Chris Logie

The gruelling final few months of the presidential election campaign are notorious in political circles. Candidates get by on as little as four hours sleep most days due to huge demands on their attention and judgement as the campaign reaches its zenith. With the current election teetering on a knife edge, presidential candidates Barack Obama and Mitt Romney will have to pack as much into their schedules as possible whilst they power toward the finish line.

But what kind of effect does chronic sleep deprivation have and what sort of mental challenges must the candidates endure?

Ever since the introduction of artificial lighting two centuries ago, the time the average person spends sleeping has begun to decrease. Whilst the precise role of sleep on our physiology and function is not yet clear, the effects of its absence are well-documented:

It has been shown that even mild sleep deprivation can ‘fog’ the mind. One study, carried out by an Australian research group, found that mild sleep deprivation caused similar deficits to those seen following alcohol consumption. Specifically, performance on a computer-based movement task was impaired equally by both 22 hours without sleep and having a blood-alcohol content of 0.08% (above the legal driving limit).

Both movement-related tasks, such as this, and non-movement-related tasks are well-documented to be affected by sleep deprivation. In fact, most executive functioning tasks are inhibited! MRI scans have shown that activity in an area of the brain known as the prefrontal cortex declines when subjects are sleep-deprived. This part of the brain integrates all sorts of processes including perception, movement and verbal reasoning. As a result, any task that requires a lot of attention becomes difficult or, in some cases, almost impossible. Any form of novelty, including being placed in an unusual situation or answering unexpected questions becomes difficult.

Sleep deprivation is also known to negatively affect a person’s ability to memorise new information, a problem which can have a serious knock-on effect on their ability to plan and make decisions. The part of the brain which deals with memory is known as the hippocampus. Scientists believe that, when learning something new, sleep allows connections in this brain region to be modified and strengthened which consolidates memories into more permanent forms. Thus it’s not surprising that not getting enough sleep can lead to memory problems. Indeed, even when awake, neurons in this part of the brain in sleep-deprived individuals don’t fire as frequently or function as they should.

Another major problem anyone who has experienced sleep deprivation will recognise is the affect it can have on our emotions. Of course, it is common for people to become short-tempered and irritable when tired. However, research has shown that lack of sleep can also lead to more serious emotional changes including a reduction in an individual’s ability to solve problems using moral reasoning. Rather than making decisions based upon internal moral values, sleep-deprived people can shift to more external, rule-based decision making (more akin to the ‘black and white’ reasoning used by many children). Emotional memory also seems to be impaired, making it more difficult for a person to empathise with others.

People also become hungrier when they aren’t sleeping. This is not thought to be caused by extra energy expenditure (basal metabolic rate when asleep is 90% of that when awake) but instead, is believed to be due to an adverse increase in ghrelin (a hormone that causes hunger) and concurrent decrease in leptin (a hormone which prevents hunger).

All of these impairments combine to induce a haze that puts incredible stress on the individual. That two older men (Obama and Romney are 51 and 65 respectively) can debate, write speeches, plan meetings, strategise and campaign whilst mentally and physically strained is testament to their indefatigability. However, with recent polls showing less than 1% between the two rivals, even the smallest misjudgement or gaff could mean the difference between despair or delight.

Given the campaign suspension from both candidates during hurricane Sandy, it’s possible that each enjoyed a precious full night’s sleep during this critical period. Now that the race has returned to its usual punishing final sprint, it may be that whoever can best deal with the sleepless nights will be at a crucial and possibly decisive advantage.

Post by: Chris Logie

Salamanders are interesting creatures. When attacked by a predator, they will shed their tail and flee. The tail will wriggle around on its own for long enough to hopefully distract the predator and allow the salamander to escape. Fortunately, losing a tail is not a huge bother for the little guy; he’ll just grow back a new one.

Outside a select group of amphibians, the ability of vertebrate species to regenerate complex organs and body parts is extremely limited. In humans, it is almost non-existent (with the notable exception of the liver). But what cannot be done by nature, we can achieve though science! Or at the least, it may be possible in the future…

Regenerative medicine is a relatively new field that is creating new organs and new possibilities. Last month, it was reported in The Lancet that a 10 year old Swedish girl received a successful transplant of a vein grown in a lab from her own stem cells¹. The girl was suffering from a liver portal vein obstruction, a potentially fatal disease. If she had been an adult, a vein would have been removed from her neck or leg and used as a replacement. However in the case of a still growing child, this procedure carries unacceptable difficulties. Instead, they grew one.

A vein from a deceased donor was stripped of all its cells and the remaining scaffold “seeded” with the girl’s own stem cells. This scaffold was then placed in a “bioreactor” which bombarded the structure with chemicals necessary for programming the stem cells to develop in a specific way. This allowed the new vein to mature before transplantation. Following a second similar procedure the girl returned to full health.

When it comes to organ regeneration experts have identified 4 levels of complexity:

1. Simple flat structures such as skin and endothelium.
2. Tubular structures such as blood vessels and tracheae.
3. “Hollow” organs such as bladders.
4. Organs with complex substructures such as kidneys or lungs.

The Lancet report is just the latest example of engineered organs being transplanted into humans. Indeed, similar results have previously been achieved with bladders, urethras and tracheae^2-4. These manufactured organs have the advantage over normal transplants of being wholly compatible with the patient’s immune system, rendering the need to take dangerous immunosuppressants moot. However, whilst the scaffold technique is useful as a proof-of-concept, in practice problems can arrise. The scaffold may not be a suitable size, causing it to mismatch with surrounding tissue. The growth of cells on the scaffold may be uneven or insufficient. Furthermore, no group have yet created a level D organ using this method.

These challenges have led scientists to look for other options. 3D printing is an industrial manufacturing technique that has recently adapted and expanded into biomedical applications. A 3D printer creates objects by the process of “additive manufacturing”. The printer deposits layers of material (usually small, discrete pieces of metal or plastic) on top of one another onto a flat surface according to a programmed input. These layers are then melted together to form a complete object. This process is used to form many complex objects including machine components, jewellery and toys.

[youtube http://www.youtube.com/watch?v=hk8u5CefYsc]

 

Very recently, 3D printers have become capable of laying down material at the micrometre resolution (one-thousandth of a millimetre), a scale which allows accuracy at the level of a single cell. Biologists have since been experimenting with using 3D printers to print human organs. Small clumps of cells are bound together with a rapidly-degrading film that allows these clumps to be printed three-dimensionally in a fairly structured manner. The cells are then deposited in a shape and structure similar to a specific organ. Whilst the arrangement of the printed cells is not quite the same as a naturally occurring organ, the cells are able to detect their environment and re-organise themselves into a more conventional structure. One example is shown below.

The printed cells used for this technique can either be specific cell types as shown above or more generic stem cells. Once 3D constructs have been formed, the tissue is maturated in a bioreactor to form a stable organ, similar to previous techniques. The now consolidated organ is essentially functional and in theory could be used for transplantation. However, such is the novelty of this technique that it hasn’t yet been put into practice.

Bioprinting has huge strengths over similar techniques including customisation, flexibility and reproducibility whilst not relying on donor material. In theory any cell type, body structure or tissue may be used in this technique providing the correct design and the correct type of “ink” is used. Even bone may be printable using a combination of osteogenic cells and temporary connective tissue replacements.

The potential for this technology is vast. Imagine if we were to bear the maximum fruits of regenerative research. Organ donor waiting lists would become a thing of the past. No more children on dialysis. No more diabetics on insulin. No more hormone disorders (we could replace faulty hormone-releasing organs). Men and women injured in wars or in car crashes would have limbs replaced or healed.

And what about non-therapeutic uses? Want a breast implant? No need to implant a silicon or saline bag – just add more breast. The number of animals killed for research purposes would greatly decrease. When you can test drugs and conduct experiments on organs grown in a lab, the need to extract these organs from animals would no longer exist.

Whatever the possibilities may be, research is still at an early stage. Printers of adequate sophistication cost in the range of tens of thousands of pounds, choking research in this area. We can only hope that as prices collapse, so will the barriers to progress.

Post by Chris Logie

References

1.     Olausson M. et al. (2012). “Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof of concept study.” Lancet 380 9838:230-7.

2.     Atala, A. et al (2006). “Tissue-engineered autologous bladders for patients needing cystoplasty”. Lancet 367 9518:1241-6.

3.     Raya-Rivera, A. et al. (2011). “Tissue-engineered autologous urethras for patients who need reconstruction: an observational study.” Lancet 377 9772:1175-82.

4.     Macchiarini, P. (2009). “Clinical transportation of a tissue-engineered airway.” Lancet 372 9655:2023-30.

5.     Jakab, K. (2010). “Tissue engineering by self-assembly and bio-printing of living cells.” Biofabrication 2 2:022001

6.     Fedorovich, N. E. (2009). “Organ printing: the future of bone regeneration.” Trends Biotechnol 29 12:601-6

In the last few years a small piece of science-fiction has become science-fact. In a recent study a woman, paralysed from the neck down, was able to move a robotic arm using only the power of her mind. Through this robotic appendage she was able to do something she hadn’t done for many years: pick up a cup of coffee and drink from it out without help.
This life changing feat was achieved through the surgical implantation of a computer chip within her motor cortex (the area of your brain which activates when you initiate a movement). The chip detected activity within this region of the brain, forming what is known as a ‘neural interface’. This chip was then connected to a computer which controlled the robotic arm. After some practice, the participant’s brain adapted to the neural interface allowing her to control the arm. What makes this amazing is that despite being paralysed for 15 years, only 20 minutes of adaptation was needed to manipulate the arm adequately.

This research is the latest in a long line of studies showing how machines or devices linked directly to the brain (so called “neuroprostheses”) can be controlled by thoughts alone. First pioneered in rodents and monkeys, this technology is now showing promise for improving the lives of many handicapped people. Potentially, anyone suffering from paralysis in the future will be able to regain a degree of independence and control over their surroundings.

These interfaces also have scope beyond treatment of paralysis, they have in fact been applied to the treatment of many different disorders. A few examples include: Locked-in syndrome, a state where a person is completely unable to move or signify that they are conscious. These patients are unable to speak or in some cases even blink. Trapped in a prison of their own body, patients have gone years before anyone has known that they are conscious. Thankfully, neural interfaces have been developed that allow direct control of a cursor on a computer screen and control of text selection systems for communication. For these people, neural interfaces will provide an outlet through which they can communicate with and interact with the outside world. Similarly, a neural interface in the visual cortex connected to a camera has enabled blind subjects to regain some of their sight. Although sight is only restored to a level that allows them to perceive the outline of shapes and to read, this is still an amazing breakthrough.

Taking the research further, the ‘Holy Grail’ would involve a neural interface coupled with muscle stimulation (a therapy already in use). This would give the patient direct control over their own limbs; providing what could be described as a substitute nervous system which could bypass the injury causing the initial paralysis. Although such complex limb control is still just an ambitious long term goal, more basic control is already within reach and is currently being implemented.

And what about amputees? There are already advanced mechanical prosthetic limbs that can be controlled by muscle movements. One example is shown below:

[youtube http://www.youtube.com/watch?v=fsakrBzTdoA]

However, whilst the control and range of motion of these hands is already sophisticated, a direct neural implant would provide numerous advantages in the complexity of movement as well as the ability to perceive touch, temperature and position. Were all of these incorporated into a neural interface, a prosthetic limb would feel more like a new arm or leg rather than simply a mechanical appendage.

Of course in fiction, people with neuroprosthetic implants are often depicted as psychotic transhuman abominations bent upon the destruction or corruption of normal society. But, given the brain’s incredible ability to adapt, what sort of non-therapeutic implants should we realistically consider? What if instead of recovering some form of lost function, neural interfaces were instead used by healthy people to gain some new function? For example, what about a new sense? Birds can navigate thousands of miles across featureless ocean by intrinsically perceiving the earth’s magnetic field. If there was a compass in your head that was always on and as easy to interpret as your sense of hearing, you might never get lost again. What if a neuroprosthetic implant allowed you to perceive sounds beyond the normal range of human hearing, like a supercharged hearing aid? Or perceive light beyond the normal range of human vision in conjunction with eye augmentation? You then quite literally would have x-ray vision.

Precisely how neural implants will develop in the next few decades is difficult to predict. Significant technical challenges exist in the long term function of these devices and their ability to resist problems such as tissue deterioration, movement and the body’s own immune response. Despite these issues, they undoubtedly will play a huge role in the lives of people with debilitating injuries, but how much of a role will they play in the lives of the rest of us? We will simply have to wait and see.

Post by: Chris Logie

Have you ever left your house in the morning and wondered whether you locked the door or remembered to close the window? Have you ever arrived at your destination and realised you had no recollection of the journey? Have you ever completed any mundane task, whilst thinking about, well… nothing? If you have, it’s not the case that your memory is leaving you or that something is wrong with the inside of your head. In fact, things are probably working better than you think.

Every one of us is perpetually bombarded with an assortment of stimuli. You are constantly seeing, hearing, smelling, tasting and touching. There are also the less recognised senses such as balance, proprioception (your sense of your “body position”) and changes in temperature. Whilst you are not consciously aware of most of these sensations, under the bonnet your brain works through this huge array of information and sorts the important stuff from the chaff. Even when you are asleep, you might awaken only to critical sounds such as a baby crying in the next room but not, say, a car driving past the window.

But your brain doesn’t just subconsciously extract the interesting stuff. It takes this information and combines it with your internal body state (Hungry? Tired? Bored?) and uses this to decide how you should act. This processing allows you to interact with your environment, seamlessly performing the most complex or the most humble of tasks.

An example: you are sitting in a chair in a room and the window is open. There is a cold draft so you get up to close the window. You probably don’t think about how to rise out of the chair. When you walk over to the window, you aren’t aware of the hundreds of muscles working in concert to move you. You aren’t considering the position of your legs, how balanced you are or the sense of touch on the soles of your feet. But your brain takes these sensations and executes movements. It all happens automatically without any need for you to be consciously aware of the process.

Below is a different example. This man is playing music on his guitar. He has to make a series of movements that are precise in both time and space. He does this in response to the sound of the notes and feeling and seeing the position of his hands. As he progresses, the subsequent sensations trigger the movements for the next section of the piece. It’s not entirely automatic but he wouldn’t be able to play this piece without having practiced and learned it first.

[youtube http://www.youtube.com/watch?v=OhaFINynWqY?rel=0&w=480&h=360]

So why is such concentration required for playing a guitar but not for walking? From your brain’s perspective, any movement that you repeat can be considered “practice”. The more you do something, the better you become and the less you actively think about it. Therefore, it’s simply the case that you spend a rather huge amount of time “practicing” walking but not playing a guitar. Even the greatest Rock God doesn’t spend as much time swinging his axe as he does putting one foot in front of the other. If you picked up a completely new instrument, how much time do you think you would need to learn how to play it? A month? Two months? And how long was it before you learned to walk properly?

Practicing, learning and then reciting these movements is part of your procedural memory. Unlike other forms of memory which are governed by the hippocampus, procedural memory is controlled mainly by the basal ganglia, with a bit of tweaking by the cerebellum. In a previous post, Sarah wrote of HM, an individual who suffered damage to his hippocampi resulting in permanent amnesia. Despite this, he could still be taught mirror writing when encouraged by the scientists working with him. When prompted, he was able to write in reverse with no effort, despite insisting he had no knowledge of ever having done it before!

Learning a new skill requires a large amount of effort and attention. However, through repetition, the effort and attention required to perform the task can be reduced. For some the practice of complex motor skills consumes their entire lives. In particular, sportsmen and women have huge demands placed upon them during matches, both physical and mental. Whilst the activity of the basal ganglia and procedural memory is certainly not the brain’s only toil, players that are quick thinking and can dictate play are thought to have greater automation of their movement skills, thus freeing up their conscious mind to analyse the game around them.

Even for everyday souls like us this system is utterly indispensable. Below is a man with Parkinson’s disease, which primarily damages the basal ganglia. He is still able to move his limbs, but coordinating himself is a huge challenge.  In the second part of the video he is given a common treatment, L-DOPA, which provides temporary respite. However, eventually even this will not restore normality.

[youtube http://www.youtube.com/watch?v=sf1N0Zf5IqA?rel=0&w=480&h=360]

Illnesses such as Parkinson’s highlight why the basal ganglia, like so many parts of the brain, are fundamental to our everyday lives. Helping to treat such disorders is the primary reason for scientific research in this area. However, if it also helps us to understand why sometimes we don’t pay attention when we pack our bags in the morning or lock our front doors, then I think that can be quite interesting too.

Post by: Chris Logie