Stratification of unresponsive patients by an independently validated index of brain complexity

Abstract

ObjectiveValidating objective, brain‐based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness—the Perturbational Complexity Index (PCI)—in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs).MethodsThe benchmark population encompassed 150 healthy controls and communicative brain‐injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]).ResultsWe found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition.InterpretationGiven its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high‐PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718–729

Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness

“…Further, the strength of the relationship between the best brain network metrics we use here and the CRS-R based diagnosis is comparable to that reported in previous literature that has employed EEG-based analysis (King et al, 2013;Sitt et al, 2014). PET (Stender et al, 2016) and TMS-EEG (Casarotto et al, 2016) have been shown to perform better, but both require much more complex technology that is either impossible or difficult to deploy at the patient's bedside. Hence bedside EEG assessments of brain connectivity, potentially estimated with fewer sensors than the high density configuration employed here (Engemann et al, 2015), could valuably complement other neuroimaging technologies.…”

“…Further, as patients recover beyond MCS, it appears that both positive and negative correlations of activity within and between networks also reappear (Thibaut et al, 2012;Di Perri et al, 2016). This relationship between the complexity of activity in brain networks and the state of consciousness has been demonstrated across mechanistically diverse natural, pharmacological and pathological modulations of consciousness using transcranial magnetic stimulation (TMS, Casali et al, 2013;Casarotto et al, 2016) as well as resting state EEG (Schartner et al, 2015). Further, recent literature has highlighted high frequency (20-50 Hz) activity in the parietal cortex (a 'posterior hot zone') as a neural correlate of conscious contents (Koch et al, 2016;Siclari et al, 2017).…”

“…We propose that repeated and regular bedside EEG assessments would cover a greater range of arousal fluctuations, would improve our ability to accurately track and predict the recovery of consciousness in individual patients. Indeed, Casarotto et al (2016) have shown that taking the maximum value of the complexity of brain activity measured over multiple TMS-EEG assessments can considerably improve the reliability of the estimation. Hence, developing a framework and analytical pipeline for repeatable bedside assessments could enable robust estimation of EEG-based metrics for quantifying brain networks in disorders of consciousness.…”

Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?

“…Fortunately, more recent investigations with carefully controlled psychophysical methods (Del Cul et al, 2009;Fleming et al, 2014) have investigated how, in representative groups of patients, even incomplete PFC lesions can specifically impact subjective perceptual experiences. Similar to short-term impairments induced by transcranial magnetic stimulation (Rounis et Brickner, 1952). Patient A was reported as the first human subject to undergo "bilateral" frontal lobectomy.…”

“…Annotated postmortem anatomy for Patient A (Brickner, 1952). A, Anatomical definition of cerebral sulci according to a standard neurosurgical postmortem atlas (Ono et al, 1990).…”