Predictive timing disturbance is a precise marker of schizophrenia

Abstract

Timing disturbances have being proposed as a key component of schizophrenia pathogenesis. However, the contribution of cognitive impairment to such disorders has not been clarified. Here, we investigated duration estimation and predictive timing in 30 patients with DSM-5 diagnosis of schizophrenia (SZ) compared to 30 healthy controls (HC). Duration estimation was examined in a temporal and colour discrimination task, fully controlled for working memory (WM) and attention requirements, and by more traditional temporal production and temporal bisection tasks. Predictive timing was measured in a temporal and spatial orienting of attention task. Expectations about stimulus onset (temporal condition) or location (spatial condition) were induced by valid and invalid symbolic cues. Results showed that discrimination of temporal and colour stimulus attributes was equally impaired in SZ. This, taken with the positive correlation between temporal bisection performance and neuropsychological measures of WM, indicates that duration estimation impairments in SZ are underpinned by WM dysfunction. Conversely, we found dissociation in temporal and spatial predictive ability in SZ. Unlike controls, patients were selectively unperturbed by events appearing at an unexpected moment in time, though were perturbed by targets appearing at an unexpected location. Moreover, patients were able to generate temporal expectations more implicitly, as their performance was influenced by the predictive nature of the flow of time itself.Our findings shed new light on the debate over the specificity of timing distortions in SZ, providing evidence that predictive timing is a precise marker of SZ, more sensitive than duration estimation, serving as a valid heuristic for studying the pathophysiology of the disorder.

Metastable States of Multiscale Brain Networks Are Keys to Crack the Timing Problem

“…On one hand it would be able to capture the local-to-global properties of neural processes that give rise to timing, on the other hand it would allow to grasp the integration processes among brain regions responsible for timing by means of metastability of network states (Friston, 1997 ; Fingelkurts and Fingelkurts, 2004 , 2017 ; Deco and Kringelbach, 2016 ). Accordingly, our perspective view about the best strategy able to provide a coherent and complete description of timing can be divided in three steps: (1) the choice of tasks involving different aspects of timing (Coull and Nobre, 1998 , 2008 ; Coull, 2004 ; Coull et al, 2013 ; Ciullo et al, 2018a ) to be administered on a steady-state fashion (Gonzalez-Castillo and Bandettini, 2018 ; Tommasin et al, 2018 ) in order to saturate the activity of the areas interacting during the specific task; (2) the brain activity should be monitored by means of different techniques able to highlight different temporal and spatial scales (e.g., fMRI, hd-EEG, MEG). Specifically the different scales can be cast in a common framework according to the multilayer representation (De Domenico et al, 2013 ) (different spatial scales for the same time scale or different temporal scales for the same spatial one); (3) the temporal dynamics from each task will be finally analyzed and fitted to theoretical models of neuronal synchronization (Deco et al, 2017 ; Cavanna et al, 2018 ) in order to cluster the dynamics of brain's activity during time processing.…”

“…These findings support also the hypothesis of a network of multiple central clocks and distributed processes of timing mechanisms (Merchant et al, 2008 ). The ability to organize behaviors within periods in the range of seconds to minutes, depends on a cognitive system that requires multiple neuropsychological functions (Buhusi and Meck, 2005 ; Coull and Nobre, 2008 ), consequently pathophysiological distortions in time might reflect neuropsychological deficits typical of definite neuropsychiatric disorders as schizophrenia (Ciullo et al, 2016 , 2018a ), acquired brain injury (Piras et al, 2014 ), Parkinson's disease (Wearden et al, 2008 ), Huntington's disease (Beste et al, 2007 ) and attention-deficit hyperactivity disorder (Zelaznik et al, 2012 ). Thus, the understanding of timing mechanisms and of the related cognitive processes may also allow the realization of a model system aiming to characterize cognitive dysfunctions in order to define novel tools for early diagnosis and to develop novel targeted cognitive therapies.…”

Sensitivity to statistical structure facilitates perceptual analysis of complex auditory scenes

“…It is remarkable that listeners in the present experiments exhibited the ability to track the regularity of sources even in very crowded scenes, populated by many simultaneous sound streams. That normal, young, listeners rely on this capacity so routinely, makes it an interesting feature to investigate in certain clinical populations typically linked to failure to extract temporal regularities (Schapiro et al, 2014;Davalos et al, 2018;Ciullo et al, 2018) as well as during healthy aging (Rimmele et al, 2012).…”

The Potential Interaction Between Time Perception and Gaming: A Narrative Review

“…Time loss may potentially be explained by impaired time perception, resulting in difficulty in keeping track of within-session gaming duration. Although the present paper focuses on gaming disorder, it is worth noting that impaired time control has been related to a wide range of psychopathological disorders, including attention deficit and hyperactivity disorder (e.g., Bielefeld et al 2017), bipolar disorder (e.g., Bolbecker et al 2014), schizophrenia (e.g., Ciullo et al 2018), and substance use disorder (e.g., Wittmann et al 2007). Consequently, compromised time control constitutes a trans-diagnostic etiopathological process (e.g., Dudley et al 2011).…”