We were interested in Professor Rothwell’s views on the future of brain research. This is what he had to say…
Professor John Rothwell, heads up the Physiology and Pathophysiology of Human Motor Control laboratory at the University College London. Here they specialise in devising new techniques to study the physiology of the human motor system in intact, awake volunteers.
The work undertaken in Professor Rothwell’s lab has provided insights into the mechanisms of actions of deep brain stimulation for the treatment of Parkinson’s Disease and the disorganisation of cortical and brainstem circuitry in different forms of myoclonus.
The lab also has a long history of TMS and has been at the forefront of its use to study cortical connectivity, as a virtual lesion technique and as a method of provoking long terms changes in the excitability of cortical synapses.
They have also devised new methods for rTMS that lead to effects on brain function that outlast the period of stimulation giving insight into how the rest of the brain reacts to changes in function to other parts as well as to possibilities for therapeutic applications.
What have been some of the recent exciting advances in technology for brain research?
I think that’s optogenetics, where people are genetically modifying cells so that they can stimulate them directly or record them very easily en masse. This is the main technical advancement in the last few years. It looks very exciting.
Have there been many advances in non-invasive stimulation?
The one that has perhaps raised the greatest interest has been tACS – that’s alternating current stimulation – people think they can use it to reset or entrain brain activity – it’s a young field and whether or not it can actually do anything remains to be seen but that’s an area of current development in non-invasive methods.
The other method on the horizon is the possibility of using pulsed ultrasound for non-invasive stimulation of deep structures within the brain. This is something that is still in its infancy.
What are your thoughts of the cTMS?
I think from our point of view, cTMS is very interesting because it allows us to employ more specific forms of stimulation. I hope that once we get all these papers written up people will become interested.
What new non-invasive brain stimulation applications or research avenues are you keen to see develop?
I’m really very interested in the pulsed ultrasound stimulation.
It’s been used with humans for peripheral stimulation for many years. There is quite a large Russian literature about it. What is interesting at the present time is that it comes at a time when neurosurgeons are also interested in ultrasound, at a much higher power, which they use focally to produce lesions in the brain. So there is technology that can very accurately focus ultrasound onto a small target in the middle of the brain quite well. In the neurosurgical scenario the ultrasound heats up the brain to produce lesions but with different frequencies and intensities of ultrasound you can get stimulation of the same areas, in theory.
The challenge is that it’s a collaboration in a very technical field, where experts in engineering and neurophysiologists work together to figure out what’s going on and whether it’s safe.
Potentially you could explore whether or not stimulation of a structure deep in the brain (such as the subthalamus in Parkinson’s disease) reduced the symptoms of a particular neurological condition. If it did, you could then think of going ahead to implant a permanent stimulation electrode.
What are the questions we need to be addressing in brain research?
One thing that a lot of people are thinking about is how to make methods more reproducible within and between individuals. It’s not only a problem for brain stimulation but is a widespread concern throughout neuroscience.
Where do you see the future of brain research heading?
A lot of interest is directed towards therapy. At the one end of the scale there are people exploring brain-machine interfacing in order to use ongoing brain activity to direct prosthetic robots. At the other end of the scale, you have people who want to employ techniques to improve physical therapies.
If you had to guess, what do you think the next big discoveries in brain research will be?
Ahhh….the best new discoveries all generally depend on new technologies. As soon as you can do something that no one has done before, that’s when the rate of progress really jumps. It’s one reason for thinking that pulsed ultrasound could be interesting because it allows you to do something novel.
Do you think that technologically there need to be advances in pulsed ultrasound or is it just a matter of applying what’s currently available?
I think technologically there is a lot to do. For one thing, we need to know how it activates nerve tissue. Even something as basic as that is unclear. Until you know how it works, you can’t really refine the method to perfection.