Cerebellum-cingulo-opercular network connectivity strengthens in adolescence and supports attention efficiency only in childhood.

Posterior cerebellar lobules are active during executive function (EF) tasks and are functionally connected to EF-associated cortical networks such as the fronto-parietal network (FPN) and cingulo-opercular network (CON). Despite evidence that EF and cerebello-cortical connectivity develop on a similar time scale, developmental relationships between EFs and cerebello-cortical connectivity have not been directly investigated. We therefore examined relationships between cerebello-cortical connectivity and EF performance in a typically developing sample ages 8 - 21. Resting-state functional connectivity between posterior cerebellum and FPN (middle frontal gyrus, posterior parietal lobules)/CON (anterior cingulate, insula) was computed using independent components analysis. Using conditional process models, we tested the hypothesis that cerebellum - PFC connectivity would mediate the relationship between FPN/CON and EF, and that cerebello-cortical connectivity, and connectivity - EF relationships, would become stronger with increasing age. Cerebellum - CON connectivity strengthened with age, but a relationship between cerebellum - anterior cingulate cortex (ACC) connectivity and attention efficiency was significant only in younger children. Results suggest that during childhood, the posterior cerebellum and ACC may support sustained and executive attention, though age has a stronger effect on EF. These findings may help to guide further studies of executive dysfunction in neurodevelopmental disorders.

Cerebellar-Subcortical-Cortical Systems as Modulators of Cognitive Functions.

Over the past few decades, research has established that the cerebellum is involved in executive functions; however, its specific role remains unclear. There are numerous theories of cerebellar function and numerous cognitive processes falling under the umbrella of executive function, making investigations of the cerebellum's role in executive functioning challenging. In this review, we explored the role of the cerebellum in executive functioning through clinical and cognitive neuroscience frameworks. We reviewed the neuroanatomical systems and theoretical models of cerebellar functions and the multifaceted nature of executive functions. Using attention deficit hyperactivity disorder and cerebellar tumor as clinical developmental models of cerebellar dysfunction, and the functional magnetic resonance imaging literature, we reviewed evidence for cerebellar involvement in specific components of executive function in childhood, adolescence, and adulthood. There is evidence for posterior cerebellar contributions to working memory, planning, inhibition, and flexibility, but the heterogeneous literature that largely was not designed to study the cerebellum makes it difficult to determine specific functions of the cerebellum or cerebellar regions. In addition, while it is clear that cerebellar insult in childhood affects executive function performance later in life, more work is needed to elucidate the mechanisms by which executive dysfunction occurs and its developmental course. The limitations of the current literature are discussed and potential directions for future research are provided.

Weaker Cerebellocortical Connectivity Within Sensorimotor and Executive Networks in Schizophrenia Compared to Healthy Controls: Relationships with Processing Speed.

Background: The cognitive dysmetria theory of schizophrenia proposes that communication between the cerebellum and cerebral cortex is disrupted by structural and functional abnormalities, resulting in psychotic symptoms and cognitive deficits. Methods: Using publicly available data, resting-state functional connectivity (rsFC) was calculated from 20 hemispheric cerebellar lobules as seed regions of interest to the rest of the brain. Group differences in rsFC between individuals with schizophrenia (SZ) and healthy controls (HCs) were computed, and relationships between rsFC and symptom severity and cognitive functioning were explored. Results: HCs demonstrated stronger connectivity than SZ between several cerebellar lobules and cortical regions, most robustly between motor-related cerebellar lobules (V and VIIIa/b) and temporal and parietal cortices. In addition, seven of nine lobules in which reduced cerebellocortical connectivity was observed showed diagnosis × processing speed interactions; HC showed a positive relationship between connectivity and processing speed, whereas SZ did not show this relationship. Other cognitive domains and symptom severity did not show relationships with connectivity. Conclusions: These findings partially support the cognitive dysmetria theory, and suggest that disrupted cerebellocortical connectivity is associated with slowed processing speed in schizophrenia. Impact statement We show in this work that in chronic schizophrenia, there is weaker functional connectivity between previously unstudied inferior posterior cerebellar lobules and cortical association areas. These findings align and extend previous work showing abnormal connectivity of anterior cerebellar lobules. Further, we present a novel finding that these connectivity deficits are differentially associated with processing speed in the schizophrenia versus healthy control groups. Findings provide further evidence for cerebellocortical dysconnectivity and processing speed deficits as biomarkers of schizophrenia, which may have implications for downstream effects on higher order cognitive functions, in line with the cognitive dysmetria theory.

Cerebellar Contributions to Proactive and Reactive Control in the Stop Signal Task: A Systematic Review and Meta-Analysis of Functional Magnetic Resonance Imaging Studies.

The cerebellum facilitates and modulates cognitive functions using forward and inverse internal models to predict and control behavior, respectively. Despite neuroimaging evidence that regions of the cerebellum are active during executive function (EF) tasks in general, little is known about the cerebellum's role in specific EFs and their underlying neural networks. Inhibitory control specifically may be facilitated by cerebellar internal models predicting responses during proactive control (withholding), and controlling responses during reactive control (inhibiting). The stop signal task (SST) is an inhibitory control task often used in neuroimaging studies to measure neural responses to both proactive and reactive control. Thus, in this review, we examine evidence for the cerebellum's role in inhibitory control by reviewing studies of healthy adults that utilized the SST in event-related functional magnetic resonance imaging (fMRI) experiments. Twenty-one studies that demonstrated cerebellar results were eligible for review, including 749 participants, 28 contrasts, and 38 cerebellar clusters. We also performed activation likelihood estimation (ALE) meta-analysis of contrasts derived from reviewed studies. This review illustrates evidence for the cerebellum participating in inhibitory control independent of motor control. Most significant cerebellar clusters were located in the left posterior cerebellum, suggesting that it communicates with the established cortical right-lateralized inhibitory control network. Cerebellar activity was most consistently observed for contrasts that measured proactive control, and ALE analysis confirmed that left Crus I is most likely to be activated in studies of proactive control measuring monitoring and anticipation. Results suggest that the left posterior cerebellum may communicate with right frontal and parietal cortices, using forward models to predict appropriate responses. Reactive control contrasts indicated a possible role for cerebellar regions in enhancing inhibition efficiency through inverse models, but ALE meta-analysis did not confirm this hypothesis. Limitations in the current literature, clinical implications, and directions for future research are discussed.

Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders.

Impaired clinical insight (CI) is a common symptom of psychotic disorders and a promising treatment target. However, to date, our understanding of how variability in CI is tied to underlying brain dysfunction in the clinical high-risk period is limited. Developing a stronger conception of this link will be a vital first step for efforts to determine if CI can serve as a useful prognostic indicator. The current study investigated whether variability in CI is related to major brain networks in adolescents and young adults at ultra high-risk (UHR) of developing psychosis. Thirty-five UHR youth were administered structured clinical interviews as well as an assessment for CI and underwent resting-state magnetic resonance imaging scans. Functional connectivity was calculated in the default mode network (DMN) and fronto-parietal network (FPN), two major networks that are dysfunctional in psychosis and are hypothesized to affect insight. Greater DMN connectivity between the posterior cingulate/precuneus and ventromedial prefrontal cortex (DMN) was related to poorer CI (R2=0.399). There were no significant relationships between insight and the FPN. This is the first study to relate a major brain network to clinical insight before the onset of psychosis. Findings are consistent with evidence if a hyperconnected DMN in schizophrenia and UHR, and similar to a previous study of insight and connectivity in schizophrenia. Results suggest that a strongly connected DMN may be related to poor self-awareness of subthreshold psychotic symptoms in UHR adolescents and young adults.

Clinical correlates of bipolar disorder in a large, referred sample of children and adolescents.

OBJECTIVE: To compare the prevalence, clinical correlates, and comorbidity among children and adolescents with bipolar disorder (BPD) assessed in the early 1990s (first cohort) with those evaluated over the last 7 years (second cohort). METHODS: Subjects were consecutively referred children (N=108) and adolescents (N=197) with a DSM-III-R BPD diagnosis, referred to a child psychiatry service and evaluated with identical structured assessment methods. RESULTS: Mania was identified in 16% of referred youth in both age groups and cohorts; in both age groups and cohorts, the clinical picture was predominantly irritable and mixed, and the course was chronic. Youth with BPD in both age groups and cohorts frequently had comorbidity with ADHD, psychosis and anxiety disorders. They also had high rates of psychiatric hospitalization and evidence of severely impaired psychosocial functioning. CONCLUSIONS: The consistency of clinical features of bipolar disorder seen across age groups (children vs. adolescents) and cohorts (early and late cohorts) over the past decade supports the hypothesis that BPD in the young is a severe condition afflicting a sizeable minority of referred youth. These findings replicate and extend our previous characterization of an early onset mania, which may represent a developmental subtype of BPD.