Background: Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically.Method: Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2.Results: rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance.Conclusions: Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.

Background: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non‐motor functioning remain to be elucidated.Objective: To quantify cross‐sectional regional cerebellar lobule volumes using three dimensional T1‐weighted anatomical brain magnetic resonance imaging from the global ENIGMA‐PD working group.Methods: Cerebellar parcellation was performed using a deep learning‐based approach from 2487 people with PD and 1212 age and sex‐matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age‐ and sex‐ matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated.Results: Overall, people with PD had a regionally smaller posterior lobe (d_max = −0.15). HY stage‐specific analyses revealed a larger anterior lobule V bilaterally (d_max = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (d_max = −0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = −0.17).Conclusions: We provide evidence of a dissociation between anterior “motor” lobe and posterior “non‐motor” lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non‐motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross‐sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA‐Epilepsy working group.Methods: A state‐of‐the‐art deep learning‐based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness.Results: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (d_max = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (d_max = .47), crus I/II (d_max = .39), VIIIA (d_max = .45), and VIIIB (d_max = .40). Earlier age at seizure onset ( = .05) and longer epilepsy duration ( = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE‐HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls.Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.

The cerebellum, a subcortical structure, is traditionally linked to sensorimotor integration and coordination, although its role in cognition and affective behavior, as well as epilepsy, is increasingly recognized. Cerebellar dysfunction in patients with epilepsy can result from genetic disorders, antiseizure medications, seizures, and seizure‐related trauma. Impaired cerebellar function, regardless of cause, can cause ataxia (imbalance, impaired coordination, unsteady gait), tremor, gaze‐evoked nystagmus, impaired slow gaze pursuit and saccade accuracy, as well as speech deficits (slurred, scanning, or staccato). We explore how cerebellar dysfunction can contribute to epilepsy, reviewing data on genetic, infectious, and neuroinflammatory disorders. Evidence of cerebellar dysfunction in epilepsy comes from animal studies as well as human neuropathology and structural magnetic resonance imaging (MRI), functional and diffusion tensor MRI, positron emission and single photon emission computerized tomography, and depth electrode electro‐encephalography studies. Cerebellar lesions can infrequently cause epilepsy, with focal motor, autonomic, and focal to bilateral tonic–clonic seizures. Antiseizure medication–resistant epilepsy typically presents in infancy or before age 1 year with hemifacial clonic or tonic seizures ipsilateral to the cerebellar mass. Lesions are typically asymmetric benign or low‐grade tumors in the floor of the fourth ventricle involving the cerebellar peduncles and extending to the cerebellar hemisphere. Electrical stimulation of the cerebellum has yielded conflicting results on efficacy, although methodological issues confound interpretation. Epilepsy‐related comorbidities including cognitive and affective disorders, falls, and sudden unexpected death in epilepsy may also be impacted by cerebellar dysfunction. We discuss how cerebellar dysfunction may drive seizures and how genetic epilepsies, seizures and seizure therapies may drive cerebellar dysfunction, and how our understanding of epilepsy‐related comorbidities through basic neuroscience, animals models and patient studies can advance our understanding and improve patient outcomes.