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.

Keywords: SDM-meta-analysis; cognition; cognitive control; neuroimaging studies; schizophrenia; timing.

Figure 1

(A) Brain regions engaged during tasks requiring cognitive control: differences between healthy controls and schizophrenia patients. (B) Brain regions engaged during tasks requiring cognitive control: differences between healthy controls and schizophrenia patients. Multislice.

Figure 2

(A) Overlap and lack of overlap between brain regions engaged during time perception tasks and during tasks requiring cognitive control. Axial slices in neurological convention showing regions with statistically signification activation only during time perception tasks (SDM meta-analysis, green) and regions with statistically signification activation during tasks requiring cognitive control (SDM meta-analysis, blue, and red). Red for hyperactivations (patients > controls in difficult > easy) or for failures of deactivation (patients < controls in difficult < easy), and blue for hypoactivations (patients < controls in difficult > easy) or hyperdeactivations (patients > controls in difficult < easy). (B) Overlap and lack of overlap between brain regions engaged during time perception tasks and during tasks requiring cognitive control. Axial slices in neurological convention showing regions with statistically signification activation both during time perception tasks and during tasks requiring cognitive control (blue).