Background Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits.Method A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment.Results At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus.Conclusions OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striatopallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.

Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.

No abstract

While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D 2 /D 3 receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [18 F]fallypride to measure striatal dopamine D 2 /D 3 receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales ( p Ͻ 0.001). Volume-of-interest analysis found lower striatal D 2 /D 3 receptor availability in methamphetamine-dependent than in healthy control subjects ( p Ͻ 0.01) and a negative relationship between impulsiveness and striatal D 2 /D 3 receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D 2 /D 3 receptor availability in left caudate nucleus and right lateral putamen/claustrum ( p Ͻ 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold ( p Ͻ 0.12 corrected). The findings suggest that low striatal D 2 /D 3 receptor availability may mediate impulsive temperament and thereby influence addiction.

Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of alpha 4 beta 2* nAChRs, indicating that tobacco-dependent smokers maintain alpha 4 beta 2* nAChR saturation throughout the day. Because prolonged binding of nicotine to alpha 4 beta 2* nAChRs is associated with desensitization of these receptors, the extent of receptor occupancy found herein suggests that smoking may lead to withdrawal alleviation by maintaining nAChRs in the desensitized state.