̽��ֱ�� of Cambridge - Tristan Bekinschtein

Simple ‘sniff test’ reliably predicts recovery of severely brain-injured patients

jg533 — Wed, 29 Apr 2020 15:24:14 +0000

Published on 29 April in the journal Nature, the study involved brain-injured patients showing very minimal or no signs of awareness of the external world. It found that 100% of patients who reacted to the sniff test went on to regain consciousness, and over 91% of these patients were still alive three and a half years after injury.

“ ̽��ֱ��accuracy of the sniff test is remarkable - I hope it will help in the treatment of severely brain injured patients around the world,” said Anat Arzi, a researcher in the ̽��ֱ�� of Cambridge’s Department of Psychology and the Weizmann Institute of Science Israel, who led the research, together with Professor Noam Sobel from the Weizmann Institute of Science Israel and Dr Yaron Sacher from the Loewenstein Rehabilitation Hospital Israel.

It is often difficult for doctors to determine a patient’s state of consciousness after a severe brain injury. Errors in diagnosis are made in up to 40% of cases. A patient that is minimally conscious differs from one in a vegetative state, and their future outcomes differ. An accurate diagnosis is critical because it informs treatment strategies such as pain management, and can underlie end-of-life decisions.

Our sense of smell is a very basic mechanism and relies on structures deep within the brain. ̽��ֱ��brain automatically changes the way we sniff in response to different smells - for example, when presented with an unpleasant smell we automatically take shorter, shallower breaths. In healthy humans the sniff-response happens in both waking and sleeping states of consciousness.

Research was conducted on 43 severely brain-injured patients. ̽��ֱ��experimenter first explained to each patient that different smells would be presented to them in jars, and the breathing through their nose would be monitored using a small tube called a nasal cannula. There was no indication that the patients heard or understood.

Next, a jar containing either a pleasant smell of shampoo, an unpleasant smell of rotten fish, or no smell at all was presented to each patient for five seconds. Each jar was presented ten times in a random order, and a measurement was made of the volume of air sniffed by the patient.

̽��ֱ��researchers found that minimally conscious patients inhaled significantly less in response to smells, but did not discriminate between nice and nasty smells. These patients also modified their nasal airflow in response to the jar with no smell. This implies awareness of the jar or a learned anticipation of a smell. Vegetative state patients varied - some did not change their breathing in response to either of the smells, but others did.

A follow-up investigation three and a half years later found that over 91% of the patients who had a sniff response shortly after injury were still alive, but 63% of those who had showed no response had died.

By measuring the sniff-response in severely brain injured patients, the researchers could measure the functioning of deep-seated brain structures. Across the patient group they found that sniff-responses differed consistently between those in a vegetative state and those in a minimally conscious state - providing further evidence for an accurate diagnostic.

“We found that if patients in a vegetative state had a sniff response, they later transitioned to at least a minimally conscious state. In some cases, this was the only sign that their brain was going to recover - and we saw it days, weeks and even months before any other signs,” said Arzi.

In a vegetative state the patient may open their eyes, wake up and fall asleep regularly and have basic reflexes, but they don’t show any meaningful responses or signs of awareness. A minimally conscious state differs because the patient may have periods where they can show signs of awareness or respond to commands.

“When the sniff response is functioning normally it shows that the patient might still have some level of consciousness even when all other signs are absent,” said Dr Tristan Bekinschtein in the ̽��ֱ�� of Cambridge’s Department of Psychology, who was involved in the study. “This new and simple method to assess the likelihood of recovery should be immediately incorporated in the diagnostic tools for patients with disorders of consciousness.”

This research was funded by the Rob and Cheryl McEwen Fund for Brain Research, the Blavatnik family Foundation, the Royal Society and the European Molecular Biology Organisation.

Reference
Arzi, A. et al: ‘Olfactory Sniffing Signals Consciousness in Unresponsive Patients with Brain Injuries.’ Nature, April 2020. DOI: 10.1038/s41586-020-2245-5

̽��ֱ��ability to detect smells predicts recovery and long-term survival in patients who have suffered severe brain injury, a new study has found. A simple, inexpensive ‘sniff test’ could help doctors to accurately diagnose and determine treatment plans for patients with disorders of consciousness.

̽��ֱ��accuracy of the sniff test is remarkable - I hope it will help in the treatment of severely brain injured patients around the world.

Anat Arzi

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

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

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution

Listen to your heart: why your brain may give away how well you know yourself

sc604 — Mon, 20 Apr 2015 23:01:17 +0000

In research published today in the journal Cerebral Cortex, a team of scientists led by the ̽��ֱ�� of Cambridge and the Medical Research Council (MRC) Cognition and Brain Sciences Unit, Cambridge, studied not only whether volunteers could be trained to follow their heartbeat, but whether it was possible to identify from brain activity how good they were at estimating their performance.

Dr Tristan Bekinschtein, a Wellcome Trust Fellow and lecturer in the Department of Psychology at the ̽��ֱ�� of Cambridge, says: “‘Follow your heart’ has become something of a cliché, but we know that, consciously or unconsciously, there is a relationship between our heart rate and our decisions and emotions. There may well be benefits to becoming more attuned to our heartbeat, but there’s very little in scientific literature about whether this is even technically possible.”

A recent study from Dr Bekinschtein and colleagues showed that people with ‘depersonalisation-derealisation disorder’ – in which patients repeatedly feel that they are observing themselves from outside their body or have a sense that things around them are not real – perform particularly badly at listening to their heart. Another study from the team, looking at a man with two hearts – his natural, diseased heart and a replacement artificial heart – found that he was better able to tune into the artificial heart than the diseased one.

Other studies have highlighted a possible connection between heart rate and task performance. For example, in one study, volunteers given the drug propranolol to increase their heart rate performed worse at emotional tasks than the control group. Changing heart rate is part of our automatic and unconscious ‘fight or flight’ response – being aware of the heart’s rhythm could give people more control over their behaviour, believe the researchers.

Thirty-three volunteers took part in an experiment during which scientists measured their brain activity using an electroencephalograph (EEG). First off, the volunteers were asked to tap in synchrony as they listened to a regular and then irregular heartbeat. Next, they were asked to tap out their own heartbeat in synchrony. Then, they were asked to tap out their own heartbeat whilst listening to it through a stethoscope. Finally, the stethoscopes were removed and they were once again asked to tap out their heartbeat.

During the task, when the volunteers were tapping out their heartbeat unaided, they were asked to rate their performance on a scale of 1 to 10, with 1 being ‘inaccurate’ and 10 ‘extremely accurate’. Once the task was completed, they were asked how much they thought they had improved from 1 (‘did not improve’) to 10 (‘improved a lot’).

“Perhaps unsurprisingly, we found that brain activity differed between people who improved at tapping out their heartbeat and those who did not,” says Andrés Canales-Johnson from the MRC Cognition and Brain Sciences Unit. “But interestingly, brain activity also differed between people who knew whether or not they had improved and those people who under- or over-estimated their own performance.”

Just over four in ten (42%) of the participants showed significant improvement in their ability to accurately tap along unaided with their heartbeat. This is most likely due to the fact that listening to their heartbeat through a stethoscope had allowed them to fine tune their attention to the otherwise faint signal of their heartbeat. In those whose performance had improved, the researchers saw a stronger brain signal known as the ‘heartbeat evoked potential’ (HEP) across the brain.

̽��ֱ��researchers found no significant differences in the HEP when grouping the participants by how well they thought they had performed – their subjective performance. This suggests that the HEP provides a marker of objective performance.

In the final part of the test – after the participants had listened to their heartbeat through the stethoscope and were once again tapping unaided – the researchers found differences in brain activity between participants. Crucially, they found an increase in ‘gamma phase synchrony’ – coordinated ‘chatter’ between different regions in the brain – in only those learners whose subjective judgement of their own performance matched their actual, objective performance. In other words, this activity was seen only in learners who knew they had performed badly or knew they had improved.

“We’ve shown that for just under half of us, training can help us listen to our hearts, but we may not be aware of our progress,” adds Dr Bekinschtein. “Some people find this task easier to do than others do. Also, some people clearly don’t know how good or bad they actually are – but their brain activity gives them away.

“There are techniques such as mindfulness that teach us to be more aware of our bodies, but it will be interesting to see whether people are able to control their emotions better or to make better decisions if they are aware of how their heart is beating.”

̽��ֱ��research was supported by the Wellcome Trust and the MRC in the UK, and the Chilean National Fund for Scientific and Technological Development, the Argentinean National Research Council for Science and Technology, and the Argentinean Agency for National Scientific Promotion.

“Listen to your heart,” sang Swedish pop group Roxette in the late Eighties. But not everyone is able to tune into their heartbeat, according to an international team of researchers – and half of us under- or over-estimate our ability.

'Follow your heart’ has become something of a cliché, but we know that, consciously or unconsciously, there is a relationship between our heartrate and our decisions and emotions

Tristan Bekinschtein

Larissa S.

listen to your heart

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution

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)

̽��ֱ��text in this work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.

Yes

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

This work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page.

Yes