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From Bioethics Briefings

Brain Injury: Neuroscience and Neuroethics

  • Not long ago, patients with severe brain injury and no apparent consciousness were presumed to be in a permanent vegetative state, without hope of recovery.
  • New evidence shows that some of these patients are, in fact, misdiagnosed and actually in the minimally conscious state, that they may comprehend speech and be able to, occasionally speak and gesture.
  • Unlike patients such as Terri Schiavo, who was in a permanent vegetative state, patients in the minimally conscious state can sometimes recover, even after a decade or more. Research suggests that they may also respond to experimental interventions, such as drugs and neuroprosthetic devices, ,and neuroimaging as means to restore functional communication.
  • Distinguishing the vegetative state from the minimally conscious state requires careful clinical evaluation. While bedside neuropsychological assessment remains the clinical gold standard, experimental advances in neuroimaging may help identify patients in the minimally conscious state.
  • Differences between brain states have ethical implications for patient care, scientific research, and public policy, most notably the civil rights of people with disorders of consciousness, a long-marginalized population.

Framing the Issue

The national conversation over Terri Schiavo illustrated how questions about severe brain injury became central to the past decade’s most convulsive bioethics debate. As is well appreciated by anyone who witnessed the events of spring 2005, the Schiavo case divided a family, and much of the nation, over the question of whether it was ethically proper–and legally permissible–to remove a feeding tube from a young woman in a permanent vegetative state. Could a patient like Terri Schiavo ever recover? And beyond the question of prognosis, is a patient is such a brain state aware? Could she perceive starvation or feel pain?

Responses to questions like these, though decidedly settled in the negative for permanently vegetative patients like Ms. Schiavo, have increasingly become more nuanced in light of new evidence about severe brain injury and how the injured brain recovers. The advent of new diagnostic categories to describe both the severity of brain injury and its time course complicate questions about prognosis and perceptual awareness. Differences between these diagnostic categories, or brain states, have ethical implications for patient care, scientific research, and public policy and the civil rights of a long marginalized population, people with disorders of consciousness, a central theme in my book, Rights Come to Mind. (See Resources.)

Terminology: Defining Different Brain States

Much to the confusion of lay readers, there are a host of newly defined brain states (and their acronyms, such as MCS for minimally conscious state, MCS-E for emergence from minimally conscious state) beyond the ubiquitous, but still confusing PVS, or persistent vegetative state. These categories for different disorders of consciousness have both clinical and ethical implications.

The persistent vegetative state was first described by the Scottish neurosurgeon Bryan Jennett and the American neurologist Fred Plum in 1972. In a landmark article in the British journal The Lancet, they described PVS as a state of “wakeful unresponsiveness” in which the eyes are open but there is no awareness of self or others. Patients who are vegetative do not have cognitive or higher brain functions, such as the ability to think and reason. But they do have autonomic ones, such as the direction of cardiac and respiratory function and sleep-wake cycles, which originate in the brain stem, the lower part of the brain just above the spinal cord. Vegetative patients may also have a startle reflex, but this behavior is not intentional and involves only brain stem activity.

As was evident in the Schiavo case, the vegetative state remains a disquieting one. It defies normal expectations about awareness and consciousness. Usually when the eyes are open there is awareness, but in the vegetative state a patient is stripped of ability to interaction with others or the environment.

The vegetative state is often confused with a coma, especially by nonclinicians. This is an important error to correct. Although comatose and vegetative patients are unresponsive and unarousable, there are important differences. Coma is an eyes-closed state while the vegetative state is an eye-open one. Moreover, coma is the initial presentation of severe brain injury and is self-limited, usually lasting a couple of weeks. A coma can progress in a number of ways, from brain death to complete recovery. The most ominous of comas progress to brain death, defined as death of the whole brain, including brain stem and higher brain functions. Brain death is recognized as the equivalent of cardiopulmonary death in all states, although some states allow for a religious or moral objection to this neurological definition of death.

Comatose states can also evolve into a vegetative state. A vegetative state is labeled as persistent once it lasts more than a month. It is considered permanent after three or 12 months, depending upon the nature of the initial injury. If the injury is from anoxia, or oxygen deprivation, as would be the case in a cardiac arrest or drowning accident, a vegetative state persisting for three months is considered permanent. In contrast a vegetative state resulting from traumatic brain injury, such as from a motor vehicle accident or a fall, would need to last for 12 months to be designated as permanent.

The different time courses to a permanent vegetative state relate to the nature of the injury and the patient’s prognosis. The potential for recovery for a traumatically injured brain exceeds that of the anoxically injured brain. Roughly 77% of anoxic comas result in death or the permanent vegetative state, while 50% of patients with traumatic brain injury will die or be permanently unconscious. (Patients with anoxic brain injury who received therapeutic hypothermia, or chilled intravenous fluids, after cardiac arrest have a better prognosis than untreated anoxic patients, although the data on outcomes has yet to be clearly defined.) This differential degree of recovery from anoxic versus traumatic injury helps explain why it takes longer for clinicians to conclude that a traumatic injury has resulted in a permanent vegetative state.

If a vegetative state has yet to become permanent, a patient may move into the minimally conscious state. MCS is a new clinical designation that has its origins in the Aspen Criteria published in the journal Neurology in 2002. This potential for recovery is the salient difference between the persistent versus the permanent vegetative state. Until a patient is permanently vegetative this potential remains. For this reason, it is important to distinguish the temporal aspects of the duration of the vegetative state and avoid abbreviations like PVS, which could erroneously conflate these prognostic implications.

Unlike the vegetative state, MCS is a state of consciousness. MCS patients demonstrate unequivocal, but fluctuating, evidence of awareness of self and the environment. They may say words or phrases and gesture. They also may show evidence of memory, attention, and intention. They may reach for a cup, say their name or track a family member who walks into the room.

However, these behaviors may be fleeting.  The inability to reproduce telltale signs of awareness is part of the biology of MCS, and an expected and confounding part of the clinical picture.

A patient who reaches the minimally conscious state is open to a degree of prognostic uncertainty about the possibility of further cognitive recovery. The prognosis can be fixed or open-ended, with rare occurrences of dramatic recoveries of emergence from MCS years and decades after injury.

Patients who have regained the ability to consistently engage with others and re-establish functional communication are considered to have emerged from MCS. Emergence from MCS, or MCS-E, is taken to be the consistent and reproducible recovery of consciousness and an awareness of self, others and the environment. In the last few years, there  have been several well-known cases of emergence from MCS in the United States.

Arkansan Terry Wallis emerged from MCS in 2003, bringing international media attention to this phenomenon against the backdrop of the evolving Schiavo saga. Wallis regained fluent speech after lingering for 19 years in a nursing home after sustaining traumatic brain injury in a motor vehicle accident. During that time he had been labeled erroneously as being in a coma or vegetative state, although he was most certainly minimally conscious for nearly two decades. In July 2003, he began to speak fluently. His first words were “mom” and “Pepsi.” In his mind it was still 1984 and Ronald Reagan was still president. A modern Rip Van Winkle, as of 2016 he continues to regain a better sense of time and his chronological age. (The Wallis family has been part of a cohort of families with whom I have conducted narrative interviews to prepare Rights Come to Mind. I have their permission to share their story.)

Another compelling case of emergence from MCS involved Don Herbert, a Buffalo firefighter. Herbert was injured in a 1995 fire, sustaining a mix of traumatic and hypoxic brain injury. For the first few months after his injury he met criteria for MCS with occasional and episodic signs of awareness and verbalization.  For the next nine years he lingered, presumed to be vegetative, until he spontaneously regained fluent speech in 2005, emerging after a number of psychoactive drugs were given to him by a physiatrist.


Diagnostic precision and intellectual honesty are important when we consider the biological underpinning of the minimally conscious state and emergence from MCS. Neuroimaging techniques may hold promise in improving diagnosis, although their use remains investigational. Consider the case of Terry Wallis, who was in an MCS state for 19 years. Studies using a functional magnetic resonance imaging (fMRI) technique called diffuse tensor imaging (DTI) by my colleagues at Weill Cornell Medical College revealed changes in his brain two decades after injury. Their study described “axonal sprouting”–or new connections between existing neurons–which may have had something to do with his late recovery from the minimally conscious state.

Other imaging studies from Weill Cornell and Columbia University have revealed the capability of minimally conscious brains to activate a widely distributed functional language network when exposed to spoken narratives. These studies suggested that MCS patients retain the capability to process language and semantic content. This capability may even be retained in vegetative patients who have not reached the permanent vegetative state. A highly provocative 2006 study from the University of Cambridge in the United Kingdom, using another language paradigm, demonstrated the ability of a patient in the vegetative state to activate integrated networks. The patient had sustained traumatic brain injury five months earlier (so the vegetative state was not yet permanent).

In findings reported in Science, the patient was able to activate networks in the brain when asked to imagine walking in her home, playing tennis, or parsing linguistically ambiguous phrases. At the time I suggested, with my colleague Nicholas Schiff, in the Hastings Center Report that this patient was in a nonbehavioral MCS state as she responded to her environment with normal language and spatial brain networks, as evidenced by the flares identified on neuroimaging. More recently Schiff has elaborated this state as a stage of cognitive motor dissociation. It may either be permanent or a gateway to further recovery. The individual presented in the 2006 Science paper did progress. At 11 months the patient was clearly engaging in behaviors that indicated she was in MCS, and two years after injury she was speaking, suggesting that what was seen on neuroimaging at five months was likely evidence of her transitioning from the vegetative to minimally conscious states.

In 2010, the dissociation between overt behaviors and what was happening inside the brain became even more fascinating when Martin Monti and colleagues repurposed the active stimulation paradigm previously used to attempt communication with a subject who was otherwise unable to communicate. In a paper published in the New England Journal of Medicine, the investigators asked a subject to imagine playing tennis or walking about one’s house and toggled these volitional responses to “yes” and “no,” thereby creating a “communication neuroprosthetic” in a patient thought to be in the vegetative state, but who actually was in a state of nonbehavioral MCS. (See Resources.)

While these data are intriguing, and progress continues to be made, it is important to caution against viewing any of these neuroimaging modalities as anything but investigative tools. They have yet to be validated outside of the research context and it is the consensus in the research community that it would be premature to disseminate them into routine clinical practice for the assessment of patients. There are questions about test sensitivity (true positive results) and specificity (risk of true negatives), although investigators pay special attention to positive neuroimaging results in patients who exhibit no behavioral signs of consciousness as such combinations can indicate covert consciousness. Indeed, in the Monti paper described above, the subject demonstrated behaviors consistent with being in MCS after investigators redoubled their bedside assessments. This confirmed the presence of consciousness which would have been unrecognized save for the findings on neuroimaging.

Distinguishing the Vegetative and Minimally Conscious States

People have asked how Terry Wallis or Don Herbert could have recovered when experts were so definitive in asserting that Terri Schiavo was permanently unconscious. The answer is found in the diagnostic categories just reviewed and in the important biological differences between the permanent vegetative state of Schiavo and the minimally conscious states of Wallis and Herbert. Unlike patients in the permanent vegetative state, patients in MCS have preserved brain networks that retain the potential for activation.

Both Wallis and Herbert emerged from their long period of quiescence from the minimally conscious state, not the vegetative state, thus retaining the potential for additional recovery. And, interestingly, both had been injured and progressed to the minimally conscious state before there was a diagnostic category to describe their condition. While such dramatic recoveries are uncommon and should not be overstated, they should not be entirely discounted.

Because of the biological and prognostic differences between the minimally conscious and the permanent vegetative states, it is critical that these patients be distinguished from each other. This is easier said than done because of the evolving nature of brain states after injury and discontinuities of care as patients are transferred from hospitals to chronic care facilities.

Patients may leave the hospital with a vegetative diagnosis that has yet to become permanent, and then over time migrate into MCS while in chronic care. If a clinician does not notice this change in status, the patient may be assumed to be in a permanent vegetative state. This potential for misdiagnosis is only compounded by the episodic nature of displays of consciousness in MCS. Typically, families will see behavioral evidence of awareness and seek to reproduce these signs for wary staff. But because these behaviors are only episodic in MCS, they are not reliably reproduced.

This situation can cause diagnostic confusion when a family member who has witnessed these behaviors asks a doctor to examine the patient and the behaviors are demonstrated. Physicians, most of whom are still unfamiliar with MCS as a diagnostic category, may conclude that family observations are the result of wishful thinking or denial. Notably, studies have found a high level of diagnostic error in the assessment of patients who are in chronic care. One study found that 41% of patients with traumatic brain injury thought to be vegetative were in fact minimally conscious when assessed with the validated bedside assessment metric, the JFK Coma Recovery Scale-Revised.

Wallis and Herbert were among those who were misdiagnosed. Because of the diagnostic and prognostic importance of these brain states, greater precision in discussions about a patient’s vegetative state is now recommended. Medical staff should specify  the type of injury (anoxia or traumatic) and its duration. When a patient thought to be in the permanent vegetative state shows signs of the minimally conscious state the patient has not breached the futility of permanent vegetative state; the patient was not permanently vegetative to begin with. Instead, such evidence–whether behavioral or from neuroimaging findings– allows for the recognition of an unidentified minimally conscious state. Biologically, MCS patients are distinct from permanently vegetative patients because they retain the latent capacity for the activation of dormant neural networks necessary to manifest consciousness. Patients who are permanently vegetative do not retain this potentiality.

These distinctions are important because  “recoveries” are often misrepresented in the media and considered  “proof” that recovery from the permanent vegetative state remains possible for patients, fueling ideological debates on how to care for them. Proper diagnosis can avoid this confusion.

Taken together, neuroimaging data and other findings indicate that patients with severe brain injury may sustain late recoveries and that even severely injured brains may harbor residual functional residual capacity. My colleagues and I (Schiff et al) conducted a clinical trial using deep brain stimulation in the minimally conscious state.

Our results, the first to demonstrate that deep brain stimulation in MCS can promote late functional recovery after traumatic brain injury, were published in Nature in August 2007. We implanted electrodes, such as those used routinely to treat drug refractory Parkinson’s disease, into the brain of a 38-year-old man who had been in MCS for six years after traumatic brain injury. Prior to the study the subject was unable to eat without a feeding tube or communicate reliably. The procedure resulted in statistically validated improvements in cognitively-mediated behaviors, as well as the ability to eat by mouth and to control motor activity. The subject has regained the ability to communicate in six-to-seven-words sentences when prompted and to interact more fully and consistently with his family.

Drugs have also begun to be employed to aid in the treatment of disorders of consciousness. The sleeping pill Ambien (zolpidem) has been shown to activate networks and restore overt evidence of consciousness in a small percentage of patients likely in a nonbehavioral minimally conscious state. The anti-influenza medication, Amantadine, has also been shown to accelerate the recovery of overt consciousness in a randomized clinical trial. Both drugs are now being used off-label in brain injury rehabilitation centers.

Values, Ethical Considerations, and Legal Ramifications

Beyond scientific precision, it is the important to avoid turning a diagnostic assessment into a values choice, as was the case with Schiavo. Attempting to assert that Ms. Schiavo was minimally conscious in order to forestall a decision to withdraw her feeding tube has implications for patients who are actually in MCS. Because Ms. Schiavo would never regain consciousness, labeling her as an MCS patient represents a disservice to patients who are actually in MCS, because it implies that they, too, will never recover.

While each of us, in a liberal democracy is entitled to placing a moral valuation on life in a vegetative or minimally conscious state, we should be careful not to distort the diagnostic act. Neither ideological motivation nor scientific ignorance is an acceptable cause for diagnostic imprecision. Diagnostic errors of omission or commission have the potential to either perpetuate false hope in the case of the permanently vegetative or to blind us to the recuperative potential of minimally conscious patients.

Disorders of consciousness highlight fundamental bioethical concerns. Modern American bioethics was founded on the centrality of patient self-determination and autonomy. These rights have coalesced in two discrete arenas: reproductive ethics and end-of-life care. The evolution of the right to die is centrally linked to disorders of consciousness, most notably through the case of Karen Ann Quinlan, a New Jersey woman who was in a vegetative state following a drug overdose and anoxic brain injury. Her parents sought to remove her ventilator and allow her to die.

In a landmark 1976 ruling the New Jersey Supreme Court permitted the removal of Ms. Quinlan’s life support, citing the irreversible nature of her vegetative state. As the court opined, based on testimony given by Dr. Fred Plum, Ms. Quinlan had forever –and irretrievably–lost the possibility of returning to a “cognitive sapient state.” The irreversible nature of her injury, and its futility, became the ethical and legal justification for the removal of her ventilator. This case, in turn, launched the era of patients’ rights at life’s end.

This right-to-die was further codified in other cases involving the vegetative state, including Nancy Beth Cruzan and Schiavo, both young women in the permanent vegetative state. In Cruzan v. Director in 1990, the U.S. Supreme Court recognized the constitutional right of a competent person to refuse life-sustaining therapy, equated artificial nutrition and hydration with other life-sustaining therapies, and ruled that each state could set evidentiary standards for the withdrawal of these therapies. Cruzan also led to the increased use of advance directives. Justice Sandra Day O’Connor’s decision was the inspiration for the Patient Self-Determination Act, which was signed  into law on December 1, 1991. With the passage of the PSDA, which requires many hospitals and other health care providers to inform patients of their rights under state laws governing advance directives, advance directives gained a central role in efforts to improve end-of-life care in the 1990’s.

The advent of new brain states like MCS and their potential treatment have upset many of the presumptions that gave rise to modern bioethics and the right to die. Where it was once presumed that severe brain injury was invariably as dire as the vegetative state, we now know that prognostic outcomes can be variable. Therefore, it is increasingly inappropriate to view brain injured patients as untreatable.

To pursue therapeutic possibilities without engendering false hope, it is critically important to diagnose brain states as precisely as possible in order to balance burdens and benefits. As I wrote in the journal Supportive & Palliative Care, clinicians and policymakers need to preserve the right to die, but also to affirm the right to care for those who might be helped. (See Resources.) The purpose of this ethical imperative is to carefully distinguish the vegetative from minimally conscious states, and avoid the diagnostic shortfalls that stem from clinical ignorance or ideological intent.

There is an irony in that the establishment of the right to die, the futility of the permanent vegetative state was over-generalized to other patients with disorders of consciousness who retained the possibility for additional recovery. Sadly, after receiving brilliant acute medical care that saved their lives, many of these patients become victims of therapeutic nihilism, marginalized in chronic care, misdiagnosed, and abandoned. What is at stake is that conscious individuals, dependent upon the care and concern of others, end up  in chronic care, segregated from their families and their communities. As neuroscience develops the capacity to identify patients with cognitive motor dissociation – who show of consciousness on brain imaging but not in their behavior – and restore functional communication using neuroprosthetics, drugs, and rehabilitation, neuroethics should advance the human rights of individuals too long relegated to the margins.

Joseph J. Fins, MD, MACP, is The E. William Davis, Jr., MD Professor of Medical Ethics and Professor of Medicine and Chief of Medical Ethics at Weill Cornell Medical College; codirector of the Consortium for Advanced Study of Brain Injury at Weill Cornell Medicine and Rockefeller University; Solomon Center Distinguished Scholar in Medicine, Bioethics and Law at Yale Law School; and a Hastings Center Fellow.

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  • Hastings Center Resources on Brain Injury and Neuroethics
  • Joseph J. Fins, MD, MACPThe E. William Davis, Jr., M.D. Professor of Medical Ethics and Professor of Medicine, Chief, Division of Medical Ethics, Weill Cornell Medical College; codirector, C.A.S.B.I. (Consortium for the Advanced Study of Brain Injury), Weill Cornell Medicine and Rockefeller University; Solomon Center Distinguished Scholar in Medicine, Bioethics and the Law, Yale Law School; Hastings Center Fellow
  • Bruce Jennings, MASenior Advisor, The Hastings Center; Adjunct Associate Professor, Vanderbilt University’s Center for Biomedical Ethics; Senior Fellow, Center for Humans and Nature; Hastings Center Fellow