Multivariate sharp‐wave ripples in schizophrenia during awake state

Abstract

AimsSchizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp‐wave ripples (SPW‐Rs) have been reported in SZ. As SPW‐Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW‐Rs in human SZ.MethodsWe measured whole‐brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex‐ and age‐matched healthy participants (n = 20) during open‐eye rest. We identified SPW‐Rs and analyzed their occurrence and time‐frequency traits. Furthermore, we developed a novel multivariate analysis method, termed “ripple‐gedMEG” to extract the global features of SPW‐Rs. We also examined the association between SPW‐Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ.ResultsWe found that SPW‐Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW‐Rs were found to be PANSS‐positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW‐Rs underlies the symptoms of SZ.ConclusionWe identified irregularities in SPW‐Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.