Elsevier

Biological Psychiatry

Volume 63, Issue 2, 15 January 2008, Pages 222-230
Biological Psychiatry

Original Article
Expectation Modulates Human Brain Responses to Acute Cocaine: A Functional Magnetic Resonance Imaging Study

https://doi.org/10.1016/j.biopsych.2007.03.021Get rights and content

Background

Human expectation of psychoactive drugs significantly alters drug effects and behavioral responses. However, their neurophysiological mechanisms are not clear. This study investigates how cocaine expectation modulates human brain responses to acute cocaine administration.

Methods

Twenty-six right-handed non–treatment-seeking regular cocaine abusers participated in this study. Changes in blood oxygenation level-dependent (BOLD) signals were measured, and online behavioral ratings during cocaine expectation and acute cocaine administration were recorded.

Results

Distinct regional characteristics in BOLD responses to expected and unexpected cocaine infusions were observed in the medial orbitofrontal gyrus (Brodmann area [BA] 11), frontal pole (BA 10), and anterior cingulate gyrus regions. Active engagement in the amygdala and the lateral orbitofrontal cortex (OFC; BA 47) by unexpected but not expected cocaine infusion was discovered. Cocaine expectation did not change BOLD responses to acute cocaine administration in a set of subcortical substrates, the nucleus accumbens, ventral putamen, ventral tegmental area, and thalamus.

Conclusions

These results suggest that cocaine expectation modulates neural-sensitivity adaptation between the expected events and the actual outcomes but did not modulate the pharmacological characteristics of cocaine. In addition, the amygdala–lateral OFC circuitry plays an important role in mediating stimulus-outcome relations and contextual factors of drug abuse.

Section snippets

Human Subjects and Drug Run-Up

Detailed inclusion and exclusion criteria as well as run-up procedures for the participants were described previously in the literature (17, 22). In brief, 26 right-handed non–treatment-seeking regular cocaine abusers from the greater Milwaukee area participated in this study. A consent form approved by the Institutional Review Board was obtained from each subject before any experiments were conducted. During the consent process, participants were informed that they might receive either saline

Behavioral Measures

Throughout each fMRI run, the subject reported his or her subjective feelings of five variables by moving a joystick-controlled cursor below VAS ratings of high, craving, pleasant, nervous, and sour (Figure 1B). After cocaine infusion, there were several behavioral VAS ratings that significantly changed. For example, the mean of the high VAS ratings was significantly elevated from pre-infusion baseline levels in both the unexpected-cocaine (UC) (two-sample unpaired t test, p < .005) and

Discussion

Expected- and unexpected-cocaine infusion activated a common set of neural substrates. The brain areas commonly activated by expected- and unexpected-cocaine infusion (Table 1, Table 2) are in general agreement with results of our previous study (17), with additional loci of activation due to the whole-brain coverage of the BOLD acquisition. This pattern might indicate a set of neural substrates related to the pharmacological and behavioral effects of cocaine. The ventral striatum (NAc and

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