Disorders of consciousness and the self are at the forefront of schizophrenia symptomatology. Patients are impaired in feeling themselves as the authors of their thoughts and actions. In addition, their flow of consciousness is disrupted, and thought fragmentation has been suggested to be involved in the patients’ difficulties in feeling as being one unique, unchanging self across time. Both impairments are related to self disorders, and both have been investigated at the experimental level. Here we review evidence that both mechanisms (...) of motor control and the temporal structure of signal processing are impaired in schizophrenia patients. Based on this review, we propose that the sequencing of action and perception plays a key role in the patients’ impairments. Furthermore, the millisecond time scale of the disorders, as well as the impaired sequencing, highlights the cooperation between brain networks including the cerebellum, as proposed by Andreasen (1999). We examine this possibility in the light of recent knowledge on the anatomical and physiological properties of the cerebellum, its role in timing, and its involvement in known physiological impairments in patients with schizophrenia, e.g., resting states and brain dynamics. A disruption in communication between networks involving the cerebellum, related to known impairments in dopamine, glutamate and GABA transmission, may help to better explain why patients experience reduced attunement with the external world and possibly with themselves. (shrink)

AimWhite matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology.MethodsSixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global (...) and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations.ResultsUltra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = −0.34, p = 0.011) and increased sleep fragmentation index (r = −0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses.ConclusionCompromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target. (shrink)