On the Operational Utility of Measures of Multichannel EEGs.

Multichannel EEGs were obtained from healthy participants in the eyes-closed no-task condition and in the eyes-open condition (where the alpha component is typically abolished). EEG dynamics in the two conditions were quantified with two related binary Lempel-Ziv measures of the first principal component, and with three measures of integrated information, including the more recently proposed integrated synergy. Both integrated information and integrated synergy with model order p=1 had greater values in the eyes-closed condition. When the model order of integrated synergy was determined with the Bayesian Information Criterion, this pattern was reversed, and in line with the other measures, integrated synergy was greater in the eyes-open condition. Eyes-open versus eyes-closed separation was quantified by calculating the between-condition effect size. The Lempel-Ziv complexity of the first principal component showed greater separation than the measures of integrated information.

Which Spreading Depolarizations Are Deleterious To Brain Tissue?

Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.

Spreading depolarizations have prolonged direct current shifts and are associated with poor outcome in brain trauma.

Cortical spreading depolarizations occur spontaneously after ischaemic, haemorrhagic and traumatic brain injury. Their effects vary spatially and temporally as graded phenomena, from infarction to complete recovery, and are reflected in the duration of depolarization measured by the negative direct current shift of electrocorticographic recordings. In the focal ischaemic penumbra, peri-infarct depolarizations have prolonged direct current shifts and cause progressive recruitment of the penumbra into the core infarct. In traumatic brain injury, the effects of spreading depolarizations are unknown, although prolonged events have not been observed in animal models. To determine whether detrimental penumbral-type depolarizations occur in human brain trauma, we analysed electrocorticographic recordings obtained by subdural electrode-strip monitoring during intensive care. Of 53 patients studied, 10 exhibited spreading depolarizations in an electrophysiologic penumbra (i.e. isoelectric cortex with no spontaneous activity). All 10 patients (100%) with isoelectric spreading depolarizations had poor outcomes, defined as death, vegetative state, or severe disability at 6 months. In contrast, poor outcomes were observed in 60% of patients (12/20) who had spreading depolarizations with depression of spontaneous activity and only 26% of patients (6/23) who had no depolarizations (χ2, P<0.001). Spontaneous electrocorticographic activity and direct current shifts of depolarizations were further examined in nine patients. Direct current shift durations (n=295) were distributed with a significant positive skew (range 0:51-16:19 min:s), evidencing a normally distributed group of short events and a sub-group of prolonged events. Prolonged direct current shifts were more commonly associated with isoelectric depolarizations (median 2 min 36 s), whereas shorter depolarizations occurred with depression of spontaneous activity (median 2 min 10 s; P<0.001). In the latter group, direct current shift durations correlated with electrocorticographic depression periods, and were longer when preceded by periodic epileptiform discharges than by continuous delta (0.5-4.0 Hz) or higher frequency activity. Prolonged direct current shifts (>3 min) also occurred mainly within temporal clusters of events. Our results show for the first time that spreading depolarizations are associated with worse clinical outcome after traumatic brain injury. Furthermore, based on animal models of brain injury, the prolonged durations of depolarizations raise the possibility that these events may contribute to maturation of cortical lesions. Prolonged depolarizations, measured by negative direct current shifts, were associated with (i) isoelectricity or periodic epileptiform discharges; (ii) prolonged depression of spontaneous activity and (iii) occurrence in temporal clusters. Depolarizations with these characteristics are likely to reflect a worse prognosis.

Relationship between orientation to a blast and pressure wave propagation inside the rat brain.

Exposure to a blast wave generated during an explosion may result in brain damage and related neurological impairments. Several mechanisms by which the primary blast wave can damage the brain have been proposed, including: (1) a direct effect of the shock wave on the brain causing tissue damage by skull flexure and propagation of stress and shear forces; and (2) an indirect transfer of kinetic energy from the blast, through large blood vessels and cerebrospinal fluid (CSF), to the central nervous system. To address a basic question related to the mechanisms of blast brain injury, pressure was measured inside the brains of rats exposed to a low level of blast (~35kPa), while positioned in three different orientations with respect to the primary blast wave; head facing blast, right side exposed to blast and head facing away from blast. Data show different patterns and durations of the pressure traces inside the brain, depending on the rat orientation to blast. Frontal exposures (head facing blast) resulted in pressure traces of higher amplitude and longer duration, suggesting direct transmission and reflection of the pressure inside the brain (dynamic pressure transfer). The pattern of the pressure wave inside the brain in the head facing away from blast exposures assumes contribution of the static pressure, similar to hydrodynamic pressure to the pressure wave inside the brain.

Intravenous perfluorocarbon after onset of decompression sickness decreases mortality in 20-kg swine.

INTRODUCTION: Decompression sickness (DCS) occurs when bubbles form due to pressure decreases with severity ranging from trivial to fatal. Standard treatment requires a hyperbaric chamber, not likely to be available at remote sites or during a disabled submarine escape or rescue. Alternative (non-recompressive) treatments are needed. Intravenous administration of emulsified perfluorocarbons (PFCs) enhances oxygen delivery to, and inert gas removal from, tissues. Swine studies show PFCs administered with supplemental oxygen before symptom onset can decrease DCS incidence. We used a swine model to test whether PFC plus supplemental oxygen could improve outcome when infused after DCS symptom onset. METHODS: After rapid decompression from 31 min at 200 fsw (7.06 ATA) animals were observed for signs of DCS. Upon DCS onset animals received 100% 02 and were randomized to receive either saline or PFC. Oxygen administration was continued for 1 h and the primary outcomes of mortality and/or abnormal gait were noted 24 h after surfacing. RESULTS: PFC significantly improved survival, with 18/25 (72%) PFC treated animals and 13/29 (45%) saline treated animals alive at 24 h post-exposure. Objective measures of stance/gait trended toward improvement; spinal cord lesions correlated with severity of stance/gait abnormalities. CONCLUSION: PFC administered after DCS onset improved survival in this 20-kg swine model. Further study into the mechanisms of benefit and delayed DCS therapy are warranted.

Recovery of slow potentials in AC-coupled electrocorticography: application to spreading depolarizations in rat and human cerebral cortex.

Cortical spreading depolarizations (spreading depressions and peri-infarct depolarizations) are a pathology intrinsic to acute brain injury, generating large negative extracellular slow potential changes (SPCs) that, lasting on the order of minutes, are studied with DC-coupled recordings in animals. The spreading SPCs of depolarization waves are observed in human cortex with AC-coupled electrocorticography (ECoG), although SPC morphology is distorted by the high-pass filter stage of the amplifiers. Here, we present a signal processing method to reverse these distortions and recover approximate full-band waveforms from AC-coupled recordings. We constructed digital filters that reproduced the phase and amplitude distortions introduced by specific AC-coupled amplifiers and, based on this characterization, derived digital inverse filters to remove these distortions from ECoG recordings. Performance of the inverse filter was validated by its ability to recover both simulated and real low-frequency input test signals. The inverse filter was then applied to AC-coupled ECoG recordings from five patients who underwent invasive monitoring after aneurysmal subarachnoid hemorrhage. For 117 SPCs, the inverse filter recovered full-band waveforms with morphologic characteristics typical of the negative DC shifts recorded in animals. Compared with those recorded in the rat cortex with the same analog and digital methods, the negative DC shifts of human depolarizations had significantly greater durations (1:47 vs. 0:45 min:sec) and peak-to-peak amplitudes (10.1 vs. 4.2 mV). The inverse filter thus permits the study of spreading depolarizations in humans, using the same assessment of full-band DC potentials as that in animals, and suggests a particular solution for recovery of biosignals recorded with frequency-limited amplifiers.