A psychobiological model of cravings in substance dependence: Electrophysiological and neuropsychological correlates.

摘要

The role of cravings in drug dependence is controversial, and the neural mechanism is not understood. This dissertation presents the Lateralized Dual-Pathway Model, which attempts to unite disparities found in the literature. The pathways represent baseline deprivation state, and phasic increases in stimulus salience. We suggest a common deficit in addiction is prefrontal damage of the right hemisphere (RH), associated with difficulties in processing affective or novel stimuli, denial, and impaired interpersonal behaviour. RH dysfunction results in a loss of tonic inhibition to the left hemisphere (LH). Similarly, stressful circumstances requiring active coping selectively activate the LH. Frontal LH hyperactivity is associated with approach behaviour, such as compulsive drug taking and relapse, and symptoms including excitement, symptom minimization, and social disinhibition.; To examine this model, we measured brain electrical activity of 42 abstinent cocaine- or alcohol-dependent subjects. Using a 128-channel electrode array, we recorded event-related potentials (ERPs) while administering a reinforcement-based learning task. In addition, we conducted neuropsychological tests and questionnaire measures. Our independent variable consisted of a novel computer-administered craving questionnaire.; ERP results demonstrated that craving severity varied inversely with amplitude of the N2-P3a peak-to-peak waveform measure for "high-risk" cues, extending previous findings of decreased amplitudes in drug abusers vs. controls. This waveform component is associated with response inhibition and automatic processing of novel or salient stimuli. No difference was found in the P3b waveform, thought to reflect context updating. In terms of reinforcers (i.e., winning or losing points), few significant group differences were noted. In support of the model, lateralized effects reflected the finding that negativities were mainly centered over the LH.; Craving correlated strongly with questionnaire measures of mood and personality, particularly anxiety, depression, and disinhibition.; Few correlations were found between craving and neuropsychological test scores. This may be because craving represents a transitory state, or may represent the relatively greater ability of neuropsychological tests to measure dorsolateral rather than ventromedial frontal lobe damage. However, a MANOVA comprised of lateralization measures indicated a significant difference between craving groups.; Taken together, these results provide support for lateralization as a functional neural mechanism underlying cravings in substance dependence.