Category: Inside the Brain

Wired has an excellent article on the Allen Institute for Brain Science’s ambitious mission to map where each gene is expressed in the brain.

We tend to think of genes in terms of their ability to pass on characteristics to new generations, but the moment the egg and the sperm combine, genes start coding for proteins which the body uses to do its work.

Of course, this includes the brain, so knowing what type of genes produce proteins in which areas of the brain gives us a big clue to some of the brain’s functions.

The article is, perhaps, a little overly hopeful about the significance of a having a gene map for understanding complex mind functions or disorders (autism is mentioned as an example) – suggesting that some research hits a dead end without it.

Perhaps something useful to mention is that one of the key pieces in the puzzle of gene expression in the brain is not where genes are expressed but under what conditions they are expressed.

While your DNA has the ability to express every protein it has genes for, the cell regulates this process so it reacts to current conditions dynamically.

In other words, the genes are more of a reference book, and the cell’s other regulation processes decide how and when to use this information.

As far as we know, all learning in the brain happens through proteins, meaning that experience, learning, thought, motivation – or any other ‘psychological level’ process we can think of, acts through the many, complex and not fully understood regulation processes.

So understanding the reference book is an essential but insufficient part of the picture. The real deal is in understanding how the brain’s cellular workers use the information to mediate between genes and the processes we understand at the psychological, behavioural or experiential level.

This is part of the new science of epigenetics, and there are high hopes that this will be a big part of future neurobiology.

This doesn’t imply that we don’t need to understand the role of experience and the environment in deference to purely reductionist neurobiological models. In fact, these new developments have stressed the importance of integrating these bigger concepts.

And this is largely because we now have the beginnings of a science that could help us make links between these different levels of explanation.

Nevertheless, the Allen Brain Atlas is an important and exciting part of this new science and the Wired article is a great introduction to the project.

Link to Wired article ‘Scientists Map the Brain, Gene by Gene’.
Link to Wired image gallery of the Allen project.

The New York Times has an obituary for Earl Wood, the man who invented the G-suit, the pressurised suit for fighter pilots that prevents them losing consciousness when g-forces drain blood from the brain.

The problem became apparent as fighter plane technology advanced to the stage where they became so fast and manoeuvrable that pulling tight corners or sharply accelerating put huge strains on the pilots’ bodies.

The acceleration temporarily impedes the heart‚Äôs pumping power and cuts blood supply to the brain. A tight turn might cause the pilot to lose consciousness briefly, leading to a crash…

To counter a precipitous drop in blood pressure, the team designed a suit that placed air bladders at a pilot’s calves, thighs and abdomen; a valve inflated the bladders as G-forces increased. Constriction of the bladders on the arteries raised blood pressure and helped keep blood flowing to the brain. The suit’s prototype was tested successfully by Dr. Wood and others in a dive bomber on flights that involved steep descents.

At the same time, the Mayo team developed an exercise, called the M1 maneuver, in which a pilot would shout or grunt under G-force conditions. The grunting compressed arteries and tensed muscles and was at least as important as the revolutionary suit for resisting G-forces.

Link to obituary for Earl Wood, G-suit inventor.

A surgical team from Italy have just reported that they’ve altered human brain function through neurosurgery conducted from outside the skull, by using beams of radiation.

The technique is known as radiosurgery and, in itself, isn’t novel. The team used the Cyberknife system, specifically designed to do this sort of operation.

However, the technique is typically used to treat brain tumours, and what is new is that the team have adapted this method to permanently knock out targeted areas to alter overall brain function.

They were inspired by deep brain stimulation and functional brain surgery. These aim to do a similar thing and are most commonly used to treat tremors and movement problems in Parkinson’s disease by altering the movement circuits in the brain.

This new operation aimed to do something similar, but with radiosurgery.

Their report appears in the journal Medical Physics, where they describe the treatment of two patients with, until then, untreatable disorders. One with chronic pain, stemming from nerve damage, and other with dystonia, a neurological disorder that causes certain muscles to painfully contract.

One of the challenges with this sort of operation is hitting exactly the right spot, and to achieve the necessary accuracy the team built a 3D computer model of the key areas from the brain scans which they then used to electronically direct the radiosurgery equipment.

The patient with dystonia had a pallidotomy, where part of his basal ganglia was ablated (destroyed), whereas the patient with chronic pain had a thalamotomy, taking out a section of his medial thalamus.

Both patients recovered well, significantly improved and showed no major side-effects at 15 months.

The image on the left shows where the radiation beams entered the head during the operation on the patient with chronic pain.

Link to research report.
Link to PubMed entry for same.

Discover Magazine has an excellent article on the science of anaesthesia and why doctors need to struggle with the problem of consciousness to make someone comfortably numb.

If you’re not familiar some of the mysteries of anaesthesia, you may be surprised to know that we don’t actually know how most anaesthetics work and we have no reliable way of telling whether someone is unconscious.

This is important because general anaesthesia usually involves two types of drug, muscle relaxants and hypnotics. It’s possible that the muscle relaxants have their paralysing effect but the hypnotics don’t fully work, so you’re awake and aware, but don’t respond when you’re touched or talked to.

Hence anaesthetists would love a device which says whether someone is concious or not, but unfortunately, divining consciousness from the brain is one of the hardest problems in science. So, they’ve come up with various other methods:

Sometimes the anesthesiologist will use a blood pressure cuff on a patient’s arm to block the muscle relaxants in the bloodstream. Then the doctor asks the patient to squeeze a hand.

This sort of test can distinguish between a patient who is awake and one who is out cold. But at the borderline of consciousness, it is not very precise. The inability to raise your hand, for example, doesn’t necessarily mean that you are unconscious. Even a light dose of anesthesia can interfere with your capacity to keep new pieces of information in your brain, so you may not respond to a command because you immediately forgot what you were going to do. On the other hand, squeezing an anesthesiologist’s hand may not mean you’re wide awake. Some patients who can squeeze a hand will later have no memory of being aware.

Seeking a more reliable measuring stick, some researchers have started measuring brain waves. When you are awake, your brain produces fast, small waves of electrical activity. When you are under total anesthesia, your brain waves become deep and slow. If you get enough of certain anesthetics, your brain waves eventually go flat. Most anesthesiologists monitor their patients using a machine known as a bispectral index monitor, which reads brain waves from electrodes on a patient’s scalp and produces a score from 100 to 0. But these machines aren’t precise either. Sometimes patients who register as unconscious can still squeeze a hand on command.

The article then goes on to discuss some fascinating neuroscience studies that use anaesthesia to try and understand what changes in the brain as someone slips into unconsciousness.

It’s a great read and an interesting look into what you might called ‘applied consciousness research’.

Link to ‘Could a Dose of Ether Contain the Secret to Consciousness?’

Frontiers in Human Neuroscience has a great two page article that nicely summarises the thinking about how blood flow measured by brain scans relates to the workings of the neurons.

No one with common sense would believe that in a house, water movements in pipes could tell you how many lamps are on and how much fuel is used for heating. Surprisingly most neuroscientists are convinced that in the brain monitoring local cerebral blood flow (CBF) what I call plumbing, is a reliable surrogate method to localize electrical neuronal activity and monitor metabolic events.

The piece is by neuroscientist Jean Rossier, and he discusses the two main theories of how blood flow relates to what the neurons are doing.

The ‘metabolic hypothesis’ assumes there is a causal link between how much energy the neurons need, in the form of glucose, and the subsequent regulation of blood flow in the brain. In other words, the neurons signal the need for energy, which is delivered later.

The ‘neurogenic hypothesis’ hypothesis, suggest that blood flow can be ‘pre-ordered’, in anticipation of neural activity.

Needless to say, it’s important to understand the exact relation between the operation of the neurons and blood flow, because brain scanning studies typically measure blood flow to infer the working of neurons and hence the relationship to cognitive or mental processing.

The Frontiers in Human Neuroscience article is a concise piece which discuss the neuroscience of this link, and covers some of the most recent studies which have attempted to make sense of what brain scans tell us when we’re doing psychology experiments.

Link to article ‘Wiring and plumbing in the brain’.
Link to PubMed entry for same.

I like this sentence in the summary from a recent paper on an unusual penetrating head injury:

We present a unique instance of a severe, high-energy, penetrating orbitocranial injury caused by a solid metallic rod that corresponded to the spray valve lever handle of a kitchen sink pre-rinse spray tap, which was fractured and projected at high speed for an unknown reason.

Link to PubMed entry for article.

An article just published online for the Behavioural Science and Law journal discusses whether magnetic brain stimulation could be used in lie detection and interrogation.

It is based on the premise that as cognitive neuroscience works out the brain circuits for lying, a technique called transcranial magnetic stimulation (TMS) could be used during an interview to disrupt the function of these pathways.

The article specifically pitches this idea as a possible ‘lie detection’ method, as so far, research conducted by the authors suggest that disrupting parietal cortex function, on average, slows the response time for lies and but doesn’t affect response time for truthful responses – albeit in a very controlled laboratory experiment.

In other words, the idea is that TMS could be used to help distinguish truthful responses from untruthful ones.

My first thought on reading this was that someone is bound to be thinking of this technique as a way of inhibiting the relevant circuits to prevent lying, or at least increase the likelihood of truthful responses.

It’s probably true to say that deception research is in its very early days and its not even clear whether such things as distinct ‘deception circuits’ even exist.

However, from what we know from now-public secret military research in this area, it’s clear that many of these sorts of techniques are simply tested empirically.

Essentially, whether there is a good theoretical basis or not, national security agencies are much more likely simply to try the techniques and see what the outcome is.

The Behavioural Science and Law article sticks firmly to the possible civilian uses for this technology, discussing the legal and ethical issues within a domestic law framework, but you can bet that the spooks are already thinking ahead on this one.

Link to ‘Non-invasive brain stimulation in the detection of deception’.
Link to PubMed entry for same.

We’ve reported before on brain imaging research that shows brain activity in those in a ‘persistent vegetative state’. What I didn’t know until today was that one subject in this research, Kate, has since woken up. This YouTube video tells Kate’s story:

Kate suffered from what was probably brain stem encephalitis at the age of 23. She was the first patient to be scanned by <a href="http://www.mrc-cbu.cam.ac.uk/people/adrian.owen/
“>Adrian Owen as part of his research into the mental lives of those in persistent vegetative states. Findings from this research support what Kate herself is able to say in the video: we need to be very careful before making life and death decisions on behalf of people who appear unresponsive.

Wired has just published an excellent two part article on neuroengineering, the practice of altering the brain with electronics or optics.

It looks at a number of interesting projects, from light controlled neurons to magnetic brain stimulation, and focuses on the work of talented neuroengineer Ed Boyden who I had the pleasure of doing a joint talk with at a SciFoo conference.

In fact, TMS gets electricity into the brain peacefully, without either cutting it open or shocking it with millions of volts.

The target area of the brain is treated like the coil in a generator, subjected to rapidly changing magnetic fields until electricity begins to dance across its neurons. Unlike the optical switch developed by Boyden and Stanford’s Dr. Karl Deisseroth, TMS doesn’t reach the deeper regions of the brain, but there are a lot of important and interesting areas in the cortex where TMS delivers its current. It’s also far less precise than the optical switch, although TMS seems positively surgical when compared to the imprecisions of the pharmaceuticals we pump into our bodies.

The second part is probably the highlight, discussing the possibilities of having these technologies more widely available so your average garage hacker can tinker with them (and themselves), and what ethical dilemmas this might cause.

Link to ‘Inside the New Science of Neuroengineering’.
Link to ‘How Neuroengineering May Change Your Brain.

This week’s Nature has an interesting article on the ethics of electronic brain enhancements. It does something quite unusual for an article on technological brain enhancements – it talks about the side effects.

Brain implants and ‘neuroprosthetics’ have been widely covered by the science media in recent years owing to a number of impressive advances but very little discussion has focused on the adverse effects.

In considering the ethics of using brain implants to enhance both the damaged and healthy brain, this article actually touches on some of the research on unwanted effects of deep brain stimulation.

Many patients with Parkinson’s disease who have motor complications that are no longer manageable through medication report significant benefits from DBS. Nevertheless, compared with the best drug therapy, DBS for Parkinson’s disease has shown a greater incidence of serious adverse effects such as nervous system and psychiatric disorders and a higher suicide rate. Case studies revealed hypomania and personality changes of which the patients were unaware, and which disrupted family relationships before the stimulation parameters were readjusted.

Such examples illustrate the possible dramatic side effects of DBS, but subtler effects are also possible. Even without stimulation, mere recording devices such as brain-controlled motor prostheses may alter the patient’s personality. Patients will need to be trained in generating the appropriate neural signals to direct the prosthetic limb. Doing so might have slight effects on mood or memory function or impair speech control.

The author of the piece argues that this does not raise any new ethical questions, as many psychiatric drugs also have side effects.

However, it’s probably true to say that ethical difficulties often arise with regard to specific side effects – talking about unwanted effects in general is a bit too vague to be useful.

Risk-benefit analyses are only useful when you know both the extent and quality of the risks and benefits and this is where it truly gets interesting.

The neuropsychology literature is full of surprising findings about what sort of functions the brain performs, suggesting that specific effects, wanted and unwanted, may have to be traded off against each other.

For example, is the loss of the ability to have an unconscious emotional reaction to a loved one worth a change in pathological gambling behaviour?

This is a hypothetical example based on the role of the ventromedial cortex in both situations, but who knows what sort of effects might need to be weighed up against each other.

Nature Network has an online discussion about the issues the piece raises which also links to the weekly podcast which has an interview with the author.

Link to Nature article ‘Man, machine and in between’.

I’ve just found this remarkable CT scan in a 1997 article entitled ‘Trans-orbital penetrating head injury with a door key’.

The paper reports that “A 71-year-old-female was answering the door when she misjudged the step and fell forward impaling herself on the large key protruding from the lock.”

She was found with the key still embedded in her head and was transferred to neurosurgery where the key was removed.

Thankfully, the patient recovered with no neurological impairment and only slight difficulties with her vision.

Link to PubMed entry for the case report.

Time magazine has an interesting article on the neuroscience of spiritual experience and why religious belief has been linked to better health.

It’s not the most gripping article in the world and starts with some annoying experience = brain area phrenology but it does gives a good overview of some of the main research areas.

Probably the most interesting aspect is where it tackles the link between religious belief and health in light of other belief based health benefits such as the placebo effect or beliefs about illness itself.

The section on the effects of prayer also has this fascinating snippet about early experimental psychologist Francis Galton:

As long ago as 1872, Francis Galton, the man behind eugenics and fingerprinting, reckoned that monarchs should live longer than the rest of us, since millions of people pray for the health of their King or Queen every day. His research showed just the opposite — no surprise, perhaps, given the rich diet and extensive leisure that royal families enjoy.

Studies on the curative properties of prayer have a long and interesting history, with one of the most striking moments also linked to a psychologist and an (in)famous study – discussed in a 2002 Wired article.

Link to Time article ‘The Biology of Belief’.

Stanford University have put a series of engaging TED style 10 minute lectures up on YouTube where some of their leading researchers discuss cutting-edge cognitive science research – curing blindness with neural implants, brain computer interfaces, neural pathway mapping, creating brain inspired computer hardware, visualising desire and controlling neurons with light.

Getting lab scientists to do short, engaging online lectures aimed at a bright and curious audience is a fantastic idea. These new Stanford talks have a high production quality and have obviously been prepared with a great deal of care as they are incredibly easy to watch.

I’ve not watched them all yet, but so far the talk on the neuroscience and stem cell treatment of blindness is a particular highlight.

In this presentation, psychologist Brian Wandell discusses the science of perception and the treatment, as well as the remarkable case of Mike May, the world-record holder for blind downhill skiing who volunteered to try the experimental treatment.

A fantastic series that’s well worth checking out.

Link to Stanford neuroscience TED-style talks.

Locked-in syndrome is a dramatic condition where, after brain stem damage, patients are conscious but paralysed and can only communicate with the outside world by an eye-blink or muscle twitch.

Because of limited communication it has been difficult to assess the impact of the damage on thinking and reasoning, but a French team have created tests that can be completed by simple yes / no movements – allowing the first comprehensive study into the cognition of the locked-in mind.

The syndrome usually occurs after a stroke, where an interruption to the blood supply selectively damages the neurological ‘relay station’ that transmits movement impulses to the rest of the body, leaving an almost total paralysis – classically except for a facial muscle.

It has been assumed that affected people are paralysed but cognitively intact – their thinking isn’t affected.

In one famous example, the editor of Elle magazine, Jean Dominique Bauby, wrote the book The Diving Bell and the Butterfly after suffering locked-in syndrome by painstakingly selecting letters with an eye-blink. It’s both stunningly beautiful and eloquent, demonstrating a keen and focused mind.

But because of extremely limited communication, it’s difficult to say whether this level of preserved mental ability is common because traditional neuropsychological tests usually require relatively complex responses.

To address the problem, a French team, led by neurologist Marc Rousseaux, designed tests to assess nine patients that included everything from visual recognition tasks to logical-mathematical reasoning problems, all which could be answered with yes / no responses – just eye-blinks in some cases.

The appendix of their article has the full list of the tests and they are remarkable for their ingenious design.

They team found that while the patients were generally mentally sharp, problems in particular areas were not uncommon, with a significant minority showing selective impairments in areas such as comprehension, understanding meaningful connections, or problem solving.

Sadly, this means that it is unlikely that all locked-in patients share Jean-Dominique Bauby’s remarkably preserved intellect, but the development of these ingenious tests means that we can better understand the impact of the syndrome, and the strengths and weakness of affected patients.

Link to full-text of study on locked-in patients.

Sportsmen who suffer concussion in early adulthood may experience long-term reduction in brain function well into later life, according to a study released this week.

Although the study had only 40 participants, it is striking as it looked at the effects 30 years after the original concussions and used a wide and diverse range of tests for cognitive and neurological function, the majority of which showed some level of impairment.

This comes in the same week that Boston University School of Medicine reported that former American football player, Tampa Bay Buccaneer Tom McHale, was suffering from chronic traumatic encephalopathy (CTE), a degenerative brain disease caused by head trauma, when he died in 2008 at the age of 45.

CNN has a good write-up of the news with photos and images of the long-term effects of persistent sports concussion and we covered the work of Dr Bennet Oamlu, who does post-mortems on cognitively impaired American football players, back in 2007.

Repititive sports concussion is now recognised as having a significant neurological impact and has also been found in rugby and boxing.

Interestingly, ex-professional football players (known as soccer players to Americans and other football philistines) probably have higher levels of dementia and there is an ongoing debate about whether this is due to the low level impact of heading the ball.

Some think it is, other think it might be due to the fact footballers consume a lot of alcohol, and so the higher levels of dementia just might be wear and tear from all the booze.

Link to full text of long-term sports concussion study.
Link to CNN on sports concusion and dementia (via NeuronCulture).

Neuroscience textbooks often suggest that the ability to image the structure of the brain in living patients started in the 1970s with the introduction of the CT scanner. What they tend to forget is that brain surgeon Walter Dandy was already neuroimaging patients as early as 1918.

We think of x-rays as only being useful for getting pictures of bones but soft tissue does show up on an x-ray.

The images rely on certain bits of the body having a higher density and therefore blocking more of the rays falling on the photographic plate.

Bones are obviously very dense so show up well but look at this image of a hand x-ray. You can clearly see the difference between bone, flesh and air. What you can’t see is any difference in the soft tissue.

The crucial difference that struck Walter Dandy was the possibility of distinguishing flesh and air on an x-ray.

Knowing that the brain is surrounded by cerebrospinal fluid (CSF), which also fills internal spaces called the ventricles, he decided to simply replace the fluid with air and x-ray the patient.

He published his first results in 1918. He described how he drilled a hole in the skull of a patient and carefully removed the CSF from the ventricles and replaced it with air.

Now known as ventriculography, one of the images he took is illustrated on the top left. For the first time, you could clearly see the ventricles in a living patient.

During the procedure, he noted that some of the air has escaped the ventricles and was occupying the space between the skull and the brain.

The following year he published another study where he deliberately filled this space with air as well, so the surface of the brain was surrounded by the gas and so could show up on an x-ray.

The bottom left image shows the result of this, and you can see it clearly shows some of the ‘trenches’, the cerebral sulci, on the surface of the brain.

Now called pneumoencephalography, the procedure was immensely useful, but, extremely unpleasant. In his 1918 article he noted that the patient’s reaction “was characterized by a rise of temperature, nausea, vomiting, and increased headache”.

Furthermore, it takes weeks, if not months, for the CSF to be replaced by the body, leaving the patient in a debilitated and fragile state.

However, it was used throughout the 20th century and the research literature is peppered with the results of this early neuroimaging research.

Link to 1918 paper on imaging of the ventricles.
Link to 1919 paper on imaging the brain surface.