Altered resting state effective connectivity in long-standing vegetative state patients: An EEG study
Introduction
Brain injuries due to anoxic, hemorrhagic or traumatic events often give rise to severe disorders of consciousness (DOC). Interest in DOC has increased over recent year and this has led to an increase in the “functional” evaluation of patients, mainly using fMRI-based techniques and to a lesser extent neurophysiological parameters. This is certainly partly because technological improvements now allow the better assessment of brain functions, but it is also due to the greater attention being given to the increasing number of patients who survive extreme brain damage as a result of improved emergency medicine and resuscitation techniques (Laureys and Boly, 2008). Unfortunately, a considerable proportion of such survivors enter a persistent vegetative state (VS) (Jennett and Plum, 1972), which is defined as a condition of wakefulness insofar as patients spontaneously open their eyes, but unawareness as their responses to the environment are inconsistent or absent.
Functional studies indicate that some severely impaired patients may retain some awareness and cognition (Boly, 2011, Boly et al., 2011, Kotchoubey et al., 2005), and have shown the capability of fMRI-based passive paradigms (Monti et al., 2010) in revealing a decrease in large-scale cerebral connectivity related to the level of consciousness impairment (Soddu et al., 2012, Vanhaudenhuyse et al., 2010).
The spectral properties of EEG signals have been widely used to assess brain insult severity in analytical methods (Wu et al., 2011a, Gosseries et al., 2011). In comparison with metabolic signals, EEG and magnetoencephalography (MEG) have the advantage of better temporal resolution; moreover, they allow the assessment of the connectivity patterns in different frequency bands that have different functional significance.
Functional connectivity is a suitable means of evaluating network characteristics based on the statistical interdependence of physiological time series recorded in different brain areas (Aertsen et al., 1989, Friston, 2001). Previous studies have revealed alterations in various central nervous system disorders including cognitive dysfunction (Stam et al., 2009) and traumatic brain injury (Castellanos et al., 2010). Differently from functional connectivity, which is a symmetric measure of coupling between two signals, effective connectivity allows the evaluation of the influence that one neural system has over another (causal effects) and makes it possible to determine the direction of the information flow within a brain network.
The aim of this study was to evaluate effective connectivity in different EEG frequency bands in a population of chronic VS patients using partial directed coherence (PDC), a frequency-domain measure derived from the multivariate autoregressive (MVAR) modelling of multichannel EEG signals (Baccalà and Sameshima, 2001).
Section snippets
Patients
The study involved 18 brain-injured patients with a clinical diagnosis of persistent VS: 9 had experienced a global post-hypoxic brain insult (the ABI group), and nine a hemorrhagic or traumatic insult (the non-ABI group) insult. Table 1 shows their age, the time from the brain insult, the damage revealed by means of MRI, and the mean scores of the Revised Coma Recovery Scale (Giacino et al., 2004) and the Coma Near Coma Scale (Rappaport et al., 1992), which were repeatedly administered by
Spectral analysis
Fig. 1 shows the grand average of EEG relative power of the four frequency bands averaged over the whole electrode set in the controls, and the ABI and non-ABI patients. The Kruskal–Wallis test revealed highly significant between-group differences in all of the frequency bands, and the post hoc comparison showed that both the ABI and non-ABI groups had significantly different relative power values from the controls in all of the frequency ranges (p < 0.00001). In particular, there was a higher
Discussion
Spectral analysis in long-standing VS patients showed that the relative power of delta activity was significantly higher in the patients than the controls regardless of the cause of the brain damage, while PDC analysis indicates a widespread decreased connectivity in the delta frequencies, but hyper-connected alpha frequencies in the cortical regions close to the midline.
The finding of prevailing delta EEG activity is in line with those of many previous studies, most of which involved patients
Acknowledgements
The project 2CRC, “Coma Research Centre” was supported by Grant No. N° IX/000407 (05/08/20109 awarded by Regione Lombardia.
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