and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern
a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may
Human drug addiction has come to be viewed as a complex pro-
cess of the brain (Goldstein and Volkow, 2002), in which cogni-
tive factors such as the inability to control one’s own behavior in
light of the strong motivation to consume a drug are considered
critical. A recent hypothesis has argued for the role of executive
control of behavior contribute directly to the addiction process.
Repeated use of cocaine is associated with structural (Franklin et
structures considered important for executive control (Miller
neuropsychological impairments on tests of executive function
(Ardila et al., 1991; Di Sclafani et al., 2002).
Recent functional neuroimaging research examined whether
the neural changes that accompany cocaine use contribute to
executive dysfunction, finding an association between activation
changes and greater difficulty with inhibiting a prepotent re-
al., 2003). This effect was particularly evident within the anterior
cingulate cortex (ACC), consistent with the postulated effect of
cocaine on the mesencephalic dopamine system (which includes
the ACC, prefrontal cortex, and orbitofrontal cortex). Cocaine is
dopamine and increasing its concentration in dopamine
receptor-rich regions such as the ACC (Koob and Bloom, 1988),
and repeated exposure to this hyperdopaminergic state may ac-
count for decreased dopamine receptor levels in users and, con-
sequently, decreased metabolism (Volkow et al., 1999).
We hypothesize that the functional changes in the mesence-
phalic dopamine system that result from chronic cocaine use
render the user vulnerable to executive dysfunction. Inhibitory
control, as measured by the GO–NOGO task, provides an index
of this problem because of the requirement to exert executive
prefrontal and midline [ACC and presupplementary motor area
GO–NOGO task to allow for parametric increases in working
memory (WM) demands. These demands were of interest be-
cause previous studies with cocaine users have suggested that
cue-induced ruminative thoughts activate a “WM-like” network
of cortical regions (Bonson et al., 2002) and can interfere with
WM performance (Grant et al., 1996; Watkins and Brown, 2002;
of the requirement for greater top-down control (Bunge et al.,
2001; Hester et al., 2004). Our aim was to examine whether in-
creasing WM demands would have a greater negative impact on
cocaine users’ inhibitory control, with hypoactivity in regions
required for top-down control making users particularly vulner-
able to inhibitory failures when greater top-down control was
Subjects. Fifteen nondrug-using subjects (eight females; mean age, 31;
range, 20–40) and 15 active cocaine users (six females; mean age, 40;
range, 22–48) participated in the current study. Educational attainment
for the two groups was not significantly different (13.9 vs 11.5 years). All
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