Characterization of cognition in mild cognitive impairment with and without Parkinson's disease.

•Screening tests can diagnose PD-MCI but do not give detailed cognitive profiles.•Criteria based on a complete neuropsychological battery identify more PD patients with MCI.•The overall cognitive profile is similar in PD-MCI and MCI.•Neuropsychological batteries and definition of impairment cut-offs should be refined.

A new lexical card-sorting task for studying fronto-striatal contribution to processing language rules.

The role of fronto-striatal regions in processing different language rules such as semantic and (grapho) phonological ones is still under debate. We have recently developed a lexical analog of the Wisconsin card sorting task which measures set-shifting abilities where the visual rules color, number, shape were replaced by three language ones: semantic, rhyme and syllable onset (attack). In the present study we aimed to compare fronto-striatal activations between the different lexical rules that are required for matching the test words to the response ones. Using functional magnetic resonance imaging (fMRI), fourteen healthy, native French-speaking participants were scanned. The results showed that some regions within the brain language network are differentially involved in semantic and phonological processes. Semantic decisions activated significantly the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus, while phonological decisions produced significant activation in posterior Broca's area (area 44), the temporoparietal junction and motor cortical regions. These findings provide critical support for the existence of a ventral subcortical semantic pathway and a more dorsal phonological stream as proposed by Duffau, Leroy, and Gatignol (2008). Furthermore, we propose that the strong involvement of area 47/12 of the ventrolateral prefrontal cortex and caudate nucleus observed in semantic processing, is not specific to language, but to the fact that a category or a rule has to be retrieved amongst competing ones in memory, similarly to what is observed when planning a set-shift in the original (non-lexical) version of the Wisconsin card sorting task.

Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson's disease.

Motor studies of Parkinson's disease (PD) have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. Cognitive studies also identified increased cortical activity in PD. We have previously suggested that the hypo-activity/hyper-activity patterns observed in PD are related to the striatal contribution. Tasks that recruit the striatum in control participants are associated with cortical hypo-activity in patients with PD, whereas tasks that do not result in cortical hyper-activity. The putamen, a structure affected by the neurodegeneration observed in PD, shows increased activation for externally-triggered (ET) and self-initiated (SI) movements. The first goal of this study was to evaluate the effect of levodopa on the putamen's response to ET and SI movements. Our second goal was to assess the effect of levodopa on the hypo-activity/hyper-activity patterns in cortical areas. Patients with PD on and off levodopa and healthy volunteers performed SI, ET and control finger movements during functional magnetic resonance imaging. Healthy participants displayed significant differences in putamen activity in ET and SI movements. These differences were reduced in patients off medication, with non-task-specific increases in activity after levodopa administration. Furthermore, the ventrolateral prefrontal cortex showed significant increases in activity during SI movements in healthy controls, whereas it was hypo-active in PD. This region showed significantly increased activity during ET movements in patients off medication. Levodopa had no effect on this discrepancy. Our results suggest that dopamine replacement therapy has a non-task-specific effect on motor corticostriatal regions, and support the hypothesis that increases and decreases in cortical activity in PD are related to the mesocortical dopamine pathway imbalance.

Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging.

The Wisconsin Card Sorting Task (WCST) has been used to assess dysfunction of the prefrontal cortex and basal ganglia. Previous brain imaging studies have focused on identifying activity related to the set-shifting requirement of the WCST. The present study used event-related functional magnetic resonance imaging (fMRI) to study the pattern of activation during four distinct stages in the performance of this task. Eleven subjects were scanned while performing the WCST and a control task involving matching two identical cards. The results demonstrated specific involvement of different prefrontal areas during different stages of task performance. The mid-dorsolateral prefrontal cortex (area 9/46) increased activity while subjects received either positive or negative feedback, that is at the point when the current information must be related to earlier events stored in working memory. This is consistent with the proposed role of the mid-dorsolateral prefrontal cortex in the monitoring of events in working memory. By contrast, a cortical basal ganglia loop involving the mid-ventrolateral prefrontal cortex (area 47/12), caudate nucleus, and mediodorsal thalamus increased activity specifically during the reception of negative feedback, which signals the need for a mental shift to a new response set. The posterior prefrontal cortex response was less specific; increases in activity occurred during both the reception of feedback and the response period, indicating a role in the association of specific actions to stimuli. The putamen exhibited increased activity while matching after negative feedback but not while matching after positive feedback, implying greater involvement during novel than routine actions.

A neural model of working memory processes in normal subjects, Parkinson's disease and schizophrenia for fMRI design and predictions.

A computational model was previously developed to investigate the role of parallel basal ganglia-thalamocortical loops in solving tasks that rely on working memory. Different lesions are applied to the model in order to investigate the working memory deficits observed in Parkinson's disease and schizophrenia. The simulations predict that the working memory deficits observed in Parkinson's disease result from a local dysfunction within the brain due to a problem in the disinhibitory process arising from the basal ganglia. They also predict that the working memory deficits observed in schizophrenia involve many cortical and subcortical areas and result from a problem in selecting items in working memory which are stored in basal ganglia-thalamocortical loops. The simulations predict the temporal unfolding of neuronal activity in different brain regions, both in the normal case and in the two disease states. A specific event-related functional magnetic resonance imaging study was elaborated to test some of those predictions.