Search

Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with (H2O)-O-15 positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

Objective: Parameters of a pharmacokinetic-pharmacodynamic (PK-PD) model of levodopa have been claimed to reflect the magnitude of the dopaminergic deficit in patients with Parkinson's disease. The aim of this study was to correlate such parameters with positron emission tomography (PET) with levodopa tagged with 6-fluorine 18, an established imaging method for striatal dopaminergic neurons. Methods. Twenty-three patients in different disease stages (Hoehm. and Yahr stage 2.5-5 [Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;4:427-42]; median duration, 12 years) were studied. PK-PD modeling followed a single oral dose of levodopa/benserazide. The sum score of the Columbia Rating Scale (CURS Sigma) was used for clinical assessments. A nonparametric effect compartment approach assuming a sigmoidal E-max model was applied to the PK-PD analysis of plasma levodopa concentrations and corresponding CURS Sigma. Thereafter 6-[F-18]levodopa PET was performed, and the influx rate constants (k(c)) for the putamen and the caudatus region were correlated with the median effective concentration (EC50) and the equilibrium half-life (T-eq) of the PK-PD model. Results: (1) A significant correlation was observed between PK-PD parameters or with k(c) putamen as the dependent variable and the duration of the disease as the independent variable, which explains 33% of the variability of the EC50, 42% of the variability of T-eq, and 36% of the variability of k(c). (2) Significant correlations were observed between k(c) and either EC50 or T-eq, yielding the closest correlation for the putamen region (r = -0.47, P

We have studied dopamine D2 receptor binding by [11C]raclopride positron emission tomography in 14 patients with dopa-responsive dystonia (DRD). Data were compared with 16 levodopa-treated patients with Parkinson's disease (PD) and 26 healthy controls. The results revealed an elevated [11C]raclopride binding index in the putamen and caudate nucleus of DRD patients compared with controls as well as a significant elevation in the caudate nucleus compared with PD patients. The increase of [11C]raclopride binding may be interpreted either as reduced tracer displacement by endogenous dopamine, or as an alteration of the receptor features due to chronic dopamine deficiency. The difference in [11C]raclopride binding in DRD and PD patients in the caudate nucleus suggests that this structure may be of pathophysiological relevance in the presentation of the clinical features of both diseases.

Article abstract The authors report a patient with postischemic parkinsonism who responded neither to levodopa nor to bilateral subthalamic nucleus (STN) stimulation. MRI revealed bilateral lesions of the substantia nigra, the striatum, the external pallidum, and part of the internal pallidum. PET showed reduced striatal dopa-decarboxylase activity, D2 receptor binding, and glucose metabolism. Perioperative microrecording showed low-frequency activity of STN cells. This case suggests that parkinsonian patients who do not have a good response to levodopa or in whom a postsynaptic dopaminergic lesion can be shown may not be good candidates for STN surgery.

This article reviews neuronal activity related to reward processing in primate and human brains. In the primate brain, neurophysiological methods provide a differentiated view of reward processing in a limited number of brain structures. Dopamine neurons respond to unpredictable rewards and produce a global reinforcement signal. Some neurons in the striatum also react to the expectation and detection of reward. Other striatal neurons show reward-related activities related to the preparation, initiation and execution of movement. Orbitofrontal neurons discriminate among different rewards and code reward preferences. In the human brain, regions belonging to a meso-striatal and meso-corticolimbic loop respond to reinforcement stimuli in control subjects. These observations corroborate results obtained in primates. Additionally, reward induces activation in regions specific to task performance. Our results also show a similar pattern of reward-related activation in nicotine and opiate addicts. Thus, in contrast to healthy subjects, typical reward-related regions respond in addicts to monetary reward but not to nonmonetary reinforcement. Reduced activation in performance-related regions is also observed in both groups of dependent subjects. The results of animal and human studies suggest that dopamine and dopamine-related regions are associated with the integration of motivational information and movement execution. Dopamine-related pathological disorders can be associated with movement disorders, such as Parkinson's disease or with false motivational attributions such as drug dependence. (C) 2001 Elsevier Science B.V. All rights reserved.

We evaluated the differences in motor control organization between parkinsonian patients with (seven cases) and without(ten cases) gait disorder. We used positron emission tomography (O-15-H2O-PET) to measure regional cerebral blood flow as a correlate for local neuronal activation. This has been assessed during repetitive joystick movements of the right hand, externally triggered using a metronome as an auditory cue. In patients with Parkinson's disease (PD) without gait disorder, the contralateral supplementary motor cortex and the bilateral cerebellum were activated, while in PD patients with gait disorder the contralateral Broca's area, the contralateral sensory motor cortex and the homolateral cerebellum were activated. Our results suggest that PD patients with gait disorder creates an internal verbal cue in order to control the output of the movement of joystick, supplying the loss of control of the supplementary motor cortex that is activated in patients without gait disorder.

Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic. dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [(H2O)-O-15] positron emission tomography (PET), we measured regional cerebral blood now (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate-gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.

Regional cerebral blood flow (rCBF) in healthy controls and non-demented, non-depressed Parkinsonian patients was measured using H(2)(15)0 PET while subjects performed a prelearned pattern recognition task with delayed response. To investigate differences between the two groups in response to reward, the experimental design consisted of three reinforcement conditions: no reinforcement consisting of nonsense feedback, positive symbolic reinforcement and monetary reward. In the controls, monetary reward activated bilaterally the striatum and anterior cingulate gyrus, as well as unilaterally the left cerebellum, midbrain and medial frontal gyrus. Symbolic reinforcement revealed a similar pattern of activation, except that the striatum and left midbrain showed no activation. The Parkinsonian patients responded to monetary reward with increased activation bilaterally in the cerebellum, medial frontal gyrus, and anterior cingulate gyrus as well as unilaterally in the right fusiform gyrus and midbrain and left caudate nucleus and precentral gyrus. Symbolic reinforcement induced significantly increased rCBF in the right cerebellum only. Compared with symbolic reinforcement, monetary reward produced extended activation of temporoparietal association cortex. The pattern observed in the controls demonstrates the role in reward processing of dopaminergic mesolimbic pathways in the healthy human brain, whereas the pattern in the Parkinsonian patients suggests the involvement of compensatory cortical loops in the diseased brain. NeuroReport 11:3681-3687 (C) 2000 Lippincott Williams & Wilkins.