Scientists find ‘hidden brain signatures’ of consciousness in vegetative state patients

There has been a great deal of interest recently in how much patients in a vegetative state following severe brain injury are aware of their surroundings. Although unable to move and respond, some of these patients are able to carry out tasks such as imagining playing a game of tennis. Using a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, researchers have previously been able to record activity in the pre-motor cortex, the part of the brain which deals with movement, in apparently unconscious patients asked to imagine playing tennis.

Now, a team of researchers led by scientists at the University of Cambridge and the MRC Cognition and Brain Sciences Unit, Cambridge, have used high-density electroencephalographs (EEG) and a branch of mathematics known as ‘graph theory’ to study networks of activity in the brains of 32 patients diagnosed as vegetative and minimally conscious and compare them to healthy adults. The findings of the research are published today in the journal PLOS Computational Biology. The study was funded mainly by the Wellcome Trust, the National Institute of Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC).

The researchers showed that the rich and diversely connected networks that support awareness in the healthy brain are typically – but importantly, not always – impaired in patients in a vegetative state. Some vegetative patients had well-preserved brain networks that look similar to those of healthy adults – these patients were those who had shown signs of hidden awareness by following commands such as imagining playing tennis.

Dr Srivas Chennu from the Department of Clinical Neurosciences at the University of Cambridge says: “Understanding how consciousness arises from the interactions between networks of brain regions is an elusive but fascinating scientific question. But for patients diagnosed as vegetative and minimally conscious, and their families, this is far more than just an academic question – it takes on a very real significance. Our research could improve clinical assessment and help identify patients who might be covertly aware despite being uncommunicative.”

The findings could help researchers develop a relatively simple way of identifying which patients might be aware whilst in a vegetative state. Unlike the ‘tennis test’, which can be a difficult task for patients and requires expensive and often unavailable fMRI scanners, this new technique uses EEG and could therefore be administered at a patient’s bedside. However, the tennis test is stronger evidence that the patient is indeed conscious, to the extent that they can follow commands using their thoughts. The researchers believe that a combination of such tests could help improve accuracy in the prognosis for a patient.

Dr Tristan Bekinschtein from the MRC Cognition and Brain Sciences Unit and the Department of Psychology, University of Cambridge, adds: “Although there are limitations to how predictive our test would be used in isolation, combined with other tests it could help in the clinical assessment of patients. If a patient’s ‘awareness’ networks are intact, then we know that they are likely to be aware of what is going on around them. But unfortunately, they also suggest that vegetative patients with severely impaired networks at rest are unlikely to show any signs of consciousness.”

Results of the World’s Largest Medical Study of the Human Mind and Consciousness at the Time of Death published

The results of a four-year international study of 2060 cardiac arrest cases across 15 hospitals published and available now on ScienceDirect. The study concludes:

• The themes relating to the experience of death appear far broader than what has been understood so far, or what has been described as so called near-death experiences.
• In some cases of cardiac arrest, memories of visual awareness compatible with so called out-of-body experiences may correspond with actual events.
• A higher proportion of people may have vivid death experiences, but do not recall them due to the effects of brain injury or sedative drugs on memory circuits.
• Widely used yet scientifically imprecise terms such as near-death and out-of-body experiences may not be sufficient to describe the actual experience of death. Future studies should focus on cardiac arrest, which is biologically synonymous with death, rather than ill-defined medical states sometimes referred to as ‘near-death’.
• The recalled experience surrounding death merits a genuine investigation without prejudice.

Recollections in relation to death, so-called out-of-body experiences (OBEs) or near-death experiences (NDEs), are an often spoken about phenomenon which have frequently been considered hallucinatory or illusory in nature; however, objective studies on these experiences are limited.

In 2008, a large-scale study involving 2060 patients from 15 hospitals in the United Kingdom, United States and Austria was launched. The AWARE (AWAreness during REsuscitation) study, sponsored by the University of Southampton in the UK, examined the broad range of mental experiences in relation to death. Researchers also tested the validity of conscious experiences using objective markers for the first time in a large study to determine whether claims of awareness compatible with out-of-body experiences correspond with real or hallucinatory events.

Results of the study have been published in the journal Resuscitation and are now available online.

Dr Sam Parnia, Assistant Professor of Critical Care Medicine and Director of Resuscitation Research at The State University of New York at Stony Brook, USA, and the study’s lead author, explained: “Contrary to perception, death is not a specific moment but a potentially reversible process that occurs after any severe illness or accident causes the heart, lungs and brain to cease functioning. If attempts are made to reverse this process, it is referred to as ‘cardiac arrest’; however, if these attempts do not succeed it is called ‘death’. In this study we wanted to go beyond the emotionally charged yet poorly defined term of NDEs to explore objectively what happens when we die.”

Thirty-nine per cent of patients who survived cardiac arrest and were able to undergo structured interviews described a perception of awareness, but interestingly did not have any explicit recall of events.

“This suggests more people may have mental activity initially but then lose their memories after recovery, either due to the effects of brain injury or sedative drugs on memory recall,” explained Dr Parnia, who was an Honorary Research Fellow at the University of Southampton when he started the AWARE study.

Among those who reported a perception of awareness and completed further interviews, 46 per cent experienced a broad range of mental recollections in relation to death that were not compatible with the commonly used term of NDE’s. These included fearful and persecutory experiences. Only 9 per cent had experiences compatible with NDEs and 2 per cent exhibited full awareness compatible with OBE’s with explicit recall of ‘seeing’ and ‘hearing’ events.

One case was validated and timed using auditory stimuli during cardiac arrest. Dr Parnia concluded: “This is significant, since it has often been assumed that experiences in relation to death are likely hallucinations or illusions, occurring either before the heart stops or after the heart has been successfully restarted, but not an experience corresponding with ‘real’ events when the heart isn’t beating. In this case, consciousness and awareness appeared to occur during a three-minute period when there was no heartbeat. This is paradoxical, since the brain typically ceases functioning within 20-30 seconds of the heart stopping and doesn’t resume again until the heart has been restarted. Furthermore, the detailed recollections of visual awareness in this case were consistent with verified events.

“Thus, while it was not possible to absolutely prove the reality or meaning of patients’ experiences and claims of awareness, (due to the very low incidence (2 per cent) of explicit recall of visual awareness or so called OBE’s), it was impossible to disclaim them either and more work is needed in this area. Clearly, the recalled experience surrounding death now merits further genuine investigation without prejudice.”

Further studies are also needed to explore whether awareness (explicit or implicit) may lead to long term adverse psychological outcomes including post-traumatic stress disorder.

Dr Jerry Nolan, Editor-in-Chief of Resuscitation, stated: “The AWARE study researchers are to be congratulated on the completion of a fascinating study that will open the door to more extensive research into what happens when we die.”

Speech processing while unconscious: Sleep inhibits action but not preparation and meaning

In a team effort between the Medical Research Council Cognition and Brain Sciences Unit (Cambridge, UK) and the Laboratory of Cognitive and Psycholinguistics Sciences, Ecole Normale Superiore (Paris), part of what we are capable of while sleeping has been unravelled.

People were asked to classify words belonging to one of two categories – animals or objects – by pressing buttons with the left or the right hand, and continued to do so until they have fallen asleep. Their brain activity indicated that they were able to decode the meaning of the words and intended to act but the unconscious state during sleep prevented them from responding (no movement of the fingers).

This result indicates that once a rule (animals press left/objects press right) is established during wakefulness it can still be implemented even during sleep. This means that the decoding networks in the brain process the spoken words and that information (if it is an animal or an object for instance) is passed to a motor plan signaling the intention and subsequent action. During sleep that action is inhibited (we do not purposefully move during sleep) but this study has found that the meaning extraction and subsequent action preparation remained but was slower and lasted longer.

To confirm this result a second study tested whether people could classify word or nonwords (like boat or foat). A similar pattern emerged, showing appropriate brain preparation activity for left or right button presses even if responses were inhibited by the sleep mechanisms.

Major dopamine system helps restore consciousness after general anesthesia

Researchers may be one step closer to better understanding how anesthesia works. A study in the August issue of Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®), found stimulating a major dopamine-producing region in the brain, the ventral tegmental area (VTA), caused rats to wake from general anesthesia, suggesting that this region plays a key role in restoring consciousness after general anesthesia. Activating this region at the end of surgery could provide a novel approach to proactively induce consciousness from anesthesia in surgical patients, researchers say.

"While generally safe, it is well known that patients should not be under general anesthesia longer than necessary," said Ken Solt, M.D., lead author, Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine and assistant professor of anesthesia, Harvard Medical School, Boston. "Currently, there are no treatments to reverse the effects of general anesthesia. We must wait for the anesthetics to wear off. Having the ability to control the process of arousal from general anesthesia would be advantageous as it might speed recovery to normal cognition after surgery and enhance operating room (O.R.) efficiencies."

Although the brain circuits that drive the process of emerging from general anesthesia are not well understood, recent studies suggest that certain arousal pathways in the brain may be activated by certain drugs to promote consciousness. The authors previously reported that methylphenidate (Ritalin), a drug used to treat attention deficit hyperactivity disorder, awakened rats from general anesthesia by activating dopamine-releasing pathways.

In the current study, rats were given the general anesthetics isoflurane or propofol. Once unconscious, researchers performed targeted electrical stimulation, through implanted steel electrodes, on the two major regions of the rats’ brains that contain dopamine-releasing cells – the VTA (the area of the brain that controls cognition, motivation and reward in humans) and the substantia nigra, which controls movement.

Researchers found that electrical stimulation of the VTA caused the rats to regain consciousness, suggesting that dopamine released from cells in this area of the brain is likely involved in arousal. Interestingly, electrical stimulation of the VTA had an effect similar to that of the drug methylphenidate in restoring consciousness after anesthesia.

"We now have evidence that dopamine released by cells in the VTA is mainly responsible for the awakening effect seen with methylphenidate," said Dr. Solt. "Because dopamine-releasing cells in the VTA are important for cognition, we may be able to use drugs that act on this region not only to induce consciousness in anesthetized patients, but to potentially treat common postoperative emergence-related problems such as delirium and restore cognitive function."

Understanding Consciousness

Why does a relentless stream of subjective experiences normally fill your mind? Maybe that’s just one of those mysteries that will always elude us. 

Yet, research from Northwestern University suggests that consciousness lies well within the realm of scientific inquiry — as impossible as that may currently seem. Although scientists have yet to agree on an objective measure to index consciousness, progress has been made with this agenda in several labs around the world.

“The debate about the neural basis of consciousness rages because there is no widely accepted theory about what happens in the brain to make consciousness possible,” said Ken Paller, professor of psychology in the Weinberg College of Arts and Sciences and director of the Cognitive Neuroscience Program at Northwestern.

“Scientists and others acknowledge that damage to the brain can lead to systematic changes in consciousness. Yet, we don’t know exactly what differentiates brain activity associated with conscious experience from brain activity that is instead associated with mental activity that remains unconscious,” he said.

In a new article, Paller and Satoru Suzuki, also professor of psychology at Northwestern, point out flawed assumptions about consciousness to suggest that a wide range of scientific perspectives can offer useful clues about consciousness.

“It’s normal to think that if you attentively inspect something you must be aware of it and that analyzing it to a high level would necessitate consciousness,” Suzuki noted. “Results from experiments on perception belie these assumptions.

“Likewise, it feels like we can freely decide at a precise moment, when actually the process of deciding begins earlier, via neurocognitive processing that does not enter awareness,” he said. 

The authors write that unconscious processing can influence our conscious decisions in ways we never suspect.

If these and other similar assumptions are incorrect, the researchers state in their article, then mistaken reasoning might be behind arguments for taking the science of consciousness off the table. 

“Neuroscientists sometimes argue that we must focus on understanding other aspects of brain function, because consciousness is never going to be understood,” Paller said. “On the other hand, many neuroscientists are actively engaged in probing the neural basis of consciousness, and, in many ways, this is less of a taboo area of research than it used to be.”

Experimental evidence has supported some theories about consciousness that appeal to specific types of neural communication, which can be described in neural terms or more abstractly in computational terms. Further theoretical advances can be expected if specific measures of neural activity can be brought to bear on these ideas.

Paller and Suzuki both conduct research that touches on consciousness. Suzuki studies perception, and Paller studies memory. They said it was important for them to write the article to counter the view that it is hopeless to ever make progress through scientific research on this topic.

They outlined recent advances that provide reason to be optimistic about future scientific inquiries into consciousness and about the benefits that this knowledge could bring for society.

“For example, continuing research on the brain basis of consciousness could inform our concerns about human rights, help us explain and treat diseases that impinge on consciousness, and help us perpetuate environments and technologies that optimally contribute to the well being of individuals and of our society,” the authors wrote.

They conclude that research on human consciousness belongs within the purview of science, despite philosophical or religious arguments to the contrary.

Their paper, “The Source of Consciousness,” has been published online in the journal Trends in Cognitive Sciences.

(Image: Shutterstock)

Hypnosis: The day my mind was ‘possessed’

I am lying on my back and trapped in a gleaming white tunnel, the surface barely six inches from my nose. There is a strange mechanical rumbling in the background, and I hear footsteps padding around the room beyond. In my mounting claustrophobia, I ask myself why I am here – but there is no way out now. A few moments later, the light dims, and as the man speaks, my thoughts begin to fade.

“The engineer has developed a way of taking control of your thoughts from the inside. He does this because he is fascinated by mind control, and wants to apply the most direct method of controlling your thoughts. He is doing this to advance his research into mind control. You will soon be aware of the engineer inserting his thoughts.”

A strange serenity descends as I realise that soon, my will won’t be my own. Then the experiment begins. I am about to be possessed.

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Those with episodic amnesia are not ‘stuck in time,’ says philosopher Carl Craver

In 1981, a motorcycle accident left Toronto native Kent Cochrane with severe brain damage and dramatically impaired episodic memory. Following the accident, Cochrane could no longer remember events from his past. Nor could he predict specific events that might happen in the future.

When neuroscientist Endel Tulving, PhD, asked him to describe what he would do tomorrow, Cochrane could not answer and described his state of mind as “blank.”

Psychologists and neuroscientists came to know Cochrane, who passed away earlier this year, simply as “KC.” Many scientists have described KC as “stuck in time,” or trapped in a permanent present.

It has generally been assumed that people with episodic amnesia experience time much differently than those with more typical memory function. 

However, a recent paper in Neuropsychologia co-authored by Carl F. Craver, PhD, professor of philosophy and of philosophy-neuroscience-psychology, both in Arts & Sciences at Washington University in St. Louis, disputes this type of claim.

“It’s our whole way of thinking about these people that we wanted to bring under pressure,” Craver said. “There are sets of claims that sound empirical, like ‘These people are stuck in time.’ But if you ask, ‘Have you actually tested what they know about time?’ the answer is no.”

Time and consciousness

A series of experiments convinced Craver and his co-authors that although KC could not remember specific past experiences, he did in fact have an understanding of time and an appreciation of its significance to his life.

Interviews with KC by Craver and his colleagues revealed that KC retained much of what psychologists refer to as “temporal consciousness.” KC could order significant events from his life on a timeline, and he seemed to have complete mastery of central temporal concepts.

For example, KC understood that events in the past have already happened, that they influence the future, and that once they happen, they cannot be changed. 

He also knew that events in the future don’t remain in the future, but eventually become present. Even more interestingly, KC’s understanding of time influenced his decision-making.

If KC truly had no understanding of time, Craver argues, then he and others with his type of amnesia would act as if only the present mattered. Without understanding that present actions have future consequences or rewards, KC would have based his actions only upon immediate outcomes. However, this was not the case.

On a personality test, KC scored as low as possible on measures of hedonism, or the tendency to be a self-indulgent pleasure-seeker.

In systematic tests of his decision-making, carried out with WUSTL’s Len Green, PhD, professor of psychology, and Joel Myerson, PhD, research professor of psychology, and researchers at York University in Toronto, KC also showed that he was willing to trade a smaller, sooner reward for a larger, later reward.

In other words, KC’s inability to remember past events did not affect his ability to appreciate the value of future rewards. 

‘Questions are now wide open’

KC’s case reveals how much is left to discover about memory and how it relates to human understanding of time.

“If you think about memory long enough it starts to sound magical,” Craver said. “How is it that we can replay these events from our lives? And what’s going on in our brains that allows us to re-experience these events from our past?”

Craver hopes that this article — the last to be published about KC during his lifetime — brings these types of questions to the forefront. 

“These findings open up a whole new set of questions about people with amnesia,” Craver said. “Things that we previously thought were closed questions are now wide open.”

(Image credit)

Study examines how brain ‘reboots’ itself to consciousness after anesthesia

One of the great mysteries of anesthesia is how patients can be temporarily rendered completely unresponsive during surgery and then wake up again, with all their memories and skills intact.

A new study by Dr. Andrew Hudson, an assistant professor of anesthesiology at the David Geffen School of Medicine at UCLA, and colleagues provides important clues about the processes used by structurally normal brains to navigate from unconsciousness back to consciousness. Their findings are currently available in the early online edition of Proceedings of the National Academy of Sciences.

Previous research has shown that the anesthetized brain is not “silent” under surgical levels of anesthesia but experiences certain patterns of activity, and it spontaneously changes its activity patterns over time, Hudson said.

For the current study, the research team recorded the brain’s electrical activity in a rodent model that had been administered the inhaled anesthesia isoflurane by placing electrodes in several brain areas associated with arousal and consciousness. They then slowly decreased the amount of anesthesia, as is done with patients in the operating room, monitoring how the electrical activity in the brain changed and looking for common activity patterns across all the study subjects.

The researchers found that the brain activity occurred in discrete clumps, or clusters, and that the brain did not jump between all of the clusters uniformly.

A small number of activity patterns consistently occurred in the anesthetized rodents, Hudson noted. The patterns depended on how much anesthesia the subject was receiving, and the brain would jump spontaneously from one activity pattern to another. A few activity patterns served as “hubs” on the way back to consciousness, connecting activity patterns consistent with deeper anesthesia to those observed under lighter anesthesia.

"Recovery from anesthesia, is not simply the result of the anesthetic ‘wearing off’ but also of the brain finding its way back through a maze of possible activity states to those that allow conscious experience," Hudson said. "Put simply, the brain reboots itself."

The study suggests a new way to think about the human brain under anesthesia and could encourage physicians to reexamine how they approach monitoring anesthesia in the operating room. Additionally, if the results are applicable to other disorders of consciousness — such as coma or minimally conscious states — doctors may be better able to predict functional recovery from brain injuries by looking at the spontaneously occurring jumps in brain activity.

In addition, this work provides some constraints for theories about how the brain leads to consciousness itself, Hudson said.

Going forward, the UCLA researchers will test other anesthetic agents to determine if they produce similar characteristic brain activity patterns with “hub” states. They also hope to better characterize how the brain jumps between patterns.