Sleep EEG and thalamocortical circuit abnormalities in schizophrenia

Nataliia Kozhemiako, PhD

Brigham and Women’s Hospital
Sleep EEG and thalamocortical circuit abnormalities in schizophrenia

Scientific Abstract

 

Background: Mounting evidence indicates that patients with schizophrenia (SZ) display an abnormality in NREM sleep – reduced sleep spindles – that has been linked to dysfunction of reticular thalamic nucleus. In parallel, SZ has also been associated with disrupted auditory sensory processing similarly reflecting abnormalities in thalamocortical circuits. Here, we use a unique dataset combining sleep and wake EEG data to investigate whether the spindle deficit and auditory processing differences in SZ reflect similar or distinct circuit abnormalities.

Methods: As part of a larger ongoing study, whole night 64-channel EEG and wake auditory ERP data were collected and analyzed for 66 patients with SZ (21 females, mean age 34.8±6.95) and 57 healthy volunteers (22 females, mean age 31.9±6.32). Using our open-source package Luna, we automatically detected slow and fast spindles as well as slow oscillations (SO) and their temporal coupling with spindles. ERP analysis was performed using BrainVision Analyzer, yielding measures of auditory steady state response (ASSR) at 40Hz frequency. Statistical significance of group differences at the channel level was tested using a general linear model, adding age and sex as covariates.

Results: We observed a marked and highly significant decrease in density and amplitude of slow and fast spindles in SZ, that was not explained by medication status. The largest effect size (-1.33 SD and p-value=2.4×10-6 in FC2 channel) was observed for fast spindle density. In contrast, spindle/SO coupling was largely comparable between groups. We further confirmed the diminished 40 Hz ASSR response in SZ patients. However, spindle and ASSR abnormalities were statistically independent of each other: both accounted for unique variance in the risk for SZ, suggesting that they reflect different aspects of thalamocortical dysfunction in SZ.

Conclusions: A reproducible hallmark of SZ pathophysiology, abnormal sleep microarchitecture is independent from alterations during wake, suggesting the sleep EEG conveys unique information that could expand our knowledge of neurobiological underpinnings of SZ.

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research Areas

Authors

Nataliia Kozhemiako*, PhD, Jun Wang*, PhD, Chenguang Jiang*, PhD, Lei Wang, PhD, Guan-chen Gai, PhD, Zhe Wang, PhD, Kai Zou, PhD, Xiao-man Yu, PhD, Lin Zhou, PhD, Zhenglin Guo, MPH, Shuping Tan, PhD, Shengying Qin, PhD, Hailiang Huang, PhD, Wei Zhu•, PhD, Zhenhe Zhou•, PhD, Mei-Hua Hall•, PhD, Jen Pan•, PhD, Shaun Purcell•, PhD * – co-first authors • – co-senior authors

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