Reduced mind wandering in patients with Parkinson's disease.

BACKGROUND: Mind Wandering (MW) refers to the process of disengaging from the immediate external environment and participating in internally driven mentation. This process has been suggested to be supported by a distributed set of brain regions, collectively referred to as the Default Mode Network (DMN). Recently, reduced recruitment and connectivity of the DMN has been described in Parkinson's disease (PD) patients compared to healthy controls. We thus aimed to explore whether PD patients with normal cognitive test scores show differential MW capabilities compared to healthy controls. METHODS: Thirty PD patients and thirty age-matched controls, all with a Montreal cognitive assessment (MoCA) score of 26 or above, performed a novel yet validated thought-sampling paradigm used to assess the frequency and extent of MW irrespective of cognitive load in which participants were asked to observe a series of geometric shapes and describe their thoughts after watching them. Shapes were presented one at a time for varying durations across nine trials. RESULTS: PD patients showed significantly less MW compared to the control. ANCOVA revealed a significant interaction indicating that the difference in MW scores was driven by trials with short stimulus presentation times. CONCLUSIONS: These findings provide evidence for decreased MW in PD patients. We propose that this is due to difficulties in performing MW within short time frames.

The role of the striatum in compulsive behavior in intact and orbitofrontal-cortex-lesioned rats: possible involvement of the serotonergic system.

In the signal attenuation rat model of obsessive-compulsive disorder (OCD), 'compulsive' behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. We have recently found that lesions to the rat orbitofrontal cortex (OFC) led to an increase in compulsive lever-pressing that was prevented by systemic administration of the selective serotonin reuptake inhibitor paroxetine, and paralleled by an increase in the density of the striatal serotonin transporter. This study further explored the interaction between the OFC, the striatum, and the serotonergic system in the production of compulsive lever-pressing. Experiment 1 revealed that OFC lesions decrease the content of serotonin, dopamine, glutamate, and GABA in the striatum. Experiment 2 showed that intrastriatal administration of paroxetine blocked OFC lesion-induced increased compulsivity, but did not affect compulsive responding in intact rats. Experiments 3 and 4 found that pre-training striatal lesions had no effect on compulsive lever-pressing, whereas post-training striatal inactivation exerted an anticompulsive effect. These results strongly implicate the striatum in the expression of compulsive lever-pressing in both intact and OFC-lesioned rats. Furthermore, the results support the possibility that in a subpopulation of OCD patients a primary pathology of the OFC leads to a dysregulation of the striatal serotonergic system, which is manifested in compulsive behavior, and that antiobsessional/anticompulsive drugs exerts their effects, in these patients, by normalizing the dysfunctional striatal serotonergic system.

The orbital cortex in rats topographically projects to central parts of the caudate-putamen complex.

Disturbances of the orbitofrontal-striatal pathways in humans have been associated with several psychopathologies including obsessive-compulsive disorder and drug addiction. In nonhuman primates, different subareas of the orbitofrontal cortex project topographically to central and ventromedial parts of the striatum. Relatively little is known about the anatomical organization of the rat orbital cortex while there is a growing interest in this cortical area from a functional and behavioral point of view. The aim of the present neuroanatomical tracing study was to determine in rats the striatal target area of the projections of the orbital cortex as well as the topographical organization within these projections. To this end, anterograde tracers were injected in the different cytoarchitectonically distinct subareas of the orbital cortex. The results show that the individual orbital areas, i.e. medial orbital area, ventral orbital area, ventrolateral orbital area and lateral orbital area, project to central parts of the caudate-putamen, exhibiting a mediolateral and, to a lesser degree, rostrocaudal topographical arrangement. Orbital projections avoid the most dorsal, as well as rostral and caudal parts of the caudate-putamen. Terminal fields from cytoarchitectonically different areas show a considerable overlap. Superficial cortical layers project preferentially to the striatal matrix, deep layers to the patch compartment. The projections from the ventrolateral orbital area are strongest and occupy the most extensive striatal area. In addition to projections to the caudate-putamen, the ventrolateral, lateral and dorsolateral orbital areas have a scarce projection to the most lateral part of the nucleus accumbens shell in the ventral striatum. In contrast to nonhuman primates, the remainder of the rat nucleus accumbens is virtually free of orbital projections.

Strain differences in 'compulsive' lever-pressing.

In the signal attenuation rat model of obsessive-compulsive disorder, 'compulsive' behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. In recent years several studies have reported that Lewis rats, an inbred strain derived from the Sprague Dawley strain, exhibit addictive and/or compulsive tendencies. The aim of the present study was thus to test whether Lewis rats will also show increased compulsivity in the signal attenuation model. Because the model has been developed and validated using Wistar rats only, the present study compared the behavioral response to signal attenuation of Lewis, Sprague Dawley and Wistar rats, and assessed the effects of the anti-compulsive drug paroxetine on compulsive behavior in Lewis and Sprague Dawley rats. The results show that Lewis rats are more 'compulsive' than Sprague Dawley and Wistar rats in terms of both higher levels of compulsive lever-pressing and higher resistance to the anti-compulsive effect of paroxetine. The possibility that these strain differences are related to strain differences in the serotonergic and dopaminergic systems are discussed in light of current knowledge of the pathophysiology and pharmacotherapy of OCD.