̽��ֱ�� of Cambridge - Emmanuel Stamatakis

One in four patients in vegetative or minimally conscious state able to perform cognitive tasks, study finds

cjb250 — Wed, 14 Aug 2024 21:00:11 +0000

Severe brain injury can leave individuals unable to respond to commands physically, but in some cases they are still able to activate areas of the brain that would ordinarily play a role in movement. This phenomenon is known as ‘cognitive motor dissociation’.

To determine what proportion of patients in so-called ‘disorders of consciousness’ experience this phenomenon – and help inform clinical practice – researchers across Europe and North America recruited a total of 353 adults with disorders of consciousness, including the largest cohort of 100 patients studied at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust.

Participants had mostly sustained brain injury from severe trauma, strokes or interrupted oxygen supply to the brain after heart attacks. Most were living in specialised long-term care facilities and a few were living at home with extensive care packages. ̽��ֱ��median time from injury for the whole group was about eight months.

Researchers assessed patterns of brain activation among these patients using functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). Subjects were asked to repeatedly imagine performing a motor activity (for example, “keep wiggling your toes”, “swinging your arm as if playing tennis”, “walking around your house from room to room”) for periods of 15 to 30 seconds separated by equal periods of rest. To be able to follow such instructions requires not only the understanding of and response to a simple spoken command, but also more complex thought processes including paying attention and remembering the command.

̽��ֱ��results of the study are published today in the New England Journal of Medicine.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge said: “When a patient has sustained a severe brain injury, there are very important, and often difficult, decisions to be made by doctors and family members about their care. It’s vitally important that we are able to understand the extent to which their cognitive processes are still functioning by utilising all available technology.”

Among the 241 patients with a prolonged disorder of consciousness, who could not make any visible responses to bedside commands, one in four (25%) was able to perform cognitive tasks, producing the same patterns of brain activity recorded with EEG and/or fMRI that are seen in healthy subjects in response to the same instructions.

In the 112 patients who did demonstrate some motor responses to spoken commands at the bedside, 38% performed these complex cognitive tasks during fMRI or EEG. However, the majority of these patients (62%) did not demonstrate such brain activation. This counter-intuitive finding emphasises that the fMRI and EEG tasks require patients to have complex cognitive abilities such as short-term memory and sustained concentration, which are not required to the same extent for following bedside commands.

These findings are clinically very important for the assessment and management of the estimated 1,000 to 8,000 individuals in the UK in the vegetative state and 20,000 to 50,000 in a minimally conscious state. ̽��ֱ��detection of cognitive motor dissociation has been associated with more rapid recovery and better outcomes one year post injury, although the majority of such patients will remain significantly disabled, albeit with some making remarkable recoveries.

Dr Judith Allanson, Consultant in Neurorehabilitation, said: “A quarter of the patients who have been diagnosed as in a vegetative or minimally conscious state after detailed behavioural assessments by experienced clinicians, have been found to be able to imagine carrying out complex activities when specifically asked to. This sobering fact suggests that some seemingly unconscious patients may be aware and possibly capable of significant participation in rehabilitation and communication with the support of appropriate technology.

“Just knowing that a patient has this ability to respond cognitively is a game changer in terms of the degree of engagement of caregivers and family members, referrals for specialist rehabilitation and best interest discussions about the continuation of life sustaining treatments.”

̽��ֱ��researchers caution that care must be taken to ensure the findings are not misrepresented, pointing out, for example, that a negative fMRI/EEG result does not per se exclude cognitive motor dissociation as even some healthy volunteers do not show these responses.

Professor John Pickard, emeritus professorial Fellow of St Catharine's College, Cambridge, said: “Only positive results – in other words, where patients are able to perform complex cognitive processes – should be used to inform management of patients, which will require meticulous follow up involving specialist rehabilitation services.”

̽��ֱ��team is calling for a network of research platforms to be established in the UK to enable multicentre studies to examine mechanisms of recovery, develop easier methods of assessment than task-based fMRI/EEG, and to design novel interventions to enhance recovery including drugs, brain stimulation and brain-computer interfaces.

̽��ֱ��research reported here was primarily funded by the James S. McDonnell Foundation. ̽��ֱ��work in Cambridge was supported by the National Institute for Health and Care Research UK, MRC, Smith’s Charity, Evelyn Trust, CLAHRC ARC fellowship and the Stephen Erskine Fellowship (Queens’ College).

Reference
Bodien, YG et al. Cognitive Motor Dissociation in Disorders of Consciousness. NEJM; 14 Aug 2024; DOI: 10.1056/NEJMoa2400645

Adapted from a press release from Weill Cornell Medicine

Around one in four patients with severe brain injury who cannot move or speak – because they are in a prolonged coma, vegetative or minimally conscious state – is still able to perform complex mental tasks, a major international study has concluded in confirmation of much smaller previous studies.

When a patient has sustained a severe brain injury, there are very important, and often difficult, decisions to be made by doctors and family members about their care

Emmanuel Stamatakis

Witthaya Prasongsin (Getty Images)

Male patient in a hospital bed - stock image

Acknowledgements

̽��ֱ��multidisciplinary Cambridge Impaired Consciousness Research Group, led by Emeritus Professors John Pickard (Neurosurgery) & David Menon (Anaesthesia) and Drs Judith Allanson & Emmanuel A. Stamatakis (Lead, Cognition and Consciousness Imaging Group), started its research programme in 1997, partly in response to emerging concern over the misdiagnosis of the vegetative state. This pioneering work has only been possible by having access to the world class resources of the Wolfson Brain Imaging Centre, the NIHR/Wellcome Clinical Research Facility at Addenbrooke’s Hospital, the MRC Cognition and Brain Sciences Unit (Professors Barbara Wilson & Adrian Owen), the Royal Hospital for Neuro-disability (Putney) and the Central England Rehabilitation Unit (Royal Leamington Spa).

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 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 – 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.

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Almost half of people with concussion still show symptoms of brain injury six months later

cjb250 — Tue, 25 Apr 2023 23:00:34 +0000

Mild traumatic brain injury – concussion – results from a blow or jolt to the head. It can occur as a result of a fall, a sports injury or from a cycling accident or car crash, for example. But despite being labelled ‘mild’, it is commonly linked with persistent symptoms and incomplete recovery. Such symptoms include depression, cognitive impairment, headaches, and fatigue.

While some clinicians in recent studies predict that nine out of 10 individuals who experience concussion will have a full recovery after six months, evidence is emerging that only a half achieve a full recovery. This means that a significant proportion of patients may not receive adequate post-injury care.

Predicting which patients will have a fast recovery and who will take longer to recover is challenging, however. At present, patients with suspected concussion will typically receive a brain scan – either a CT scan or an MRI scan, both of which look for structural problems, such as inflammation or bruising – yet even if these scans show no obvious structural damage, a patient’s symptoms may still persist.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences and Division of Anaesthesia at the ̽��ֱ�� of Cambridge said: “Worldwide, we’re seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population and rising numbers of road traffic collisions in low- and middle-income countries.

“At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms.”

Dr Stamatakis and colleagues studied fMRI brain scans – that is, functional MRI scans, which look at how different areas of the brain coordinate with each other – taken from 108 patients with mild traumatic brain injury and compared them with scans from 76 healthy volunteers. Patients were also assessed for ongoing symptoms.

̽��ֱ��patients and volunteers had been recruited to CENTER-TBI, a large European research project which aims to improve the care for patients with traumatic brain injury, co-chaired by Professor David Menon (head of the division of Anaesthesia) and funded by the European Union.

In results published today in Brain, the team found that just under half (45%) were still showing symptoms resulting from their brain injury, with the most common being fatigue, poor concentration and headaches.

̽��ֱ��researchers found that these patients had abnormalities in a region of the brain known as the thalamus, which integrates all sensory information and relays this information around the brain. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain – in other words, the thalamus was trying to communicate more as a result of the injury – and the greater this connectivity, the poorer the prognosis for the patient.

Rebecca Woodrow, a PhD student in the Department of Clinical Neuroscience and Hughes Hall, Cambridge, said: “Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain’s relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience.”

By studying additional data from positron emission tomography (PET) scans, which can measure regional chemical composition of body tissues, the researchers were able to make associations with key neurotransmitters depending on which long-term symptoms a patient displayed. For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin.

Dr Stamatakis, who is also Stephen Erskine Fellow at Queens' College, Cambridge, added: “We know that there already drugs that target these brain chemicals so our findings offer hope that in future, not only might we be able to predict a patient’s prognosis, but we may also be able to offer a treatment targeting their particular symptoms.”

Reference
Woodrow, RE et al. Acute thalamic connectivity precedes chronic postconcussive symptoms in mild traumatic brain injury. Brain; 26 April 2023; DOI: 10.1093/brain/awad056

Even mild concussion can cause long-lasting effects to the brain, according to researchers at the ̽��ֱ�� of Cambridge. Using data from a Europe-wide study, the team has shown that for almost a half of all people who receive a knock to the head, there are changes in how regions of the brain communicate with each other, potentially causing long term symptoms such as fatigue and cognitive impairment.

̽��ֱ��combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms

Emmanuel Stamatakis

AleksandarGeorgiev (Getty Images)

Female Still In Shock After Getting Hit By Car With Motorcycle

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 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.

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Running on autopilot: scientists find important new role for ‘daydreaming’ network

cjb250 — Mon, 23 Oct 2017 19:00:43 +0000

When we are performing tasks, specific regions of the brain become more active – for example, if we are moving, the motor cortex is engaged, while if we are looking at a picture, the visual cortex will be active. But what happens when we are apparently doing nothing?

In 2001, scientists at the Washington ̽��ֱ�� School of Medicine found that a collection of brain regions appeared to be more active during such states of rest. This network was named the ‘default mode network’ (DMN). While it has since been linked to, among other things, daydreaming, thinking about the past, planning for the future, and creativity, its precise function is unclear.

Abnormal activity in the DMN has been linked to an array of disorders including Alzheimer’s disease, schizophrenia, attention-deficit/hyperactivity disorder (ADHD) and disorders of consciousness. However, scientists have been unable to show a definitive role in human cognition.

Now, in research published today in the Proceedings of National Academy of Sciences, scientists at the ̽��ֱ�� of Cambridge have shown that the DMN plays an important role in allowing us to switch to ‘autopilot’ once we are familiar with a task.

In the study, 28 volunteers took part in a task while lying inside a magnetic resonance imaging (MRI) scanner. Functional MRI (fMRI) measures changes in brain oxygen levels as a proxy for neural activity.

In the task, participants were shown four cards and asked to match a target card (for example, two red diamonds) to one of these cards. There were three possible rules – matching by colour, shape or number. Volunteers were not told the rule, but rather had to work it out for themselves through trial and error.

̽��ֱ��most interesting differences in brain activity occurred when comparing the two stages of the task – acquisition (where the participants were learning the rules by trial and error) and application (where the participants had learned the rule and were now applying it). During the acquisition stage, the dorsal attention network, which has been associated with the processing of attention-demanding information, was more active. However, in the application stage, where participants utilised learned rules from memory, the DMN was more active.

Crucially, during the application stage, the stronger the relationship between activity in the DMN and in regions of the brain associated with memory, such as the hippocampus, the faster and more accurately the volunteer was able to perform the task. This suggested that during the application stage, the participants could efficiently respond to the task using the rule from memory.

“Rather than waiting passively for things to happen to us, we are constantly trying to predict the environment around us,” says Dr Deniz Vatansever, who carried out the study as part of his PhD at the ̽��ֱ�� of Cambridge and who is now based at the ̽��ֱ�� of York.

“Our evidence suggests it is the default mode network that enables us do this. It is essentially like an autopilot that helps us make fast decisions when we know what the rules of the environment are. So for example, when you’re driving to work in the morning along a familiar route, the default mode network will be active, enabling us to perform our task without having to invest lots of time and energy into every decision.”

“ ̽��ֱ��old way of interpreting what’s happening in these tasks was that because we know the rules, we can daydream about what we’re going to have for dinner later and the DMN kicks in,” adds senior author Dr Emmanuel Stamatakis from the Division of Anaesthesia at the ̽��ֱ�� Of Cambridge. “In fact, we showed that the DMN is not a bystander in these tasks: it plays an integral role in helping us perform them.”

This new study supports an idea expounded upon by Daniel Kahneman, Nobel Memorial Prize in Economics laureate 2002, in his book Thinking, Fast and Slow, that there are two systems that help us make decisions: a rational system that helps us reach calculated decisions, and a fast system that allows us to make intuitive decisions – the new research suggests this latter system may be linked with the DMN.

̽��ֱ��researchers believe their findings have relevance to brain injury, particularly following traumatic brain injury, where problems with memory and impulsivity can substantially compromise social reintegration. They say the findings may also have relevance for mental health disorders, such as addiction, depression and obsessive compulsive disorder, where particular thought patterns drive repeated behaviours, and the mechanisms of anaesthetic agents and other drugs on the brain.

This research was carried out in the general context of understanding conscious processing in the human brain. ̽��ֱ��Division of Anaesthesia, headed by Professor David Menon, NIHR Senior Investigator, has a programme of research aiming to further elucidate the neural basis of consciousness and cognition in health and disease.

̽��ֱ��research was supported by the Yousef Jameel Academic Program, ̽��ֱ��Stephen Erskine Fellowship from Queens’ College Cambridge, and the NIHR Cambridge Biomedical Resource Centre.

Reference
Vatansever, D, Menon, DK, Stamatakis, EA. Default Mode Contributions to Automated Information Processing. PNAS; 23 Oct 2017; DOI: 10.1073/pnas.1710521114

A brain network previously associated with daydreaming has been found to play an important role in allowing us to perform tasks on autopilot. Scientists at the ̽��ֱ�� of Cambridge showed that far from being just ‘background activity’, the so-called ‘default mode network’ may be essential to helping us perform routine tasks.

̽��ֱ��default mode network is essentially like an autopilot that helps us make fast decisions when we know what the rules of the environment are

Deniz Vatansever

Erik Starck

Driving a car

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

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̽��ֱ��communicative brain

lw355 — Tue, 29 Nov 2011 10:00:57 +0000

̽��ֱ��ability to communicate using language is fundamental to the distinctive and remarkable success of the modern human. It is this capacity that separates us most decisively from our primate cousins, despite all that we have in common across species as intelligent social primates.

A major challenge for the cognitive neurosciences is to understand this relationship: what is the neurobiological context in which human language and communication have emerged, and what are the special human properties that make language itself possible?

For the past 150 years, scientific thinking about this relationship has been dominated by the concept of a single, central language system built around the brain’s left hemisphere. Pioneering 19th-century neurologists Paul Broca and Carl Wernicke noticed that patients with left hemisphere brain damage had difficulties with language comprehension and language production. Two areas of the left frontal and temporal lobes, Broca’s area and Wernicke’s area, and the bundle of nerve fibres connecting them, were identified as critical for speaking and understanding language.

Recent research in our laboratories suggests major limitations to this classic approach to language and the brain. ̽��ֱ��Broca–Wernicke concept captures one important aspect of the neural language system – the key role of the left hemisphere network – but it obscures another, equally important one. This is the role of bi-hemispheric systems and processes, whereby both left and right hemispheres work together to provide the fundamental underpinnings for human communicative processes.

A more fruitful approach to human language and communication will require a dual neurobiological framework in which these capacities are supported by two intersecting but evolutionarily and functionally distinguishable subsystems. ̽��ֱ��historical failure to make this separation has, we suggest, severely undermined scientific attempts to understand language, both as a neurocognitive phenomenon in the modern human, and in terms of its evolutionary and neurobiological context.

Dual systems

A strong evolutionary continuity between humans and our primate relatives is provided by a distributed, bi-hemispheric set of capacities that support the dynamic interpretation of visual and auditory signals in the service of social communication. These capacities have been the object of intensive study in monkeys and apes, and there is good evidence that their basic architecture underpins related communicative functions in the human.

In the context of human language comprehension, the bi-hemispheric systems support the ability not only to identify the words a speaker is producing – typically by integrating auditory and visual cues in face-to-face interaction – but also to make sense of these word-meanings in the general context of the listener’s knowledge of the world and of the specific context of speaking.

Where we see divergence between humans and other primates is in the domain of grammatical (or syntactic) function. Primate communication systems are not remotely comparable to human language in their expressive capacities. Human language is much more than a set of signs that stand for things. It constitutes a powerful and flexible set of grammatical devices for organising the flow of linguistic information and its interpretation, allowing us to represent and combine abstract linguistic elements, where these elements convey not only meaning but also the subtle structural cues that indicate how these elements are linked together.

It is the fronto-temporal network of regions in the left hemisphere that mediates these core grammatical functions in humans. This is a network that differs neuroanatomically from those of the brains of other primates, showing substantial increases in size, complexity and connectivity.

Although it’s not yet understood just how these evolutionary changes in the left hemisphere provide the neural substrate on which grammatical functions depend, it is clear that they are essential. When the left hemisphere system is damaged, the parallel right hemisphere regions cannot take over these functions, even when damage is sustained early in childhood.

Critically, however, the left hemisphere system that has emerged in humans neither replaces nor displaces the bi-hemispheric system for social communication and action found in both humans and other primates. It interacts and combines with it to create a co-ordinated process of linguistically guided communication and social interaction.

Functional separability

̽��ֱ��most direct evidence for a dual system approach is the ability to separate these systems in the modern human. Using a combination of behavioural and neuroimaging techniques, we have been able to demonstrate this both in patients with left hemisphere brain damage and in unimpaired young adults.

In the research with patients (conducted with Dr Paul Wright in the Department of Experimental Psychology and Dr Emmanuel Stamatakis in the Division of Anaesthesia) we focus on the comprehension of spoken words and spoken sentences. In initial testing, patients perform classic measures of syntactic function, where they match different spoken sentences to sets of pictures. Shown three pictures – a woman pushing a girl, a girl pushing a woman and a woman teaching a girl – patients will correctly match the sentence ‘ ̽��ֱ��woman pushed the girl’ to the first picture but will incorrectly match the passive sentence ‘ ̽��ֱ��woman is being pushed by the girl’ to the same picture. ̽��ֱ��second sentence requires the use of syntactic cues to extract the right meaning – just using the order of words is not sufficient.

These behavioural tests of syntactic impairment are linked, in the same patients, to their performance in the neuroimaging laboratory, where they hear sentences that vary in their syntactic demands, and where the precise extent of the injury to their brains can be mapped out. When we put these different sources of information together, we see that damage to the left hemisphere system progressively impairs the syntactic aspects of language processing – the more damage, the worse the performance.

Critically, however, the amount of left hemisphere damage, and the extent to which it involves the key fronto-temporal circuit, does not affect the patients’ ability to identify the words being spoken or to understand the messages being communicated – so long as syntactic cues are not required to do so. These capacities are supported bi-hemispherically, and can remain relatively intact even in the face of massive left hemisphere damage.

In work carried out with Dr Mirjana Bozic, then based at the Medical Research Council (MRC) Cognition and Brain Sciences Unit in Cambridge, we have been able to delineate these systems in the undamaged brain, using functional neuroimaging to tease out the different processing regions that are engaged by speech inputs with different properties.

Listeners hear either words that are specifically linguistically complex (words like played, which have the grammatical inflection ‘ed’), or words that make more general demands on the language processing system (words like ramp, which have another word, ram, embedded in them). Using an analysis technique that identifies the separate dimensions of the brain’s response to these sets of words, we see that the linguistically complex words activate a response component that is restricted to the left fronto-temporal region. By contrast, words that are perceptually complex, due to increased competition between the whole word and the embedded word, activate a strongly bi-hemispheric set of regions, partially overlapping with the linguistic component. Even in the intact brain, therefore, we can see the dynamic allocation of processing resources across the two systems, as a function of their joint roles in the communicative process.

Implications

A dual systems account of the ‘communicative brain’ is likely to have important and illuminating consequences for the sciences of language and its disorders.

In the context of left hemisphere brain damage we can better appreciate – and build upon for rehabilitation – the substantial bi-hemispheric communicative capacities the patient may still possess. In first- and second-language acquisition, we can better understand the learning trajectories that lead to language proficiency in terms of the relative contributions of these two aspects of communicative function.

̽��ֱ��approach also provides a new perspective on the variation between languages, where different languages may load more or less heavily on the different computational resources made available by the two systems. Most importantly, it enables us to clarify and focus the core issues for a neurobiological account of language and communication, a scientific domain clouded by ideology and inconsistency.

What is it about the human brain that makes language possible? Two evolutionary systems working together, say neuroscientists Professor William Marslen-Wilson and Professor Lorraine Tyler.

William Marslen-Wilson and Lorraine Tyler

Functional neuroimaging of the human brain

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