Phase-Amplitude Markers of Synchrony and Noise: A Resting-State and TMS-EEG Study of Schizophrenia.

Dominik Freche,Shmuel Hess,Avraham Peled,Jodie Naim-Feil,Nava Levit-Binnun,Alexander Grinshpoon,Elisha Moses

doi:10.1093/texcom/tgaa013

Dominik Freche, Shmuel Hess + Show 5 more

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The electroencephalogram (EEG) of schizophrenia patients is known to exhibit a reduction of signal-to-noise ratio and of phase locking, as well as a facilitation of excitability, in response to a variety of external stimuli. Here, we demonstrate these effects in transcranial magnetic stimulation (TMS)-evoked potentials and in the resting-state EEG. To ensure veracity, we used 3 weekly sessions and analyzed both resting-state and TMS-EEG data. For the TMS responses, our analysis verifies known results. For the resting state, we introduce the methodology of mean-normalized variation to the EEG analysis (quartile-based coefficient of variation), which allows for a comparison of narrow-band EEG amplitude fluctuations to narrow-band Gaussian noise. This reveals that amplitude fluctuations in the delta, alpha, and beta bands of healthy controls are different from those in schizophrenia patients, on time scales of tens of seconds. We conclude that the EEG-measured cortical activity patterns of schizophrenia patients are more similar to noise, both in alpha- and beta-resting state and in TMS responses. Our results suggest that the ability of neuronal populations to form stable, locally, and temporally correlated activity is reduced in schizophrenia, a conclusion, that is, in accord with previous experiments on TMS-EEG and on resting-state EEG.

Highlights

Schizophrenia is a mental disease with a complex pathology that dynamically evolves across the adult lifespan (Krystal et al, 2017)
Three main qualitative effects are immediately apparent across the different time scales, ranging from tens of milliseconds to seconds and affecting several frequency bands
A hallmark of schizophrenia is the appearance of profound, global alterations of brain activity (Uhlhaas and Singer, 2010)

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Introduction

Schizophrenia is a mental disease with a complex pathology that dynamically evolves across the adult lifespan (Krystal et al, 2017). Several decades of research in schizophrenia have provided extensive evidence to the pervasive, globally occurring structural, physiological, functional and genetic abnormalities that characterizes the disorder. Abnormalities of brain tissue structure from the scale of synapses to whole brain regions have been described, with connectivity degradation occurring both locally and long-range. A range of profound functional abnormalities were observed in activity, from cell assemblies to large-scale networks (Uhlhaas and Singer, 2010; Krystal et al, 2017). One way to probe the functional abnormalities in schizophrenia is by studying dynamics of brain activity using EEG in stimulus-response paradigms. The main alterations of evoked responses in schizophrenia concern reductions in amplitudes and in phase locking (Winterer et al, 2000, 2004; Spencer et al, 2003; Frantseva et al, 2012; Shin et al, 2015), as well as facilitated excitation in late-stage response (Radhu et al, 2015; Frantseva et al, 2012; Rogasch et al, 2014), increased inter-trial variability (Winterer et al, 2000, 2004), and altered spectral power (Winterer et al, 2000; Frantseva et al, 2012)

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