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.

Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort.

Background: Despite numerous observations of neuropsychological deficits immediately following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, little is known about what happens to these deficits over time and whether they are affected by changes in fatigue and any psychiatric symptoms. We aimed to assess the prevalence of neuropsychological deficits at 6-9 months and again at 12-15 months after coronavirus disease 2019 (COVID-19) and to explore whether it was associated with changes in fatigue and psychiatric symptoms. Methods: We administered a series of neuropsychological tests and psychiatric questionnaires to 95 patients (mean age = 57.12 years, standard deviation (SD) = 10.68; 35.79% women) 222 (time point 1 (T1)) and 441 (time point 2 (T2)) days on average after infection. Patients were categorised according to the severity of their respiratory COVID-19 symptoms in the acute phase: mild (no hospitalisation), moderate (conventional hospitalisation), and severe (hospitalisation in intensive care unit (ICU) plus mechanical ventilation). We ran Monte-Carlo simulation methods at each time point to generate a simulated population and then compared the cumulative percentages of cognitive disorders displayed by the three patient subgroups with the estimated normative data. We calculated generalised estimating equations for the whole sample to assess the longitudinal associations between cumulative neuropsychological deficits, fatigue, and psychiatric data (anxiety, depressive symptoms, posttraumatic stress disorder, and apathy). Results: Most participants (>50%) exhibited a decrease in their neuropsychological impairments, while approximately 25% showed an escalation in these cognitive deficits. At T2, patients in the mild subgroup remained free of accumulated neuropsychological impairments. Patients with moderate severity of symptoms displayed a decrease in the magnitude of cumulative deficits in perceptual and attentional functions, a persistence of executive, memory and logical reasoning deficits, and the emergence of language deficits. In patients with severe symptoms, perceptual deficits emerged and executive deficits increased, while attentional and memory deficits remained unchanged. Changes in executive functions were significantly associated with changes in depressive symptoms, but the generalised estimating equations failed to reveal any other significant effect. Conclusion: While most cumulative neuropsychological deficits observed at T1 persisted and even worsened over time in the subgroups of patients with moderate and severe symptoms, a significant proportion of patients, mainly in the mild subgroup, exhibited improved performances. However, we identified heterogeneous neuropsychological profiles both cross-sectionally and over time, suggesting that there may be distinct patient phenotypes. Predictors of these detrimental dynamics have yet to be identified.

Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection.

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID. Case Presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region. Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

[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.

[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.

Effects of deep brain stimulation frequency on eye movements and cognitive control.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). Varying the frequency DBS has differential effects on axial and distal limb functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson's Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes.

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.

Cognitive Deficits in the Acute Phase of COVID-19: A Review and Meta-Analysis.

This meta-analysis was conducted to quantify the risk of patients exhibiting cognitive deficits in the acute phase of COVID-19 at the time of the first variants (i.e., before the vaccine) and quantify the potential vulnerability of older patients and those who experienced more severe respiratory symptoms. To this end, we searched the LitCovid and EMBASE platforms for articles, including preprints, and included all studies (n = 48) that featured a measurement of cognition, which encompassed 2233 cases of COVID-19. Of these, 28 studies reported scores on global cognitive efficiency scales administered in the acute phase of COVID-19 (up to 3 months after infection). We were able to perform a meta-analysis of proportions on 24 articles (Npatients = 943), and a logistic regression on 18 articles (Npatients = 518). The meta-analysis for proportion indicated that 52.31% of patients with COVID-19 exhibited cognitive deficits in the acute phase. This high percentage, however, has to be interpreted taking in consideration the fact that the majority of patients were hospitalized, and some presented neurological complications, such as encephalopathy. A bootstrap procedure with random resampling revealed that an age of 59 was the threshold at which one would be more prone to present cognitive deficits. However, the severity of respiratory symptoms did not influence the scores on a global cognitive efficiency scale. Overall, our results indicated that neuropsychological deficits were a major consequence of the acute phase of the first forms of COVID-19.

Motor Symptom Asymmetry Predicts Cognitive and Neuropsychiatric Profile Following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: a 5-Year Longitudinal Study.

INTRODUCTION: Risk factors (e.g., motor symptom asymmetry) for short- and long-term cognitive and neuropsychiatric symptoms following deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease have yet to be fully identified. The objectives of the present study were to determine whether motor symptom asymmetry in Parkinson's disease is one such risk factor and to identify predictors of subnormal cognitive decline. METHODS: A total of 26 patients receiving STN-DBS (13 with left-sided motor symptoms and 13 with right-sided ones) underwent follow-up neuropsychological, depression and apathy assessments over a 5-year period. Nonparametric intergroup comparisons were performed on raw scores, as well as Cox regression analyses on standardized Mattis Dementia Rating Scale scores. RESULTS: Compared with patients who had predominantly left-sided symptoms, right-sided patients scored higher on both apathy (at 3 months and 36 months) and depressive symptoms (at 6 months and 12 months) and scored lower on global cognitive efficiency (at 36 months and 60 months). Survival analyses revealed that only right-sided patients had subnormal standardized dementia scores, which were negatively associated with the number of perseverations in the Wisconsin Card Scoring Test. CONCLUSION: Right-sided motor symptoms are a risk factor for more severe short- and long-term cognitive and neuropsychiatric symptoms following STN-DBS, confirming literature findings on left hemispheric vulnerability.

Dysfunctional cerebello-cerebral network associated with vocal emotion recognition impairments.

Vocal emotion recognition, a key determinant to analyzing a speaker's emotional state, is known to be impaired following cerebellar dysfunctions. Nevertheless, its possible functional integration in the large-scale brain network subtending emotional prosody recognition has yet to be explored. We administered an emotional prosody recognition task to patients with right versus left-hemispheric cerebellar lesions and a group of matched controls. We explored the lesional correlates of vocal emotion recognition in patients through a network-based analysis by combining a neuropsychological approach for lesion mapping with normative brain connectome data. Results revealed impaired recognition among patients for neutral or negative prosody, with poorer sadness recognition performances by patients with right cerebellar lesion. Network-based lesion-symptom mapping revealed that sadness recognition performances were linked to a network connecting the cerebellum with left frontal, temporal, and parietal cortices. Moreover, when focusing solely on a subgroup of patients with right cerebellar damage, sadness recognition performances were associated with a more restricted network connecting the cerebellum to the left parietal lobe. As the left hemisphere is known to be crucial for the processing of short segmental information, these results suggest that a corticocerebellar network operates on a fine temporal scale during vocal emotion decoding.

Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

Explicit and Implicit Emotion Processing in the Cerebellum: A Meta-analysis and Systematic Review.

The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified clusters within the posterior cerebellar hemispheres (bilateral lobule VI/Crus I/II), the vermis, and left lobule V/VI that were likely to be activated across studies, while implicit tasks activated clusters including bilateral lobules VI/Crus I/II, right Crus II/lobule VIII, anterior lobule VI, and lobules I-IV/V. A direct comparison between these categories revealed five overlapping clusters in right lobules VI/Crus I/Crus II and left lobules V/VI/Crus I of the cerebellum common to both the explicit and implicit task contrasts. There were also three clusters activated significantly more for explicit emotion tasks compared to implicit tasks (right lobule VI, left lobule VI/vermis), and one cluster activated more for implicit than explicit tasks (left lobule VI). These findings support previous studies indicating affective processing activates both the lateral hemispheric lobules and the vermis of the cerebellum. The common and distinct activation of posterior cerebellar regions by tasks with explicit and implicit attention demonstrates the supportive role of this structure in recognizing, appraising, and reacting to emotional stimuli.

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.

Principles of Brain and Emotion: Beyond the Cortico-Centric Bias.

Affective neurosciences have largely contributed to the elaboration of theoretical and neuroanatomical models through research conducted in non-primate animals and human beings. However, for methodological and historical reasons, knowledge has developed by focusing mainly on the cerebral cortex, resulting in a lack of investigations of the functional aspects of subcortical structures such as the cerebellum and the basal ganglia. The close anatomical connections revealed between these two structures, as well as their reciprocal connections with the cerebral cortex, lead to a vertically organized model of the brain. Both the cerebellum and the basal ganglia are involved in the different components required during an emotional episode. Their respective specificity in the analysis of temporal patterns contributes to the optimal processing of emotional signals such as those that can be conveyed by the voice (emotional prosody). Internal temporally structured event representation, built from the salient modulation extractions performed by the cerebellum, is used by the basal ganglia to recruit and synchronize the activity of the cortical and subcortical structures required for the relevant processes.

Reward-Based Learning and Emotional Habit Formation in the Cerebellum.

There is growing evidence of the cerebellum's contribution to emotion processing from neuroimaging studies of healthy function and clinical studies of cerebellar patients. As demonstrated initially in the motor domain, one of the cerebellum's functions is to construct internal models of an individual's state and make predictions about how future behaviors will impact that state. By utilizing widespread connections with neocortex and subcortical regions such as the basal ganglia, the cerebellum can monitor and modulate precisely timed patterns of events using prediction and reward-based error feedback in a diverse range of tasks including auditory emotion prosody recognition. In coordination with a broader affective network, the cerebellum helps to select and refine emotional responses that are the most rewarded in a particular context, strengthening neural activity in relevant regions to form a representational chunk. This chunked set of affective stimuli, cognitive evaluations, and physiological responses subsequently can be enacted as a unitary response (i.e., an emotional habit) more quickly and with less attentional control than for a novel stimulus or goal-oriented action. Such emotional habits can allow for efficient, automatic, stimulus-triggered responses while maintaining the flexibility to adapt output when prediction errors signal a renewed need for cerebellar modification of cortical activity, or, conversely, may lead to behavioral or mood disorders when habitual responses persist despite negative consequences.