Jean-Sebastien Provost

The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson's disease: support from functional MRI.

The central aim of our study was to elucidate functions mediated by the ventral and dorsal striatum, respectively, to better understand the cognitive effects of dopamine replacement in Parkinsons disease. We proposed that the ventral striatum underlies general learning of stimulus associations, whereas the dorsal striatum promotes integration of various influences on selecting. In Parkinsons disease, dopamine depletion is substantially less notable in the ventral relative to the dorsal striatum, and therefore greater improvements are expected for dorsal striatum-mediated functions with dopamine replacement. Using a simple selection task, we found that dopamine replacement impaired encoding and facilitation of consistent stimulus-stimulus relations across trials. This finding was in line with our contention that ventral striatum mediates learning stimulus associations, even when explicit feedback or reward is not provided. In contrast, dopamine replacement enhanced interference related to assimilating conflicting influences on selection across trials, consistent with our hypothesis that the dorsal striatum supports deciding in ambiguous contexts. We further confirmed these separable roles for the ventral and dorsal striatum in our selection task with healthy young volunteers using functional magnetic resonance imaging. In summary, we present a within-subject, double dissociation of the effects of dopamine replacement in patients with Parkinsons disease for ventral striatum-mediated facilitation and dorsal striatum-mediated interference, confirmed in a separate functional magnetic resonance imaging experiment. Defining the distinct functions of the ventral and dorsal striatum will have direct clinical implications. Titration of therapy in Parkinsons disease is generally geared towards optimizing dorsal striatum-mediated motor symptoms, possibly at the expense of ventral striatum operations, a consequence that is only beginning to be recognized. Enhanced awareness of these different processes will translate into medication strategies that take into account those symptoms that dopamine replacement might hinder, as well as improve. Here, we show impairments in learning new stimulus associations compared with improvements in integrating varied influences related to selection. Ultimately, this knowledge will lead clinicians to survey a broader range of symptoms in determining optimal therapy based on individual patient priorities.

Dissociating the role of the caudate nucleus and dorsolateral prefrontal cortex in the monitoring of events within human working memory

There is evidence that the dorsolateral prefrontal cortex is involved in the monitoring of information held in memory whether it is self‐ordered or externally triggered. However, the functional contribution of the caudate nucleus in the monitoring of events has not yet been studied. We have previously proposed that the striatum is involved when a novel self‐initiated action needs to be generated. The present study aimed to test the hypothesis that the caudate nucleus is significantly more required when the monitoring is self‐ordered as opposed to externally triggered. Self‐ordered monitoring refers to keeping track of which items have been selected so far in order to perform the current selection. Externally triggered monitoring refers to keeping track of which items have been selected by an outside source. Thirteen healthy young adults were scanned using functional magnetic resonance imaging while performing a monitoring task with three conditions: self‐ordered, externally triggered and recognition. As predicted, a significant increase of activity was found in the dorsolateral prefrontal cortex bilaterally when the self‐ordered and externally triggered conditions were compared with the recognition condition. Most importantly, significantly increased activity was found in the right caudate nucleus when comparing the self‐ordered with the recognition condition or with the externally triggered condition, but not when comparing the externally triggered with the recognition condition. We suggest that the caudate nucleus is involved in the planning of a self‐initiated novel action, especially when no clear indication is given for the response choice, and that this may be the case across different domains of cognition.

Altered Gray Matter Structural Covariance Networks in Early Stages of Alzheimer's Disease

Clinical symptoms observed in Alzheimers disease (AD) patients may reflect variations within specific large-scale brain networks, modeling AD as a disconnection syndrome. The present magnetic resonance imaging study aims to compare the organization of gray matter structural covariance networks between 109 cognitively unimpaired controls (CTRL) and 109 AD patients positive to beta-amyloid at the early stages of the disease, using voxel-based morphometry. The default-mode network (DMN; medial temporal lobe subsystem) was less extended in AD patients in comparison with CTRL, with a significant decrease in the structural association between the entorhinal cortex and the medial prefrontal and the dorsolateral prefrontal cortices. The DMN (midline core subsystem) was also less extended in AD patients. Trends toward increased structural association were observed in the salience and executive control networks. The observed changes suggest that early disruptions in structural association between heteromodal association cortices and the entorhinal cortex could contribute to an isolation of the hippocampal formation, potentially giving rise to the clinical hallmark of AD, progressive memory impairment. It also provides critical support to the hypothesis that the reduced connectivity within the DMN in early AD is accompanied by an enhancement of connectivity in the salience and executive control networks.

Examining dorsal striatum in cognitive effort using Parkinson's disease and fMRI

Understanding cognition mediated by the striatum can clarify cognitive deficits in Parkinsons disease (PD). Previously, we claimed that dorsal striatum (DS) mediates cognitive flexibility. To refute the possibility that variation in cognitive effort confounded our observations, we reexamined our data to dissociate cognitive flexibility from effort. PD provides a model for exploring DS‐mediated functions. In PD, dopamine‐producing cells supplying DS are significantly degenerated. DS‐mediated functions are impaired off and improved on dopamine replacement medication. Functional magnetic resonance imaging (fMRI) can confirm striatum‐mediated functions.

Neuroimaging studies of the striatum in cognition Part I: healthy individuals.

The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well-accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity.

Investigating the Long-Lasting Residual Effect of a Set Shift on Frontostriatal Activity

Previous studies have shown the involvement of the ventrolateral prefrontal cortex (PFC) and the caudate nucleus when performing a set shift. However, the effect of set shifting on the frontostriatal activity observed during the later trials within a series of same-set classifications has yet to be determined. Here, young healthy adults underwent the functional magnetic resonance imaging while performing a card-sorting task in which the classification rule was provided prior to each trial. We observed a significant activation in the dorsolateral PFC, regardless of whether a set shift occurred or not. By contrast, the ventrolateral PFC and caudate nucleus showed an increased activity in both the shifting trials versus the control and in trials where the same rule was applied for a few trials before a set shift occurred, unlike trials where the same rule was applied for a longer period. Finally, decreased activity in the caudate nucleus correlated with an increasing trial position in trials where no set shift occurred, suggesting that the more a rule is executed, the better it is established. We argue that a new rule needs to be performed multiple times until the brain areas usually associated with the set shifting are no longer significantly required anymore.

Exploration of the dynamics between brain regions associated with the default‐mode network and frontostriatal pathway with regards to task familiarity

Specific brain regions have consistently been reported to be activated during resting state period, and they were described as being part of a particular network called the default‐mode network (DMN). It has been shown that the DMN would deactivate during goal‐directed tasks, but the actual relationship between them is still a matter of debate. In a previous study, we reported a specific pattern of activation of the frontostriatal regions during a set‐shifting task in which these regions were increasing their activity as set‐shifts were performed continuously and decreasing when the same rule was executed repeatedly. The present study aimed at assessing the relationship between the frontostriatal regions and the DMN. We hypothesized that the DMN would be anticorrelated with the frontostriatal regions so the DMN would be more deactivated as set‐shifts are executed for a long period, but would start increasing when the same rule is being executed for a long period. Here, 15 participants underwent functional magnetic resonance imaging while performing a card‐sorting task. We observed increased activity in the frontostriatal regions as more set‐shifts are being performed while the DMN gets more deactivated. Interestingly, as decreased activity was observed in the frontostriatal regions during the execution of the same rule for a long period, the DMN showed increasing activity. We argue that there is an anticorrelation between the frontostriatal regions and the DMN, but also that the DMN could show positive activation during performance of a familiar goal‐directed task.

Age-Related Shift in Neuro-Activation during a Word-Matching Task

Growing evidence from the neuroscience of aging suggests that executive function plays a pivotal role in maintaining semantic processing performance. However, the presumed age-related activation changes that sustain executive semantic processing remain poorly understood. The aim of this study was to explore the executive aspects of semantic processing during a word-matching task with regard to age-related neuro-functional reorganization, as well as to identify factors that influence executive control profiles. Twenty younger and 20 older participants underwent fMRI scanning. The experimental task was based on word-matching, wherein visual feedback was used to instruct participants to either maintain or switch a semantic-matching rule. Response time and correct responses were assessed for each group. A battery of cognitive tests was administrated to all participants and the older group was divided into two subgroups based on their cognitive control profiles. Even though the percentage of correct responses was equivalent in the task performance between both groups and within the older groups, neuro-functional activation differed in frontoparietal regions with regards to age and cognitive control profiles. A correlation between behavioral measures (correct responses and response times) and brain signal changes was found in the left inferior parietal region in older participants. Results indicate that the shift in age-related activation from frontal to parietal regions can be viewed as another form of neuro-functional reorganization. The greater reliance on inferior parietal regions in the older compared to the younger group suggests that the executive control system is still efficient and sustains semantic processing in the healthy aging brain. Additionally, cognitive control profiles underlie executive ability differences in healthy aging appear to be associated with specific neuro-functional reorganization throughout frontal and parietal regions. These findings demonstrate that changes in neural support for executive semantic processing during a word-matching task are not only influenced by age, but also by cognitive control profile.

Age-Related Brain Activation Changes during Rule Repetition in Word-Matching

Objective: The purpose of this study was to explore the age-related brain activation changes during a word-matching semantic-category-based task, which required either repeating or changing a semantic rule to be applied. In order to do so, a word-semantic rule-based task was adapted from the Wisconsin Sorting Card Test, involving the repeated feedback-driven selection of given pairs of words based on semantic category-based criteria. Method: Forty healthy adults (20 younger and 20 older) performed a word-matching task while undergoing a fMRI scan in which they were required to pair a target word with another word from a group of three words. The required pairing is based on three word-pair semantic rules which correspond to different levels of semantic control demands: functional relatedness, moderately typical-relatedness (which were considered as low control demands), and atypical-relatedness (high control demands). The sorting period consisted of a continuous execution of the same sorting rule and an inferred trial-by-trial feedback was given. Results: Behavioral performance revealed increases in response times and decreases of correct responses according to the level of semantic control demands (functional vs. typical vs. atypical) for both age groups (younger and older) reflecting graded differences in the repetition of the application of a given semantic rule. Neuroimaging findings of significant brain activation showed two main results: (1) Greater task-related activation changes for the repetition of the application of atypical rules relative to typical and functional rules, and (2) Changes (older > younger) in the inferior prefrontal regions for functional rules and more extensive and bilateral activations for typical and atypical rules. Regarding the inter-semantic rules comparison, only task-related activation differences were observed for functional > typical (e.g., inferior parietal and temporal regions bilaterally) and atypical > typical (e.g., prefrontal, inferior parietal, posterior temporal, and subcortical regions). Conclusion: These results suggest that healthy cognitive aging relies on the adaptive changes of inferior prefrontal resources involved in the repetitive execution of semantic rules, thus reflecting graded differences in support of task demands.

Differential Involvement of the Anterior Temporal Lobes in Famous People Semantics

The ability to recognize a famous person occurs through semantic memory. Previous neuroimaging studies have shown that the anterior temporal lobes (ATLs) are involved in the recognition of famous people. However, it is still a matter of debate whether the semantic processing of names or pictures of famous people has an impact on the activation of ATLs. The aim of this study was to explore the pattern of activation associated with a semantic processing of famous people based on face and written name stimuli. Fifteen healthy young individuals participated in our fMRI study, in which they were asked to perform a semantic categorization judgment task, based on profession, of visually presented pictures, and names of famous people. Neuroimaging findings showed a common pattern of activation for faces and names mainly involving the inferior frontal regions, the posterior temporal lobe, the visual cortex, and the ATLs. We found that the comparison names vs. pictures lead to significant activation in the anterior superior temporal gyrus. On the other hand, faces vs. names seemed associated with increased activation in the medial ATL. Moreover, our results demonstrated that the functional connectivity network anchored to the medial ATL, compared to the anterior STG, is more connected to the bilateral occipital lobe and fusiform gyrus that are regions implicated in the visual system and visual processing of faces. This study provides critical evidence of the differential involvement of ATL regions in semantics of famous people.