̽��ֱ�� of Cambridge - Srivas Chennu

Brain, body and mind: understanding consciousness

lw355 — Tue, 23 Feb 2016 10:27:50 +0000

In 10 minutes, Srivas Chennu can work out what’s going on inside your head.

With the help of an electrode-studded hairnet wired up to a box that measures patterns of electrical activity, he can monitor the firing of millions of neurons deep within the brain. A few minutes later, wheeling his trolley-held device away, he has enough information to tell how conscious you really are.

What Chennu is looking for with his electroencephalogram (EEG) is the brain’s electrical ‘signature’. At any one moment in the body’s most complex organ, networks of neurons are firing up and creating ‘brain waves’ of electrical activity that can be detected through the scalp net.

This isn’t new technology – the first animal EEG was published a century ago – but computational neuroscientist Chennu has come up with a way of combining its output with a branch of maths called graph theory to measure the level of a person’s consciousness. What’s more, he’s developing the technology as a bedside device for doctors to diagnose patients suffering from consciousness disorders (such as a vegetative state caused by injury or stroke) to work out the best course of action and to support family counselling.

“Being conscious not only means being awake, but also being able to notice and experience,” he explains. “When someone is conscious, there are patterns of synchronised neural activity arcing across the brain that can be detected using EEG and quantified with our software.”

So for a healthy brain, the brain’s signature might look like a raging scrawl of lines sweeping back and forth, as integrated groups of neurons perceive, process, understand and sort information. When we sleep, this diminishes to a squiggle of the faintest strokes as we lose consciousness, flaring occasionally if we dream.

“Understanding how consciousness arises from neural interactions is an elusive and fascinating 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.

“ ̽��ֱ��patient might be awake, but to what extent are they aware? Can they hear, see, feel? And if they are aware, does their level of awareness equate to their long-term prognosis?”

Chennu points to charts showing the brain signature of two vegetative patients. On one chart, just a few lines appear above the skull. In the other, the lines are so many they resemble, as Chennu describes, a multi-coloured mohican, almost indistinguishable from the signature one would see from a healthy person.

Did either of the patients wake up? “Yes, the second patient did, a year after this trace was taken. ̽��ֱ��point is, if you think that a patient will wake up, what would you do differently as a clinician, or as a family member?”

̽��ֱ��research is based on the finding that a patient in a vegetative state could respond to yes or no questions, as measured by distinct patterns of brain activity using functional magnetic resonance imaging. It was discovered by Chennu’s colleagues in the Department of Clinical Neurosciences and the Medical Research Council Cognition and Brain Sciences Unit (MRC CBSU), led by Dr Adrian Owen.

In 2011, the group found the same attention to commands could be measured using EEG – a less expensive and more widely available technology. Three years later, Chennu and Dr Tristan Bekinschtein from the CBSU, and now in the Department of Psychology, showed that their mathematical analysis of the EEG outputs was enough to measure the ambient amount of connectivity in a patient’s brain.

Chennu hopes that the machine will fill a technology gap: “Misdiagnosis of true levels of consciousness in vegetative patients continues to be around 40% and depends on behavioural examination. In part this is because there is no gold standard for the assessment of a patient’s awareness at the bedside.”

With funding from the Evelyn Trust, he will assess and follow the treatment and rehabilitation trajectory of 50 patients over a three-year period. This will be the first time that a study has linked diagnosis, treatment and outcome to regular real-time assessment of the activity of a patient’s brain.

Meanwhile he is continuing to develop the medical device with industry as part of the National Institute for Health Research Healthcare Technology Co-operative for Brain Injury, which is hosted within the Department of Clinical Neurosciences.

“Medical advances mean that we are identifying subtypes of brain injury and moving away from ‘one size fits all’ to more-targeted treatment specific for an individual’s needs,” adds Chennu, who is also funded by the James S. McDonnell Foundation and works as part of a team led by Professors John Pickard and David Menon.

Intriguingly the device could even offer a channel of communication, as Chennu speculates: “ ̽��ֱ��question that fascinates us is what type of consciousness do patients have? Perhaps we can create systems to translate neural activity into commands for simple communication – interfaces that could provide a basic but reliable communication channel from the ‘inbetween place’ in which some patients exist.

“Moreover, we think that the measurement of brain networks will provide clinically useful information that could help with therapeutics for a larger majority of patients, irrespective of whether they are able to demonstrate hidden consciousness.”

How conscious is my dog? Can robots become conscious? Are people in a vegetative state conscious? Don't miss Philosopher Professor Tim Crane and neuroscientist Dr Srivas Chennu at the Cambridge Science Festival, where they will look into our minds and wrestle with the meaning of what it is to be conscious. 'Brain, body and mind: new directions in the neuroscience and philosophy of consciousness', the Research Horizons Public Lecture, will be on Wednesday 16 March 2016, 8pm–9pm, Mill Lane Lecture Rooms, Mill Lane, Cambridge. Pre-booking required.

A bedside device that measures ‘brain signatures’ could help diagnose patients who have consciousness disorders – such as a vegetative state – to work out the best course of treatment and to support family counselling.

̽��ֱ��patient might be awake, but to what extent are they aware? Can they hear, see, feel? And if they are aware, does their level of awareness equate to their long-term prognosis?

Srivas Chennu

Electrical brain 'signatures'. ̽��ֱ��patient to the left is in a vegetative state; the patient in the middle is also in a vegetative state but their brain appears as conscious as the brain of the healthy individual at the right.

New directions in the study of the mind

We know a great deal about the brain but what does it actually mean to be conscious, asks a new research programme in the Faculty of Philosophy.

In what way are newborn babies, or animals, conscious? Why do some experiences become part of one’s consciousness yet others do not?

“It’s sometimes assumed that it’s obvious what consciousness is, and the only question is how it is embodied in the brain,” says Professor Tim Crane. “But many people now recognise that it’s not clear what it means to say that something has a mind, or is capable of thought or conscious experience. My view is that there are lots of assumptions that are being made in order to get to that conclusion and not all of the assumptions are correct.”

Crane leads a new research initiative in the Faculty of Philosophy supported by the John Templeton Foundation that aims to tackle the broad question of the essence of the mind. And to do this they are moving beyond the reductionist view that everything can be explained in terms of the nuts and bolts of neuroscience.

“That doesn’t mean we are interested in proving the existence of the immortal soul, or defending any religious doctrine – we are interested in the idea that the brain’s-eye view isn’t everything when it comes to understanding the mind.

“ ̽��ֱ��nervous system clearly provides the mechanism for thought and consciousness but learning about it doesn’t tell us everything we need to know about phenomena like the emotion of parental love, or ambition or desire. ̽��ֱ��mere fact that something goes on in your brain when you think does not explain what thinking essentially is.”

̽��ֱ��team in Cambridge are also distributing funds for smaller projects elsewhere in the world, each of which is tackling similar questions of consciousness in philosophy, neuroscience and psychology.

“Collectively we want to recognise ‘the reality of the psychological’ without saying that it’s really just brain chemicals,” adds Crane. “It’s important to face up to the fact that we are not just our neurons.”

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Opinion: Scientists find way to predict who is likely to wake up during surgery

Anonymous — Fri, 22 Jan 2016 15:52:53 +0000

Measuring certain kinds of brain activity may help doctors track and predict how patients will react to anaesthesia before going under for surgery, our research has found.

Doctors currently have no perfectly reliable way of ensuring patients are adequately unconscious before an operation begins. Although rare, the uncertainty sometimes results in traumatic experiences of patients “waking up” during surgery.

Using a technique that measures electrical impulses in the brain of those in various states of sedation, we discovered network “signatures” that can indicate when loss of consciousness will occur.

Doctors can use similar techniques to accurately identify the concentration of drug needed for a patient to lose consciousness and maintain that loss throughout an operation.

Everyone is different

Every day in Australia, more than 6,000 people are anaesthetised for surgery. Doctors need to figure out exactly how much sedative to give them, and keep them unconscious throughout the operation.

Anaesthetists estimate the concentration of sedative required using calculations mainly based on a patient’s weight. As the patient “goes under”, their level of awareness is monitored by observing indirect – and somewhat crude – measures, such as blood pressure, heart rate or physical movement.

This method works well in most cases, but people’s susceptibility to anaesthesia varies. One to two in every 1,000 people report having some awareness or recall during surgery. This equates to 2,000 to 4,000 such cases each year in Australia.

Recollections include hearing people speaking during surgery, sensations of not being able to breathe, and experiencing pain.

Naturally, experiences such as these are emotionally traumatic. What’s more, many suffer mental distress long after the surgery, resulting in negative memories of their hospital experience. Some have even reported a reduction in their quality of life.

Losing consciousness

Figuring out the best way to sedate someone essentially comes down to understanding how the brain gains and loses consciousness; that is, the inner world of awareness, feelings and sensations. Although a challenging theme in neuroscience, rapid advances have been made in this area.

Some theories suggest that key networks of brain areas communicate with each other to integrate information processing and generate consciousness. This communication network gives off signals that indicate how conscious an individual is.

̽��ֱ��networks come about from brain neurons firing simultaneously at a certain frequency. We can observe them by using a non-invasive technique called electroencephalogram (EEG), where sensors placed on the scalp record the neurons' electrical impulses. These recordings provide us with a brain “signature” indicative of awareness levels.

Brain monitoring such as this is not commonly used in the operating theatre today. One reason is that current devices are unable to deal with the considerable variability in how people respond to sedatives. But our study shows that devices calibrated for accurate monitoring based on the latest neuroscientific advances could help reduce the incidence of awareness during surgery.

Our study

We have previously shown that network signals of consciousness can also be seen in some people in a vegetative state.

This gave us an indication of the types of signals that could be seen in those who experience some awareness during surgery, but are unable to communicate. But we also needed to show that a similar brain-based measure worked well in cases where we could manipulate the level of consciousness.

Our latest study, published in the journal PLOS Computational Biology, helped us better understand the transition to unconsciousness during sedation, and how this transition varies from person to person.

We gave a steadily increasing dose of a commonly used anaesthetic called propofol to 20 people. At the same time, we measured the brain networks known to be associated with consciousness using EEG. ̽��ֱ��drug was administered at different dosages, causing varying degrees of mild to moderate sedation across our participant group, rather than complete unconsciousness in all of them.

We also measured the behavioural responsiveness of the participants with a simple task. They were asked to press one button if they heard a “ping” and a different button if they heard a “pong”.

Alongside this, we recorded the concentration of the drug in their blood at different times. Altogether, we got the information needed to connect the activity of their brain networks to their individual drug responses.

̽��ֱ��right measure

We found that the strength of a participant’s brain network was clearly linked to their behavioural responsiveness. In other words, as the brain network indicating consciousness weakened, behavioural evidence of awareness also diminished.

Interestingly, while some participants showed behavioural evidence of consciousness at moderate levels of the anaesthetic, others remained responsive.

We found that it was actually the strength of their brain networks before sedation that predicted why some eventually lost consciousness while others did not. In other words, people with weaker baseline networks of consciousness were able to lose it more quickly than those with stronger baselines.

Our current findings indicate the change in consciousness due to the sedative was clearly correlated with specific patterns of brain network activity. This gives us confidence in making the “reverse inference” that tracking this network activity can be used to infer the true level of consciousness in the absence of behaviour.

Further engineering and testing could help advance and adapt current brain monitoring technology for use in the operating theatre. It is clear that networks measured by an appropriate EEG can capture and explain why people respond differently to anaesthesia.

This monitoring can help doctors optimise the amount of drug needed for someone to become unconscious without increasing risk of complications or awareness during surgery.

Srivas Chennu, Senior Research Associate, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Srivas Chennu (Department of Clinical Neurosciences) discusses how doctors could use brain waves to help predict how patients will respond to general anaesthetics.

UCD School of Medicine

Surgery Image 8

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Brain waves could help predict how we respond to general anaesthetics

cjb250 — Thu, 14 Jan 2016 18:54:14 +0000

Currently, patients due to undergo surgery are given a dose of anaesthetic based on the so-called ‘Marsh model’, which uses factors such as an individual’s body weight to predict the amount of drug needed. As patients ‘go under’, their levels of awareness are monitored in a relatively crude way. If they are still deemed awake, they are simply given more anaesthetic. However, general anaesthetics can carry risks, particularly if an individual has an underlying health condition such as a heart disorder.

As areas of the brain communicate with each other, they give off tell-tale signals that can give an indication of how conscious an individual is. These ‘networks’ of brain activity can be measured using an EEG (electroencephalogram), which measures electric signals as brain cells talk to each other. Cambridge researchers have previously shown that these network signatures can even be seen in some people in a vegetative state and may help doctors identify patients who are aware despite being unable to communicate. These findings build upon advances in the science of networks to tackle the challenge of understanding and measuring human consciousness.

In a study published today in the open access journal PLOS Computational Biology, funded by the Wellcome Trust, the researchers studied how these signals changed in healthy volunteers as they received an infusion of propofol, a commonly used anaesthetic.

Twenty individuals (9 male, 11 female) received a steadily increasing dose of propofol – all up to the same limit – while undergoing a task that involved pressing one button if they heard a ‘ping’ and a different button if they heard a ‘pong’. At the same time, the researchers tracked their brain network activity using an EEG.

By the time the subjects had reached the maximum dose, some individuals were still awake and able to carry out the task, while others were unconscious. As the researchers analysed the EEG readings, they found clear differences between those who were responding to the anaesthetic and those who remained able to carry on with the task. This ‘brain signature’ was evident in the network of communications between brain areas carried by alpha waves (brain cell oscillations in the frequency range of 7.5–12.5 Hz), the normal range of electrical activity of the brain when conscious and relaxed.

In fact, when the researchers looked at the baseline EEG readings before any drug was given, they already saw differences between those who would later succumb to the drug and those who were less responsive to its effects. Dividing the subjects into two groups based on their EEG readings – those with lots of brain network activity at baseline and those with less – the researchers were able to predict who would be more responsive to the drug and who would be less.

̽��ֱ��researchers also measured levels of propofol in the blood to see if this could be used as a measure of how conscious an individual was. Although they found little correlation with the alpha wave readings in general, they did find a correlation with a specific form of brain network activity known as delta-alpha coupling. This may be able to provide a useful, non-invasive measure of the level of drug in the blood.

“A very good way of predicting how an individual responds to our anaesthetic was the state of their brain network activity at the start of the procedure,” says Dr Srivas Chennu from the Department of Clinical Neurosciences, ̽��ֱ�� of Cambridge. “ ̽��ֱ��greater the network activity at the start, the more anaesthetic they are likely to need to put them under.”

Dr Tristan Bekinschtein, senior author from the Department of Psychology, adds: “EEG machines are commonplace in hospitals and relatively inexpensive. With some engineering and further testing, we expect they could be adapted to help doctors optimise the amount of drug an individual needs to receive to become unconscious without increasing their risk of complications.”

Srivas Chennu will be speaking at the Cambridge Science Festival on Wednesday 16 March. During the event, ‘Brain, body and mind: new directions in the neuroscience and philosophy of consciousness’, he will be examining what it means to be conscious.

Reference
Chennu, S et al. Brain connectivity dissociates responsiveness from drug exposure during propofol induced transitions of consciousness. PLOS Computational Biology; 14 Jan 2016

Image
Brain networks during the transition to unconsciousness during propofol sedation (drug infusion timeline shown in red). Participants with robust networks at baseline (left panel) remained resistant to the sedative, while others showed characteristically different, weaker networks during unconsciousness (middle). All participants regained similar networks when the sedative wore off (right).

̽��ֱ��complex pattern of ‘chatter’ between different areas of an individual’s brain while they are awake could help doctors better track and even predict their response to general anaesthesia – and better identify the amount of anaesthetic necessary – according to new research from the ̽��ֱ�� of Cambridge.

A very good way of predicting how an individual responds to our anaesthetic was the state of their brain network activity at the start of the procedure

Srivas Chennu

Brain networks during the transition to unconsciousness during propofol sedation

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

cjb250 — Thu, 16 Oct 2014 18:00:24 +0000

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 ̽��ֱ�� 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. ̽��ֱ��findings of the research are published today in the journal PLOS Computational Biology. ̽��ֱ��study was funded mainly by the Wellcome Trust, the National Institute of Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC).

̽��ֱ��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 ̽��ֱ�� 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.”

̽��ֱ��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. ̽��ֱ��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, ̽��ֱ�� 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.”

Listen to Srivas Chennu interviewed on the BBC Radio 4 Today Programme below:

listen to ‘How to determine brain activity in someone in a persistent vegetative state’ on audioBoom

Reference
Chennu S et al. Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness. PLOS Computational Biology; 16 Oct 2014

Scientists in Cambridge have found hidden signatures in the brains of people in a vegetative state, which point to networks that could support consciousness even when a patient appears to be unconscious and unresponsive. ̽��ֱ��study could help doctors identify patients who are aware despite being unable to communicate.

Understanding how consciousness arises [in the brain] 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

Srivas Chennu

Brain networks in two behaviourally-similar vegetative patients (left and middle), but one of whom imagined playing tennis (middle panel), alongside a healthy adult (right panel)

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Patient in ‘vegetative state’ not just aware, but paying attention

sj387 — Thu, 31 Oct 2013 12:14:31 +0000

A patient in a seemingly vegetative state, unable to move or speak, showed signs of attentive awareness that had not been detected before, a new study reveals. This patient was able to focus on words signalled by the experimenters as auditory targets as successfully as healthy individuals. If this ability can be developed consistently in certain patients who are vegetative, it could open the door to specialised devices in the future and enable them to interact with the outside world.

̽��ֱ��research, by scientists at the Medical Research Council Cognition and Brain Sciences Unit (MRC CBSU) and the ̽��ֱ�� of Cambridge, is published today, 31 October, in the journal Neuroimage: Clinical.

For the study, the researchers used electroencephalography (EEG), which non-invasively measures the electrical activity over the scalp, to test 21 patients diagnosed as vegetative or minimally conscious, and eight healthy volunteers. Participants heard a series of different words - one word a second over 90 seconds at a time - while asked to alternatingly attend to either the word ‘yes’ or the word ‘no’, each of which appeared 15% of the time. (Some examples of the words used include moss, moth, worm and toad.) This was repeated several times over a period of 30 minutes to detect whether the patients were able to attend to the correct target word.

They found that one of the vegetative patients was able to filter out unimportant information and home in on relevant words they were being asked to pay attention to. Using brain imaging (fMRI), the scientists also discovered that this patient could follow simple commands to imagine playing tennis. They also found that three other minimally conscious patients reacted to novel but irrelevant words, but were unable to selectively pay attention to the target word.

These findings suggest that some patients in a vegetative or minimally conscious state might in fact be able to direct attention to the sounds in the world around them.

Dr Srivas Chennu at the ̽��ֱ�� of Cambridge, said: ”Not only did we find the patient had the ability to pay attention, we also found independent evidence of their ability to follow commands – information which could enable the development of future technology to help patients in a vegetative state communicate with the outside world.

“In order to try and assess the true level of brain function and awareness that survives in the vegetative and minimally conscious states, we are progressively building up a fuller picture of the sensory, perceptual and cognitive abilities in patients. This study has added a key piece to that puzzle, and provided a tremendous amount of insight into the ability of these patients to pay attention.”

Dr Tristan Bekinschtein at the MRC Cognition and Brain Sciences Unit said: “Our attention can be drawn to something by its strangeness or novelty, or we can consciously decide to pay attention to it. A lot of cognitive neuroscience research tells us that we have distinct patterns in the brain for both forms of attention, which we can measure even when the individual is unable to speak. These findings mean that, in certain cases of individuals who are vegetative, we might be able to enhance this ability and improve their level of communication with the outside world.”

This study builds on a joint programme of research at the ̽��ֱ�� of Cambridge and MRC CBSU where a team of researchers have been developing a series of diagnostic and prognostic tools based on brain imaging techniques since 1998. Famously, in 2006 the group was able to use fMRI imaging techniques to establish that a patient in a vegetative state could respond to yes or no questions by indicating different, distinct patterns of brain activity.

Research raises possibility of devices in the future to help some patients in a vegetative state interact with the outside world.

These findings mean that, in certain cases of individuals who are vegetative, we might be able to [...] improve their level of communication with the outside world

Dr Tristan Bekinschtein

Clinical Neurosciences

This scan depicts patterns of the vegetative patient's electrical activity over the head when they attended to the designated words, and when they when they were distracted by novel but irrelevant words

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