Tuesday, October 11, 2016

Rethinking Irreversibility and Its Implications on Determining Death

By Alex Lin

Alex Lin is an undergraduate student at Rutgers University pursuing a dual degree in Biological Sciences and Philosophy. As an aspiring physician, he is interested in medical ethics and runs the Rutgers Bioethics Society alongside a diverse team of student thinkers. Alex is from Paramus, New Jersey, and volunteers as an emergency medical technician for his community.

Death, by definition, is irreversible. The notion of irreversibility is a central component of the current standards of death, cardiopulmonary and neurological alike. Given that the neurological criteria−the irreversible cessation of whole brain function−is the legally recognized criterion of death in many countries, including the United States [1], forthcoming advancements in neurotechnology under the BRAIN Initiative will be crucial to the accurate determination of death. With the development of technologies that allow scientists to study how individual neurons interact in significantly greater detail, questions emerge concerning the particular moment of truly irreversible total brain failure.

Consider the relatively new discovery of human adult neurogenesis. The established view was that the nervous system is fixed and neurons are unable to regenerate. However, this old dogma has been confounded by recent research in neuroscience. Studies have revealed that new neurons are continuously generated in the hippocampus and olfactory bulb, and adult hippocampal neurogenesis may even contribute to human brain function [2]. Modern technologies and research techniques enable scientists to study neurogenesis, which demonstrates the role that new scientific discoveries have in debunking long-standing views of neuroanatomy.

Image courtesy of WikiCommons.
Also, recent advancements in neuroimaging have enabled physicians to detect signs of awareness in patients diagnosed as being in a vegetative state, whereas traditional clinical assessments that attempt to elicit predictable behavioral responses fail to do so. In recent years, numerous studies have recommended the practice of neuroimaging techniques, such as fMRI and EEG, in addition to standard behavioral assessments in order to obtain a more accurate diagnosis of various disorders of the consciousness [3,4,5]. For example, in Dr. Adrian Owen's pioneering 2006 study, fMRI revealed that a patient in a vegetative state demonstrated residual cortical activity, and the patient was able to express signs of her covert awareness by following specific mental imagery tasks [5].

With the advancement of neuroimaging and development of more sensitive brain electrography monitoring devices, researchers may start detecting previously undetectable brain activity. Negative readings may become positive readings with more sensitive devices. In order to diagnose irreversible brain failure, the physician must perform a series of neurological examinations. These examinations can include assessing the absence of certain brainstem reflexes, such as the corneal reflex and the pharyngeal or gag reflex, as well as other muscle movement tests [6]. Still, the clinical examination of brain death is not consistent, even across the U.S. [7]. To achieve a confirmatory diagnosis, physicians can request additional tests, such as electroencephalography (EEG). However, current EEGs have a number of limitations. A few square centimeters of the cortex have to be activated simultaneously in order to generate readings that can be detected by the electrodes, which makes EEG insufficiently sensitive to less robust neural activities [8]. Furthermore, false readings can occur due to electronic background noise, especially in the ICU setting [6]. With increasingly sensitive neuroimaging devices, perhaps the determination of total brain failure, and generally what is considered irreversible, can be further refined.

In 2013, President Obama announced the BRAIN Initiative, a collaborative research initiative to advance our understanding of the human brain. The research goals of the BRAIN Initiative include generating circuit diagrams of the brain and developing new technologies that will allow researchers to rigorously study the most complex organ of the human body. In addition to previous investments made by the NIH, the BRAIN Working Group outlined a commitment of $4.5 billion in federal funding over the next 10 years, starting in fiscal year 2016. Thus, this year marks the start of the first five-year phase of the BRAIN Initiative: technological development and validation. Ultimately, research projects of the BRAIN Initiative will continue to redefine what counts as physiologically irreversible and thus challenge the moment of death.

The ethical consequences of such developments should be explored. In particular, it would be important to encourage research projects that explore irreversibility as a component of our scientific conceptions of death. It is important to note that legal death, namely death by neurological criteria, is biological death [9]. Grasping the role of irreversibility in brain death will advance our understanding of death as a biological phenomenon. Moreover, the swiftness of post-mortem action makes urgent the need to accurately determine the moment of death. Such action includes the procurement of life-sustaining organs for transplantation and experimental research on brain-dead patients. Because organ retrieval before the patient is truly dead would be morally reprehensible, as expressed by the Dead Donor Rule, organs must be procured (albeit shortly) after death to ensure they are viable for transplantation. Thus, the determination of death must be rigorous to ensure that the condition is truly irreversible in potential organ donors.

As we obtain more information about neural networks and develop tools to measure brain activity with greater accuracy, it is likely that what is currently considered irreversible brain failure will cease to be irreversible in the near future. In this way, the identification and determination of brain death are bound by the limits of current technology. Discoveries made through the BRAIN Initiative will likely continue to challenge the notion of irreversibility in neuroscience and may lead to novel methods to treat−or even reverse−the dying process.

I would like to thank Nada Gligorov, PhD for providing inspiration and comments on these issues. 


 1. Wijdicks, E. F. (2002). Brain death worldwide Accepted fact but no global consensus in diagnostic criteria. Neurology, 58(1), 20-25.

 2. Ernst, A., & Frisén, J. (2015). Adult Neurogenesis in Humans- Common and Unique Traits in Mammals. PLoS Biology, 13(1). 

3. Cruse D, Chennu S, Chatelle C, Bekinschtein TA, Fernandez-Espejo D, et al. (2011). Bedside detection of awareness in the vegetative state. Lancet, 378(9809), 2088–94.

 4. Monti M. M., Vanhaudenhuyse A., Coleman M. R., Boly M., Pickard J. D., et al. (2010). Willful modulation of brain activity in disorders of consciousness. N. Engl. J. Med., 362(7), 579–89.

 5. Owen, A. M. (2013). Detecting Consciousness: A Unique Role for Neuroimaging. Annual Review of Psychology Annu. Rev. Psychol., 64(1), 109-33.

 6. Wijdicks, E. F. (2001). The diagnosis of brain death. N. Engl. J. Med., 344(16), 1215-1221.

 7. Greer, D. M., Wang, H. H., Robinson, J. D., Varelas, P. N., Henderson, G. V., & Wijdicks, E. F. (2016). Variability of brain death policies in the United States. JAMA neurology, 73(2), 213-218.

 8. Smith, S. J. (2005). EEG in the diagnosis, classification, and management of patients with epilepsy. Journal of Neurology, Neurosurgery & Psychiatry, 76(suppl 2).

 9. Gligorov, N. (2016). A defense of brain death. Neuroethics, 1-9.

Want to cite this post?

Lin, A. (2016). Rethinking Irreversibility and Its Implications on Determining Death. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2016/10/rethinking-irreversibility-and-its.html

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