Alfonso Fasano, MD, PhD, is an Italian Neurologist trained in Italy and Germany.
Dr. Fasano is the co-director of the surgical program at the Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital. At the time of the interview below, he was associate professor of medicine in the Division of Neurology at the University of Toronto and, in April 2019, he was promoted to full professor. He is also clinician investigator at the Krembil Research Institute. Dr. Fasano’s main areas of interest are the treatment of movement disorders with advanced technologies including infusion pumps and neuromodulation.
The following has been paraphrased from an interview with Dr. Fasano on Dec 12, 2017.
There is a lot of hype surrounding brain machine interfaces, how realistic is it that we might one day have a direct link between our brains and our machines?
I think it is very realistic, the main question is the time-frame. Many such interfaces are in place already. One example is peroneal nerve stimulation, which is the stimulation of a nerve that keeps the foot up and is used for people with stroke or who have weakness in the lower limb. The interesting part of this device is that it only activates the nerve when needed. Deep brain stimulation (DBS) for movement disorders is another example and soon we will have adaptive DBS which will be closer to a true brain machine interface.
Neurons are very sensitive to electrical fields and all of these machines use electricity to affect neurons. What makes the application difficult is we still don’t understand very well the physiology of the central nervous system. In monkeys there are experiments using DBS after completely severing their spinal cords. In these monkeys the signal through the spinal cord gets transmitted wirelessly from the brain, enabling them to move again. But human locomotion seems to be much more complex.
However the short answer to your question is yes, I think it is something that is going to happen within the next 10 years.
Will the optimal brain machine interface need to be invasive?
Yes, though there are non-invasive ways to stimulate the nervous system. The common examples are transcranial magnetic stimulation and transcranial direct current stimulation. There is also a new way using pulsed electrical fields that can focus electrical fields to stimulate deep brain structures without opening anything. Another example uses focused ultrasound, which is typically used to make lesions in the brain, however if you use it at a lower intensity you can also change the excitability of neurons. But all of them have problems because they need to be permanently attached to the person and always on to really work. People don’t want something that is visible from the outside. Companies are developing some minimally invasive stimulators for DBS that will likely be used in future brain machine interfaces.
Correct me if I am wrong but we still don’t understand precisely how DBS works, what is missing in our understanding?
Correct, in medicine quite often we use things that work even though we don’t know how. The biggest misconception about DBS is that it is a stimulator, the reality is that it actually inhibits circuits. The brain is a very complex machine with both excitatory (providing activation) and inhibitory (providing inactivation) circuits. Many diseases result from one or more of these circuits not being properly controlled and are often over-active. So we treat these problems by inhibiting their activity.
For instance in Parkinson’s disease it is well known that because of the lack of dopamine there is increased activity of two parts of the brain called the sub-thalamus and the globus pallidus. So to treat the disease we need to reduce the activity of these regions. In the past surgeons just destroyed parts of them by making lesions, which was discovered by coincidence. But this caused some permanent side effects. Then they used electrodes that can listen to and record neurons as they were firing. At some point they started stimulating those neurons using those electrodes and noticed that the stimulation mimicked the effect of the lesions. Then people connected it to pacemakers and batteries to get a constant flow and found by doing so that they could treat these problems. We believe it inhibits the circuit by jamming the signals which then confuses the neurons and then they stop doing their job.
However it is an imperfect tool. Most people with DBS do see improvements in their symptoms but they often lose other motor skills. For instance, musicians with PD who get DBS often have an improvement in their Parkinson’s symptoms but they lose some of their fine motor skills that allowed them to play their instruments.
Can you explain the next generation of DBS that is in development, the so-called closed loop (or adaptive) DBS?
I should start by saying that pacemakers for the heart began in the 1950s and it only took them 12 years to move from a continuous pacemaker to an adaptive one. This was because EKG’s gave us a good biomarker that allowed us to give this stimulation on demand.
DBS for movement disorders started in 1987, yet we still haven’t moved to adaptive DBS mainly because the brain is more complicated than the heart, and we haven’t had a biomarker that would enable us to build an adaptive system. But recently we found neurons deep in the brain start to oscillate with a given frequency that we call the Beta band that correlates with Off times in Parkinson’s. This allowed us to start developing machines that can be turned on or off by these Beta bands. This would have been impossible in the past because of all the noise created by the stimulation, but now we also have filters that can block out this noise. This seems to give us better results with less negative effects. There is still some unknown but we will be starting a randomized double blind trial for it in a couple months.
Will this version of DBS be applied to non-motor symptoms or other diseases?
Yes, first simply because some of what we call non-motor symptoms are really just effects of motor problems. For example a lot of sleep problems are just the result of not being able to move properly during the night when the medication has worn off.
DBS gives us a much more targeted approach to treatment than medications which tend to flood the whole brain with drugs. So it is very useful for diseases that are just the result of damage to one part of the brain. But brain areas do often overlap which can complicate things. Also we still don’t know how to properly stimulate degenerating circuits, so we often get results that we can’t predict. One interesting example was a case of obesity. By targeting the region of the brain responsible for appetite in this patient, researchers also triggered the recall of memories that he had completely forgotten from earlier in his life. This led people to use DBS for other memory problems, but it was difficult to replicate the same results.
But there is growing evidence that we may also be able to use DBS for mood disorders, Alzheimer, brain trauma, coma, spinal cord injuries, and other gait and balance problems.
What are the minimally invasive devices that you mentioned before?
Companies are developing devices that are much lighter, smaller and easier to insert than the ones we have today. The decrease in size and weight alone will remove some of the complications that we get from current DBS devices. These will likely come on the market within the next 5 years. The biggest challenge we have is with the battery which now can last for years but is fairly bulky and needs to be implanted into the patient along with the electrodes. So we are looking towards rechargeable batteries that are much smaller.
One final note regarding cures. I am quite sure that we will have cures that are effective for some of the diseases we treat with DBS in the future, but it will be hard to cure everyone, especially those with very rare forms of those diseases. These neuromodulation techniques we are developing are symptomatic treatments that will make life easier for people until we get to a cure while also helping those for whom a cure is less likely to be found.
Keep an eye out for more entries in this section soon, and go here to view all Benjamin Stecher's unique blog posts for JPD! See all entries his Tomorrow Edition blog on that website here.