Local cortical dynamics of burst suppression in the anaesthetized brain

Abstract

Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric ‘suppressions’ lasting seconds or minutes, and high-voltage ‘bursts’. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a ‘global’ state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly, subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice.

Hemodynamic response to burst-suppressed and discontinuous electroencephalography activity in infants with hypoxic ischemic encephalopathy

“…Bursts can occur asynchronously in different regions and BS can be observed at one location while continuous activity is apparent at others. 39 These findings contradict the traditional model of BS and support the use of neuroimaging methodologies with better spatial specificity than scalp EEG to investigate BS and discontinuous EEG phenomena. To date, there have been only a small number of studies of the hemodynamic correlates of BS and discontinuous electrocortical activity in the animal model 22 and fewer still in human infants.…”

“…So far, there is limited scientific evidence to show that the phenomenon of BS can be dependent on local dynamics rather than a global state. 39 Future studies on animal models of neonatal asphyxia combining cortical EEG and DOT measures could potentially elucidate this further. It is also of interest that the MRI of patient 5 revealed swelling of the bilateral medial temporal cortices and a possible hemorrhagic lesion over the right parietal lobe.…”

A Lazarus effect: A case report of Bupropion overdose mimicking brain death

“…Burst suppression is an EEG waveform pattern of alternating isoelectric suppressions and high voltage bursts. [1] Our patient ultimately made a full neurologic recovery a few days later. While there are two other cases in the literature of bupropion overdose resulting in EEG burst-suppression and loss of brainstem reflexes, we believe this is the only reported adult case complicated by cardiac arrest.…”

“…[13] They are considered by the neurology community to be a poor prognostic marker for neurologic recovery in the context of overdose, post-cardiac arrest and coma. [1,12,14] Despite the EEG and clinical findings, our patient had a full neurologic recovery once the medication was metabolized and excreted. This emphasizes the importance of a thorough evaluation and utilization of all diagnostic modalities prior to prognostication.…”

Sparse spectral estimation from point process observations

“…Finally, we apply our algorithm to multi-unit recordings in [22] from a human subject under Propofol-induced general anesthesia. The original sampling rate of 1 kHz was reduced by the factor of 40 to reduce computational complexity, and a time window of 50s was considered (K = 1250).…”