Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia

Coesmans, Michael; Röder, Christian; Smit, Albertine Ellen; Koekkoek, S.K.E.; Zeeuw, Chris I. De; Frens, Maarten A.; Geest, Jos N. van der

doi:10.1503/jpn.120205

Cited by 31 publications

(29 citation statements)

References 39 publications

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“…Patients with schizophrenia often show specific deficits on those tasks for both saccadic and smooth pursuit eye movements, suggesting an impaired or non-veridical CD signal that affects action plans (Figure 2) and visual perception (Figure 3). At the level of action control, individuals with schizophrenia show performance deficits consistent with altered CD on the double-step [17], smooth pursuit [18], predictive pursuit [19–23], and saccade adaptation [24–26] tasks. One exception here is in the rapid correction of saccades that are inconsistent with higher-level goals: for instance, fast corrections after errors in the anti-saccade test are purported to rely on CD.…”

Section: Evidence For Disturbed Oculomotor CD In Psychosismentioning

confidence: 99%

Oculomotor Prediction: A Window into the Psychotic Mind

Thakkar

Diwadkar

Rolfs

2017

Trends in Cognitive Sciences

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Psychosis—an impaired contact with reality—is a hallmark of schizophrenia. Many psychotic symptoms are associated with disruptions in agency—the sense that I cause my actions. A failure to predict sensory consequences of one’s own actions may underlie agency disturbances. Such predictions rely on corollary discharge (CD) signals, “copies” of movement commands sent to sensory regions prior to action execution. Here, we make a case that the oculomotor system is a promising model for understanding CD in psychosis, building on advances in our understanding of the behavioral and neurophysiological correlates of CD associated with eye movements. We provide an overview of recent evidence for disturbed oculomotor CD in schizophrenia, potentially linking bizarre and disturbing psychotic experiences with basic physiological processes.

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Section: Evidence For Disturbed Oculomotor CD In Psychosismentioning

confidence: 99%

Oculomotor Prediction: A Window into the Psychotic Mind

Thakkar

Diwadkar

Rolfs

2017

Trends in Cognitive Sciences

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“…This effect became apparent toward the end of the adaptation and it was stronger in participants who demonstrated enhanced sensitivity to the stress manipulation, as indicated by the total cortisol output. Although saccadic adaptation has been used previously in different psychiatric populations (Coesmans et al, 2014;Connolly et al, 2016;Mosconi et al, 2013), it is unclear in these studies whether performance differences are due to antecedents, concomitants or consequences of the disorder or medication effects. This study is the first to demonstrate that saccadic adaptation in healthy individuals is reduced following an experimental stress induction and that this adaptation level correlated with cortisol output.…”

Section: Discussionmentioning

confidence: 99%

Psychosocial stress affects the acquisition of cerebellar-dependent sensorimotor adaptation

Gheorghe

Panouillères

Walsh

2018

Psychoneuroendocrinology

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Despite being overlooked in theoretical models of stress-related disorders, differences in cerebellar structure and function are consistently reported in studies of individuals exposed to current and early-life stressors. However, the mediating processes through which stress impacts upon cerebellar function are currently unknown. The aim of the current experiment was to test the effects of experimentally-induced acute stress on cerebellar functioning, using a classic, forward saccadic adaptation paradigm in healthy, young men and women. Stress induction was achieved by employing the Montreal Imaging Stress Task (MIST), a task employing mental arithmetic and negative social feedback to generate significant physiological and endocrine stress responses. Saccadic adaptation was elicited using the double-step target paradigm. In the experiment, 48 participants matched for gender and age were exposed to either a stress (n = 25) or a control (n = 23) condition. Saliva for cortisol analysis was collected before, immediately after, and 10, and 30 min after the MIST. Saccadic adaptation was assessed approximately 10 min after stress induction, when cortisol levels peaked. Participants in the stress group reported significantly more stress symptoms and exhibited greater total cortisol output compared to controls. The stress manipulation was associated with slower learning rates in the stress group, while control participants acquired adaptation faster. Learning rates were negatively associated with cortisol output and mood disturbance. Results suggest that experimentally-induced stress slowed acquisition of cerebellar-dependent saccadic adaptation, related to increases in cortisol output. These 'proof-of-principle' data demonstrate that stress modulates cerebellar-related functions.

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“…Considered together, these findings provide converging evidence for cerebellar Crus I as a key node involved in both high-level cognition and severe psychopathology. More broadly, functional neuroimaging studies consistently report reduced cerebello-cerebral connectivity in schizophrenia patients (69,70) and high-risk groups (71,72), while behavioral studies find impaired cerebellar learning in both patients with schizophrenia (73)(74)(75) and their firstdegree relatives (76).…”

Section: Discussionmentioning

confidence: 99%

Cerebellar grey matter volume in adolescence is associated with prodromal psychotic symptoms and norm-violating behavior

Moberget

Alnæs

Kaufmann

et al. 2018

Preprint

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250 words | Article body: 3999 words, 0 tables, and 5 figures.Supplementary Information: 1 word document, 9 tables and 17 figures. AbstractBackground: Accumulating evidence supports cerebellar involvement in mental disorders such as schizophrenia, bipolar disorder, depression, anxiety disorders and attention-deficit hyperactivity disorder. However, little is known about the cerebellum in developmental stages of these disorders. In particular, whether cerebellar morphology is associated with early expression of specific symptom domains remains unclear. Methods:We used machine learning to test whether cerebellar morphometric features could robustly predict general cognitive function and psychiatric symptoms in a large and well-characterized developmental community sample centered on adolescence (the Philadelphia Neurodevelopmental Cohort, N=1401, age-range: 8 -23).Results: Cerebellar morphology was associated with both general cognitive function and general psychopathology (mean correlations between predicted and observed values: r = .20 and r = .13; p-values < .0009). Analyses of specific symptom domains revealed significant associations with rates of norm-violating behavior (r = .17; p < .0009), as well as psychosis (r = .12; p < .0009) and anxiety (r = .09; p =.0117) symptoms. In contrast, we observed no associations with attention deficits, depressive, manic or obsessivecompulsive symptoms. Crucially, across 52 brain-wide anatomical features, cerebellar features emerged as the most important for prediction of general psychopathology, psychotic symptoms and norm-violating behavior. Moreover, the association between cerebellar volume and psychotic symptoms, and to a lesser extent norm violating behavior, remained significant when adjusting for several potentially confounding factors. Conclusions:The robust associations with psychiatric symptoms in the age range when these typically emerge highlight the cerebellum as a key brain structure in the development of severe mental disorders.

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Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia

Cited by 31 publications

References 39 publications

Oculomotor Prediction: A Window into the Psychotic Mind

Oculomotor Prediction: A Window into the Psychotic Mind

Psychosocial stress affects the acquisition of cerebellar-dependent sensorimotor adaptation

Cerebellar grey matter volume in adolescence is associated with prodromal psychotic symptoms and norm-violating behavior

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