Long range temporal correlations (LRTCs) in MEG-data during emerging psychosis: Relationship to symptoms, medication-status and clinical trajectory

Gabriela Cruz,Tineke Grent-'T-Jong,Rajeev Krishnadas,J Matias Palva,Satu Palva,Peter J Uhlhaas

doi:10.1016/j.nicl.2021.102722

Gabriela Cruz, Tineke Grent-'T-Jong + Show 4 more

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https://doi.org/10.1016/j.nicl.2021.102722

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Abstract

Long-Range Temporal Correlations (LRTCs) index the capacity of the brain to optimally process information. Previous research has shown that patients with chronic schizophrenia present altered LRTCs at alpha and beta oscillations. However, it is currently unclear at which stage of schizophrenia aberrant LRTCs emerge. To address this question, we investigated LRTCs in resting-state magnetoencephalographic (MEG) recordings obtained from patients with affective disorders and substance abuse (clinically at low-risk of psychosis, CHR-N), patients at clinical high-risk of psychosis (CHR-P) (n = 115), as well as patients with a first episode (FEP) (n = 25). Matched healthy controls (n = 47) served as comparison group. LRTCs were obtained for frequencies from 4 to 40 Hz and correlated with clinical and neuropsychological data. In addition, we examined the relationship between LRTCs and transition to psychosis in CHR-P participants, and the relationship between LRTC and antipsychotic medication in FEP participants. Our results show that participants from the clinical groups have similar LRTCs to controls. In addition, LRTCs did not correlate with clinical and neurocognitive variables across participants nor did LRTCs predict transition to psychosis. Therefore, impaired LRTCs do not reflect a feature in the clinical trajectory of psychosis. Nevertheless, reduced LRTCs in the beta-band over posterior sensors of medicated FEP participants indicate that altered LRTCs may appear at the onset of the illness. Future studies are needed to elucidate the role of anti-psychotic medication in altered LRTCs.

Highlights

Schizophrenia (ScZ) is a severe psychiatric condition that typically emerges during the transition from adolescence to adulthood (Uhlhaas and Singer, 2011) and is associated with a range of neurobiological and cognitive impairments (Insel, 2010)
To further characterize alterations of temporal processing in neural networks in emerging psychosis, we examined Long-Range Temporal Correlations (LRTCs) in resting-state oscillations obtained from magnetoencephalographic (MEG) re cordings in participants who met clinical high-risk of psychosis (CHR-P) (n = 115) and first-episode of psychosis (FEP)-criteria (n = 25)
We examined if antipsychotic medication (APM) status is associated with attenuated LRTCs observed at 20.7 Hz

Summary

Introduction

Schizophrenia (ScZ) is a severe psychiatric condition that typically emerges during the transition from adolescence to adulthood (Uhlhaas and Singer, 2011) and is associated with a range of neurobiological and cognitive impairments (Insel, 2010). Pathophysiological theories have focussed on the crucial role of dopamine as a mechanism for the manifestation of psychotic symptoms, in particular hallucina tions and delusions, and certain cognitive deficits associated with pre frontal cortex (Howes and Kapur, 2009). It is currently unclear whether aberrant dopaminergic neurotransmission is the primary disturbance since the cortex-wide occurrence of cognitive dysfunctions as well as basic circuit deficits are difficult to reconcile with the dopa mine hypothesis (Kantrowitz and Javitt, 2010). In ScZ, post-mortem (Lewis et al, 2012) as well as genetic data (Pocklington et al, 2015) have highlighted that rhythm-generating PV + interneurons and NMDA-Rs (Woo et al, 2004) are dysfunctional, leading to widespread disinhibition in neural circuits

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