Category Archives: Brain and Behaviour

What is cognitive neuroscience, and why should anyone care?

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I often have trouble explaining to people what I am doing for my PhD. This is not a consequence of the topic being so fiendishly complex that no-one else can understand it. Instead it comes from a fact that the area of study seems to fall between several difference subject areas. When I tell people that I am doing my PhD within the Neuroscience department I imagine this provokes images of test-tubes, microscopes and pipettes, and perhaps associations with genetics, animal testing and stem cells. In reality I have little knowledge or experience of any of these topics, having last done ‘traditional’ lab work while I was at secondary school. If you asked me to dissect something, I would probably run a mile! When I instead say that I work within the psychiatry department this probably brings up an altogether different set of images, of drug therapies, ECT and perhaps of ‘talking therapies’ such as CBT (cognitive behavioural therapy). In fact both the above statements regarding my PhD are true, as the Psychiatry department sits within the Neuroscience department, but neither appear to give an accurate impression of what I actually do.

The best description of my area of research is ‘cognitive neuroscience’, but what does this mean? Cognitive Neuroscience relates to the study of the neural basis of behaviour. Roughly, it bridges the gap between biological sciences, and behavioural sciences such as psychology and psychiatry. It attempts to determine how the brain achieves the legion of processes that it performs – crudely ‘what part of the brain does what’! Cognitive neuroscience has only been seen as a separate area of study relatively recently, partly because the advanced brain imaging techniques which the discipline now heavily relies on have only been developed within the last 30 years (according to Wikipedia the term ‘cognitive neuroscience’ itself was coined in the back of a taxi in 1979!!). However scientists from various disciplines have been trying to understand how the brain functions, using whatever methods were available, since at least the 19th century.

Cognitive Neuroscience relies heavily on work done within behavioural sciences, which have served to define how human behaviour and cognition can be classified into concepts that can be studied. Unsurprisingly therefore, cognitive neuroscience research normally involves the application of a behavioural task which has already been utilised without the use of brain imaging techniques. One question this raises is what does knowing how the brain achieves it function tell us that purely behavioural science does not?  Psychologists have been ably investigating the details of mental processes for well over a century without knowing (or even caring) what part(s) of the brain are involved. The knowledge that spatial processing is largely dependent on the Hippocampus is not necessary for studying the intricacies and individual differences in spatial processing. So what does an understanding of the neural basis of mental processes achieve?

Firstly understanding the neural basis of a mental process can help distinguish between different theories relating to how that process is performed. Behavioural data is often not sufficient to distinguish between competing theories (e.g. whether a particular process is performed in totality, or whether it is split into components processes that are dealt with separately, and whether such component processes are performed in parallel or in series). Neuroimaging data can be used to provide strong evidence in relation to these questions (1).  Secondly cognitive neuroscience can provide insight into areas of cognition that were difficult or impossible to address without neuroimaging techniques. For example much work has been done on trying to understand what the brain does ‘at rest’ (i.e. when no task is being performed, effectively ‘mind wandering’) which can allow us to understand how the brain might work as an self-contained integrative mechanism. As, by definition, non-task related mental processes can’t be manipulated systematically, it is hard to investigate these processes from a purely behavioural standpoint. Similarly neuroimaging has enabled scientists to begin to uncover the neural basis of ‘consciousness’, raising interesting questions about how our experience of the world is constructed (3). These achievements of cognitive neuroscience help elucidate the nature of human thought and behaviour, shedding light on why we act the way that we do. 

On a larger scale, understanding how the brain is able to processes such a large variety of information, and produce such a wide variety of responses, can help guide the design of artificial intelligence systems intended to mimic human abilities, facilitating advances in medicine and engineering. Finally, and perhaps most importantly, knowing how the brain produces certain responses can lead to the development of interventions to alter the functioning of the appropriate brain areas when those responses become problematic (e.g. during mental health disorders). One of the major aims of cognitive neuroscience is to identify the neural deficiencies that mark various psychiatry and neurodegenerative disorders. From this information it becomes potentially possible to identify methods of combating such deficiencies. Indeed biological interventions are being developed that can target specific brain areas, potentially offering great hope for improving the therapeutic treatment of mental disorders.  

References

(1) Jonides et al (2006). What has Functional Neuroimaging told us about the Mind? So many examples, so little space. Cortex, 42, 414-417 http://www-personal.umich.edu/~jjonides/pdf/2006_3.pdf

(2) Van den Heuval & Pol (2010) Exploring the brain network: A review on resting-state fMRI functional connectivity. European Neuropsychopharmacology, 20(8), 519-534 http://www.sciencedirect.com/science/article/pii/S0924977X10000684

(3) Dehaene & Changeux (2011) Experimental and Theoretical Approaches to Conscious Processing. Neuron, 70. 200-225 http://www.sciencedirect.com/science/article/pii/S0896627311002583

Neurological disorders and science funding: a plea.

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Being a lowly PhD student and thus spending most of my work-time focusing on a very narrow research programme, I actually know embarrassingly little about the wider field in which my work sits.  This is something that to some extent, I accept as inevitable for now, though it is something I very much hope will change over time as I get more chances to meet and talk with people from different areas of research, and maybe in the future be involved with multiple research projects.
At the moment, I have something particular in mind and that is the broad and complex area of neurological disorders and neurodegenerative disease.  Wikipedia returns a terrifyingly long list of these.  Of course, many people are familiar with some of these afflictions and their effects, such as Alzheimer’s disease.  Then there are those which many people have heard of, but common misconceptions abound as to their symptoms and progression, such as schizophrenia, which, contrary to popular belief, is neither classified by nor typically includes ‘multiple personalities.’   
But far fewer people may be familar with Fatal Familial Insomnia, an extremely rare inherited disease in which sufferers literally lose the ability to sleep, along with experiencing hallucinations, panic attacks and dementia.  Death eventually follows, usually within three years of diagnosis, and there is currently no cure.
The problems resulting from neurological disease are however, broader than the direct symptoms the disease may cause.  In Williams’ syndrome, for example, a chromosomal disorder, sufferers show (amongst many other things) extreme sociability.  This is possibly due to the disorder’s effects on the amygdala, a subcortical brain structure important in regulating our fear response.  While this may at first not seem to be problematic, our wariness and mistrust of strangers is an important behavioural tool in helping to ensure our safety, and its disordered function – as in Williams’ syndrome – can put sufferers in real danger.
There is a good reason for my broaching this saddening subject, and that is the government.  With just days to go before the Tory-Lib Dem coalition unveil their plans for making £83billion worth of cuts, there is growing concern that science funding will be disproportionately hit.  Beyond my common sense, I cannot speak for other areas of science and why reducing their funding will be disastrous.  Nor am I going to claim to be an expert about the other effects of these cuts,  such as the oft-cited inevitable ‘brain drain’ that will ensue or the ultimate detriment to the economy that I believe science cuts will cause.
One thing I do know about, though, is a set of nuclei called the basal ganglia.  I’ve mentioned them before in this blog and the Inside TRAK blog.  They sit in the middle of the brain, beneath the cortex.  They’re common to all vertebrates, and while their functions are many and varied, our research group believes their primary role is that of ‘action selection’, or choosing what to do next. We think their other functions enhance or complement their ability to do this.  They rely heavily on a ‘neuromodulator’ called

dopamine.  This is often referred to in the press as a ‘pleasure chemical’ but the reality is that its roles, too, are many and varied, dependent on the brain region in question, and not entirely understood.  We do know, however, that it is required for the basal ganglia to do their job properly.  They are constantly ‘bathed’ in dopamine, which is synthesised in a region called the ‘substantia nigra’ or ‘black substance’, so called because is literally appears black in brain slices.
The degeneration of this area is Parkinson’s disease.  It causes the amount of dopamine supplied to the basal ganglia to diminish, and the effects are profound and debilitating.  An inability to initiate desired movement and tremor are the most commonly known symptoms, but sufferers can also experience depression, hallucinations, anxiety, dementia and obsessive-compulsive behaviours.  Now it just so happens that at least some symptoms of Parkinson’s disease can actually be managed rather well, at least for a few years.  Some interventions, such as Deep Brain Stimulation, can provide really quite radical improvements.  This is fantastic, but our understanding of exactly why this method works is far from complete.  If we can continue to research the mechanisms by which it affects the disease, it may be that this can be applied to far more disorders.  It has already been shown to improve chronic pain and even depression in some cases.
However, the picture is not always so clear.  The basal ganglia are also implicated in schizophrenia, obsessive-compulsive disorder, Tourette’s syndrome and many others.  The awful and incurable Huntington’s disease also primarily affects the basal ganglia.  Many of these conditions are not nearly so well understood, nor is their treatment always so effective.  Subsequently, quality of life for sufferers falls drastically; levels of depression and even suicide can be very high.  Our level of understanding about these afflictions, and our ability to prevent or treat them is hugely dependent on the money that is invested into their research. That research is vital if we are to continue making progress like this from the lab in which I work towards improving the treatment, prognosis and quality of life for sufferers, and the prevention of such disease in high-risk groups.  If we don’t research these diseases, we can’t understand them, and if we can’t understand them, we can’t help.  I think this is hugely important work, and I hope that you will agree with me.  If so, it’s not too late to do a little something about it. Please go to the Science Is Vital website, and sign the petition against cuts to science funding. If you can, email your MP about it, too, and ask them to sign EDM 767.  Please spread the word and help UK science continue its vital research.

Optogenetics in 1000 words or less

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Before the start of our department’s postgraduate research conference, I gave a 20 minute presentation on the methods of systems neuroscience. The idea was to try and provide a more general idea of what was involved in experimental neuroscience than could be squeezed into the beginning of the talk about my research. At the end of the presentation, I was asked which technique was my favourite. I’ve been trained in in vivo electrophysiology so that has become my weapon of choice; however, since first learning about optogenetics, I’ve fallen in love with the most sci-fi of neuroscience methods.

So, having missed the opportunity to wax lyrical about it then and inspired by Neuroskeptic’s fMRI in 1000 words, here is…

Optogenetics in 1000 words or less

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Great balls of fire! Lightning, hallucinations and brain control.

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This isn’t actually about brain control.  Not really, anyway.  If I really knew anything about brain control, I’d be out taking over the world, not writing blog posts (and mark my words, I’d be making Jake Gyllenhaal my number one minion.  Yum).    It’s really about a technique called Transcranial Magnetic Stimulation, how amazing it would be if speculations that it might happen in nature were true, and why I’m not 100% convinced that they are.

 

I read this article the other week in New Scientist.  It describes a (not so*) new idea suggesting that the elusive phenomenon of ball lightning may in fact be a hallucination brought on by transient powerful magnetic fields caused by (ordinary) lightning strikes.  The mechanism suggested to be behind this is the same one that is exploited by Transcranial Magnetic Stimulation (TMS), which I had the joy of playing with as part of my undergraduate research project.  The principles of TMS are fairly simple.

 

Firstly, it’s important to understand that neurons (brain cells) communicate chemically, not electrically**.  But the signal within individual neurons that generates this chemical communication is electrical.  The process of neurotransmission is an endlessly fascinating one, but one I’m not going to go into here, for reasons of brevity and because there is a pretty good summary on the ever marvellous wikipedia.  You’ll probably remember from your schooldays that if you pass an electric current through a coil of wire, a magnetic field is generated around that wire.  Placing a ‘conductor’ within that magnetic field causes electric current to flow in loops perpendicular to the magnetic field, and parallel to the coil itself.  If that conductor is a human head, that electric current is being induced in neurons close to the brain’s surface in the region of the coil.  If this all sounds complicated, it’s probably because I haven’t explained it very well; I’m no physicist!  A much nicer

explanation can be found in box 1 of this article.  Anyway, the upshot of all this is that by sending brief pulses of current through such a coil, TMS can be used to externally evoke temporary neuronal activity, and we can observe the behavioural results.  So, if we do this with the coil placed over motor cortex – the part of our brain that sends movement instruction to our muscles – we can make the arms or legs twitch, for example.  As someone who has been subject to this bizarre procedure, I can tell you it’s both hilarious and a little unsettling to watch your hand flail about wildly seemingly of its own volition.  It’s a bit like watching your dad dancing to The Mavericks; amusing, but a bit unnatural and there’s nothing you can do to stop it.

 

I digress.  Now, what I find super interesting is that by placing the TMS coil over the occipital cortex, which includes our visual cortex, people often report seeing visual artifacts such as flashes of light, or pale shapes like ovals or lines.  Awesome stuff.   So, what this article was suggesting was that something similar is going on when ball lightning is perceived.  The idea is that a bolt of lightning creates fluctuating magnetic fields similar to those used in TMS.  If an observer happens to be about the right distance away from that lightning, this magnetic field will be strong enough to induce electrical activity in that person’s visual cortex, causing hallucinations just like those artifacts we get with TMS.  This idea totally blows me away.  This idea of a kind of naturally occuring TMS is just amazing – I mean lightning being able to make you see things?!  It’s one of those flukey little quirks of nature that make science so interesting.  I just love it.

 

I’m certainly no expert on lightning, so I am holding my hands up and admitting that the next couple of paragraphs are at least 73.87% speculation on my part, but I’m not entirely convinced by this idea.  Let’s, for a start, write off all the supposed photographs of ball lightning.  I’m fairly certain you can’t photograph a hallucination, but you can do some remarkable things with photoshop, and other phenomena like St. Elmo’s Fire can be mistaken for ball lightning.  Let’s also ignore all those reports coming from groups of people who all claim to have seen the same instance of ball lightning.  Social pressure and the desire to conform can cause people to say all sorts of things.  So far, no solid evidence that ball lightning even exists, suggesting the hallucinations idea is actually quite plausible.   But there are a couple of things that bother me about it. Firstly, the remarkable consistency in descriptions of ball lightning.  As far as I have been able to find out, there don’t seem to be reports of lines, or squares, or lights of different colours.  Always a glowing, sometimes moving orb.  This seems quite bizarre to me, as such consistent effects would surely require a really focused, specific region of effect of the magnetic field.  We might expect that a generalised magnetic field could affect any number of brain regions, causing all sorts of different effects.  Not only might we expect a wider variety of visual hallucinations, but we might also expect to hear unusual sounds, or experience twitching of the limbs like I described above.  

 

Secondly – though this is related to the first point – the fact that people seem to be able to choose to watch this lightning.  Our visual cortex is mapped out in a similar way to our retina, such that picking a particular point on the visual cortex is like picking out a corresponding point in the visual field.  If the perception of ball lightning really were a result of abnormal brain activity, we might expect that this ball lightning would stay firmly in the same part of our visual field.  What I mean by this is that if the induced activity were in a part of the brain that corresponded to the left half of the visual field, it wouldn’t matter how far left we tried to look, the image would remain to the left of our point of focus.  If you’ve ever suffered a visual aura, you’ll understand what I mean by this.  It should also be perceptible with the eyes closed.  I have no idea if this has been documented either way though.  

 

Finally, the authors themselves suggest that only around half of all instances of ball lightning might be explained by this type of hallucination.  Which not only leaves the obvious question of what is causing the others – but also the question of the quite astounding coincidence that hallucination-ball lightning would result in the same visual experience as non-hallucination-ball lightning.  The reports just seem to consistent to be able to draw a divide between those instances that are likely to be hallucinations, and those that aren’t.  

 

Given that ball lightning has effectively defied explanation for centuries, far be it from me to undermine what might be a really strong theory.  Of course, I only really know about the brain stuff, so my questions about this idea might be totally misguided.  I don’t know much about lightning or electromagnetic induction.  I think this highlights why it’s really important for scientists of different disciplines to collaborate and debate more; it’s only then that the really interesting ideas and discussions come about.  So on that note, if anyone has any more ideas about this, or has any response to the questions I’ve raised, I’d be really interested to hear them, and please feel free to leave comments below!

 

                                                                                                                                 

* This has actually been suggested in the past by Cooray and Cooray, 2008; paper available here, though the paper doesn’t appear to have been cited, and I couldn’t even find the (obscure) journal’s impact factor.

** Usually.  There are exceptions.

Chocolate cravings: ‘it weren’t my fault guv, my orbitofrontal cortex dun it’

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Given my own over-indulgence this Easter, I needed little excuse to hunt around in the neuroscience literature for some possibly-beyond-consious-control neural mechanism that means my unabashed chocolate scoffing is entirely not my fault (of course, that raises the whole issue of consciousness and the neural basis of free will, but that’s another story for another blog post…).

It’s an issue that isn’t entirely out of my remit, so this is also a great opportunity to intoduce a few key ideas related to my own research that will probably form the bulk of some future blogposts.  I spend most of my time studying a group of structures bang in the middle of the brain known as the ‘basal ganglia’ (not, as my sister calls them, the basal danglies).  They’re pretty old, evolutionarily speaking, and are heavily implicated in lots of different functions.

A couple of important functions here are believed to be learning associations between stimuli and reward (think Pavlov’s dog learning to associate a bell with food), and in representing predictions of the ‘reward value’ of an event or stimulus.  A quick caveat here: in the neurosciences, ‘reward’ is a term that can be bandied about a bit carelessly without being properly defined.  This can lead to a lot of talking across purposes and confusing poor PhD students in meetings (true story).  So, just to be clear, by reward I don’t just mean something that is intrinsically pleasurable, though this is included in the term. I regard reward as something that tends to ‘reinforce’ the behaviour that brought it about; it encourages us to do again whatever caused the reward**. So, ‘reward value’ may be thought of as the degree to which an event or stimulus is either pleasurable or reinforcing.

It has been demonstrated widely that (expected) reward value may be encoded in a region of the basal ganglia known as the ventral striatum (though trying to figure out whether it’s pronounced stree-ah-tum, stree-ay-tum or stry-ay-tum has robbed me of a disproportionate amount of good procrastination time).  This part of the brain is also implicated in influencing the actions we take based on motivational information.  Projecting to this area is a region known as orbitofrontal cortex.  This is a ‘new’ part of the brain in evolutionary terms, and sits just above the eyeballs.  It too appears to represent information relating to reward value, and has also been implicated in high level functions like suppressing instinctive responses and urges.  People who have damage to this region often show behavioural dysfunction such as impulsitivity and compulsiveness.***

So – where does chocolate come into all this?  I can only speak for myself of course, but I certainly find chocolate rewarding.  Spectacularly rewarding.  So rewarding that I’ve had to stop bringing spare change to work since the arrival of ‘Claudia’, our beautiful new departmental vending machine, for fear of ending up the size of a house before the year is out (it’s the galaxy caramels that really do a lot of damage).  To study the – rewarding, amongst other – effects of the sight and taste of chocolate on neural activity, Edmund Rolls and Ciara McCabe of Oxford University**** performed an fMRI study examining neural responses to chocolate in chocolate cravers and non-cravers.  The results were pretty interesting.

First of all, cravers showed more brain activity than non-cravers at the sight and the taste of chocolate in the orbitofrontal cortex (which I have mentioned above).  Even more interesting, sight and taste combined produced an effect even greater than the sum of the effects of sight and taste alone, and this was also yet more pronounced in cravers.  Cravers also showed a high correlation between brain activity here and how pleasant they said they found chocolate.  This shows that the higher the ‘pleasantness’ rating, the stronger the activity was.  Again, this was the case more for cravers than non cravers.

What is really interesting though, is that brain regions involved directly in the representation of taste, most specifically the anterior insula, did not show greater activation in cravers.  Neither was activity here correlated with pleasantness ratings.  Also, while ventral striatum showed greater activation in cravers at the sight of chocolate, there was no difference here between cravers and non cravers for the taste of chocolate.

This might all seem like an awful lot of interactions, but let’s look at it simply:  brain regions involved in representing reward value, and those involved in suppressing instinctive behaviour, were generally more active in cravers, particularly when anticipating – rather than consuming – chocolate.  Regions involved in taste showed no difference. Cravers also seemed more aware of their own future responses to receiving chocolate.  The upshot is that it probably isn’t the actual sensory experience of eating chocolate that influences cravings, but that the anticipation of a pleasurable experience is greater for cravers, and the subsequent reward is represented to a greater degree.  It may be that cravers have a stronger learned association between the notion of chocolate (including the sight of it) and the expectation of reward – this would explain the greater drive for cravers to eat chocolate.

So next time you find yourself craving a dairy milk, don’t be too hard on yourself.  Clearly, you’re just a brilliant learner, and that association between chocolate and reward is incredibly strongly represented in your highly efficient brain.  At least, that’s what I like to tell myself…

 

              

* Disclaimer bumpf: I nabbed this picture from wikipedia.  I don’t own it… I think I’m allowed to use it.

**Those in the know will be surprised that I haven’t mentioned the ‘phasic dopamine’ signal here. It is certainly relevant and may well act as a ‘do-it-again’ signal.  The reason I haven’t gotten into it here is because the exact nature of the signal is still hotly debated and to attempt to outline it in a paragraph or two would be to traverse a minefield/labyrinth/dreary conference hall of empassioned academics. However, watch this space, and it may well form the bulk of an extended future blog post.

***One famous case is that of Phineas Gage whose frontal lobes were severely damaged when a tamping iron impaled his skull. 

 

****The super interested can find the original paper here

Spiritual Machines

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I’m lucky enough that I discovered my passion for understanding the brain at an age when I could easily pursue it at university.  Some of the more baffling, interesting, and exciting ideas I’ve come across so far I hope to share here.  These come from a whole range of subject areas, including psychology, neuroscience, philosophy, cognitive science and computer science.  I’ll also be talking a bit here and there about the research I’m working on for my PhD.  But to begin this blog, I thought it might be fitting to talk a little about how I became interested in the subject.  

The very first time I considered the brain and its function in any real way, I was about seventeen and listening to a concept album by a little known (and underrated) Canadian alt rock get-up called Our Lady Peace.  The album was called Spiritual Machines, and between tracks were brief recordings of some guy talking about the progression of artificial intelligence.  These tiny speeches covered things like the first time a computer beat the world champion at chess (Deep Blue beat Garry Kasparov in 1997), and the potential for heavy ethical dilemmas in the future if computers ever become autonomous enough to be truly considered conscious or independent.  The album concluded with a hidden track; a short dialogue between what appears to be a character from a future age, ‘Molly’, and an inquisitive present day person, quizzing Molly on whether she is a machine.  Molly replies that it ‘is really not for me to say.  It’s like asking me if I’m brilliant, or inspiring.’

After minimal research, I discovered that the album was named in honour of a book entitled ‘The age of spiritual machines’ by the brilliant Ray Kurzweil.  Turns out the snippets of speech on the album were actually excerpts from the book, read by Kurzweil himself.  The book describes a future in which the majority of society is artificially enhanced to various degrees, and the line between machine and human has become truly ambiguous.  Non-augmented humans or ‘MOSHs’ (Mostly Original Substrate Humans) are rare and comparatively primitive; incapable of understanding many things that are apparently commonplace, like music.

The idea that one day humans and machines could be two ends of a spectrum really got me interested in artificial intelligence and all its associated philosophical issues.  In turn, for the first time I began to think of the brain itself as a machine.  While this might seem like an unpleasantly cold and reductionist view, I believe that it has opened my eyes to some quite amazing possibilities.  For me, the most exciting part of this intellectual journey was the realisation that this machine - the brain – is just so spectacular.

Fine, so we can’t perform arithmetic like a calculator, or store information as accurately as a database, but the computations performed by the brain are infinitely more sophisticated.  We are flexible in our behaviour. We incorporate emotions and reason in our decisions – we don’t do things based on some explicit rule based system, but just know when something ‘feels’ right or wrong.  We have the ability to empathise, to understand the concept of existence.  Our brains tell our muscles when to adjust our posture to avoid falling over, keep us breathing and tell our hearts to beat, all completely outside of our awareness.  They transform photons and sound waves into the subjective experiences of seeing and hearing.  We can imagine things we know to be impossible, and visualise things we’ve never seen.  We are constantly learning new things and adapting our behaviour, sometimes realising it and sometimes not.  We prepare ourselves for the immediate and distant future and constantly make predictions about what’s going to happen next.  When our predictions are wrong, we refine them so they are better next time.  The particularly ineffable mystery, consciousness, is mediated by this machine, this slimy, grey mass of goop.  And all of this goes on for our entire lives.  It’s a pretty heart-stoppingly amazing machine that can do that.