bna2013

How ‘free will’ is implemented in the brain and is it possible to intervene in the process?

Researchers have been able to identify the precise moment when a network of nerve cells (neurons) in the brain creates the signal to perform an action, before a person is even aware of deciding to take that action. Now they are building on this work to make initial attempts to interfere with consciously made decisions by decoding the pattern of brain activity in real time before an action is taken.

Professor Gabriel Kreiman will tell the British Neuroscience Association Festival of Neuroscience (BNA2013) today (Tuesday): “This could be useful to help elucidate the mechanistic basis by which neuronal circuits orchestrate ‘free’ will.”

Normally it is difficult to research the activity of neurons in the brain because it involves implanting electrodes – an invasive procedure that would not be ethical to do simply for scientific curiosity alone. However, Prof Kreiman, who is an associate professor at the Harvard Medical School, Boston, USA, together with neurosurgeon Itzhak Fried from University of California at Los Angeles (UCLA), had a rare opportunity to record the activity of over 1,000 neurons in two areas of the brain, the frontal and temporal lobes, when patients with epilepsy had had electrodes implanted to try to identify the source of their seizures.

“These patients have epilepsy that does not respond to drug treatment; Itzhak Fried implanted their brains with very thin electrodes (microwires) of about 40 micrometres in diameter in order to localise the focus of a seizure onset for a potential surgical procedure to alleviate the seizures. The microwires capture the extracellular electrical activity of neurons. Patients stay in the hospital for about a week. During this time, we have a unique opportunity to interrogate the activity of neurons and neural ensembles in the human brain at high spatial and temporal resolution,” explains Prof Kreiman.

The researchers asked the patients to move their index finger to click a computer mouse and to report when they made that decision. “Based on the activity of small groups of neurons, we could predict this decision several hundreds of milliseconds and, in some cases, seconds before the action. In a variant of the main experiment, the patients were allowed to choose whether to use their left hand or right hand and we showed that we could also predict this decision.”

The researchers found that an increasing number of neurons in two specific brain regions started to become active before the person was aware of their decision to move their finger. The two regions were the supplementary motor area, which is thought to be the area for preparing to perform motor actions, and the anterior cingulate cortex, which has a number of roles including the signalling processes associated with reward.

Prof Kreiman believes that these results provide initial steps to elucidate the mechanism for the emergence of conscious will in humans. “The activity of multiple neurons in extremely simple neural circuits precedes volition – in this case the decision to make a simple movement – until a threshold is crossed and the action is taken,” he will say.

Knowing when this threshold will be reached could enable researchers to see whether it is possible to interfere and maybe change the decision before any action is taken. “We are now making initial attempts to interfere with volition by decoding the neural responses in real time and asking whether there is a ‘point of no return’ in the hierarchical chain of command from unconscious decisions to volition to action,” says Prof Kreiman.

How these findings fit into the concept of “free will” is more complicated. “The concept of free will has been debated for millennia. Ultimately, current scientific understanding strongly suggests that ‘will’ has to be orchestrated by neurons in our brains (as opposed to magic or religious beliefs or other notions). We have provided initial steps to try to disentangle which neurons are involved, to show where and how ‘will’ or ‘volition’ could be implemented in the brain.

“Our work does not say that life is predetermined, that we can predict the future and that we can, for instance, determine what you are going to eat for lunch two weeks from now, or who you are going to marry.

“We are saying that volition (like other aspects of consciousness) is a brain phenomenon that is instantiated by physical hardware, i.e. neurons.  We are making claims about volition for very simple tasks, such as moving an index finger or choosing which hand to use, over scales of hundreds of milliseconds to seconds. Nothing more. Nothing less.

“Ultimately, our actions depend on multiple variables, several of which are external (for instance, it rains, hence, I will take my umbrella) and cannot be decoded or predicted from neurons. However, our volitional decision of whether to take the red umbrella or the blue one today – ultimately perhaps the real core of free will – is dictated by neurons,” Prof Kreiman will conclude.

I Never Knew You Were Such a Monster Shortlisted for the 2013 Blog North Awards!

Somehow this here little blog has been shortlisted (for the second year in a row, whutt?!!) for a prize in the category of Best Writing On a Blog at the 2013 Blog North Awards! 

I share some fabulous company with some terrific bloggers, thinkers, activists and writers who’ve also been shortlisted (check out the full list here!: http://www.blognorthawards.com/2013-shortlist) and am delighted to announce that I’ll also be performing one of my wretched tales at the ceremony once again this year.

The show is taking place on Wednesday 16th October at Gorilla, Manchester. If you see me, give me some charitable wine and a high five. Hopefully I’ll be wearing a victory tiara fashioned out of tin foil. 

http://www.blognorthawards.com/the-event

Foetal exposure to excessive stress hormones in the womb linked to adult mood disorders

Exposure of the developing foetus to excessive levels of stress hormones in the womb can cause mood disorders in later life and now, for the first time, researchers have found a mechanism that may underpin this process, according to research presented today (Sunday) at the British Neuroscience Association Festival of Neuroscience (BNA2013) in London.

The concept of foetal programming of adult disease, whereby the environment experienced in the womb can have profound long-lasting consequences on health and risk of disease in later life, is well known; however, the process that drives this is unclear. Professor Megan Holmes, a neuroendocrinologist from the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science in Scotland (UK), will say: “During our research we have identified the enzyme 11ß-HSD2 which we believe plays a key role in the process of foetal programming.”

Adverse environments experienced while in the womb, such as in cases of stress, bereavement or abuse, will increase levels of glucocorticoids in the mother, which may harm the growing baby. Glucocorticoids are naturally produced hormones and they are also known as stress hormones because of their role in the stress response.

“The stress hormone cortisol may be a key factor in programming the foetus, baby or child to be at risk of disease in later life. Cortisol causes reduced growth and modifies the timing of tissue development as well as having long lasting effects on gene expression,” she will say.

Prof Holmes will describe how her research has identified an enzyme called 11ß-HSD2 (11beta-hydroxysteroid dehydrogenase type 2) that breaks down the stress hormone cortisol to an inactive form, before it can cause any harm to the developing foetus. The enzyme 11ß-HSD2 is present in the placenta and the developing foetal brain where it is thought to act as a shield to protect against the harmful actions of cortisol.

Prof Holmes and her colleagues developed genetically modified mice that lacked 11ß-HSD2 in order to determine the role of the enzyme in the placenta and foetal brain. “In mice lacking the enzyme 11ß-HSD2, foetuses were exposed to high levels of stress hormones and, as a consequence, these mice exhibited reduced foetal growth and went on to show programmed mood disorders in later life. We also found that the placentas from these mice were smaller and did not transport nutrients efficiently across to the developing foetus. This too could contribute to the harmful consequences of increased stress hormone exposure on the foetus and suggests that the placental 11ß-HSD2 shield is the most important barrier.

“However, preliminary new data show that with the loss of the 11ß-HSD2 protective barrier solely in the brain, programming of the developing foetus still occurs, and, therefore, this raises questions about how dominant a role is played by the placental 11ß-HSD2 barrier. This research is currently ongoing and we cannot draw any firm conclusions yet.

“Determining the exact molecular and cellular mechanisms that drive foetal programming will help us identify potential therapeutic targets that can be used to reverse the deleterious consequences on mood disorders. In the future, we hope to explore the potential of these targets in studies in humans,” she will say.

Prof Holmes hopes that her research will make healthcare workers more aware of the fact that children exposed to an adverse environment, be it abuse, malnutrition, or bereavement, are at an increased risk of mood disorders in later life and the children should be carefully monitored and supported to prevent this from happening.

In addition, the potential effects of excessive levels of stress hormones on the developing foetus are also of relevance to individuals involved in antenatal care. Within the past 20 years, the majority of women at risk of premature delivery have been given synthetic glucocorticoids to accelerate foetal lung development to allow the premature babies to survive early birth.

“While this glucocorticoid treatment is essential, the dose, number of treatments and the drug used, have to be carefully monitored to ensure that the minimum effective therapy is used, as it may set the stage for effects later in the child’s life,” Prof Holmes will say.

Puberty is another sensitive time of development and stress experienced at this time can also be involved in programming adult mood disorders. Prof Holmes and her colleagues have found evidence from imaging studies in rats that stress in early teenage years could affect mood and emotional behaviour via changes in the brain’s neural networks associated with emotional processing.

The researchers used fMRI (Functional Magnetic Resonance Imaging) to see which pathways in the brain were affected when stressed, peripubertal rats responded to a specific learned task.

Prof Holmes will say: “We showed that in stressed ‘teenage’ rats, the part of the brain region involved in emotion and fear (known as amygdala) was activated in an exaggerated fashion when compared to controls. The results from this study clearly showed that altered emotional processing occurs in the amygdala in response to stress during this crucial period of development.”

(Image: iStockphoto)

New research shows how our bodies interact with our minds in response to fear and other emotions

New research has shown that the way our minds react to and process emotions such as fear can vary according to what is happening in other parts of our bodies.

In two different presentations today (Monday) at the British Neuroscience Association Festival of Neuroscience (BNA2013) in London, researchers have shown for the first time that the heart’s cycle affects the way we process fear, and that a part of the brain that responds to stimuli, such as touch, felt by other parts of the body also plays a role.

Dr Sarah Garfinkel, a postdoctoral fellow at the Brighton and Sussex Medical School (Brighton, UK), told a news briefing: “Cognitive neuroscience strives to understand how biological processes interact to create and influence the conscious mind. While neural activity in the brain is typically the focus of research, there is a growing appreciation that other bodily organs interact with brain function to shape and influence our perceptions, cognitions and emotions.

“We demonstrate for the first time that the way in which we process fear is different dependent on when we see fearful images in relation to our heart.”

Dr Garfinkel and her colleagues hooked up 20 healthy volunteers to heart monitors, which were linked to computers. Images of fearful faces were shown on the computers and the electrocardiography (ECG) monitors were able to communicate with the computers in order to time the presentation of the faces with specific points in the heart’s cycle.

“Our results show that if we see a fearful face during systole (when the heart is pumping) then we judge this fearful face as more intense than if we see the very same fearful face during diastole (when the heart is relaxed). To look at neural activity underlying this effect, we performed this experiment in an MRI [magnetic resonance imaging] scanner and demonstrated that a part of the brain called the amygdala influences how our heart changes our perception of fear.

“From previous research, we know that if we present images very fast then we have trouble detecting them, but if an image is particularly emotional then it can ‘pop’ out and be seen. In a second experiment, we exploited our cardiac effect on emotion to show that our conscious experience is affected by our heart. We demonstrated that fearful faces are better detected at systole (when they are perceived as more fearful), relative to diastole. Thus our hearts can also affect what we see and what we don’t see – and can guide whether we see fear.

“Lastly, we have demonstrated that the degree to which our hearts can change the way we see and process fear is influenced by how anxious we are. The anxiety level of our individual subjects altered the extent their hearts could change the way they perceived emotional faces and also altered neural circuitry underlying heart modulation of emotion.”

Dr Garfinkel says that her findings might have the potential to help people who suffer from anxiety or other conditions such as post traumatic stress disorder (PTSD).

“We have identified an important mechanism by which the heart and brain ‘speak’ to each other to change our emotions and reduce fear. We hope to explore the therapeutic implications in people with high anxiety. Anxiety disorders can be debilitating and are very prevalent in the UK and elsewhere. We hope that by increasing our understanding about how fear is processed and ways that it could be reduced, we may be able to develop more successful treatments for these people, and also for those, such as war veterans, who may be suffering from PTSD.

“In addition, there is a growing appreciation about how different forms of meditation can have therapeutic consequences. Work that integrates body, brain and mind to understand changes in emotion can help us understand how meditation and mindfulness practices can have calming effects.“

In a second presentation, Dr Alejandra Sel, a postdoctoral researcher in the Department of Psychology at City University (London, UK), investigated a part of the brain called the somatosensory cortex – the area that perceives bodily sensations, such as touch, pain, body temperature and the perception of the body’s place in space, and which is activated when we observe emotional expressions in the faces of other people.

“In order to understand other’s people emotions we need to experience the same observed emotions in our body. Specifically, observing an emotional face, as opposed to a neutral face, is associated with an increased activity in the somatosensory cortex as if we were expressing and experiencing our own emotions. It is also known that people with damage to the somatosensory cortex find it difficult to recognise emotion in other people’s faces,” Dr Sel told the news briefing.

However, until now, it has not been clear whether activity in the somatosensory cortex was simply a by-product of the way we process visual information, or whether it reacts independently to emotions expressed in other people’s faces, actively contributing to how we perceive emotions in others.

In order to discover whether the somatosensory cortex contributes to the processing of emotion independently of any visual processes, Dr Sel and her colleagues tested two situations on volunteers. Using electroencephalography (EEG) to measure the brain response to images, they showed participants either a face showing fear (emotional) or a neutral face. Secondly, they combined the showing of the face with a small tap to an index finger or the left cheek immediately afterwards.

Dr Sel said: “By tapping someone’s cheek or finger you can modify the ‘resting state’ of the somatosensory cortex inducing changes in brain electrical activity in this area. These changes are measureable and observable with EEG and this enables us to pinpoint the brain activity that is specifically related to the somatosensory cortex and its reaction to external stimuli.

“If the ‘resting state’ of the somatosensory cortex when a fearful face is shown has greater electrical activity than when a neutral face is shown, the changes in the activity of the somatosensory cortex induced by the taps and measured by EEG also will be greater when observing fearful as opposed to neutral faces.

“We subtracted results of the first situation (face only) from the second situation (face and tap), and compared changes in the activity related with the tap in the somatosensory cortex when seeing emotional faces versus neutral faces. This way, we could observe responses of the somatosensory cortex to emotional faces independently of visual processes,” she explained.

The researchers found that there was enhanced activity in the somatosensory cortex in response to fearful faces in comparison to neutral faces, independent of any visual processes. Importantly, this activity was focused in the primary and secondary somatosensory areas; the primary area receives sensory information directly from the body, while the secondary area combines sensory information from the body with information related to body movement and other information, such as memories of previous, sensitive experiences.

“Our experimental approach allows us to isolate and show for the first time (as far as we are aware) changes in somatosensory activity when seeing emotional faces after taking away all visual information in the brain. We have shown the crucial role of the somatosensory cortex in the way our minds and bodies perceive human emotions. These findings can serve as starting point for developing interventions tailored for people with problems in recognising other’s emotions, such as autistic children,” said Dr Sel.

The researchers now plan to investigate whether they get similar results when people are shown faces with other expressions such as happy or angry, and whether the timing of the physical stimulus, the tap to the finger or cheek, makes any difference. In this experiment, the tap occurred 105 milliseconds after a face was shown, and Dr Sel wonders about the effect of a longer time interval.

(Image: Shutterstock)

Legal high Benzo Fury may be dangerous due to stimulant and hallucinogenic effects

The ‘legal high’ known as Benzo Fury may have stimulant as well as hallucinogenic effects according to new research presented at the British Neuroscience Association Festival of Neuroscience today (Tuesday 9 April 2013).

In a poster presentation at the meeting, Dr Jolanta Opacka-Juffry and Dr Colin Davidson reported that one of the main ingredients of Benzo Fury (also known as 5-APB) acts on brain tissue like both a stimulant and a hallucinogen – a combination of properties that is often found in illegal drugs and which can make them dangerous to users. The researchers believe this information should be disseminated to let potential users know the possible dangers of the drug.

Dr Opacka-Juffry, who is a principal lecturer in neuroscience and director of the health sciences research centre at the University of Roehampton, and Dr Davidson, senior lecturer in neuropharmacology and expert in drugs of addiction at St George’s, University of London, studied the effect of 5-APB samples from the brains of rats. In particular, they looked at the effect it had on serotonin receptors, which are affected by hallucinogenic drugs, and on a protein called the dopamine transporter (DAT), which pumps a neurotransmitter, dopamine, back in to nerve cells, terminating its activity, and which is involved in addiction. They compared the effects of 5-APB with those caused by cocaine and amphetamine.

“We have found that 5-APB behaves a little like amphetamine – that is, like a stimulant with addictive potential – and a bit like a hallucinogen, acting via serotonin receptors. This kind of mixed properties can be found in some illegal ‘designer’ drugs,” the presenting author, Dr Opacka-Juffry said.

“This finding is significant because it demonstrates that some ‘legal highs’ may have addictive properties, which are unlikely to be well-known amongst the users of these drugs. In addition, its effects on the serotonin receptors – known as 5-HT2A receptors – would suggest that it may lead to high blood pressure by causing constriction of the blood vessels, which would make the drug more dangerous. It is possible that the reason these drugs are so popular is because they are seen as safer than their illegal counterparts. It is important to challenge these assumptions.”

The researchers also found that 5-APB caused “reverse transport of dopamine”.

Dr Davidson said: “In theory, drugs which cause reverse transport could cause damage to the dopamine nerve cells. Other drugs such as amphetamines can also cause reverse transport, where dopamine is displaced from the nerve rather than mopped up by the dopamine transporter.“

Dr Opacka-Juffry said: “It is in the combination of these stimulant and hallucinogenic properties that the greatest danger lies. Pure hallucinogens are not addictive as such because they do not cause an increase in dopamine release, unlike amphetamine or cocaine. They are attractive to many people who enjoy the ‘mind altering’ properties of hallucinogens. But Benzo Fury with its mixed properties is a trap as its repetitive use for the hallucinogenic effects could lead to dependence, which the user may not expect.”

Further work needs to be carried out to find out more. “Rat data are quite informative as the brain addiction pathway is similar in rodents and humans. Long-term effects should be tested in rodents to investigate the potential toxic effects on the nervous system and the cardiovascular system, in addition to its liability for abuse due to addiction. We also need to collate data from human users. Taken together we can determine how dangerous this drug is,” she said.

Benzo Fury is currently one of the most popular legal highs in the UK and is also sold in the USA. It appears to be fairly easy to buy via the internet, at music festivals and clubs, and its street price is around £10 a pill or £25 for three. “However, tragedies such as the death of 19-year-old Alex Heriot at a music festival in June 2012 after taking Benzo Fury demonstrate the importance of making as much information available as possible about the potential adverse effects of these ‘highs’ as quickly as possible,” said Dr Opacka-Juffry.

Drs Opacka-Juffry and Davidson report that the approach they used to study Benzo Fury could be applied to other drugs as well, so that as new legal high drugs emerge, they can be tested quickly against the “gold standard” drugs such as cocaine and amphetamines to establish their relative danger.

Dr Davidson said: ”Over the last few years 40 or more new legal highs have appeared each year. Given the speed with which legal highs are developed and reach the market, it is important to be able to respond quickly to assess their potential dangers, and disseminate this information accordingly.”