The Cerebellum and Cognitive Function: Anatomical Evidence from a Transdiagnostic Sample.

Multiple lines of evidence across human functional, lesion, and animal data point to a cerebellar role, in particular of crus I, crus II, and lobule VIIB, in cognitive function. However, a mapping of distinct facets of cognitive function to cerebellar structure is missing. We analyzed structural neuroimaging data from the Healthy Brain Network (HBN). Cerebellar parcellation was performed with a validated automated segmentation pipeline (CERES) and stringent visual quality check (n = 662 subjects retained from initial n = 1452). Canonical correlation analyses (CCA) examined regional gray matter volumetric (GMV) differences in association to cognitive function (quantified with NIH Toolbox Cognition domain, NIH-TB), accounting for psychopathology severity, age, sex, scan location, and intracranial volume. Multivariate CCA uncovered a significant correlation between two components entailing a latent cognitive canonical (NIH-TB subscales) and a brain canonical variate (cerebellar GMV and intracranial volume, ICV), surviving bootstrapping and permutation procedures. The components correspond to partly shared cerebellar-cognitive function relationship with a first map encompassing cognitive flexibility (r = 0.89), speed of processing (r = 0.65), and working memory (r = 0.52) associated with regional GMV in crus II (r = 0.57) and lobule X (r = 0.59) and a second map including the crus I (r = 0.49) and lobule VI (r = 0.49) associated with working memory (r = 0.51). We show evidence for a structural subspecialization of the cerebellum topography for cognitive function in a transdiagnostic sample.

Preserved Metacognition for Undetected Visuomotor Deviations.

Humans can successfully correct deviations of movements without conscious detection of such deviations, suggesting limited awareness of movement details. We ask whether such limited awareness impairs confidence (metacognition). We recorded functional magnetic resonance imaging data while 31 human female and male participants detected cursor deviations during a visuomotor reaching task and rated their confidence retrospectively. We show that participants monitor a summary statistic of the unfolding visual feedback (the peak cursor error) to detect visuomotor deviations and adjust their confidence ratings, even when they report being unaware of a deviation. Crucially, confidence ratings were as metacognitively efficient for aware and unaware deviations. At the neural level, activity in the ventral striatum tracks high confidence, whereas a broad network encodes cursor error but not confidence. These findings challenge the notion of limited conscious action monitoring and uncover how humans monitor their movements as they unfold, even when unaware of ongoing deviations.SIGNIFICANCE STATEMENT We are unaware of the small corrections we apply to our movements as long as our goals are achieved. Here, although we replicate the finding that participants deny perceiving small deviations they correct, we show that their confidence reliably reflects the presence or absence of a deviation. This observation shows they can metacognitively monitor the presence of a deviation, even when they deny perceiving it. We also describe the hemodynamic correlates of confidence ratings. Our study questions the extent to which humans are unaware of the details of their movements; describes a plausible mechanism for metacognition in a visuomotor task, along with its neural correlates; and has important implications for the construction of the sense of self.

Understanding the relationship between cerebellar structure and social abilities.

BACKGROUND: The cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the "cognitive" lobules of the cerebellum would be associated with social difficulties. METHODS: We analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities-assessed with the social component of the Social Responsiveness Scale (SRS)-were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis. RESULTS: In 850 children and teenagers (mean age 10.8 ± 3 years; range 5-18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model. LIMITATIONS: Cerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders. CONCLUSION: Our results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Cerebellar and cortico-striatal-midbrain contributions to reward-cognition processes and apathy within the psychosis continuum.

Negative symptoms in the psychosis continuum are linked to impairments in reward processing and cognitive function. Processes at the interface of reward processing and cognition and their relation to negative symptoms remain little studied, despite evidence suggestive of integration in mechanisms and neural circuitry. Here, we investigated brain activation during reward-dependent modulation of working memory (WM) and their relationship to negative symptoms in subclinical and early stages of the psychosis continuum. We included 27 persons with high schizotypal personality traits and 23 patients with first episode psychosis as well as 27 healthy controls. Participants underwent functional magnetic resonance imaging while performing an established 2-back WM task with two reward levels (5 CHF vs. no reward), which allowed us to assess common reward-cognition regions through whole-brain conjunction analyses and to investigate relations with clinical scores of negative symptoms. As expected for behavior, reward facilitated performance while cognitive load diminished it. At the neural level, the conjunction of high reward and high cognitive load contrasts across the psychosis continuum showed increased hemodynamic activity in the thalamus and the cerebellar vermis. During high cognitive load, more severe apathy but not diminished expression in the psychosis continuum was associated with reduced activity in right lateral orbitofrontal cortex, midbrain, posterior vermal cerebellum, caudate and lateral parietal cortex. Our results suggest that hypoactivity in the cerebellar vermis and the cortical-striatal-midbrain-circuitry in the psychosis continuum relates to apathy possibly via impaired flexible cognitive resource allocation for effective goal pursuit.

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: Functional neurological disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with FND, suggesting that gaps remain in our systems-level neurobiological understanding. As such, other important physiological variables, including autonomic, endocrine, and inflammation findings, need to be contextualized for a more complete mechanistic picture. METHODS: The investigators conducted a systematic review and meta-analysis of available case-control and cohort studies of FND. PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1900, to September 1, 2020, that investigated autonomic, endocrine, and inflammation markers in patients with FND. Sixty-six of 2,056 screened records were included in the review, representing 1,699 patients; data from 20 articles were used in the meta-analysis. RESULTS: Findings revealed that children and adolescents with FND, compared with healthy control subjects (HCs), have increased resting heart rate (HR); there is also a tendency toward reduced resting HR variability in patients with FND across the lifespan compared with HCs. In adults, peri-ictal HR differentiated patients with functional seizures from those with epileptic seizures. Other autonomic and endocrine profiles for patients with FND were heterogeneous, with several studies highlighting the importance of individual differences. CONCLUSIONS: Inflammation research in FND remains in its early stages. Moving forward, there is a need for the use of larger sample sizes to consider the complex interplay between functional neurological symptoms and behavioral, psychological, autonomic, endocrine, inflammation, neuroimaging, and epigenetic/genetic data. More research is also needed to determine whether FND is mechanistically (and etiologically) similar or distinct across phenotypes.

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Pathophysiology of negative symptom dimensions of schizophrenia - Current developments and implications for treatment.

Negative symptoms of schizophrenia comprise a group of severe symptoms contributing to high disease burden and poor long-term prognosis. Conceptual work has shown that these symptoms can be mapped onto, at least, two distinct dimensions: apathy including the domains avolition, asociality and anhedonia, and diminished expression including the domains blunted affect and alogia. Growing evidence suggest that these dimensions have partly distinct behavioral, cognitive and neural correlates. Nonetheless, modulation and treatment of specific processes and brain correlates related to these negative symptom dimensions through behavioral, pharmacological, and brain stimulation interventions remains poorly understood. Here, we address this question by employing an integrative approach and comprehensively synthesizing the current literature on neuroimaging, behavior and clinical studies of both negative symptom dimensions. While considerable progress has been made, it remains an open challenge to develop integrative mechanistic pathophysiological models for apathy and diminished expression. We conclude that such multi-level frameworks are key for the development of new biological and psychosocial treatments and may advance progress towards an individualized treatment of negative symptoms.

The Confidence Database.

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at https://osf.io/s46pr/) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects.

Structural alterations in functional neurological disorder and related conditions: a software and hardware problem?

Functional neurological (conversion) disorder (FND) is a condition at the interface of neurology and psychiatry. A "software" vs. "hardware" analogy describes abnormal neurobiological mechanisms occurring in the context of intact macroscopic brain structure. While useful for explanatory and treatment models, this framework may require more nuanced considerations in the context of quantitative structural neuroimaging findings in FND. Moreover, high co-occurrence of FND and somatic symptom disorders (SSD) as defined in DSM-IV (somatization disorder, somatoform pain disorder, and undifferentiated somatoform disorder; referred to as SSD for brevity in this article) raises the possibility of a partially overlapping pathophysiology. In this systematic review, we use a transdiagnostic approach to review and appraise the structural neuroimaging literature in FND and SSD. While larger sample size studies are needed for definitive characterization, this article highlights that individuals with FND and SSD may exhibit sensorimotor, prefrontal, striatal-thalamic, paralimbic, and limbic structural alterations. The structural neuroimaging literature is contextualized within the neurobiology of stress-related neuroplasticity, gender differences, psychiatric comorbidities, and the greater spectrum of functional somatic disorders. Future directions that could accelerate the characterization of the pathophysiology of FND and DSM-5 SSD are outlined, including "disease staging" discussions to contextualize subgroups with or without structural changes. Emerging neuroimaging evidence suggests that some individuals with FND and SSD may have a "software" and "hardware" problem, although if structural alterations are present the neural mechanisms of functional disorders remain distinct from lesional neurological conditions. Furthermore, it remains unclear whether structural alterations relate to predisposing vulnerabilities or consequences of the disorder.

Confidence of emotion expression recognition recruits brain regions outside the face perception network.

Metacognitive beliefs about emotions expressed by others are crucial to social life, yet very little studied. To what extent does our confidence in emotion expression recognition depend on perceptual or other non-perceptual information? We obtained behavioral and magnetic resonance imaging measures while participants judged either the emotion in ambiguous faces or the size of two lines flanking these faces, and then rated their confidence on decision accuracy. Distinct behavioral and neural mechanisms were identified for confidence and perceptual decision in both tasks. Participants overestimated their emotion recognition (ER) accuracy, unlike visual size judgments. Whereas expression discrimination recruited several areas in the face-processing network, confidence for ER uniquely engaged the bilateral retrosplenial/posterior cingulate complex and left parahippocampal gyrus. Further, structural white matter connectivity of the former region predicted metacognitive sensitivity. These results highlight a key role for brain mechanisms integrating perception with contextual mnemonic information in the service of confidence during ER.

Metacognition of visuomotor decisions in conversion disorder.

Motor conversion disorder (CD) entails genuine disturbances in the subjective experience of patients who maintain they are unable to perform a motor function, despite lack of apparent neurological damage. Abilities by which individuals assess their own capacities during performance in a task are called metacognitive, and distinctive impairment of such abilities is observed in several disorders of self-awareness such as blindsight and anosognosia. In CD, previous research has focused on the recruitment of motor and emotional brain systems, generally linking symptoms to altered limbic-motor interactions; however, metacognitive function has not been studied to our knowledge. Here we tested ten CD patients and ten age-gender matched controls during a visually-guided motor paradigm, previously employed in healthy controls (HC), allowing us to probe for motor awareness and metacognition. Participants had to draw straight trajectories towards a visual target while, unbeknownst to them, deviations were occasionally introduced in the reaching trajectory seen on the screen. Participants then reported both awareness of deviations and confidence in their response. Activity in premotor and cingulate cortex distinguished between conscious and unconscious movement corrections in controls better than patients. Critically, whereas controls engaged the left superior precuneus and middle temporal region during confidence judgments, CD patients recruited bilateral parahippocampal and amygdalo-hippocampal regions instead. These results reveal that distinct brain regions subserve metacognitive monitoring for HC and CD, pointing to different mechanisms and sources of information used to monitor and form confidence judgments of motor performance. While brain systems involved in sensory-motor integration and vision are more engaged in controls, CD patients may preferentially rely on memory and contextual associative processing, possibly accounting for how affect and memories can imbue current motor experience in these patients.