Spontaneous slow waves index multiple dimensions of recovery in Disorders of Consciousness

Abstract

Whether and how residual awareness is expressed in patients with Disorders of Consciousness (DoC) depends on the severity of brain damage and the transient functional state of the cortex at assessment. Classically, DoC are associated with electroencephalographic (EEG) slowing, marked by high-amplitude slow waves, even during the day. Yet, slow waves are also a hallmark of healthy sleep, where they are thought to serve restorative functions and to help maintain network homeostasis. Here, we asked whether slow waves in DoC can provide insights into the severity of cortical dysfunction or, conversely, into the preservation of residual awareness and recovery potential, by characterizing their spatial, temporal and morphological properties. We analyzed 256-channel EEG recorded during the Local-Global auditory paradigm in 236 DoC patients, including 123 in Unresponsive Wakefulness Syndrome (UWS), 62 in a Minimally Conscious State minus (MCS-) and 29 in MCS plus (MCS+). High-amplitude slow waves were detected as local events, and their density, amplitude and slopes were quantified scalp-wide and channel-wise, by mean level and temporal variability across the recording. Slow-wave features were related to concurrent (Coma Recovery Scale-Revised - CRS-R, Local-Global paradigm) and follow-up (one-year Glasgow Outcome Scale-Extended - GOS-E) assessments of consciousness and functional recovery. Associations with MRI-derived measures of cortical integrity and structural connectivity, and differences between anoxic and traumatic etiologies, were also examined. Slow waves were more frequent in less severe DoC patients (i.e., MCS) compared to UWS. Slow-wave slopes were also steeper frontally and increased at a faster rate in patients exhibiting higher levels of consciousness and/or markers of conscious access during the Local-Global paradigm. More frequent and steeper slow waves at baseline further predicted recovery of consciousness and of functional independence at one year. At the individual level, slow-wave features classified states of consciousness above chance (AUC = 0.62 and 0.71 for MCS- and MCS+ versus UWS), whereas outcome prediction remained modest (0.56-0.58). These clinical associations had a structural basis: slow-wave occurrence was greater after traumatic than anoxic injury and scaled with the integrity of subcortico-cortical projection fibers and consciousness-related cortical networks. Contrary to the classical view of delta activity as a non-specific marker of impaired consciousness, prominent spontaneous slow waves indexed behavioral and neurophysiological signs of awareness and better recovery. Beyond reflecting a propensity for pathological bistability, they may also signal the integrity of the networks required to generate them, together with their residual capacity for dynamic regulation.