2009 Lie of the Year Redux: Palin's so-called Death Panels

In 2009, a straw man was introduced into the U.S. health care debate. Death panels invoked the specter of rationing medical procedures provided for the sick and the elderly. In the name of cost cutting, blared the phony rhetoric on talk radio and Sarah Palin's Facebook page, the Obama administration would sanction euthanasia for elders and the terminally ill under provisions of the health care bill. This would save on expensive treatments that prolong patients' lives but increase the deficit, claimed the conservative crew. However, these scare tactics were an outright lie.

A year ago, Palin's "death panel" charge was named Lie of the Year, as covered here by the Wall Street Journal:

Former Alaska GOP Gov. Sarah Palin’s Facebook allegation that the Democrats’ health-care overhaul would include “death panels” to decide whether seniors and disabled people were worthy of care was named “Lie of the Year” by fact-checkers at Politifact.com.

PolitiFact.com is the 2009 Pulitzer Prize-winning, non-partisan project of the St. Petersberg Times newspaper. Its Truth-O-Meter^TM carefully evaluates the statements of political figures, pundits, and organizations and finds them to be TRUE, MOSTLY TRUE, HALF TRUE, BARELY TRUE, FALSE, or PANTS ON FIRE [as defined here].

They don't exactly give Barack Obama a free pass:

PANTS ON FIRE = The statement is not accurate and makes a ridiculous claim.

So the crowning of Palin's so-called death panels as lie of the year was not a politically motivated act.

PolitiFact's Lie of the Year: 'Death panels'

By Angie Drobnic Holan
Published on Friday, December 18th, 2009 at 5:15 p.m.

Of all the falsehoods and distortions in the political discourse this year, one stood out from the rest.

"Death panels."

The claim set political debate afire when it was made in August, raising issues from the role of government in health care to the bounds of acceptable political discussion. In a nod to the way technology has transformed politics, the statement wasn't made in an interview or a television ad. Sarah Palin posted it on her Facebook page.

Her assertion — that the government would set up boards to determine whether seniors and the disabled were worthy of care — spread through newscasts, talk shows, blogs and town hall meetings. Opponents of health care legislation said it revealed the real goals of the Democratic proposals. Advocates for health reform said it showed the depths to which their opponents would sink. Still others scratched their heads and said, "Death panels? Really?"

The editors of PolitiFact.com, the fact-checking Web site of the St. Petersburg Times, have chosen it as our inaugural "Lie of the Year."

Why is this story relevant again now?? It's because of a new article in the New York Times:

Obama Returns to End-of-Life Plan That Caused Stir

By ROBERT PEAR
Published: December 25, 2010

WASHINGTON — When a proposal to encourage end-of-life planning touched off a political storm over “death panels,” Democrats dropped it from legislation to overhaul the health care system. But the Obama administration will achieve the same goal by regulation, starting Jan. 1.

Under the new policy, outlined in a Medicare regulation, the government will pay doctors who advise patients on options for end-of-life care, which may include advance directives to forgo aggressive life-sustaining treatment.

One of the issues that has most riled the conservative commentariat is the secrecy advocated by some Democrats, such as Oregon Representative Earl Blumenauer:

After learning of the administration’s decision, Mr. Blumenauer’s office celebrated “a quiet victory,” but urged supporters not to crow about it.

“While we are very happy with the result, we won’t be shouting it from the rooftops because we aren’t out of the woods yet,” Mr. Blumenauer’s office said in an e-mail in early November to people working with him on the issue. “This regulation could be modified or reversed, especially if Republican leaders try to use this small provision to perpetuate the ‘death panel’ myth.”

I don't agree with this strategy at all. It's bound to backfire, and it already has. Instead, the logical way to counteract the ‘death panel’ myth is with evidence to the contrary. But this doesn't work with those who are already convinced otherwise (e.g, the tea party, Palin fans, etc.). Because of pre-existing cognitive biases, no amount of scientific evidence, or quotation of the actual provisions of the legislation/regulation, will change their minds.

So why bother, you say? What's the point? As a scientist, I'm not going to sit idly by while a vast swath of the American populace tries to influence personal health care decisions with their ignorance. The NYT cited a peer-reviewed study that supports the benefits of end-of-life planning: The impact of advance care planning on end of life care in elderly patients: randomised controlled trial (Detering et al., 2010; PDF). They also linked to a letter to the editor of the Journal of the American Geriatrics Society that reviewed the literature on advanced directives (Fischer et al., 2010; PDF) and concluded that ADVANCE DIRECTIVE DISCUSSIONS DO NOT LEAD TO DEATH.

Yet, the conservative pundits are trying to convince everyone that the opposite is true, without presenting a shred of evidence. Previously, I wrote about how a study in the New England Journal of Medicine (Temel et al., 2010) showed that the Limbaugh/Palin "death panels" extend the lives of terminally ill patients. This paper demonstrated that the introduction of palliative care shortly after the diagnosis of metastatic lung cancer not only improved the patients' quality of life, but also extended median survival from 8.9 months to 11.6 months:

The NEJM study enrolled 151 patients with newly diagnosed metastatic non–small-cell lung cancer. Seventy-four received standard care and 77 patients received palliative care, which included meetings with a member of the palliative care team (board-certified palliative care physicians and advanced-practice nurses). The first meeting was within 3 weeks of enrollment, and subsequent meetings were held on a monthly basis, with additional sessions at the discretion of the patient and the clinical treatment team. Patients assigned to standard care did not meet with the palliative care team (unless requested). All patients continued to receive standard oncology care for the duration of the study.

These meetings are the so-called "death panels" that would have been covered by Medicare...

Don't believe the rhetoric. The true death panels are those who want to deny health care to low-income Americans. Do they plan to pay all medical care for the uninsured out of their own pockets? If not, then who will, besides the government? Oops, looks like the anti-Obamacare crowd has just condemned them to die.

The Art of Resurrection

Resurrection, Raffaellino del Garbo (1510)

In the world outside of Christianity, horror, and science fiction, the dead cannot be brought back to life. Or can they? A feature in the The Observer from earlier this year profiled Dr. Sam Parnia, critical care physician and author of Erasing Death: The Science That Is Rewriting the Boundaries Between Life and Death (called The Lazarus Effect in the UK). The article begins in a dramatic fashion:

Sam Parnia – the man who could bring you back from the dead

Sam Parnia MD has a highly sought after medical speciality: resurrection. His patients can be dead for several hours before they are restored to their former selves, with decades of life ahead of them.

That's a pretty outrageous claim! Clinically dead for several hours? No brain activity the entire time? Even if anyone could emerge alive and conscious from such a state (unless it's a state of suspended animation, perhaps), they'd have severe brain damage (as we'll see below). There'd be no way they could have encoded their near-death experiences (NDEs), much less remembered any light at the end of a tunnel or a soothing presence drawing them home.

There may be a semantic problem here: the definition of “death.”

I haven't read the book, but the issue is described in a one-star review at Amazon:

The core of this linguistic mess is his inconsistent use of the word "death". At times he uses this term properly, as defined by the Uniform Determination of Death Act (UDDA, 1981): "An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem is dead." This definition was developed in cooperation with the American Medical Association ... [etc.] and has been adopted by most states. It is the standard definition of death. [NOTE: I thought brain death is THE standard definition of death.] ¹

Unfortunately, he also refers to "death" as cardiac arrest (e.g. pages 1, 2, 23, 42, 43, 128, 131, 139, 140, and many more). This definition of death is inconsistent with the UDDA because cardiac arrest is reversible in some cases. In fact, much of this book includes accounts of individuals who have suffered cardiac arrest and been resuscitated...

Dr. Parnia was quoted in my previous post about the “End of Life Gamma Waves” study in rats. He was skeptical that EEG during the 30 second interval after the heart stopped beating was anything more than a massive influx of calcium into the dying neurons. It wasn't a state of heightened consciousness that can explain the NDEs reported by 10-20% of his cardiac arrest patients.

Instead, Parnia is a mind-body dualist, believing that the soul (or self) can persist separately from the body for several hours at a time:

"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."

Memory is not neuronal! And Death can be cured. Who knew. But how?? [NOTE: according to Parnia and The Observer, at least.]

Extracorporeal membrane oxygenation (ECMO) is a temporary method of life support that introduces and circulates oxygen into the bloodstream of patients with acute respiratory failure or cardiac failure. It involves placing one or more large catheters into the patient's vessels (cannulation) and relies on an external pump to circulate and oxygenate blood and remove carbon dioxide (PDF). Primarily used in critically ill infants, its application to adults is risky and controversial, and the benefits are unclear.

A meta-analysis of ECMO in adult patients found a mortality rate of 54% at 30 day follow-up, with almost half the fatalities occurring during ECMO (Zangrillo et al., 2013). On the other hand, the procedure is a last-ditch life saving effort in critically ill patients, so a 46% survival rate seems like an improvement over probable death. However, one review stated that "Credible evidence for mortality benefit of ECMO is lacking" in cases of acute respiratory distress (Hirshberg et al, 2013). Another study concluded that ECMO is even less successful in cases of acute heart failure, with the worst survival rate for those who experience cardiac arrest (Tsuneyoshi & Rao, 2012).

Complications can be severe (Zangrillo et al., 2013) and include renal failure (occurring in 52%), bacterial pneumonia (33%), bleeding (33%), oxygenator dysfunction requiring replacement (29%), sepsis (26%), and liver dysfunction (16%).

The rest of the post will focus on the possible neurological complications of ECMO (Mateen et al., 2011).


Neurological Injury Associated with Heroic Resuscitation

I do not want to detract in any way from the dedication of practioners who do heroic things every day to save people's lives, or from advances in medicine. What I would like to point out, however, is that sometimes one may resuscitate the heart but lose the brain (to paraphrase Horstman et al., 2010).

Modified from Fig. 4 (Mateen et al., 2011). Brain scans of adult patients who received extracorporeal membrane oxygenation (ECMO). (A) parafalcine subarachnoid hemorrhage and hydrocephalus on axial-view head CT, (B) diffuse subarachnoid hemorrhage on T1-weighted MRI, and (C) septic cerebral emboli on axial-view MRI.


Neurological events occurred in at least 50% (n=42) of patients treated with ECMO at one medical center over an 8 year period (Mateen et al., 2011). This is a conservative estimate, because a neurological exam was not performed in 21%, and over 70% did not have neuroimaging. Clinical presentation included new onset of coma and new loss of brainstem reflexes. Diffuse brain injury due to lack of oxygen (anoxia), global brain dysfuction (encephalopathy), subarachnoid hemorrhage (bleeds), and ischemic watershed infarction (stroke) were among the diagnoses. Of the 24 patients with brain scans, the findings were pathologically abnormal in 15 (see examples in figure above).

Autopsy was performed on 10 brains (out of 40 patients who died). Nine of these brains showed gross abnormalities (see examples in figure below).

Read more »

Existential Neuroscience: a field in search of meaning

What separates prior from subsequent is exactly nothing. This nothing is absolutely impassable, just because it is nothing...

–Jean-Paul Sartre, Being and Nothingness (p. 28).

If you read the journal Social Cognitive and Affective Neuroscience (SCAN), you might think that Existential Neuroscience is a hot new field, since three recent papers on the topic have been published there. Can it provide profound new insights into the human condition? From what I can tell, these references to a formal discipline of “Existential Neuroscience” are based entirely on terror management theory, which was developed by Greenberg and colleagues in the 1980s (Greenberg et al., 1986; Rosenblatt et al., 1989). How does this relate to existentialism?


“Existence precedes essence” (Sartre, 1946).

But first, what is Existentialism? The Stanford Encyclopedia of Philosophy is reluctant to admit that it's an actual philosophy, rather than a literary or artistic trend:

By the mid 1970s the cultural image of existentialism had become a cliché, parodized in countless books and films by Woody Allen. It is sometimes suggested, therefore, that existentialism just is this bygone cultural movement rather than an identifiable philosophical position; or, alternatively, that the term should be restricted to Sartre's philosophy alone.

Stanford Encyclopedia eventually tells us that the most distinctive aspect of existentialism is that standard notions of identity are wrong:

The fundamental contribution of existential thought lies in the idea that one's identity is constituted neither by nature nor by culture, since to “exist” is precisely to constitute such an identity. It is in light of this idea that key existential notions such as facticity, transcendence (project), alienation, and authenticity must be understood.

The first known account of “Existential Neuroscience” (EN) was written by mirror neuron researcher Dr. Marco Iacoboni in 2006 (PDF).¹ It was published as a book chapter in Social Neuroscience: Integrating Biological and Psychological Explanations of Social Behavior (Harmon-Jones & Winkielman, 2007). Thus, EN appears to be a branch of Social Neuroscience.

But what is Existential Neuroscience, exactly? A group of French intellectuals discussing brain research in a cafe while smoking and sipping espresso? An authentic neuroscience of utter freedom that embraces a state of perpetual despair² over the meaninglessness of existence? Or independent groups of German-speaking neuroscientists who scan subjects while they ponder death?

Sartre and Friends

If you guessed the latter, you'd be correct.  More precisely, EN thus far consists of neuroimaging studies of mortality salience, as you might expect by its reliance on terror management theory (TMT).³  Therefore, EN should be called “Fear of Death” Neuroscience. TMT holds that when people are confronted with their own mortality, they respond in ways to boost their self-esteem, reinforce their own values, and punish outsiders.

In an ironic twist for the existentialist neuroscientists, however, Existentialism rejects science as means of understanding what it is to be human. Here's Sartre on the futility of science:

From the outset physiology is condemned to understand nothing of life since it conceives life simply as a particular modality of death, since it sees the infinite divisibility of the corpse as primary, and since it does not know the synthetic unity of the "surpassing towards" for which infinite divisibility is the pure and simple past. Even the study of life in the living person, even vivisection, even the study of the life of protoplasm, even embryology or the study of the egg can not rediscover life; the organ which is observed is living, but it is not established in the synthetic unity of a particular life; it is understood in terms of anatomy—i.e., in terms of death.

-Jean Paul Sartre, Being and Nothingness (p. 348).

Even if one is a firm believer in the potential of neuroscience to lead to better treatments for mental illness, it's hard to envision what brain research can tell us about a philosophical system opposed to science (or most other philosophies, for that matter). Can we imagine what a Taoist Neuroscience or an Epicurean Neuroscience would be like? Not to mention the prospect of a Nihilist Neuroscience or a Post-Structural Neuroscience...

By necessity, a true Existential Neuroscience must deal with human beings as the focus of study, since the withdrawal reflex of Aplysia might not be a valid model of existential angst. It's unlikely we'll see circuit models and optogenetic studies of the alienated self any time soon. As currently formulated, EN has more concrete goal: to study one specific element of existentialist thought that might be more closely related to Heidegger's views (see Quirin et al., 2012).

This leads us to the most recent of the EN studies in SCAN (Silveira et al., 2013), which I'll discuss in some detail. This study is based on a different reaction to mortality salience, one that is derived from evolutionary psychology: the drive to reproduce. The heterosexual participants in the study viewed attractive opposite-sex faces and made decisions about whether they would like to meet them (a proxy for sexual desire) after being primed by death-related words (or not). Already, this seems like a bridge too far, but let us go on.

Sixteen female and 16 male subjects participated in this fMRI experiment. They viewed a series of attractive faces (as judged by an independent group of participants) and decided, in separate blocks, if the faces were attractive or not (explicit evaluation) or whether they'd like to meet the person or not ("implicit" evaluation). The task was cued at the beginning of a block by the words Meet? or Attractive? Participants make their choice when the ? appears on the monitor. Below is an example of the implicit no-prime condition shown to the male subjects.

Fig 1 (Silveira et al., 2013).

The participants viewed a blank screen before each face is presented, instead of viewing control words that are unrelated to death. The lack of such a control condition is problematic, as we'll see later. For comparison, an example of the death-prime condition is illustrated below.

modified from Fig 1 (Silveira et al., 2013). I added two English translations for the original German exemplars that were given in the text .


Here we can see the participants are reading words, a condition that entails a number of visual, lexical (e.g., decoding the letter string), and semantic (meaning-related) processes that are completely absent from the no-prime condition. Therefore, we can't know if any differential brain activation in the death-prime vs. no-prime conditions is caused by reading a word (any word) or by comprehending a specific reference to death, thereby triggering mortality salience.

To compound matters, the study used block design methodology, so the discrete hemodynamic responses to prime presentation or face presentation or the decision screen could not be determined, as in an event-related design. The figure below shows the death-prime vs. no-prime comparison for male participants (left) and female participants (right), who did not differ from each other.

Fig. 2 (Silveira et al., 2013). Increased neural activation when viewing attractive opposite-sex faces after death-related compared to no priming in (A) men and (B) women. lPFC = lateral prefrontal cortex.


The figure shows activation in the left anterior insula and adjacent inferior prefrontal cortex, which are known to be involved in language, particularly in coordinating speech (known as articulatory planning). Although such activity is usually associated with speaking aloud, left anterior insula activation has also been observed during silent reading. To reiterate, the present result may be due to the absence of any words in the no-priming condition. This interpretation is opposed to Silveira et al.'s claim that the activity "reflects an approach-motivated defense mechanism to overcome concerns that are induced by being reminded of death and dying."

Another wrinkle in the authors' world view is the fact that the death-priming manipulation increased interest in meeting an attractive member of the opposite sex only in males (76% vs. 68% in the no-prime condition) and not in females (47% vs. 48%). It's hard to know how the approach-motivated defense mechanism is operating in women, since it didn't increase their desire to meet potential [fictitious] partners.

It seems a stretch, then, to claim:

Thus insular activation suggests an increase in mating motivation under mortality salience. This interpretation is in accordance with previous findings that mortality salience motivates the formation of romantic relationships as well as reproductive desire.

Hardly. The female participants expressed no greater interest in even meeting potential partners (no less having babies with them), and yet their insular activations were highly similar to those seen in the male participants (who may or may not have shown greater reproductive desire, as this was not queried or investigated in any way).

In sum, I don't know if we've learned anything about existentialism, or sex and death, or even mortality salience and the left anterior insula.

C'est la guerre.

I emerge alone and in anguish confronting the unique and original project which constitutes my being; all the barriers, all the guard rails collapse, nihilated by the consciousness of my freedom. I do not have nor can I have recourse to any value against the fact that it is I who sustain values in being. Nothing can ensure me against myself, cut off from the world and from my essence by this nothingness which I am. I have to realize the meaning of the world and of my essence; I make my decision concerning them—without justification and without excuse.

-Jean Paul Sartre, Being and Nothingness (p. 39).

Footnotes

¹ Iacoboni called EN a “Quiet Revolution” (that to me seems more like embodied cognition... which has not been quiet in announcing itself to the world):

In fact, some empirical work in the neuroscience of sociality seems to suggest - quietly, but resolutely - that the assumptions of the subject/world, inner/outer dichotomy, of representations independent of the things they represent, and of the atomism of the input may not be easily applied in some cases. Thus, rather than the picture of a meaning-giving brain that looks at the outside world and makes sense of it with a reflective and analytic approach, what emerges from some work in social cognitive neuroscience is the view of a human brain that needs a body to exist in a world of shared social norms in which meaning originates from being-in-the-world. This view is reminiscent of motives
recurring in at least one flavor of what is called existential phenomenology (Heidegger 1927). For this reason, I call this view existential neuroscience.

² Despair:

What sets the existentialist notion of despair apart from the conventional definition is that existentialist despair is a state one is in even when he isn't overtly in despair. So long as a person's identity depends on qualities that can crumble, he is considered to be in perpetual despair. And as there is, in Sartrean terms, no human essence found in conventional reality on which to constitute the individual's sense of identity, despair is a universal human condition.

³ One might consider that Iacoboni's studies of existential mirror neurons fall under a different branch of EN; they're not cited by the "fear of death" faction and vice versa.


References

Greenberg, J., Pyszczynski, T., & Solomon, S. (1986). The causes and consequences of a need for self-esteem: A terror management theory. In R. F. Baumeister (Ed.), Public self and private self (pp. 189 –212). New York: Springer-Verlag.

Quirin M, Loktyushin A, Arndt J, Küstermann E, Lo YY, Kuhl J, & Eggert L (2012). Existential neuroscience: a functional magnetic resonance imaging investigation of neural responses to reminders of one's mortality. Social cognitive and affective neuroscience, 7 (2), 193-8. PMID: 21266462

Rosenblatt A, Greenberg J, Solomon S, Pyszczynski T, Lyon D. (1989). Evidence for terror management theory: I. The effects of mortality salience on reactions tothose who violate or uphold cultural values. J Pers Soc Psychol. 57(4):681-90.

Silveira S, Graupmann V, Agthe M, Gutyrchik E, Blautzik J, Demirçapa I, Berndt A, Pöppel E, Frey D, Reiser M, & Hennig-Fast K (2013). Existential neuroscience: Effects of mortality salience on the neurocognitive processing of attractive opposite-sex faces. Social cognitive and affective neuroscience PMID: 24078106

Jean-Paul Sartre, 1905–1980

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 experience¹

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.


Footnotes

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.


References

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 Receptor.  Journal 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)
RIP

COVID-19, Predictive Coding, and Terror Management

Pandemics have a way of bringing death into sharper focus in our everyday lives. As of this writing, 1,188,259 people around the world have died from COVID-19, including 234,218 in the United States. In the dark days of April, the death rate was over 20%. Although this has declined dramatically (to 3%), it’s utterly reckless to minimize the risks of coronavirus and flaunt every mitigation strategy endorsed by infectious disease specialists.

“He's like an evil Oprah. You're getting COVID. And you're getting COVID!”

One might think that contracting and recovering from COVID-19 would be a sobering experience for most people, but not for the Übermensch (Nietzschean 'Superman'... but really, 'Last Man' is more appropriate) who had access to the latest experimental treatments.¹ Trump's boastful reaction is exactly how the 'Coronavirus Episode' of the (scripted) White House reality show was written: “I feel better than I did 20 years ago!” and “I'm a perfect physical specimen.”

This dismissive display reinforces the partisan divide on perceptions of the pandemic and the federal response to it. A recent study by Pew Research Center found major differences in how Democrats and Republicans view the severity of COVID-19. Results from the survey (conducted Aug. 31-Sept. 7, 2020) were no surprise. 

 

 

And as we know, Democrats and Republicans exist in alternate universes constructed by non-overlapping media sources (CNN vs. Fox, to oversimplify), which in turn correlates with whether they wear masks, practice social distancing, and avoid crowds. A new paper in Science (Finkel et al., 2020) integrated data from multiple disciplines to examine the partisan political environment in the US. They found that Democratic and Republican voters have become:

“...POLITICALLY SECTARIAN -- fervently committed to a political identity characterized by three properties: (1) othering (opposing partisans are alien to us), (2) aversion (they are dislikable & untrustworthy), and (3) moralization (they are iniquitous).”

The authors concluded that the combination of all three core ingredients is especially toxic. Furthermore:

6/ None of these three properties is especially problematic in isolation. But, in combination, they instill a sense of dread -- a sense that political losses are existential threats that must be averted, no matter the cost.

— Eli Finkel (@EliJFinkel) October 29, 2020

Perfect! Dread and existential threat to a fervent political identity during a pandemic that reminds us of our own mortality. The Science paper has a sidebar about motivated (or biased) cognition and whether Democrats and Republicans are equally susceptible (many studies), or whether Republicans are more susceptible than Democrats (other studies).² 

 

We seek out information that confirms our views and push away evidence that contradicts our pre-existing beliefs about “the other”.

Death Denial to Avert Existential Crisis

We also push away thoughts of our own demise: death is something that happens to other people, not to me. Awareness of death or mortality salience — pondering the inevitability of your own death, a time when you will no longer exist — triggers anxiety, according the Terror Management Theory (TMT). In response to this threat, humans react in ways to boost their self-esteem and reinforce their own values (and punish outsiders). These cognitive processes are conceptualized as nebulous “defenses” [nebulous to me, at least] that are deployed to minimize terror. Notably, however, experimental manipulation of mortality salience did not affect “worldview defense” in the large-scale Many Labs 4 replication project, which throws cold water on this aspect of TMT.

Predictive Coding and Perceived Risk of COVID-19

An alternative view of how we disassociate ourselves from death awareness is provided by predictive coding theory. This influential framework hypothesizes that the brain is constantly generating and updating its models of the world based on top-down “biases” and bottom-up sensory input (Clark, 2013):

Brains ... are essentially prediction machines. They are bundles of cells that support perception and action by constantly attempting to match incoming sensory inputs with top-down expectations or predictions. This is achieved using a hierarchical generative model that aims to minimize prediction error within a bidirectional cascade of cortical processing. 

Prediction errors are minimized by perceptual inference (updating predictions to better match the input) or active inference (sampling the input in a biased fashion to better fit the predictions). A recent paper considered this framework with regard to beliefs generated during the pandemic, and how they're related to health precautions adopted by individuals to mitigate spread of the virus (Bottemanne et al, 2020). This paper was conceptual (not computational), and it was written in French (meaning I had to read it using Google translate). 

In brief, pandemics are massive sources of uncertainty. There was a delay in the perception of risk, followed by unrealistic optimism (“certainly I do not run the risk of becoming infected”) despite the growing accumulation of evidence to the contrary. The reduced perception of risk leads people to flaunt precautionary mandates, even in France (which is currently showing a greater spike in cases than the US). Subsequently, overwhelming media saturation on the daily death toll and the dangers of COVID-19 updates predictions of risk and triggers mortality salience (Bottemanne et al, 2020). 

And in support of TMT, Framing COVID-19 as an Existential Threat Predicts Anxious Arousal and Prejudice towards Chinese People. Every day in the US, the president and his minions call the novel coronavirus “the China virus” and other disparaging terms. Is it any wonder that discrimination and violence against Asian-Americans has increased?

If you're American, PLEASE VOTE if you haven't already.

Further Reading

Covid-19 makes us think about our mortality. Our brains aren’t designed for that.

Existential Neuroscience: a field in search of meaning

Neuroexistentialism: A Brain in Search of Meaning

Existential Dread of Absurd Social Psychology Studies

Terror Management Theory

Footnotes

¹ The Last Man is the antithesis of the Superman:

An overman [superman] as described by Zarathustra, the main character in Thus Spoke Zarathustra, is the one who is willing to risk all for the sake of enhancement of humanity. In contrary [is] the 'last man' whose sole desire is his own comfort and is incapable of creating anything beyond oneself in any form.

Trump's declaration: “...All I know is I took something, whatever the hell it was. I felt good very quickly . . . I felt like Superman.” Whether his kitchen-sink treatment regimen was a good idea has firmly challenged.

² There's a large literature on potential cognitive and neural differences between liberals and conservatives, but I won't cover that here. I wrote about many of these studies in the days of yore.

References

Bottemanne H, Morlaàs O, Schmidt L, Fossati P. (2020). Coronavirus: cerveau prédictif et gestion de la terreur [Coronavirus: Predictive brain and terror management]. Encephale 46(3S):S107-S113.

Clark A. (2013). Whatever next? Predictive brains, situated agents, and the future of cognitive science. Behavioral and Brain Sciences 36(3):181-204.

Finkel EJ et al. (2020). Political sectarianism in America. Science 370:533-536.

“What's going on with this guy?”

 

I will be leaving the great Walter Reed Medical Center today at 6:30 P.M. Feeling really good! Don’t be afraid of Covid. Don’t let it dominate your life. We have developed, under the Trump Administration, some really great drugs & knowledge. I feel better than I did 20 years ago!

— Donald J. Trump (@realDonaldTrump) October 5, 2020

 

What is the truth underneath the tweet?

  AP Photo

President Trump showed labored breathing during his first appearance on the White House balcony

Regarding his joyride in the black SUV while he was still hospitalized at Walter Reed:

He did not look tough; he looked trapped.

He looked desperate. He looked pathetic. He looked weak — not because he was ill or because he was finally wearing a mask but because instead of doing the hard work of accepting his own vulnerabilities in the face of sickness, he’d propped himself up on the strength and professionalism of Secret Service agents. Instead of focusing on the humbling task of getting better, he was consumed by the desire to simply look good.

 the end.

Limbaugh/Palin "death panels" extend the lives of terminally ill patients

What is palliative care? Until quite recently, it's something I haven't given much thought. Although there was a highly regarded article on hospice and palliative care by Atul Gawande in last month's New Yorker, I didn't read it or think it applied to my life. All that changed less than two weeks ago, when my father was hospitalized in critical condition after collapsing. First he went to the ER, then the transitional ICU, and finally he was placed in the palliative care unit by the time I arrived. You see, my father has metastatic lung cancer, for which he had refused treatment for more than a year. Instead, he decided to stay home with my mother, watch DVDs, go out to eat, and do yard work.¹

A recent paper in the New England Journal of Medicine demonstrated that the introduction of palliative care shortly after the diagnosis of metastatic lung cancer not only improved the patients' quality of life, but also extended median survival from 8.9 months to 11.6 months (Temel et al., 2010). According to the American Academy of Hospice and Palliative Medicine:

The goal of palliative care is to prevent and relieve suffering and to support the best possible quality of life for patients and their families, regardless of the stage of the disease or the need for other therapies. Palliative care is both a philosophy of care and an organized, highly structured system for delivering care. Palliative care expands traditional disease-model medical treatments to include the goals of enhancing quality of life for patient and family, optimizing function, helping with decision-making and providing opportunities for personal growth. As such, it can be delivered concurrently with life-prolonging care or as the main focus of care.

This finding is critically important for providers of medical care for terminally ill cancer patients as well as for health policy, because it provides categorical, scientific proof that the notion of "death panels" is false. As stated in the New York Times:

“It shows that palliative care is the opposite of all that rhetoric about ‘death panels,’ ” said Dr. Diane E. Meier [@DianeEMeier], director of the Center to Advance Palliative Care at Mount Sinai School of Medicine and co-author of an editorial in the journal accompanying the study. “It’s not about killing Granny; it’s about keeping Granny alive as long as possible — with the best quality of life.”

A straw man in the 2009 health care debate, "death panels" invoked the specter of rationing medical procedures provided for the sick and the elderly. In the name of cost cutting, blared the phony rhetoric on talk radio and Sarah Palin's Facebook page, the Obama administration would sanction euthanasia for elders and the terminally ill under provisions of the health care bill. This would save on expensive treatments that prolong patients' lives but increase the deficit, claimed the conservative crew. However, these scare tactics were an outright lie, as we learn from the Wall Street Journal:

Palin’s “Death Panels” Charge Named “Lie of the Year”

...

“Of all the falsehoods and distortions in the political discourse this year, one stood out from the rest,” writes Politifact.com, the non-partisan, Pulitzer Prize-winning site run by the St. Petersburg Times. Palin’s “assertion — that the government would set up boards to determine whether seniors and the disabled were worthy of care — spread through newscasts, talk shows, blogs and town hall meetings.”

“Opponents of health-care legislation said it revealed the real goals of the Democratic proposals. Advocates for health reform said it showed the depths to which their opponents would sink,” Polifact.com says.

The NEJM study enrolled 151 patients with newly diagnosed metastatic non–small-cell lung cancer. Seventy-four received standard care and 77 patients received palliative care, which included meetings with a member of the palliative care team (board-certified palliative care physicians and advanced-practice nurses). The first meeting was within 3 weeks of enrollment, and subsequent meetings were held on a monthly basis, with additional sessions at the discretion of the patient and the clinical treatment team. Patients assigned to standard care did not meet with the palliative care team (unless requested). All patients continued to receive standard oncology care for the duration of the study.

These meetings are the so-called "death panels" that would have been covered by Medicare, as mentioned by the NYT in Palliative Care Extends Life, Study Finds:

During the debate over President Obama’s 2009 health care bill, provisions to have Medicare and insurers pay for optional consultations with doctors on palliative and hospice care led to rumors, spread by talk-show hosts like Rush Limbaugh and Glenn Beck and by the former vice-presidential candidate Sarah Palin, that the bill empowered “death panels” that would “euthanize” elderly Americans. [emphasis mine]

The primary outcome measure of the study was quality of life at 12 weeks (compared to baseline), as assessed by the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale. Mood was assessed using the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire 9 (PHQ-9).

Results indicated that patients in the palliative care group had a significantly higher quality of life at 12 weeks (see Table 2) and a lower incidence of depression (but similar levels of anxiety).

[click on Table for larger image]

Table 2 (Temel et al., 2010). Plus–minus values are means ±SD. Quality of life was assessed with the use of three scales: the FACT-L scale, on which scores range from 0 to 136, with higher scores indicating better quality of life; the lung-cancer subscale (LCS) of the FACT-L scale, on which scores range from 0 to 28, with higher scores indicating fewer symptoms; and the Trial Outcome Index (TOI), which is the sum of the scores on the LCS and the physical well-being and functional well-being subscales of the FACT-L scale (scores range from 0 to 84, with higher scores indicating better quality of life).

In addition, patients in the palliative care group lived longer:

Despite receiving less aggressive end-of-life care,² patients in the palliative care group had significantly longer survival than those in the standard care group (median survival, 11.6 vs. 8.9 months; P=0.02).

The study has its limitations, however, as noted by Dr. Meier in Palliative Care: We Still Have a Lot to Learn:

...The patients (and doctors) were not blinded to their treatment group, that is, they knew which group they were in, which could have affected their outcomes. Also, there was no “attention-control” group—a group that got the same amount of human time and attention that the palliative care group got but without the palliative care skill and expertise.

Nonetheless, the purpose and goals of palliative care cannot be understated. As I mentioned in my previous post (Ketamine for Depression: Yay or Neigh?), reducing the pain and suffering of terminally ill patients is of utmost importance. Watching a terminally ill loved one suffer from unbearably excruciating pain is one of the most emotionally wrenching experiences you'll ever have. Anything, and I mean anything, that will relieve this sort of suffering (including heroin) should be administered without reservation or stigma. The options offered by hospice and palliative care should be made freely available to patients as part of a comprehensive health care plan. But Sarah Palin is still spewing her falsehoods a year after she started, despite all the evidence to the contrary.

UPDATE Sept 6, 2010: My father died at 12:30PM today. I'll miss him terribly.

Footnotes

¹ In other words, he chose to live as normally as possible.

² Aggressive care was defined as chemotherapy within 14 days before death; no hospice care; or admission to hospice 3 days or less before death.

Reference

J.S. Temel et al. (2010). Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer. N Engl J Med, 363, 733-742. 10.1056/NEJMoa1000678

Additional Reading from Pallimed blog:

Game Changer: Early Palliative Care for Lung Cancer Patients Improves QOL AND Median Survival

You had me at 'improves HRQOL'...

Blast Wave Injury and Chronic Traumatic Encephalopathy: What's the Connection?

Fig. 3 (Goldstein et al., 2012). Single-blast exposure induces CTE-like neuropathology in wild-type C57BL/6 mice.


In a tour de force, a group of 35 Boston-area scientists¹ (Goldstein et al., 2012) developed a mouse model of blast-related neurotrauma that resulted in pathological changes similar to chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease seen most often in athletes with repeated concussions. They also reported post-mortem neuropathological findings from the brains of war veterans and amateur football players who had sustained concussions and traumatic brain injuries (TBIs).

Diagnosis of CTE occurs after autopsy, because the brain tissue has to be stained for characteristic protein abnormalities which cannot be visualized in a living human. A defining pathological feature is tauopathy - abnormal accumulations of the tau protein seen in other dementias (e.g., Alzheimer's disease). Aggregations of hyperphosphorylated tau into neurofibrillary tangles (NFTs) are a defining feature, as in frontotemporal lobar degeneration and amyotrophic lateral sclerosis - yet CTE is distinct from both of these (McKee et al., 2009). CTE results in cognitive and behavioral changes including memory impairments, poor impulse control, alterations in mood, suicidal behavior, disorientation, and ultimately dementia.


Can Blast Waves Cause Chronic Traumatic Encephalopathy?

The major conclusion drawn from the human data in this study is that exposure to blasts from IEDs causes CTE (Goldstein et al., 2012). However, my contention is that the cause of tauopathies in these military veterans is unclear. Three of the four had histories of concussion from other events.


Much of what you've read about this paper in the media is wrong.

The worst offender by far was Business Insider:

Scientists Looked Inside The Brains Of Troops Killed By Bombs And Made This Shocking Discovery

Trauma from exposure to a single improvised explosive device (IED) blast can result in long-term brain impairment, according to new research.

The study, published today in the journal Science Translational Medicine, is the first to examine postmortem brains of U.S. military personnel who were exposed to a blast and/or a concussive injury.

It found evidence that a single blast from a typical IED can cause traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).

Really?

1) None of the troops were killed by bombs -- they all died from other causes.

2) None of the troops had a single isolated blast exposure.

3) It is not the first study to examine postmortem brains of U.S. military personnel who were exposed to a blast and/or a concussive injury. That would be the paper by Omalu, Hammers, et al. (2011). I wrote about it here.²

4) The evidence that a single IED blast can cause TBI and CTE did not come from looking inside the brains of troops, it was obtained from a mouse model of neurotrauma.

Next, let's take a look at what the paper actually did.


Part 1 - Human CTE

The brain banks at the Center for the Study of Traumatic Encephalopathy and the Alzheimer's Disease Center at Boston University provided the brains of 12 human subjects:

• 4 male military veterans (ages 22-45 yrs) with histories of explosive blast and/or concussive injury 1 to 6 years before death
• 4 male athletes (ages 17-27 yrs) with histories of repetitive concussive injury, including 3 football players and a professional wrestler
• 4 male controls (ages 18-24 yrs) with no known blast exposure, trauma history, or neurological disease

Case histories of the military veterans are presented below, to show that 3 of the 4 had concussions that were not due to explosive blast.

Case 1, a 45-year-old male U.S. military veteran with a single close-range IED blast exposure, experienced a state of disorientation without loss of consciousness that persisted for ~30 min after blast exposure. He subsequently developed headaches, irritability, difficulty sleeping and concentrating, and depression that continued until his death 2 years later from a ruptured basilar aneurysm. His medical history is notable for a remote history of concussion associated with a motor vehicle accident at age 8 years.

Case 2, a 34-year-old male U.S. military veteran without a history of previous concussive injury, sustained two separate IED blast exposures 1 and 6 years before death. Both episodes resulted in loss of consciousness of indeterminate duration. He subsequently developed depression, short-term memory loss, word-finding difficulties, decreased concentration and attention, sleep disturbances, and executive function impairments. His neuropsychiatric symptoms persisted until death from aspiration pneumonia after ingestion of prescription analgesics.

Case 3, a 22-year-old male U.S. military veteran with a single close-range IED blast exposure 2 years before death. He did not lose consciousness, but reported headache, dizziness, and fatigue that persisted for 24 hours after the blast. He subsequently developed daily headaches, memory loss, depression, and decreased attention and concentration. ... He was diagnosed with PTSD 3 months before death from an intracerebral hemorrhage. His past history included 2 years of high school football and multiple concussions from fist fights.

Case 4, a 28-year-old male U.S. military veteran with two combat deployments, was diagnosed with PTSD after his first deployment 3 years before death. His history was notable for multiple concussions as a civilian and in combat, but he was never exposed to blast. ... He died from a self-inflicted gunshot wound 2 years after his last concussion.

In brief, Case 1 had a concussion in a car accident as a child, Case 3 had multiple concussions from football and fist fights, and Case 4 had major concussions at 12 yrs (bicycle accident with loss of consciousness and amnesia), 17 yrs (football injury with no loss of consciousness), 25 yrs (altered mental status during military deployment), and 26 yrs (accident with loss of consciousness and amnesia).

Case 4 had no history of blast exposure at all, so his results are not even related to the title of the paper. Only Case 2 had blast exposures with no other cause of concussion. And here we don't know the duration of unconsciousness, so it's difficult to know the severity of the TBIs.


Part 2 - Mouse CTE

In addition to reporting the post-mortem pathology, the authors developed an animal model of blast injury. The paper was truly a collaborative effort, as it involved physics, engineering, immunology, neuropathology, immunohistochemistry, neuroanatomy, electron microscopy, behavioral neurobiology, electrophysiology, and biochemistry. I'm surprised there weren't more than 35 authors. You'd certainly need a small army of bloggers to adequately describe all the experiments, so I'll merely outline some of the methods and results in the Appendix at the end of this post.

The take home message is that CTE-like pathology, cellular dysfunction, and impairments in learning and memory were observed within 2 weeks of a single blast exposure. Two weeks.


What does it all mean for veterans and athletes with brain injury?

We don't know the full implications yet. Many questions remain.

1) Do such dramatic changes really occur within 2 weeks of a single blast wave or concussive injury in humans? Most individuals (up to 90%) with a single concussion recover fully within 3 months (Bigler, 2008).

2) Would the mice continue to get worse if followed over a longer time interval? CTE is a degenerative disease, yet most individuals with concussions improve over time.

3) Is the damage dose-dependent? How many hits do you need for cognitive and behavioral changes to occur? Two of the athletes had such severe injuries that they died shortly after the last concussion.

4) Are some people more susceptible to developing CTE? One might guess that's the case, or else there would be hundreds of thousands of former athletes with very severe cognitive and psychiatric issues.

5) Studies have shown there are risk genes, such as polymorphisms of apolipoprotein E (APOE), that influence outcomes after head injury (Teasdale et al., 1997; Omalu, Bailes et al., 2011). It would be nice to have a more complete picture of the cases reported here.

6) I believe none of the CTE pathology is evident from in vivo MRI scans of various sorts. That's why diagnosis is done at autopsy. However, it might be time to explore the use of 18F-FDDNP (Shin et al., 2011; Small et al., 2012), a molecular imaging probe that labels tau and NFTs, in PET studies of living persons considered at risk for CTE.


Footnotes

¹ ...with 26 separate sources of funding.

² This case also involved multiple concussions from football and auto accidents in addition to blasts. Omalu et al. linked the pathology to PTSD rather than concussion. I argued there was Little Evidence for a Direct Link between PTSD and Chronic Traumatic Encephalopathy.



References

Bigler ED. (2008). Neuropsychology and clinical neuroscience of persistent post-concussive syndrome. J Int Neuropsychol Soc. 14:1-22.

Goldstein, L., Fisher, A., Tagge, C., Zhang, X., Velisek, L., Sullivan, J., Upreti, C., Kracht, J., Ericsson, M., Wojnarowicz, M., Goletiani, C., Maglakelidze, G., Casey, N., Moncaster, J., Minaeva, O., Moir, R., Nowinski, C., Stern, R., Cantu, R., Geiling, J., Blusztajn, J., Wolozin, B., Ikezu, T., Stein, T., Budson, A., Kowall, N., Chargin, D., Sharon, A., Saman, S., Hall, G., Moss, W., Cleveland, R., Tanzi, R., Stanton, P., & McKee, A. (2012). Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model. Science Translational Medicine, 4 (134), 134-134 DOI: 10.1126/scitranslmed.3003716

McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. (2009). Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 68:709-35.

Omalu B, Bailes J, Hamilton RL, Kamboh MI, Hammers J, Case M, Fitzsimmons R. (2011). Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 69:173-83; discussion 183.

Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, & Fitzsimmons RP (2011). Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurgical focus 31 (5): E3.

Shin J, Kepe V, Barrio JR, Small GW. (2011). The merits of FDDNP-PET imaging in Alzheimer's disease. J Alzheimers Dis. 26 Suppl 3:135-45.

Small GW, Siddarth P, Kepe V, Ercoli LM, Burggren AC, Bookheimer SY, Miller KJ, Kim J, Lavretsky H, Huang SC, Barrio JR. ( 2012). Prediction of cognitive decline by positron emission tomography of brain amyloid and tau. Arch Neurol. 69:215-22.

Teasdale GM, Nicoll JA, Murray G, Fiddes M. (1997). Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350:1069-71.


Appendix

Part 1 - Human CTE

Athletes

Case 5, a 17-year-old male high school football player who died from second impact syndrome 2 weeks after concussion
Case 6, an 18-year-old high school football and rugby player with a history of 3-4 previous concussions, one requiring hospitalization, who died 10 days after last concussion
Case 7, a 21-year-old male college football player, who played as a lineman and linebacker but had never been diagnosed with a concussion during 13 seasons of play beginning at age 9, and who died from suicide
Case 8, a 27-year-old male professional wrestler who experienced more than 9 concussions during his 10-year professional wrestling career who died from an overdose of OxyContin

Controls

Case 9, an 18-year-old male who died suddenly from a ruptured basilar aneurysm
Case 10, a 19-year-old male who died from a cardiac arrhythmia
Case 11, a 21-year-old male who died from suicide
Case 12, a 24-year-old male who died from suicide



Fig. 1 (modified from Goldstein et al., 2012). CTE neuropathology in postmortem brains from military veterans with blast exposure and/or concussive injury and young athletes with repetitive concussive injury.


Part 2 - Mouse CTE

Developed a blast neurotrauma model (using a compressed gas blast tube) to investigate the mechanistic linkage between blast exposure, CTE neuropathology, and neurobehavioral sequelae

• Measured intracranial pressure dynamics and head kinematics during real or sham blasts

Assessed subsequent CTE-linked neuropathology, ultrastructural pathology, and phosphorylated tau proteinopathy

• Examined brains 2 weeks after single blast or sham
• Gross examination was unremarkable, but immunohistochemical analysis revealed marked neuropathology in the blasted brains, which included:

1. reactive astrocytosis throughout the cortex, hippocampus, brainstem, etc.
2. enhanced phosphorylated tau CP-13 immunoreactivity in superficial cortical layers
3. hippocampal CA1 neurons intensely Tau-46–immunoreactive with evidence of frank neurodegeneration in hippocampal CA1 and CA3 subfields and dentate gyrus
4. activated perivascular microglia throughout the brain, especially in the cerebellum

Examined ultrastructural pathology using electron microscopy


Confirmed the presence of phosphorylated tau proteinopathy using immunoblot analysis of tissue homogenates prepared from mouse brains 2 weeks after single-blast or sham-blast

• Immunoblot analysis revealed a significant blast-related elevation of various phosphorylated tau protein epitopes

Found persistent functional impairments in hippocampal neurophysiology

• Slowed axonal conduction
• Deficient long-term potentiation (LTP) of activity-dependent synaptic transmission (a candidate mechanism of memory storage)

Single-blast exposure induced long-term behavioral deficits

• Acquisition and long-term retention of hippocampal-dependent spatial learning and memory was impaired
• These deficits were prevented by head immobilization during blast exposure