Consensus Paper: Cerebellum and Reward.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs.

[Post-COVID-19 neuropsychological syndrome]. / Syndrome post-Covid-19 neuropsychologique.

Recent observations suggest the persistence of neurological and neuropsychological symptoms in the long-term following SARS-CoV-2 infection. Currently described within the post-COVID-19 syndrome. The objective of this article is to discuss recent epidemiological data and data from neuroimaging studies. Finally, a discussion is proposed regarding recent suggestions regarding the existence of distinct phenotypes of post-COVID-19 syndrome.

De récentes observations suggèrent la persistance de symptômes neurologiques et neuropsychologiques à long terme suite à une infection par le SARS-CoV-2, actuellement décrit au sein du syndrome post-Covid-19. L'objectif de cet article est d'aborder les récentes données épidémiologiques et les données provenant d'études en neuro-imagerie. Finalement, une discussion est proposée quant aux récentes suggestions concernant l'existence de phénotypes distincts au sein du syndrome post-Covid-19.

[Long COVID : neurological aspects]. / Covid long : aspects neurologiques.

The study of post-COVID-19 symptomatology revealed a first wave of post-acute (persistence of symptoms less than 3 months) neurocognitive symptoms. However, some of these symptoms worsened, while others improved. To our knowledge, these symptoms may persist for up to 1 to 2 years after infection. The intensity, variability and persistence of neurocognitive symptoms may rise the hypotheses of accelerated neurodegenerative processes, as well as neuropsychiatric and/or genetic vulnerabilities that are still poorly understood. Moreover, the multi-organ manifestations of post-COVID-19 symptoms remind us of the importance of promoting an interdisciplinary perspective at both clinical and fundamental levels. Finally, many social and economic issues parallel to the neuropathological consequences remain to be investigated.

L'étude de la symptomatologie post-Covid-19 a permis de mettre en évidence une première vague de symptômes neurocognitifs postaigus (persistance des symptômes inférieurs à 3 mois). Certains se sont aggravés, tandis que d'autres se sont améliorés. Ils peuvent perdurer jusqu'à 1 à 2 ans après l'infection. L'intensité, la variabilité et la persistance des symptômes neurocognitifs pourraient suggérer des hypothèses d'accélération de processus neurodégénératifs et des vulnérabilités neuropsychiatriques et/ou génétiques encore mal comprises. De plus, les manifestations multi-organiques des symptômes post-Covid-19 nous rappellent l'importance de promouvoir une perspective multidisciplinaire sur les plans clinique et fondamental. Finalement, de nombreuses questions sociales et économiques parallèles aux conséquences neuropathologiques restent à investiguer.

Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson's disease.

BACKGROUND: Non-motor symptoms are an important early feature of Parkinson's disease (PD), encompassing a variety of cognitive and psychiatric symptoms that seem to manifest differently depending on motor symptom asymmetry. Different factors, such as uric acid (UA) and sex, seem to influence cognitive and psychiatric expression in PD, however their interplay remains to be better understood. METHODS: Participants taking part in the Parkinson's Progression Marker Initiative were studied based on the side of motor symptom asymmetry and sex. Three-way interaction modeling was used to examine the moderating effects of sex and UA on cognitive functions and psychiatric symptoms. RESULTS: Significant three-way interactions were highlighted at 1-year follow-up between motor symptom asymmetry, UA and sex for immediate and long-term memory in female patients exhibiting predominantly left-sided motor symptoms, and for processing speed and sleepiness in female patients exhibiting predominantly right-sided motor symptoms. No significant interactions were observed for male patients. Moreover, female patients exhibiting predominantly right-sided motor symptoms demonstrated lower serum UA concentrations and had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor outcomes. CONCLUSIONS: These findings suggest that in the earliest stages of the disease, UA and sex moderate cognitive functions and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.

Parkinson's disease is characterized by motor symptoms that usually manifest in an asymmetrical fashion. Given this motor symptom asymmetry, it is possible to distinguish patients that exhibit predominantly right-sided motor symptoms from those that exhibit predominantly left-sided motor symptoms. Patients also often develop non-motor symptoms, such as cognitive and psychiatric complaints. Recent studies have found that non-motor symptoms can manifest differently depending on motor symptom asymmetry. Furthermore, different factors, such as uric acid, a natural antioxidant in the human body, and the patient's sex seem to influence cognitive and psychiatric manifestations, however their interplay remains to be better understood. The present study aimed to examine the interactions between motor symptom asymmetry, serum uric acid and patient's sex on the manifestation of cognitive and psychiatric symptoms. Using regression models, it was found that at 1 year from diagnosis, uric acid and sex moderated cognitive and psychiatric symptoms differently according to motor symptom asymmetry. Indeed, female patients with predominantly left-sided motor symptoms had better memory performances with lower concentrations of serum uric acid, whereas female patients with predominantly right-sided symptoms presented better psychomotor speed and less sleepiness with higher concentrations of uric acid. Moreover, female patients with predominantly right-sided motor symptoms had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor clinical outcomes. These findings suggest that in the earliest stages of the disease, uric acid and sex moderate cognitive and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.

Personality as a Predictor of Disability in Multiple Sclerosis.

OBJECTIVE: As personality changes and personality disorders are frequently observed in multiple sclerosis (MS), personality may be a prognostic factor for this disease. The present study investigated the influence of personality on disability, progression, and treatment adherence in MS. METHOD: Personality was assessed in 41 patients with Relapsing-Remitting MS (30 females; mean age = 42.63 years) using the NEO Personality Inventory-3rd edition. Disability was measured with the Expanded Disability Status Scale, and treatment adherence information was collected from the Swiss MS Cohort. Correlation, multiple linear and partial least square regressions were performed to examine relations between personality, disability, and treatment adherence in MS. RESULTS: After accounting for age and time since disease onset, our analysis revealed that Neuroticism (ß = 0.32, p = 0.01) and its Vulnerability facet (ß = 0.28, p < 0.05) predicted greater disability, whereas Extraversion (ß = -0.25, p = 0.04) and its Activity facet (ß = -0.23, p < 0.05) predicted milder disability. Regarding disability progression, correlational analysis revealed that it was negatively correlated with Extraversion (r = -0.44, p = 0.02) and the Feelings facet of Openness (r = -0.41, p = 0.03), but regressions failed to highlight any predictive links. No significant results could be demonstrated for treatment adherence. CONCLUSIONS: Overall, our study showed that some personality traits can impact disability in MS, indicating that these should be considered in clinical practice, as they could be used to adapt and improve patients' clinical support.

Biomarkers and non-motor symptoms as a function of motor symptom asymmetry in early Parkinson's disease.

INTRODUCTION: The longitudinal trajectories of cognitive-neuropsychiatric symptoms from the early stages of Parkinson's disease, as a function of motor symptom asymmetry at the onset of the disease, remain to be fully explored. Moreover, the relationship to biomarkers warrants further investigation. METHODOLOGY: Non-motor and biospecimen data from 413 patients with Parkinson's disease, dissociating predominantly left-sided motor symptoms patients (n = 179), predominantly right-sided motor symptoms patients (n = 234), and matched healthy controls (n = 196), were extracted from the Parkinson's Progression Marker Initiative database during a 3-Year follow-up. Non-parametric and conservative corrections for multivariate comparisons were carried out on neuropsychiatric and biomarker data. RESULTS: A decline for global cognitive efficiency scores in predominantly right-sided motor symptoms patients was observed, whereas depressive and anxiety symptoms were greater overtime for predominantly left-sided motor symptoms patients. Biomarker analysis revealed that predominantly right-sided patients expressed decreased levels of total-tau and phospho-tau over time, while left-sided patients didn't differ from healthy controls. CONCLUSION: From the early course of the disease, the existence of different clinical phenotypes is proposed, associated to emerging evidences of distinct pathological pathways and a left-hemispheric vulnerability for cognitive decline.

[Neuropsychological long-COVID : neurologic or psychiatric origin?] / Covid long neuropsychologique : origine neurologique ou psychiatrique ?

Among the long-COVID symptoms, neuropsychological sequelae are frequent after an infection by SARS-CoV-2, whatever the severity of the respiratory disease in the acute phase. These deficits seem to result from a neurological disorder, but also from psychiatric symptoms. Not only inflammatory components, which can play a major role in the genesis of the neuropsychological sequelae, but also the hypotheses of vascular systemic lesions, the neurotropism of SARS-CoV-2, or the effect of the stress and the hypothalamic-pituitary-adrenal axis (HPA) are suggested. Psychiatric complications due to SSARS-CoV-2 infection would partly explain these neuropsychological sequelae.

Parmi les symptômes de Covid long, les séquelles neuropsychologiques sont fréquentes dans les suites d'une infection par le SARS-CoV-2, et ce quel que soit le degré de sévérité de l'atteinte respiratoire en phase aiguë. Ces déficits semblent résulter d'une atteinte neurologique, mais aussi de l'installation de troubles psychiatriques. En plus de l'inflammation, qui joue un rôle majeur dans la genèse des séquelles neuropsychologiques, les hypothèses de lésions endothéliales systémiques, de l'existence d'un neurotropisme du SARS-CoV-2, de même que de celles de l'effet du stress et de la mise en jeu de l'axe hypothalamo-hypophysaire-surrénalien, sont proposées. Les complications psychiatriques de l'infection par le SARS-CoV-2 semblent, quant à elles, n'expliquer qu'une partie des séquelles neuropsychologiques.

Shame in Parkinson'S Disease: A Review.

Shame is a self-conscious emotion marked by an intensely negative self-evaluation. It is exhibited by an individual upon realizing that she/he has violated an important (usually social) norm. Shame can be a source of emotional distress leading to social withdrawal and depression, with a significant negative impact on quality of life. In Parkinson's disease (PD), shame is rarely addressed. Based on reports of persons affected with Parkinson's disease (PwP) as well as a literature review, this article describes PD-related shame. PD-related shame may emerge from motor and non-motor symptoms, from self-perception of inadequacy due to loss of autonomy and need for help, or from perceived deterioration of body image. The neurobiology of shame delineates neuronal networks involved in cognitive and emotions regulation, self-representation and representation of the others mental states. Although this hypothesis remains to be demonstrated, these substrates could be modulated, at least partially, by dopaminergic depletion related to PD, which may open a window for pharmacotherapy. Owing to the negative impact that shame can produce, shame should be actively explored and addressed in the individual PwP. Teaching PwP how to develop resilience to shame may be a useful strategy in preventing the vicious circle of shame. The paucity of existing data on prevalence and management of PD-specific shame contrasts with the manifold reported situations inducing suffering from shame. There is a crucial need for further investigations of shame in PD and the development of interventions to reduce its impact on PwP's quality of life.