Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network

Abstract

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile.

Slower Time estimation in Post-Traumatic Stress Disorder

“…It is also interesting to note that the time overestimation pattern reported in our research for the PTSD sample appears similar to data in schizophrenic patients (ref. 52 , for a review 53 ). This parallelism is not surprising as the links between childhood trauma, PTSD and psychotic disorders is increasingly recognized 54 , and because in a discrete number of patients these two conditions might even overlap (see ref.…”

Predictive timing disturbance is a precise marker of schizophrenia

“…Moreover, temporal variability in the production task increased linearly with both duration of illness and age of SZ patients thus suggesting that dysfunctions in a fronto-thalamo-striatal control network ( Andreasen et al, 1998 ; Banaj et al, 2018 ), presumably hypo-activated ( Alústiza et al, 2016 ) or disorganized already at early stages of the illness ( Alústiza et al, 2016 ; Lambe et al, 2006 ), might mediate the observed variability, as it is involved in both time processing and the cognitive resources required for timing tasks ( Radua et al, 2014 ).…”

Neural Correlates of Interval Timing Deficits in Schizophrenia

“…Voss et al (2017) identified the angular gyrus and DLPFC as being implicated in matching outcomes to actions and observed decreased connectivity between these regions in SZ. As hypoactivation of the inferior parietal gyri has been observed in SZ patients in TP (Alustiza et al, 2016), future studies should employ binding paradigms (e.g., Haggard et al, 2003) to examine neural activation during TP in SZ. Interestingly, Lošák et al (2016) found decreased activation of the cerebellar vermis in SZ patients correlated with a faster clock during a time prediction task, suggesting that this region is critical for time prediction during salient events.…”