Thursday, August 15, 2013

End of Life Gamma Waves: Altered State of Consciousness or Artifactual Brain Activity?

"I had been in labor for my daughter for 16 hours. The labor was difficult and the Dr. approached me and told me it may come down to a choice between the child or myself.  ...  The labor dragged on and on and finally they came in and broke my water. I was rushed into delivery and within minutes my heart had stopped. I remember seeing a beautiful being of light enter the room. She told me I had to return as it was not my time yet. I was sucked back into my body as they restarted my breathing. My daughter began crying the moment I opened my eyes."

-Description of a near-death experience

Are you afraid to die? We all are. Fear of pain and suffering, fear of the unknown, fear of eternal damnation (for the religious), fear of nothingness (for the atheist). Fear of the end. The finality of it all.

The existential fear of death is part of the human condition. For a neuroscientist, studying what happens to conscious thought during the brain's own demise is one of the most profound of all questions. Short of conducting ill-advised scifi experiments on your med school classmates, how does one go about studying such a phenomenon? By using an animal model of cardiac arrest.

thanks to Chris Chambers for the video idea

Surge of neurophysiological coherence and connectivity in the dying brain

A popular new study by Borjigin et al. (2013) recorded EEG activity directly from the brains of nine dying rats. This paper was widely reported in mainstream media outlets, and has been nicely covered by bloggers Ed Yong, Mark Stokes, Chris Chambers, and Shelly Fan. What I would like to do here is to more closely examine the conditions surrounding the clinical death of these rats.

Fig. 1A (modified from Borjigin et al., 2013). The time scale is in seconds.The y-axis is in microvolts.

The figure above shows brain waves recorded from six electrodes implanted on the cerebral cortex, along with electrical activity from the muscles (EMG) and heart (EKG). The time period is 80 minutes before and 20 minutes after cardiac arrest (at time zero), which was induced by injection of potassium chloride into the heart. On its own, potassium chloride would cause a very painful death. Along with anesthetic and paralytic agents, potassium chloride is part of the drug sequence used for lethal injection in some U.S. states.

In the present study, the animals were deeply anesthetized using ketamine (a dissociative anesthetic) and xylazine (veterinary sedative/analgesic which affects alpha-2 adrenergic receptors), a commonly used method of anesthesia in rodents. Fig. 1A shows that the animals were anesthetized for 30 min before cardiac arrest. The EEG exhibits fairly constant large amplitude activity during this time, shown spread out for a small interval of time in Fig. 1B below.

Fig. 1B (modified from Borjigin et al., 2013). The time scale is in seconds. CAS =  cardiac arrest state. CAS3 (from 12 sec to 30 sec after cardiac arrest) is the critical time of increased EEG activity.

To briefly summarize, the rats' brains were surprisingly active during the CAS3 period, showing highly coherent neural oscillations in the low gamma frequency band for a 20 sec interval after the heart and lungs stopped working.

Fig. 1C below expands the vertical gray bars in Fig. 1B to show greater detail. Of note is the high amplitude rhythmic oscillations during CAS3. This low gamma activity (35-55 Hz) was strongly coupled to EEG activity in other frequency bands (theta and alpha) -- to an even greater extent than during active waking. The authors viewed this as a state of heightened consciousness, but such speculation is premature.

- click on image for a larger view -

Fig. 1C (modified from Borjigin et al., 2013). CAS = cardiac arrest state.

Why would the authors maintain that a dying brain can generate the neural correlates of heightened conscious processing? Gamma (aka 40 Hz activity) has been viewed as a possible solution to the "binding problem" of how consciousness arises since the late 80s. In the visual system, synchronous gamma might be how the brain combines distributed activity conveying separate aspects of a stimulus (e.g., its color, shape, and form) into a unified percept. Furthermore, gamma might account for phenomenal awareness and consciousness, according to some. However, more recent evidence suggests that gamma band responses do not reflect conscious experience.

In addition, it is not at all clear how highly synchronized low gamma can index "heightened conscious processing" in deeply anesthetized dying rats. Do the rats transition from ketamine/xylazine anesthesia (associated with altered thalamocortical connectivity) to a hyperaware internal state of....?  Of what?  The CAS3 activity is so abnormal that it might be artifactual or epiphenomenal, "a tale told by an idiot, full of sound and fury, signifying nothing" (Shakespeare, 1606).

Near-death experience (NDE) researcher Sam Parnia believes the low gamma activity could be caused by a massive influx of calcium, as he stated in Ed Yong's fine piece:
...Parnia says that there could be other explanations for the results. “After blood flow to the brain is stopped, there is an influx of calcium inside brain cells that eventually leads to cell damage and death,” he says. “That would lead to measurable electroencephalography (EEG) activity, which could be what is being measured.” This would explain why Borjigin saw the same pattern in every dying rat, while only 20 percent of people experience NDEs after a heart attack.

Ketamine administration itself is associated with an increase in gamma activity in cortical and subcortical structures. And most importantly, ketamine-altered states of consciousness have been used as a model of NDEs (Jansen, 1997). Although Borjigin et al. note differences in the specific oscillatory couplings seen during ketamine/xylazine anesthesia and cardiac arrest state #3, extrapolation of their findings to NDEs in humans “is extremely premature and unsupported by evidence” (Parnia, quoted in Yong).2

Despite these limitations, the results provide a fascinating beginning to a line of research exploring consciousness at the end of life. Obviously, the use of a rat model precludes any recounting of NDEs by those who might be brought back from the brink in the future. Although the precise neurobiological mechanisms are largely unknown, NDEs do have a scientific explanation (Mobbs & Watt, 2011).3

The truth is out there... Enjoy life while you can.


1 According to the scientific view promoted here, There is nothing paranormal about near-death experiences: how neuroscience can explain seeing bright lights, meeting the dead, or being convinced you are one of them:
Contrary to popular belief, research suggests that there is nothing paranormal about these experiences. Instead, near-death experiences are the manifestation of normal brain function gone awry, during a traumatic, and sometimes harmless, event.

2 Other views held by Dr. Parnia are a bit odd:
"It seems that when consciousness shuts down in death, psyche, or soul – by which I don't mean ghosts, I mean your individual self – persists for a least those hours before you are resuscitated. From which we might justifiably begin to conclude that the brain is acting as an intermediary to manifest your idea of soul or self but it may not be the source or originator of it… I think that the evidence is beginning to suggest that we should keep open our minds to the possibility that memory, while obviously a scientific entity of some kind – I'm not saying it is magic or anything like that – is not neuronal."

3 And they can be mimicked in ways that do not involve cardiac arrest.


Borjigin J, Lee U, Liu T, Pal D, Huff S, Klarr D, Sloboda J, Hernandez J, Wang MM, & Mashour GA (2013). Surge of neurophysiological coherence and connectivity in the dying brain. Proceedings of the National Academy of Sciences of the United States of America PMID: 23940340

Jansen KLR (1997). The Ketamine Model of the Near-Death Experience: A Central Role for the N-Methyl-D-Aspartate ReceptorJournal of Near-Death Studies 16: 5-26.

Mobbs D, Watt C. (2011). There is nothing paranormal about near-death experiences: how neuroscience can explain seeing bright lights, meeting the dead, or being convinced you are one of them. Trends Cogn Sci. 15:447-9.

For Andrew (June 4 1968- Aug 15 2013)

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At August 15, 2013 10:07 PM, Anonymous Bill Skaggs said...

I did some work on gamma when I was in grad school, but the fascination disappeared a long time ago. One thing I observed is that the easiest way to get huge globally synchronized gamma is to provoke an epileptic seizure. Another thing I learned is that anesthetics, and particularly ketamine, do very strange things to brain waves. So I agree with you that these findings don't mean much.


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