Attacked by your own hand: when the brain acts against you

Sometimes it might feel like your brain acts against your own interests. Who hasn’t regretted that extra pint or an unaffordable shopping spree? But what if your brain was controlling a part of your body against your will?

This is a relatively rare but mind-boggling condition called alien hand syndrome, where patients have the sensation of a limb acting without their control. It can feel like their arm is disobedient, and has “a will of its own”. The condition appears in the 1964 film Dr Strangelove, where the eponymous character is shown to have the condition. Medically, it was first documbetween the two hemispheres of the brain (the corpus callosum) cut. ented in patients who had undergone surgery to treat epilepsy, though it can occur after other types of brain surgery, stroke, brain tumours, infections or certain degenerative brain diseases. It is best understood in patients with epilepsy who have had the connection Following this surgery patients are generally able to continue their lives as normal, but in some cases the effects can be dramatic.

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Patients with alien hand syndrome report that following the surgery one arm (and sometimes leg) feels like someone else’s, and describe the arm’s behaviour as not their own. Some patients may even be unaware of the actions of their hand. One patient who suffered a severe case of alien hand syndrome and appeared in the 2011 BBC documentary “The Brain: a Secret History”, described how her “alien” left hand would take things out of her handbag without her knowledge, or stub out a cigarette that her right hand had just lit. In cases where the “alien” hand performs goal-directed behaviours such as these, it may perform actions directly opposed to the unaffected hand, leaving the hands apparently bickering. For instance, while the unaffected hand tries to pick up a mug, the other moves it away. Conversely, the affected hand may involuntarily mirror the actions of the other hand. For these patients, when instructed to perform an action with the unaffected hand, they may be unable to do so without the affected hand attempting the same movement. In another case, reminiscent of a horror film plotline, following serious heart surgery, a patient found that her left hand was no longer under her control, and would even try to choke her. Frighteningly she had to physically restrain it with her right hand to avoid injury.

So what is going on in the brain to allow this to happen? Brain imaging research has found that alien hand movements, like normal hand movements, are accompanied by activity in the primary motor cortex (a part of the brain critical to producing movements). But this occurs without the usual preceding activity in the premotor cortex (another part of the brain involved in planning and producing motor actions), and other regions involved in planning behaviours. In patients who have had the connection between the hemispheres cut, it is possible that interhemispheric premotor to motor cortex activity is disrupted. So, in effect, the motor cortex is acting without the usual sequence of brain activity that controls it and gives us a sense of the action being one we’ve chosen to do. In addition, in the healthy brain, motor actions are accompanied by a signal to the sensory parts of the brain that will experience it (an efferent signal; see an earlier post on this blog about how this stops us from being able to tickle ourselves here). If this efferent signal is absent or faulty, your own actions may feel like someone else’s.

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Although it is still not fully understood what changes in the brain lead to alien hand syndrome, it seems possible that a combination of these disturbances in the brain may contribute to the sensation of the hand being autonomous. This condition has fascinated scientists for many years, and raises interesting questions about how we experience physical sensations.

Post by: Claire Scofield

Nerve regeneration: do good things come in small packages?

The 3101400087_b3cd617096holy grail of treating neuronal injuries is to persuade damaged neurones to regrow exactly as they were. Currently doctors lack the tools to do this, but hope is in sight in the world of nanotechnology.

Unfortunately, once nerves have suffered damage they don’t simply grow back to their original position. There are a number of reasons for this:

  • Inflammation gets in the way
  • Molecules found primarily in the mature nervous system inhibit growth
  • Gaps formed in nervous tissue caused by the “cleaning up” of injured cells form a barrier to growing cells
  • Cells fail to start regrowing

But how can nanotechnology help?

Nanotechnology is the science of the very small (on the scale of billionths of a millimetre) but it’s an enormous area of research – in many countries nanoscience is the priority for science budgeters.

Successful attempts have now been made to use nanotubules as a type of molecular scaffolding to support nerve growth. A nanotubule is a tiny (on the nanometer scale) tube-like structure – like a microscopic drinking straw. The first application of these tubes showed that, when coated with substances that encourage neuronal growth, carbon nanotubles were able to promote extension of rat embryonic nerve cells. These tiny tubes acted as a physical scaffold to guide the cells, while also providing chemical signals ‘telling’ them to grow and survive.

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Nanotubes made of amino acids (the building blocks of proteins) have also been developed. These amino acids can interact directly with receptors on nerve cell membranes and have proved effective at encouraging growth and limiting the damaging effects of scar tissue. Because these are composed of naturally-occurring amino acids they are not toxic to cells and caused no inflammation or immune response in animals. This is a serious benefit, as inflammation can be very damaging in neuronal injury.

However, the unique features of nanomaterials could also be associated with unique problems. At high concentrations, some studies have found nanotubes of certain sizes to cause DNA damage, accumulation and inflammation in the lungs. Another concern is that nanoparticles can move around the body: one study showed that nanoparticles could be transmitted up nerves and into the brain. Nanotechnology may represent an exciting opportunity in medical science, but it also comes with the major challenge of understanding how the behaviour of these materials interacts with the human body.

Post by: Claire Scofield

How Bluetooth could save your life

“The iPhone is great, but what if I wanted to put it in my brain?” John A Rogers from the University of Illinois asked this question at a recent talk about electronics that work inside our bodies. From stretchy electronic devices on the surface of our skin to implanted devices that “talk” to our smartphones; the future of medicine could be getting under your skin.

We are now able to produce silicone circuits which are as flexible as a rubber band and as thin as a temporary tattoo. This means that devices can be stuck on to our skin and left to measure signs of ill health such as temperature, hydration and heartbeat. These devices are particularly useful in neonatal care. But scientists are now taking this technology even further…

dissolvableElectronic devices that are safe enough to be implanted inside our bodies and simply dissolve away when they’ve done their job are becoming a reality. They are made from silicone and magnesium, which exist naturally in small concentrations inside the body and are safe enough to be implanted. The innovation that makes these dissolvable devices possible is the development of tiny silicone membranes with imprinted magnesium circuitry. These membranes can be less than 100 millionth of a meter thick and dissolve easily in the slightly alkali conditions of our blood. Scientists can control the amount of time these devices stick around inside the body by wrapping them in a thin layer of silk protein.

800px-Silkworms3000pxSilk is non-harmful and dissolvable, so makes an ideal covering material. Silk fibres (from silk worms) are broken down by boiling in salt water to create a kind of liquid silk that is then used to coat the devices. By altering the processing of the silk protein, it is possible to control how long it will take to dissolve in the body, hence controlling how long the device will last.

The first gadgets to be produced in this way simply heat up; these can be implanted into wounds or at the site of a bone fracture during surgery. Raising the temperature by just a few degrees at the site of a wound can be enough to kill bacteria and ensure the area remains sterile. Scientists have also made devices that can measure electrical activity within the brain, though so far these have only been tested in animals. The future of this disappearing technology is very exciting, for instance in allowing controlled drug delivery in a particular location.

Another new technology being developed in the world of medical electronics involves wireless communication from inside the body. Scientists have produced a wireless implant that can predict a heart attack. This small chip can be implanted under the skin to detect various substances circulating in the bloodstream, including a molecule called troponin. This is released by heart muscle when it is under the extreme strain that precedes a heart attack. The implant has a radio transmitter that sends signals to a patch outside the body. This can then transmit data to a smartphone via Bluetooth. The chip is currently being trialled in patients in intensive care, but in the future could be used by those who are at high risk of heart problems. In the future, chips like this one could also be used to detect other metabolites in the body, so could prove useful for monitoring a wide range of conditions. For instance, in diabetes accurate and simple monitoring of blood glucose could be extremely useful. The application of Bluetooth to medical devices that operate from inside the body could prove to be a significant step forward in the monitoring of a number of serious conditions.

The future of biomedical devices is looking positive; the application of developments in physics and materials sciences to medical problems is very exciting. From the prevention of infection to predicting a heart attack these devices are likely to save many lives.

Post by: Claire Scofield

Could ‘smart’ drugs make us more productive?

“Performance-enhancing drugs” is a phrase we’re used to hearing in the context of sport. But what if the drugs in question were aimed at improving our mental ability? Smart drugs, or ‘nootropics’, have been widely hailed as the steroids of the academic world. However, like steroids, concerns are now being raised over healthy students using prescription drugs to enhance their concentration and memory, thus gaining an advantage over their peers. Commentators argue that this advantage is unfair, since it is only available to students who can afford and are willing to risk side-effects of such drugs.

However, beyond the exam hall, there may be a legitimate market for these ‘smart’ drugs. Perhaps improving concentration in shift workers or anyone with a stressful or demanding job. But what ‘smart’ drugs are currently available, how do they work and are they safe for long term use?

Piracetam

A little internet research (and there are some quite alarming websites devoted to the subject!) brings up Piracetam as the original and perhaps most popular ‘smart’ drug. Piracetam has a wide range of clinical applications, stretching from treatment of epilepsy and movement disorders to use as a cognitive enhancer (mainly in elderly people suffering from memory disorders). Aside from its regular clinical applications, it has also been found to improve reading in dyslexics and to protect the brain against the damaging effects of alcoholism. Despite its application as a cognitive enhancer in elderly patients, there are few controlled studies investigating the drug’s ability to enhance mental performance in young healthy adults. The evidence which does exist, mostly points towards a modest improvement in memory and attention across a range of tasks. But how does it work?

Piracetam affects the membrane which surrounds our cells, both in the brain and the rest of the body. This membrane is not static, instead it acts like a fluid allowing proteins within the membrane to ‘float’ around. In neurones, the main job of these proteins is to transmit and receive chemical signals. As we age, the fluidity of our cell membranes is lost therefore affecting the proteins’ ability to communicate. Piracetam is thought to restore membrane fluidity, thus restoring neural communication. Indeed, Piracetam has been found to increase transmission of information in the hippocampus (a part of the brain essential for learning and memory). Studies have also found that it increases the amount of oxygen available to brain cells, this is thought to be the mechanism by which it protects neurones from alcohol-induced damage.

Some users of Piracetam also report increased creative drive. Writers, musicians and other creative people have reported that Piracetam improved their work and encouraged experimentation; however it cannot be ruled out that this is merely a placebo effect. Some people believe that the “light bulb” moment of creativity, when a stunningly original idea hits you (not something this writer is particularly familiar with…) could occur at times when there is greater connectivity between the two hemispheres of the brain. Piracetam is thought to increase transmission of signals moving between hemispheres across the Corpus Callusom (the nerve bundle that links the two hemispheres) so, in theory, this could increase creative output.

Although side effects of Piracetam are thought to be mild, the drug has yet to be studied for long term side effects in healthy adults. Therefore, the use of Piracetam as a nootropic agent may represent an unwarranted risk for a relatively small reward.

Ritalin

Another drug commonly used by students is the ADHD drug Methylphenidate, commonly known as Ritalin. This drug is usually prescribed to children diagnosed with ADHD to improve their concentration and motivation. However, it works just as well in healthy individuals, leading to its use among students as a ‘brain-booster’. It is estimated that in some American universities around 25% of students take Ritalin to improve their concentration. The ethicist John Harris has argued that if the drug is safe enough to be given to children for a non-life-threatening condition, it is safe enough to be used by adults to improve concentration. Although this argument may be sound, there is still much controversy over the very widespread prescription of Ritalin. Indeed, it can have side effects on the cardiovascular system which, in a small number of cases, resulted in sudden death. It has also been linked with psychosis, depression and anxiety. Therefore, although the drug is considered relatively safe for short-term use (as it is currently prescribed) chronic use may prove unsafe.

Methylphenidate is a stimulant that works in the same way as cocaine; however, it has a much slower method of action and if taken as prescribed, it does not generate the same feeling of euphoria as cocaine. The drug blocks transporters on neurons which would usually remove excess dopamine, meaning that brain dopamine levels increase. Dopamine is a neurotransmitter with an important role in the brain’s reward and motivation system, indeed it is by manipulating this system that Ritalin is thought to work. However, due to its parallels with cocaine and associated scope for abuse, Ritalin is a class B drug in the UK; meaning that possession without prescription can carry a maximum five year prison sentence.

These drugs certainly have an important role to play in improving the lives of patients and treating the illnesses they were developed to treat. However, to consider these as ‘smart’ drugs for the healthy seems a little crass. It is likely that as nootropics become more refined and perhaps marketed toward healthy individuals, we will see their use become more widespread, but for now the risk to long-term health probably outweigh the rewards. So, I believe that in this case the old adage, “if it ain’t broke don’t fix it” holds true.

Post by: Claire Scofield

Ketamine: from drug of abuse to anti-depressant.

Ketamine is probably best known as a recreational drug and horse tranquilliser. However, it also has a number of beneficial medical uses. It is routinely used as an anaesthetic, it is used in medical research to replicate symptoms of schizophrenia and current work suggests it may also be an effective treatment for depression. So what do we know about ketamine and how could a popular psychedelic drug be used to treat a psychiatric disease?

Why take ketamine?

Ketamine is classed as a psychotomimetic: this means it can induce hallucinations, delusions and feelings of dissociation from the world around you (other examples of psychomimetics include LSD and cannabis). These effects make ketamine a desirable recreational drug, but they are not the drug’s only action. It can also cause people to appear unresponsive or apathetic, severely disrupt memory and concentration and, at high doses, even lead to temporary paralysis or coma. Because these effects are similar to the symptoms of schizophrenia, it is commonly administered to rats (and healthy human volunteers) to study schizophrenia and test potential new drugs.

Ketamine produces its psychotic effects by disrupting the way the brain perceives the world and how it processes information. Specifically, it blocks the transmission of signals between a group of neurons which use the neurotransmitter glutamate (a chemical signal that neurones use to communicate). It does this by selectively interfering with the regions of the cell which detect glutamate; acting preferentially in certain parts of the brain, such as the prefrontal cortex.

Prefrontal cortex (Orange)

The prefrontal cortex, at the front of the brain, is responsible for higher functions; such as problem-solving, reasoning, understanding social interactions and control of behaviour. This region is important for enabling us to understand the world around us and make decisions about how to interact with it. Activity in the prefrontal cortex is managed by ‘inhibitory’ neurons (cells that prevent other neurones becoming too excited). These cells control what signals the prefrontal cortex sends to other brain regions. Ketamine selectively targets these inhibitory neurons, making them less active. This allows activity in the prefrontal cortex to continue unchecked, leading to disorganised communication and a disruption of its communication with other brain regions. The signals coming out of the prefrontal cortex make less sense and more irrelevant information is transmitted.

This extra transmission of irrelevant information may be crucial to understanding the basis of delusional thinking. If normally uninteresting stimuli are flagged up by the brain as important, this could prevent the brain from making sense of the world in a normal way, leading to bizarre or irrational beliefs and disorganised thoughts.

The effects of ketamine are fairly short-lasting: in clinical studies effects usually wear off within a few hours. Regular use may, however, have longer-lasting effects on the brain and reports of users developing psychological dependence have increased in recent years.

Ketamine for depression

Recently a number of clinical trials have found that a single low dose of ketamine can improve the symptoms of depression in a matter of hours. These trials used volunteers suffering from severe depression that had previously shown no improvement with traditional anti-depressants. Within 24 hours of a single dose, the percentage of patients showing a considerable improvement in mood varied across trials from 25% to an impressive 85%. Some patients showed improvements that lasted for weeks, however the majority of patients showed improvement lasting only a few days. Compared with the usually prescribed anti-depressants, this is an incredibly fast response; most take weeks to act, and can actually worsen symptoms before they show beneficial effects. This is an exciting development, especially for the treatment of suicidal patients, where rapid treatment is essential. Importantly, side-effects are generally mild, because the dose is far lower than a typical recreational dose.

It isn’t clear what causes ketamine’s anti-depressant effects but it isn’t thought to be a direct result of alteration in neuronal communication. In healthy subjects, small amounts of ketamine doesn’t influence mood, indicating that it may act to correct some problems found specifically in depressed patients. One possibility is that it encourages new connections to be created between neurons. This may be beneficial since research has found reduced numbers of connections in the brains of depressed patients.

However, this research is still in the early stages. The next big challenge is to determine a schedule of treatment to maintain the short-term improvements seen after one dose. This may involve combining ketamine with other anti-depressants, or repeating the dose. Although further research is still needed to assess the long-term effects of ketamine as an anti-depressant.

These exciting results suggest that in the future, ketamine may be famous not as a club-drug or horse-tranquilliser, but as a life-changing treatment for a devastating mental condition.

Post by: Claire Scofield