Background
Impaired response inhibition is a key feature of patients with alcohol dependence.
Improving impulse control is a promising target for the treatment of alcohol dependence.
The pharmacologic agent modafinil enhances cognitive control functions in both healthy
subjects and in patients with various psychiatric disorders. However, very little
is known about the underlying neural correlates of improvements in response inhibition
following modafinil.
Methods
We conducted a randomized, double-blind, placebo-controlled, crossover study using
functional magnetic resonance imaging with a stop signal task to examine effects of
a single dose of modafinil (200 mg) on response inhibition and underlying neural correlates
in abstinent alcohol-dependent patients (AD) (n = 16) and healthy control subjects (n = 16).
Results
Within the AD group modafinil administration improved response inhibition (reflected
by the stop signal reaction time [SSRT]) in subjects with initial poor response inhibition,
whereas response inhibition was diminished in better performing subjects. In AD patients
with initial poor response inhibition, modafinil-induced SSRT improvement was accompanied
by greater activation in the thalamus and supplementary motor area (SMA) and reduced
connectivity between the thalamus and the primary motor cortex. In addition, the relationship
between baseline response inhibition and modafinil-induced SSRT improvement was mediated
by these changes in thalamus and SMA activation.
Conclusions
These findings indicate that modafinil can improve response inhibition in alcohol-dependent
patients through its effect on thalamus and SMA function but only in subjects with
poor baseline response inhibition. Therefore, baseline levels of response inhibition
should be taken into account when considering treatment with modafinil in AD.
Key Words
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Article Info
Publication History
Published online: August 03, 2012
Accepted:
June 25,
2012
Received in revised form:
June 7,
2012
Received:
January 19,
2012
Identification
Copyright
© 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
