Sunday, 19 October 2014

Transcranial Direct Current Stimulation: Remoulding the Brain by Duncan Ware

A transient tingling sensation on my scalp, accompanied by an equally fleeting phosphene across my visual field, alerts me to the fact that 2 milliamps of direct current are now passing through my brain, the dorsolateral prefrontal cortex (DLPFC) to be specific. No, I haven’t been denied extradition from a pro-electric chair state, I willingly made myself a component in the circuitry of a technology known as transcranial direct current stimulation (tDCS).

It is widely accepted that everything we do has an effect on the ‘wiring’ of our brains, a fact proposed most succinctly by neuropsychologist Donald Hebb, whose words are forever paraphrased as “neurons that fire together, wire together”. Hebb’s law is now known to rely on long-term potentiation (LTP) and long-term depression (LTD), the enhancement and reduction of synaptic efficacy, respectively. These mechanisms of synaptic plasticity are thought to be the fundamental processes which underlie learning and memory, and perhaps even mood disorders and addiction. It is therefore of little surprise that tDCS, a technology capable of modulating synaptic plasticity, has become subject to a great deal of research in recent years.

TDCS involves the application of electrodes to the scalp above particular regions of the brain, as determined by the Brodmann area map used for electroencephalography (EEG); the regions stimulated dictate the effects of the session. The anode exerts a depolarising influence on the neuronal somata (neuronal cell bodies) of the cortex and hyperpolarises the apical dendrites, whereas the cathode induces hyperpolarisation of the somata and depolarisation of the apical dendrites. Relating this back to synaptic plasticity, the areas affected by the anode become more likely to ‘fire’, meaning their synapses are more prone to LTP, and, conversely, regions of the brain affected by the cathode become less active and are more likely to undergo LTD. This is more or less the extent to our understanding of the mechanism by which the effects of tDCS are manifested.

The clinical applications of an electrical current applied to the scalp have been known for years. As far back as 43 AD, in fact, Roman emperor Claudius’ physician used the shocks of electric eels to abate the pain of headaches! Today it is known that tDCS is capable of ameliorating a multitude of pathological afflictions, from stroke damage to schizophrenia, but also that you and I, as presumably healthy individuals, might derive benefit from the occasional zap.

Attending to the former claim of therapeutic potential in the ill, the montage (electrode placement) with which I am, to use the term most loosely, experimenting today has been found to remediate depression. Some studies have found that just 20 minutes of 2 mA anodal stimulation over the DLPFC to reduce self-reported depression by as much as 10% for every week of daily use. Unfortunately, many of the studies I have come across regarding tDCS are ‘open-label’, science jargon denoting clinical trials in which both the researchers and participants know which subjects are receiving which treatments (in this case, the real treatment or a ‘sham’ control). Unlike its ‘double-blind’ antithesis, open-label studies are plagued by the expectancy effects of both the researcher’s overt enthusiasm, or lack thereof, for the treatment and the subject’s expectations of its outcome. Consequently, one might denounce the aforementioned results to be a direct outcome of the placebo effect. This criticism has been largely dismissed by more recent double-blind trials and studies investigating the relative efficacy of tDCS and established pharmacological therapies such as sertraline (an SSRI antidepressant). Such studies have found tDCS and SSRIs to be of equal efficacy, though a combination of the two was found to be of superior efficacy to either alone, a synergistic pairing I hope will soon be exploited in clinical practice.

For those who refrain from the use of recreational drugs due to their deleterious effects or illegality, perhaps you might consider potentiating your own endogenous substances for a similar effect? I recently came across a most intriguing montage which achieves just that. With the anode attached to the C3 Brodmann area, corresponding to the region of the scalp which lies above the primary motor cortex of the left hemisphere, and the cathode pressed against my upper right arm, effects reminiscent of those one might experience following consumption of a weak opiate such as codeine were elicited almost immediately. As someone who has done much experimenting, in the euphemistic sense, this was a most welcome experience I quickly sought to investigate. A google or two later and I found a publication released last year detailing the analgesic potential of tDCS, an effect they put down to the ยต-opioid system. Opioid receptors are those which transduce the effects of opiates and opioids (substances of similar pharmacological profiles to opiates), like morphine and methadone respectively. But the body possesses its own painkillers, including enkephalins, endorphins and dynorphins to name but a few, and it is these substances whose production is upregulated upon stimulation of the motor cortex. What the paper failed to mention, however, was the euphoric sensations evoked by this montage. Feeling like a character from Huxley’s Brave New World, I amused myself with the idea of becoming a junky without ever having pierced a vein or ‘chased the dragon’.

Another, more frequently studied, area of tDCS research focuses on the technology’s potential as a cognitive enhancer. The phrase is employed with ever increasing frequency as we strive to match our efficiency with the demands of modern life, or perhaps to simply mimic Bradley Cooper’s character in the film ‘Limitless’! Whilst I shan’t delve too deeply into the ethical storm which stalks this phrase, I feel that the practice must be discussed. The majority of research in this area pertains to the augmentation of working memory, the ability to hold information in one’s mind to permit its manipulation and analysis. Such research supports the idea that anodal stimulation of the left prefrontal cortex, a brain region implicated in a variety of executive functions, results in a significant improvement in the working memory of healthy participants. However, some experts admonish users of the trade-off between anodal excitation and cathodal inhibition that is so integral to the device’s mechanism of action. By this, they refer to the fact that whilst you might enhance the activity of one area, with the anode, you will also suppress activity in the area beneath the cathode. Minimising the impact of this trade-off is undoubtedly a task we must prioritise in brain stimulation research, especially given the diffuse nature of tDCS’ influence on the brain, which it seems may extend to subcortical structures.

And so, whilst I must urge you to take caution, should you proceed to plug yourself into the mains (figuratively, a 9 volt battery is sufficient) tDCS is a wonderful medical development which, along with its successors: transcranial magnetic stimulation (TMS) and high-resolution tDCS, I predict we will be seeing much more of in the coming years. 

Tuesday, 7 October 2014

Synapse Review: Sir David Attenborough opens the Life Sciences Building by Daisy Dunne

On my first visit to Bristol’s Biological Sciences School back in 2011, I was marched across campus to stare at a giant empty crater on the corner of Tyndall Avenue, which I was assured would soon become the most impressive building the university has ever attempted to construct. Now, some three years later, the end result of the £54 million project is staggering – and who better to welcome in the new build than Biology’s biggest living legend, Sir David Attenborough.

At just gone 11am on Monday, I waited excitedly with an assortment of 200 distinguished guests, including senior lecturers and the city’s Mayor, for the esteemed naturalist and wildlife broadcaster to arrive and officially open Bristol’s new world-class Life Sciences Building. The university’s Vice-chancellor Professor Sir Eric Thomas welcomed us all before the now retired Vice-chancellor Professor David Clarke, who oversaw the building’s construction, regaled us with stories of some of the project’s difficulties – including the discovery of ancient gun powder under the old physics workroom that occupied the site.
Soon after, Sir David took to the microphone to deliver a compelling and personal speech, centralised around the importance of understanding the Natural Sciences to tackle the world’s most pressing problems. He stressed:
“The only way we will deal with the problems on this planet of ours that we have created is to understand what goes on… nothing, nothing could be more important in the area of scholarship than this.”
“Unless we understand the very systems on which we live, the food we eat, the air we breathe, unless we understand how our world affects us, we’ll be in real trouble.”
What’s more, he highlighted the importance of bridging the gap between science and the wider community, to make them realise “how important it is for us to do something”.

In addition to this passionate message, he also spoke of “the joy, resonance and delight” that can be conjured from the natural world, adding “understanding the natural sciences will give you joy for the rest of your lives, it brought great joy to me.”   
To finish, he professed: “I’m proud to be a freeman of this great city and also to hold an honorary degree from this very, very distinguished university”, before unveiling the building’s new plaque and declaring the building officially open.

After Sir David’s awe-inspiring speech, guests were given tours around the building to see some of the breath-taking features – including a 20 metre living wall, which houses 11 different species of plant as well as roosting spots for birds and bats. Also, guests visited the GroDome, a state-of-the-art tropical greenhouse that resides on top of the 13,500 square metre building.
For me, the most impressive aspect of the building is the five-storey glass laboratory wing, which supports ground breaking research from a multitude of different disciplines – from bat bioacoustics studies to virtual-led palaeontology. 
The new Genomics Facility is set to transform the university’s world class study into understanding the evolution and mapping of entire genomes. Professor Keith Edwards, a cereal genomics expert from the School of Biological Sciences, says:

"From the outset the new building was designed to have a state of the art genomics facility; including two next generation sequencers and a range of genotyping and robotic platforms. The new laboratories have been designed to minimise sample to sample contamination via the use of controlled air flow between rooms operating at different pressures.”

Image Credit: Nick Smith | University of Bristol