Cognitive action control in Parkinson's disease : study with the verbal fluency tests and the rewarded Simon Task

La symptomatologie non motrice de la maladie de Parkinson s’accompagne fréquemment d’un défaut de contrôle cognitif. Le contrôle cognitif faisant référence à un ensemble de processus facilitant le traitement de l’information et la production de comportements adaptés, son altération impactera de très nombreuses capacités cognitives. Parmi ces capacités, nous nous intéresserons plus spécifiquement, d’une part, à la production orale de mots évaluée à travers les tests de fluences verbales et, d’autre part, aux processus favorisant la production d’actions intentionnelles en situation motivée comme évaluée par la Simon Task motivée. Par notre première étude nous remettrons en question l’hypothèse d’un défaut de contrôle cognitif comme origine principale de la réduction des performances aux tests de fluences verbales à la suite de la stimulation cérébrale profonde du noyau subthalamique. En effet, nous n’avons pas mis en évidence de relation entre cette altération et une modification de l’activité métabolique des régions frontales supportant le contrôle cognitif, ou une modification des performances à d’autres tests nécessitant un contrôle cognitif efficient. Les travaux suivant, portant sur le contrôle des actions motivées démontrent, d’une part, que la production d’actions guidées, non pas par des tendances d’actions impulsives, mais par des tendances d’actions en accord avec les intentions, est plus ardue lorsqu’une récompense financière est mise en jeu. D’autre part, le traitement de la maladie de Parkinson, aussi bien par dopathérapie que par stimulation cérébrale profonde du noyau sous-thalamique module le fonctionnement des processus impliqués, suggérant un rôle particulier des noyaux gris centraux. Nous discuterons des processus cognitifs et neuronaux impliqués et proposerons des perspectives de recherche aussi bien neuroscientifiques que cliniques.The nonmotor symptoms of Parkinson’s disease frequently include a cognitive control deficit. Cognitive control refers to a set of processes that promote information processing and the production of appropriate behaviours, so its impairment can have an impact on a wide range of cognitive abilities. We focused on just two of these abilities: oral word production, as assessed with phonemic and semantic verbal fluency tests; and cognitive action control in an incentive context, as assessed with a rewarded Simon Task. In our first study, we questioned the hypothesis that the reduction in verbal fluency performances observed following surgery for subthalamic nucleus deep-brain stimulation is mainly due to a cognitive control deficit. Results failed to reveal a relationship between this reduction and either modified metabolic activity in the frontal regions subtending cognitive control or modified performances on other tests requiring efficient cognitive control. In our second and third studies, investigating cognitive action control in an incentive context, we showed that the production of intention-driven actions, as opposed to impulsive ones, is more difficult when a monetary reward is at stake. We also demonstrated that treatment for Parkinson’s disease, whether it takes the form of dopaminergic medication or subthalamic stimulation, modulates the functioning of these processes, suggesting that the basal ganglia have a role in them. We discuss the cognitive and neural processes involved and outline future avenues for both neuroscientific and clinical research

Changes in electrophysiological aperiodic activity during cognitive control in Parkinson’s disease

International audienceCognitive symptoms in Parkinson’s disease are common and can significantly affect patients’ quality of life. Therefore, there is an urgent clinical need to identify a signature derived from behavioral and/or neuroimaging indicators that could predict which patients are at increased risk for early and rapid cognitive decline. Recently, converging evidence identified that aperiodic activity of the EEG reflects meaningful physiological information associated with age, development, cognitive and perceptual states or pathologies. In this study, we aimed to investigate aperiodic activity in Parkinson’s disease during cognitive control and characterize its possible association with behavior. Here, we recorded high-density EEG in 30 healthy controls and 30 Parkinson’s disease patients during a Simon task. We analyzed task-related behavioral data in the context of the activation-suppression model and extracted aperiodic parameters (offset, exponent) at both scalp and source levels. Our results showed lower behavioral performances in cognitive control as well as higher offsets in patients in the parieto-occipital areas, suggesting increased excitability in Parkinson’s disease. A small congruence effect on aperiodic parameters in pre- and post-central brain areas was also found, possibly associated with task execution. Significant differences in aperiodic parameters between the resting state, pre- and post-stimulus phases were seen across the whole brain, which confirmed that the observed changes in aperiodic activity are linked to task execution. No correlation was found between aperiodic activity and behavior or clinical features. Our findings provide evidence that EEG aperiodic activity in Parkinson’s disease is characterized by greater offsets, and that aperiodic parameters differ depending on arousal state. However, our results do not support the hypothesis that the behavior-related differences observed in Parkinson’s disease are related to aperiodic changes. Overall, this study highlights the importance of considering aperiodic activity contributions in brain disorders and further investigating the relationship between aperiodic activity and behavior

Effects of Parkinson's disease on cognitive action control: Insights on impulsive response tendencies using an oculomotor Simon task

International audienceObjectives: Cognitive action control allows suppressing automatic activation and producing a controlled response when conflicts arise. This process is modulated by the basal ganglia and recent studies have shown that it was impaired in Parkinson's disease (PD). This study gives insights regarding the effect of PD on cognitive action and more precisely on impulsive responses. Methods: 40 patients with PD with no cognitive impairment and 40 healthy controls (HC) underwent an oculomotor Simon task in which they were required to make a leftward or rightward eye movement according to the color of a target and to ignore its location. The two dimensions of the stimuli created congruent (color and location activating the same response) and incongruent (color and location activating conflicting responses) trials. Results were analyzed using distributional analysis according to the activation-suppression model. Results: PD patients had a greater congruence effect on both reaction time and accuracy rate demonstrating a greater difficulty to resolve conflicts. Distributional analysis revealed that PD patients made more fast errors than HC. The rate of impulsive errors was further correlated to the Barrat Impulsiveness Scale (BIS) scores. When they responded slower, PD patients were also impaired compared to HC. Conclusions: Our results show that both the automatic and controlled routes involved in the cognitive action control are affected in PD. Furthermore, impulsive response tendencies in PD measured by a conflict task seems related to behavioral impulsivity. Therefore, conflict tasks could be used to further study impulsivity in PD and its ability to detect early troubles should be investigate

Dynamics of cognitive action control in late-life depression during action selection

International audienceINTRODUCTION: Late-Life Depression (LLD) is characterized by deficits in cognitive control. We investigated the effect of LLD on a subset of cognitive control functions, the Cognitive Action Control (CAC), distinguishing on-line and adaptive control. METHODS: We compared LLD subjects (n = 31) and Healthy Controls (HC, n = 31) on their performance in a Simon task. The online congruency effect and adaptive effect were compared for reaction times (RT) and accuracy rates between the groups using mixed models. We applied distributional analyses of RT to differentiate the strength of impulsive action selection and the proficiency of selective action suppression. Finally, we measured correlations between the performances on the task and clinical scores of the LLD group. RESULTS: LLD had increased error rates in congruent trials compared to HC. Conversely, the adaptive CAC was equivalent between the groups. Distributional analyses showed that the fastest actions were less led by pertinent information in LLD. This phenomenon was found exclusively for congruent trials preceded by non-congruent trials. On the other hand, LLD patients, when they take time, were better than HC to suppress selectively non-relevant information. No difference was observed for adaptation to the preceding condition. No association between behavioral measurements and clinical scores were found. CONCLUSION: Our results suggest that LLD participants have a specific cognitive disturbance of CAC, showing less facilitation than HC in congruent situations. We propose that this originates in a difficulty in LLD patients in disengaging their attention from conflict situations, which is consistent with a biased CAC to aversive stimuli in depression

Chronic subcutaneous infusion therapy with apomorphine in advanced Parkinson's disease: Effects on motor and non motor symptoms with brain metabolism correlations

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Pallidal stimulation in Parkinson's patients with contraindications to subthalamic target: A 3 years follow-up

International audienceINTRODUCTION: Over a 3-year period, we monitored the efficacy and safety of deep-brain stimulation of the globus pallidus pars interna in patients with advanced Parkinson's disease whose cognitive, psychiatric impairment and/or dopa-resistant axial motor signs made them ineligible for surgery targeting the subthalamic nucleus.METHODS: A total of 25 patients were assessed before surgery, 1 year and 3 years after surgery, on the UPDRS and a neuropsychological battery. RESULTS: We noted a significant improvement of 65.9% in the Clinical global self-perceived Improvement by Visual Analog Scale and an improvement of 20.6% in the total UPDRS-III motor score at 3 years in the off-dopa condition compared to before surgery. There was an improvement in the treatment's motor complications, as measured by the UPDRS-IV, with a particularly marked reduction of 50% in the Dyskinesia subscore. Cognitive performances remained stable at 1 year but had fallen by the third year. We interpreted this deterioration as due to disease progression.CONCLUSION: Bilateral pallidal stimulation in patients with contraindications to subthalamic surgery therefore seems to be effective over the long term in treating motor symptoms, especially dyskinesias, with good neuropsychological safety

Functional atlases for analysis of motor and neuropsychological outcomes after medial globus pallidus and subthalamic stimulation.

Anatomical atlases have been developed to improve the targeting of basal ganglia in deep brain stimulation. However, the sole anatomy cannot predict the functional outcome of this surgery. Deep brain stimulation is often a compromise between several functional outcomes: motor, fluency and neuropsychological outcomes in particular. In this study, we have developed anatomo-clinical atlases for the targeting of subthalamic and medial globus pallidus deep brain stimulation. The activated electrode coordinates of 42 patients implanted in the subthalamic nucleus and 29 patients in the medial globus pallidus were studied. The atlas was built using the representation of the volume of tissue theoretically activated by the stimulation. The UPDRS score was used to represent the motor outcome. The Stroop test was represented as well as semantic and phonemic fluencies. For the subthalamic nucleus, best motor outcomes were obtained when the supero-lateral part of the nucleus was stimulated whereas the semantic fluency was impaired in this same region. For the medial globus pallidus, best outcomes were obtained when the postero ventral part of the nucleus was stimulated whereas the phonemic fluency was impaired in this same region. There was no significant neuropsychological impairment. We have proposed new anatomo-clinical atlases to visualize the motor and neuropsychological consequences at 6 months of subthalamic nucleus and pallidal stimulation in patients with Parkinson's disease

Impulsive oculomotor action selection in Parkinson's disease

International audienceThe effects of Parkinson's disease (PD) on the dynamics of impulsive action selection and suppression have recently been studied using distributional analyses, but with mixed results, especially for selection. Furthermore, some authors have suggested that impulsivity, regarded as a personality trait, shares common features with behavioral tasks' measures. The current study was designed to clarify the impact of PD on impulsive action selection and suppression, and investigate the link between cognitive action control and self-reported impulsivity. We administered an oculomotor version of the Simon task to 32 patients with PD and 32 matched healthy controls (HC), and conducted distributional analyses in accordance with the activation-suppression model. Patients and HC also filled out the Barratt Impulsiveness Scale (BIS) questionnaire. Results showed that patients with PD were faster overall and exhibited a greater congruence effect than HC. They also displayed enhanced impulsive action selection. By contrast, the suppression of impulsive responses was similar across both groups. Furthermore, patients had higher impulsivity scores, which were correlated with higher impulsive action selection and higher suppression. Our study yielded two interesting findings. First, PD resulted in a higher number of fast errors. The activation-suppression model suggests that patients with PD are more susceptible to the impulsive action selection induced by the irrelevant stimulus dimension. Second, impulsive action selection and suppression were both associated with trait impulsivity, as measured by the BIS, indicating that these two aspects of impulsivity share common features

Continuous subcutaneous apomorphine infusion does not impair the dynamics of cognitive action control in mild to moderate Parkinson's disease

International audienceIntroduction - Continuous subcutaneous apomorphine infusion (CSAI) is increasingly used in Parkinson's disease (PD), notably in patients contraindicated for subthalamic deep brain stimulation. Although it has been suggested that CSAI is safe regarding cognition, few studies have actually investigated its effect, especially on cognitive control which is a crucial process for goal-directed behavior. More specifically, its impact on the dynamics of cognitive action control, as reflected by the activation and suppression of impulsive responses, has yet to be investigated, which is the objective of the present study. Methods - We compared cognitive action control between baseline (M0) and 6 months (M6) after the start of add-on CSAI by administering an oculomotor Simon task to 20 patients with mild to moderate PD. We used the activation-suppression model to determine whether CSAI had an effect on either the impulsive errors made in conflict situations or the suppression of these responses. Results - We found no difference between M0 and M6 in the congruence effect regarding either reaction time or accuracy, indicating that overall conflict resolution was not influenced by CSAI. Furthermore, the rate of fast errors in the conflict situation and the last slope of the delta plots (reflecting the strength of impulsive response suppression) were unaffected by the treatment. The 95% confidence intervals calculated for the treatment effect on both of these measures fell below the range of usual meaningful effects. Conclusion - We found no difference between M0 and M6, which strongly suggests that CSAI does not impair the dynamics of cognitive action control

Does Facial Amimia Impact the Recognition of Facial Emotions? An EMG Study in Parkinson's Disease.

According to embodied simulation theory, understanding other people's emotions is fostered by facial mimicry. However, studies assessing the effect of facial mimicry on the recognition of emotion are still controversial. In Parkinson's disease (PD), one of the most distinctive clinical features is facial amimia, a reduction in facial expressiveness, but patients also show emotional disturbances. The present study used the pathological model of PD to examine the role of facial mimicry on emotion recognition by investigating EMG responses in PD patients during a facial emotion recognition task (anger, joy, neutral). Our results evidenced a significant decrease in facial mimicry for joy in PD, essentially linked to the absence of reaction of the zygomaticus major and the orbicularis oculi muscles in response to happy avatars, whereas facial mimicry for expressions of anger was relatively preserved. We also confirmed that PD patients were less accurate in recognizing positive and neutral facial expressions and highlighted a beneficial effect of facial mimicry on the recognition of emotion. We thus provide additional arguments for embodied simulation theory suggesting that facial mimicry is a potential lever for therapeutic actions in PD even if it seems not to be necessarily required in recognizing emotion as such