Cerebellar Morphology and Procedural Learning Impairment in Neuroleptic-Naive Youth at Ultrahigh Risk of Psychosis

Abstract

Despite evidence suggesting a role for cerebellar abnormalities in the pathogenesis of psychosis, the structure has yet to receive attention in individuals at ultrahigh risk for psychosis (UHR). Accumulating research has suggested that the cerebellum helps modulate cognition and movement, domains in which UHR individuals show impairment; understanding putative markers of risk, such as structural abnormalities and behavioral correlates, is essential. In this study, participants underwent a high-resolution structural brain scan and participated in a pursuit rotor experiment. Cerebellar regions associated with movement (anterior cerebellum) and cognition (crus I) were subsequently analyzed. UHR participants showed impaired performance on the pursuit rotor task, learned at a slower rate, and showed smaller cerebellar volumes compared with control participants. Left crus I volume was significantly associated with poor rate of learning. The present results suggest that cerebellar abnormalities and their behavioral correlates (poor learning and motor control) precede the onset of psychosis.

Self-reported sleep disturbances associated with procedural learning impairment in adolescents at ultra-high risk for psychosis

“…The current study extends our prior work, which revealed procedural learning (Dean et al, 2014) and sleep (Lunsford-Avery et al, 2013) deficits among UHR adolescents, and investigates associations between self-reported sleep disturbances and pursuit rotor (PR) task performance, a gold standard measure of procedural learning in a sample of UHR youth (Raz et al, 2000). We hypothesized that greater sleep disturbances would correlate with impaired procedural learning rate.…”

“…Specifically, the degree of impairment depends on individual characteristics (e.g., intelligence; Gomar et al, 2011) and task demands (Siegert et al, 2008). Consistent with broader memory deficits across the psychosis continuum (Bora et al, 2014), procedural learning deficits are also observed in non-clinical psychosis (Mittal et al, 2012) and high risk (Dean et al, 2014) samples. Procedural learning deficits may characterize at least a subset of schizophrenia and at-risk groups; however, biological mechanisms contributing to within-group heterogeneity are unclear.…”

“…Moreover, reduced cognitive and motor function occurs prior to psychosis onset, suggesting potential vulnerability markers (Bora et al, 2014; Dean et al, 2014; Sommer et al, 2016). Clarifying the nature of specific neurocognitive deficits among youth at ultra high-risk (UHR) for psychosis is essential for establishing early identification and prevention/intervention strategies (Bora et al, 2014).…”

“…Normative procedural learning is linked to a distributed series of circuits involving the striatum and cerebellum (Doyon et al, 2003; Hikosaka et al, 1999). Studies indicating structural and functional frontal-striatal and frontal-cerebellar circuit abnormalities may also impact procedural learning in the psychosis spectrum (Dean et al, 2014; Kumari et al, 2002). Because these circuits include key structures that have been implicated in normative and pathological sleep (i.e., thalamus; Espana and Scammell, 2011; Lunsford-Avery et al, 2013), there may be a physiological link between sleep and learning in psychosis.…”

Nicotine usage is associated with elevated processing speed, spatial working memory, and visual learning performance in youth at ultrahigh-risk for psychosis

“…The measure has been widely used in a number of psychosis spectrum studies (Cannon et al, 2008; Mittal et al, 2011; Mittal et al, 2012; Dean et al, 2014; Carol, E., and Mittal, V.M., under review) and shows excellent reliability (Long and Hollin, 2009; Moller and Linaker, 2010). …”