Ricerc@Sapienza

We report the presence of cortical electrical activity persisting for
about 120 min after cardiac arrest. The general consensus is that interruption
of brain blood flow triggers a chain of electrophysiological
phenomena: oscillatory activity rises in the first tens of seconds [1],
followed by a depression of both oscillatory and spiking activities, and
then by a slow spreading depolarization due to the beginning of irreversible
degenerative processes at the cellular level [2–4]. The
spreading depolarization is characterized by direct current changes that
can last up to tens of minutes and it has been described by using coarsegrained
electroencephalography and electrocorticography measures. As
such, low-amplitude and faster local phenomena might have been
missed. To address whether some brain activity at a microscale can
persist for longer periods after cardiac arrest, we recorded the intraparenchymal
activity in the frontal cortex of an adult male macaque
monkey using a multi-electrode miniaturized array to monitor neuronal
activities during the standard end of a protocol-established euthanasia
procedure. Both local field potentials (LFPs) and multi-unit activities
(MUAs) [5] were recorded starting from the deep sedated state (induction
by ketamine and medetomidine hydrochloride; mixture isoflurane/oxygen
to effect), and well beyond the cardiorespiratory arrest
caused by the intravascular bolus injection of pentothal sodium. During
the initial deep anaesthesia stage, neuronal activity displayed the typical
burst suppression regime with irregular LFP and MUA oscillations
(Fig. 1a-b). This activity strongly reduced after cardiac arrest (Fig. 1c).
However, after about 20 min, bursts of LFPs re-emerged sparse in time
up to about 120 min, each displaying a peak of power at 1–3 Hz in the
Fourier spectrograms. Importantly, these bursts were accompanied by a
supra- and subthreshold MUA modulations giving rise to a significant
time-delayed LFP-MUA coupling (see Fig. 1d). Although confined to a
single subject, our results prove that the dying brain at the microscale
can show electrophysiological activity for long time after cardiac arrest.
Importantly, this activity appears after a period of relative silence and it
is characterized by a peculiar temporal relationship between LFP and
MUA in several electrodes suggesting a non-local origin. This would
require a common synaptic input which in principle could be provided
by brainstem structures that are typically more resistant to anoxia [4].
We think that our data contribute in posing fundamental questions
about the nature of the transition to the death state. For example, what
is the metabolic state associated with this process? Can spontaneous (or
artificially induced) enhanced neuromodulation be of help in augmenting
the resilience to global ischemia? Our finding outlines the
importance of investigating the neurobiology of dying with intraparenchymal
high-resolution approaches. This could help in addressing
central medical questions like the definition of death, the
proper timing and the adequate sedation for organ transplantation, and
the development of resuscitation and recovery procedures. Whether this
activity is a sign of intact brain processing needs further studies.