBV responses were larger after the first high dose injection compared with the second one demonstrating tachyphylaxis. In contrast, little evidence of tachyphylaxis was seen following a second low dose nicotine injection. These results suggest that nicotine tolerance development is dose sensitive. The high-dose nicotine intake may lead to rapid tolerance development, possibly due to greater receptor desensitization, than after repeated low doses, which may play a role in maintaining smoking behavior. ? ? Neuropharmacological Consequences of Chronicle Cocaine Exposure in Rat Mesolimbic System ? The adaptations of brain function following chronic cocaine exposure appear to be long-lasting and implicate multiple brain circuits. In this study, rats were trained to self-administrate cocaine for one month followed by one month of withdrawal period. Baseline cerebral blood perfusion, resting-state functional connectivity and cerebral hemodynamic response to acute cocaine challenge after withdraw were imaged using fMRI techniques at 9.4T. Results were compared with animals experiencing the same environments but treated with either sucrose or saline as control. Preliminary results suggest that baseline perfusion in the prefrontal cortex of the cocaine-treated rats is increased, and the functional connectivity between the prefrontal cortex and the nucleus accumbens is up-regulated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000470-05
Application #
7733807
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$2,892,727
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Hahn, Britta; Ross, Thomas J; Wolkenberg, Frank A et al. (2009) Performance effects of nicotine during selective attention, divided attention, and simple stimulus detection: an fMRI study. Cereb Cortex 19:1990-2000
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