Functional Brain Imaging of Addiction
Neuropsychiatric Implications of Mapping Reward/Aversion Circuitry
Hans C. Breiter, M.D.
[Slides not available.]
SUMMARY: Dr. Hans Breiter addressed the question of how the experience of reward is similar across category of reinforcer, and how these reinforcers are experienced relative to aversive or painful events. Studies using fMRI across multiple categories of rewarding and aversive stimuli now suggest that at the scale of their measurements, there is a generalized circuitry for processing motivationally salient stimuli, comprised of subcortical gray matter and paralimbic cortices. Breiter presented evidence from his studies that the motivationally salient features of monetary gains and losses, infusions of drugs of abuse, visual processing of beautiful faces, and somatosensory experience of pain, are evaluated by these brain regions, and produce putative signatures for rewarding vs. aversive events. These studies and others point to a general integrative model for motivated behavior that has implications for understanding neuropsychiatric illness, and may point toward a new foundation for psychiatry.
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Endogenous Opioid Neurotransmission: Interfacing Reward and Stress Regulation
Jon-Kar Zubieta, M.D., Ph.D.
SUMMARY: Dr. Jon-Kar Zubieta’s presentation focused on neurotransmitter systems in the ventral basal ganglia and interconnected cortical and subcortical regions thought to mediate some of the responses to drugs of abuse and in drug reinforcement. PET studies using receptor selective radiotracers in human subjects demonstrate the activation of these circuits by nonrewarding, stressful, or noxious stimuli. Zubieta’s research showed that activation of endogenous opioid neurotransmission was associated with the suppression of affective and sensory ratings of these experiences, and accounted for some of the sex differences in the responses to these stimuli. Alterations in the metabolism of dopamine conferred by a common genetic polymorphism were also shown to dysregulate the response of the opioid system. These data demonstrate a point of interaction between the direct effect of drugs of abuse and stress regulatory responses.
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Chronic Effects of Drug Use and HIV
Linda Chang, M.D.
[Slides not available.]
SUMMARY: Dr. Linda Chang presented preliminary data demonstrating the additive effects of HIV and methamphetamine on brain injury to evaluate possible relationships between these physiological abnormalities and cognitive or behavior dysfunction. She stressed the need for further research to determine whether treatments, both pharmacological and behavioral, will lead to improvement on these physiological parameters. A major challenge in neuroimaging studies is that many drug users abuse multiple drugs concurrently; therefore, attributing the effects to a particular drug requires extensive screening for and exclusion of confounding variables (e.g., other drug use, concurrent neuropsychiatric disorders, and other medications).
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Neurobiological Substrates of Stimulant Action and Reward
Elliot A. Stein, Ph.D.
SUMMARY: Dr. Elliot Stein used fMRI to investigate the common sites of action in the human brain for methylphenidate and cocaine use. His study exploits the high spatial resolution and sensitivity of fMRI in a within-subjects design incorporating multiple doses of each drug with online behavioral measures. He showed that modeling of the pharmacokinetic profiles of IV cocaine and methylphenidate from fMRI data yield similar sites of activation, which partially agree with previous PET findings. These data suggest that incomplete overlap may reflect the influence that each drug’s different pharmacological profiles has on their behavioral consequences.
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