Autonomic responses to emotional linguistic stimuli and amplitude of low-frequency fluctuations predict outcome after severe brain injury

Gerardo Salvato,Manuela Berlingeri,Gabriele De Maio,Francesco Curto,Arturo Chieregato,Francesca Giulia Magnani,Maurizio Sberna,Mario Rosanova,Eraldo Paulesu,Gabriella Bottini

doi:10.1016/j.nicl.2020.102356

Abstract

An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC.

Highlights

Anoxic, haemorrhagic, or traumatic brain injuries may result in disorders of consciousness (DOC)
The results showed a positive relationship between the skin conductance response (SCR) delta index and the zfALFF signal of the posterior cingulate cortex (PCC)
To better explore residual lexical-semantic processing of emotionally salient linguistic stimuli in DOC patients, we implemented a simple event-related SCR paradigm based on implicit discrimination of auditorily presented words and pseudo-words

Summary

Introduction

Haemorrhagic, or traumatic brain injuries may result in disorders of consciousness (DOC). In a seminal study, Owen and colleagues (2006) used a motor imagery paradigm during fMRI to detect the neural correlates of command-following in one patient diagnosed as behaviourally vegetative. Monti and colleagues (2010) studied a group of 54 patients using a similar fMRI paradigm. They found that only 5 patients were able to modulate their brain activity wilfully. According to the most recent guidelines of the American Academy of Neurology (Giacino et al, 2018), there is currently insufficient evidence to support or refuse the routine clinical use of functional neuroimaging (fMRI, EEG, PET) in DOC, and available results fail to outline a clear-cut picture (Berlingeri et al, 2019). One of the primary aims of the research agenda is to develop prognostic approaches based on multiple and complementary techniques (Cavaliere et al, 2018; Coleman et al, 2009; Giacino et al, 2014; Gibson et al, 2014; Gosseries et al, 2014; Owen et al, 2009)

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