̽��ֱ�� of Cambridge - Medical Research Council Cognition and Brain Sciences Unit

Study suggests new treatment for impulsivity in some dementia patients

cjb250 — Thu, 25 Jun 2015 08:10:21 +0000

Around 16,000 people in the UK are estimated to be affected by frontotemporal dementia (also known as Pick’s disease). Patients are often affected at a young age, 50-65 years old. ̽��ֱ��disease affects the frontal and temporal lobes of the brain, at the front with both shrinkage and loss of important brain chemicals like serotonin. As a result, symptoms of frontotemporal dementia include changes in personality and behaviour, and difficulties with language.

One of the key symptoms is disinhibition – impulsivity and impetuous behaviour. This is partly a result of a deficiency in serotonin, an important chemical within the brain which is responsible for maintaining normal behaviour as well as mood.

A team led by Dr James Rowe from the ̽��ֱ�� of Cambridge and the Medical Research Council (MRC) Cognition and Brain Sciences Unit at Cambridge looked at whether citalopram, a commonly-prescribed antidepressant, might restore the brain function – and potentially alleviate the symptoms of disinhibition. Citalopram is known to restore levels of serotonin, even in patients who do not have depression; this increase in serotonin helps the brain activity needed make decisions about what to do, and what not to do.

̽��ֱ��researchers examined the brain activity associated with disinhibition in patients and healthy volunteers. ̽��ֱ��patients received either a dose of citalopram or a placebo, in a double-blinded placebo-controlled trial. Participants took part in a ‘Go-NoGo’ task whilst their brain activity was monitored using a combination of magnetoencephalography (MEG) and electroencephalography (EEG). In the task, the volunteers needed to intermittently hold back from a habitual action, choosing to press or not to press buttons.

As expected, patients with frontotemporal dementia made many errors on the task, with difficulty holding back from actions. ̽��ֱ��performance on the task was closely related to their everyday impulsive and disinhibited behaviours. Compared to the placebo, citalopram boosted activity in the dementia patients in their right inferior frontal gyrus, a critical region of the brain for controlling our behaviour, even though this part of the brain was shrunken by the disease.

Dr Laura Hughes from the ̽��ֱ�� of Cambridge and the MRC Cognition and Brain Sciences Unit, first author on the study, says: “This is a very promising result, which builds on a lot of basic laboratory science here in Cambridge. It suggests that it may be possible to treat patients safely and effectively for high risk and challenging impulsive behaviours, although more work is needed to identify those who are most likely to benefit from this type of drug.”

̽��ֱ��research was primarily funded by the Wellcome Trust with additional support from the Medical Research Council and the NIHR Cambridge Biomedical Research Centre.

Reference
Hughes, LE et al. Improving response inhibition systems in frontotemporal dementia with citalopram. Brain; e-pub 22 May 2015

Restoring the low levels of the chemical serotonin may help improve brain function and reduce impulsivity in some dementia patients, according to Cambridge researchers. A study published in the July edition of the journal Brain suggests a potential new treatment for people affected by frontotemporal dementia.

This is a very promising result, which suggests that it may be possible to treat patients safely and effectively for high risk and challenging impulsive behaviours

Laura Hughes

NOAA's National Ocean Service

Brain coral

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Out of mind, out of sight: suppressing unwanted memories reduces their unconscious influence on behaviour

jfp40 — Tue, 18 Mar 2014 12:09:10 +0000

̽��ֱ��study, part-funded by the Medical Research Council (MRC) and published online in PNAS, challenges the idea that suppressed memories remain fully preserved in the brain’s unconscious, allowing them to be inadvertently expressed in someone’s behaviour. ̽��ֱ��results of the study suggest instead that the act of suppressing intrusive memories helps to disrupt traces of the memories in the parts of the brain responsible for sensory processing.

̽��ֱ��team at the MRC Cognition and Brain Sciences Unit and the ̽��ֱ�� of Cambridge’s Behavioural and Clinical Neuroscience Institute (BCNI) have examined how suppression affects a memory’s unconscious influences in an experiment that focused on suppression of visual memories, as intrusive unwanted memories are often visual in nature.

After a trauma, most people report intrusive memories or images, and people will often try to push these intrusions from their mind, as a way to cope. Importantly, the frequency of intrusive memories decreases over time for most people. It is critical to understand how the healthy brain reduces these intrusions and prevents unwanted images from entering consciousness, so that researchers can better understand how these mechanisms may go awry in conditions such as post-traumatic stress disorder.

Participants were asked to learn a set of word-picture pairs so that, when presented with the word as a reminder, an image of the object would spring to mind. After learning these pairs, brain activity was recorded using functional magnetic resonance imaging (fMRI) while participants either thought of the object image when given its reminder word, or instead tried to stop the memory of the picture from entering their mind.

̽��ֱ��researchers studied whether suppressing visual memories had altered people’s ability to see the content of those memories when they re-encountered it again in their visual worlds. Without asking participants to consciously remember, they simply asked people to identify very briefly displayed objects that were made difficult to see by visual distortion. In general, under these conditions, people are better at identifying objects they have seen recently, even if they do not remember seeing the object before—an unconscious influence of memory. Strikingly, they found that suppressing visual memories made it harder for people to later see the suppressed object compared to other recently seen objects.

Brain imaging showed that people’s difficulty seeing the suppressed object arose because suppressing the memory from conscious awareness in the earlier memory suppression phase had inhibited activity in visual areas of the brain, disrupting visual memories that usually help people to see better. In essence, suppressing something from the mind’s eye had made it harder to see in the world, because visual memories and seeing rely on the same brain areas: out of mind, out of sight.

Over the last decade, research has shown that suppressing unwanted memories reduces people’s ability to consciously remember the experiences. ̽��ֱ��researchers’ studies on memory suppression have been inspired, in part, by trying to understand how people adapt memory after psychological trauma. Although this may work as a coping mechanism to help people adapt to the trauma, there is the possibility that if the memory traces were able to exert an influence on unconscious behaviour, they could potentially exacerbate mental health problems. ̽��ֱ��idea that suppression leaves unconscious memories that undermine mental health has been influential for over a century, beginning with Sigmund Freud.

These findings challenge the assumption that, even when supressed, a memory remains fully intact, which can then be expressed unconsciously. Moreover, this discovery pinpoints the neurobiological mechanisms underlying how this suppression process happens, and could inform further research on uncontrolled ‘intrusive memories’, a classic characteristic of post-traumatic stress disorder.

Dr Michael Anderson, at the MRC Cognition and Brain Sciences Unit said: “While there has been a lot of research looking at how suppression affects conscious memory, few studies have examined the influence this process might have on unconscious expressions of memory in behaviour and thought. Surprisingly, the effects of suppression are not limited to conscious memory. Indeed, it is now clear, that the influence of suppression extends beyond areas of the brain associated with conscious memory, affecting perceptual traces that can influence us unconsciously. This may contribute to making unwanted visual memories less intrusive over time, and perhaps less vivid and detailed.”

Dr Pierre Gagnepain, lead author at INSERM in France said: “Our memories can be slippery and hard to pin down. Out of hand and uncontrolled, their remembrance can haunt us and cause psychological troubles, as we see in PTSD. We were interested whether the brain can genuinely suppress memories in healthy participants, even at the most unconscious level, and how it might achieve this. ̽��ֱ��answer is that it can, though not all people were equally good at this. ̽��ֱ��better understanding of the neural mechanisms underlying this process arising from this study may help to better explain differences in how well people adapt to intrusive memories after a trauma”

New research shows that, contrary to what was previously assumed, suppressing unwanted memories reduces their influence on behaviour, and sheds light on how this process happens in the brain.

It is now clear that the influence of suppression extends beyond areas of the brain associated with conscious memory. This may contribute to making unwanted visual memories less intrusive over time, and perhaps less vivid and detailed.

Dr Michael Anderson

QThomas Bower

Self Portrait 6

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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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Noises off: the machine that rubs out noise

lw355 — Wed, 02 Oct 2013 16:20:50 +0000

A noisy restaurant, a busy road, a windy day – all situations that can be intensely frustrating for the hearing impaired when trying to pick out speech in a noisy environment. Some 10 million people in the UK suffer from hearing difficulties and, as helpful as hearing aids are, those who wear them often complain that background noise continues to be a problem.

What if hearing device wearers could choose to filter out all the troublesome sounds and focus on the voices they want to hear? Engineer Dr Richard Turner believes that this is fast becoming a possibility. He is developing a system that identifies the corrupting noise and “rubs it out”.

“ ̽��ֱ��poor performance of current hearing devices in noise is a major reason why six million people in the UK who would benefit from a hearing aid do not use them,” he said. Moreover, as the population ages, a greater number of people will be hindered by the inability to hear clearly. In addition, patients fitted with cochlear implants – devices implanted into the brain to help those whose auditory hair cells have died – suffer from similar limitations.

̽��ֱ��solution lies in the statistics of sound, as Turner explained: “Many interfering noises are immediately recognisable. Raindrops patter on a surface, a fire crackles, talkers babble at a party and the wind howls. But what makes these so-called auditory textures sound the way they do? No two rain sounds are identical because the precise arrangement of falling water droplets is never repeated. Nonetheless, there must be a statistical similarity in the sounds compared with say the crackle of a fire.

“For this reason, we think the brain groups together different aspects of sounds using prior experience of their characteristic statistical structure. We can model this mathematically using a form of statistical reasoning called Bayesian inference and then develop computer algorithms that mimic what the brain is doing.”

̽��ֱ��mathematical system that he and colleagues have developed is capable of being “trained” – a process that uses new methods from the field of machine learning – so that it can recognise sounds. “Rather surprisingly, it seems that a relatively small set of statistics is sufficient to describe a large number of sounds.”

Crucially, the system is capable of telling the difference between speech and audio textures. “What we can now do in an adaptive way is to remove background noise and pass these cleaned up sounds to a listener to improve their perception in a difficult environment,” said Turner, who is working with hearing experts Professor Brian Moore at the Department of Experimental Psychology and Dr Robert Carlyon at the Medical Research Council Cognition and Brain Sciences Unit, with funding from the Engineering and Physical Sciences Research Council.

̽��ֱ��idea is that future devices will have several different modes in which they can operate. These might include a mode for travelling in a car or on a train, a mode for environments like a party or a noisy restaurant, a mode for outdoor environments that are windy, and so on. ̽��ֱ��device might intelligently select an appropriate mode based on the characteristics of the incoming sound. Alternatively, the user could override this and select a processing mode based upon what sorts of noise they wish to erase.

“In a sense we are developing the technology to underpin intelligent hearing devices,” he added. “One possibility would be for users to control their device using an interface on a mobile phone through wireless communication. This would allow users to guide the processing as they wish.”

Turner anticipates a further two years of simulating the effect of modifications that clean up sound before they start to work with device specialists. “If these preliminary tests go well, then we’ll be looking to work with hearing device companies to try to adapt their processing to incorporate these machine learning techniques. If all goes well, we would hope that this technology will be available in consumer devices within 10 years.”

Tinnitus sufferers could also benefit from the technology. Plagued by a constant ringing in the ears, people with tinnitus sometimes use environmental sound generators as a distraction. Such generators offer a limited selection of sounds – a babbling brook, waves lapping, leaves rustling – but, with the new technology, “patients could traverse the entire space of audio textures and figure out where in this enormous spectrum is the best sound for relieving their tinnitus,” added Turner.

̽��ֱ��technology not only holds promise for helping the hearing impaired, but it also has the potential to improve mobile phone communication – anyone who has ever tried to hold a conversation with someone phoning from a crowded room will recognise the possible benefits of such a facility.

Moreover, with 100 hours of video now being uploaded to YouTube every minute, Google has recognised the potential for systems that can recognise audio content and is funding part of Turner’s research. “As an example, a YouTube video containing a conversation that takes place by a busyroadside on a windy day could be automatically categorised based on the speech, traffic and wind noises present in the soundtrack, allowing users to search videos for these categories. In addition, the soundtrack could also be made more intelligible by isolating the speech from the noises – one can imagine users being offered the chance to de-noise their video during the upload process.

“We think this new framework will form a foundation of the emerging field of ‘machine hearing’. In the future, machine hearing will be standard in a vast range of applications from hearing devices, which is a market worth £18 billion per annum, to audio searching, and from music processing tasks to augmented reality systems. We believe this research project will kick-start this proliferation.”

For more information, please contact Louise Walsh (lw355@admin.cam.ac.uk).

Inset image: Dr Richard Turner

Future hearing aids could be adjusted by the wearer to remove background noise using new technology that could also be used to clean up and search YouTube videos.

We are developing the technology to underpin intelligent hearing devices

Richard Turner

̽��ֱ��Machine that Rubs Out Noise

̽��ֱ��District

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