Deep Brain Stimulation for Therapeutics: What is the prognosis?

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Abstract: Deep brain stimulation (DBS) techniques for therapeutics were introduced in France in 1987. Since their inception a great deal of ongoing research has shed light into the potential applications of DBS to give people suffering from dystonia, Parkinson’s Disease, Tourette’s Syndrome, and Major Depressive Disorder, a chance at a better quality of life. In some cases, the DBS can be used to treat patients without the need for additional drugs that may carry a variety of side effects for individuals. More recently, DBS is also being considered for its potential to be used to put at bay Obsessive Compulsive Disorder (OCD), persons suffering overly from anxiety, among other applications. DBS requires biomedical engineers to work closely together with medical specialists and surgeons in the development of appropriate technology. DBS is not a cure, rather two electrodes (in the case of a bilateral implantation) are implanted in the brain (e.g. ventrointermediate nucleus (VIM) of the thalamus, globus pallidus internus or the subthalamic nucleus) and electric impulses sent to fend off overactivity. E.g. in the case of a patient who tremors, the stimulation helps them to stop tremoring by “zapping” that part of the brain responsible for the tremors. It follows then, for the patient who is feeling major depressive thoughts, the stimulation may help reduce periods of darkness. This is particularly the hope for those suffering from mental illness who seem to be drug resistant. Vagus Nerve Stimulation (VNS) acts in a similar way but instead of being embedded in the brain, the electrodes are placed in the vagus nerve, which is responsible for sending the mild pulses of electrical energy. A VNS sends continuous stimulation periodically, and is mainly used in those who suffer from epilepsy. There is now growing evidence to suggest that both DBS and VNS are having a positive impact on patients, but for some it has been proven to have no effect, or even a negative effect.

As the brain pacemaker industry becomes a multi-billion dollar industry, patient safety issues have entered the spotlight. The potential for infection, defective devices, devices that are misprogrammed, or even cyberhacking have received increasing attention. Some patients are now raising concerns about manufacturer discussions that devices should be linked to the Internet and what this might mean in the context of electromagnetic interference and the potential impact not only to render stimulators inoperable but the impact on the brain itself. Others hypothesise that if you can make corrections through stimulators, then you can also create problems with stimulators. How long might it be before DBS becomes a general purpose product possibly marketed for memory enhancement or use in defence contexts?

Biography: Katina Michael is a professor in the Faculty of Engineering and Information Sciences at the University of Wollongong. She has been researching both deep brain stimulation and vagus nerve stimulation from a patient perspective for the last 20 years. She is particularly interested in the social implications of emerging technologies in national security.

Link: http://www.katinamichael.com/seminars/2017/10/9/deep-brain-stimulation-for-therapeutics-what-is-the-prognosis

Contact: Nev Stephenson

 Probus Nowra Committee

Probus Nowra Committee

 Probus Nowra Members @ my talk on DBS

Probus Nowra Members @ my talk on DBS

Probus Group: Shoalhaven

Parkinson’s is a progressive neurological condition that affects people from all walks of life. It is quite common, with approximately 70,000 Australians living with Parkinson’s.
The average age of diagnosis is 65 years, however younger people can be diagnosed with Parkinson’s too. This is referred to as Young Onset Parkinson’s.
It is not easy to diagnose Parkinson’s. There are no laboratory tests (such as a blood test or brain scan), so it is important that the diagnosis is made by a specialist, such as a neurologist. The specialist will examine for any physical signs of Parkinson’s and take a detailed history of symptoms. 

I remember my first confrontation with Parkinson's disease. I was on the inner city bus 394 bound for Maroubra, New South Wales. A young man boarded the bus struggling to get his then Metro pass into the magnetic stripe reader. The bus driver got out of his seat and helped the man by pushing his hand into the reader device at the front. The man was tremoring so much that is the bus left the curb he found it difficult to set and so just placed his body against the rails in the mid-part of the bus. On witnessing this I felt uncomfortable but quickly realised this man was suffering from a debilitating condition. Almost simultaneously as the man pressed the exit button to signal that he would get off the bus, an older gentleman got up and started to motion that he was in a boxing style match exclaiming to the young man: "you lot should be ashamed! How do you border bus either having consumed alcohol or abuse drugs!" As the young man tried to defend himself and get off the bus he exclaimed: "it's called Parkinson's disease, you idiot." I felt very sad for the young man, who had obviously been misunderstood so often but had bravely boarded a bus in full view of his condition. He was dressed in an old pair of jeans, and a white T-shirt that was loosefitting. The older man who wanted to pick a fight was wearing a suit, and allegedly protecting his elderly wife. There are some scenes that never leave you… And from which you learn profound lessons. Never to judge another because you have no idea what they are going through.

It was not long after that that Michael J Fox, despite being so young, was diagnosed with Parkinson's disease. I grew up watching Family Ties as a kid, and always thought Fox was an exceptional talent. He gave this Testimony about living with Parkinson's Disease to the US Senate Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies about Parkinson's Disease Research and Treatment. 

Below is one approach to putting Parkinson's disease at bay. To my knowledge Michael J Fox does not have a deep brain stimulation device implanted in his brain.The company the has championed this solution is Medtronic.

This video shows how a patient is implanted with a brain pacemaker. First the patient is sedated slightly, but remains awake throughout the operation. In the first instance electrodes are placed in the brain. Usually between two and four electrodes are placed in specific areas of the thalamus. A patient can respond to the neurosurgeons questions. This provides the neurosurgeon with some assurance that the operation has been a success. Placing the electrodes in a particular location may mean the difference between the patient's suffering tremors or not, the patient being able to speak or not. Once the electrodes are put in place using the five bur holes as registration points in an image location the patient's head is sealed. About two weeks after that, a battery pack is implanted in the chest of the patient and hooked up to the electrodes. This part of the operation takes about two hours. After some time, the patient visits the neurologist turning on the DBS unit. The neurosurgeon begins with very low electrical pulses to the brain, so as to give themselves some room to experiment with settings over the coming months and year, ensuring that the patient does not receive an overstimulation of pulses leading to significant side-effects. Some patients describe the procedure working within days of the operation, there is other patients have described that it has taken about a year for them to feel significant change. Very few notes no change whatsoever.

Here is an explanation of how the deep brain stimulator actually works. Remember, the stimulation does not mean over exciting a particular area of the brain, but rather zapping it so as to stifling its "endless loop".

From a university hospital stakeholder perspective the following documentary follows a patient through a 2011 operation at St Louis. Every part of the procedure is explained in some detail, and the short documentary is effective in raising awareness of DBS.

The following clip contains first person testimonials of adopting Medtronic's DBS for Parkinson's disease.

The following video demonstrates how a DBS sufferer feels about his adoption of a deep brain stimulator. In the case of this video blog, it is clear that the devious recipient cannot live without his stimulator. For many people suffering from Parkinson's disease, despite that the DBS technology is still experimental and has the status of a humanitarian device exemption, some sufferers believe there is little choice but to adopt the technology given their current quality of life.

Over the last decade, while much attention has been given to conquering Parkinson's disease depending on someone's profile and age and prior medication taking history, attention has now also turned to whether or not the brain stimulators can work for things beyond movement disorders. For example can DBS help overcome issues related to major depressive disorder, obsessive-compulsive disorder, anxiety, and other potential brain diseases? Mayburg is one researcher who has been asking this question for two decades. Her researcher Emory University has been groundbreaking to some, and to others premature. It is worth watching in full, Mayburg's own presentations which have been filmed at various universities in Israel and Sweden. She has written numerous papers on her research. These papers that are peer-reviewed are accessible via University databases online. While the clinical trials have been in small-scale, Mayburg has focused her attention on the location in the brain called AL25. She believes that for some patients this is the part of the brain that needs intervention and yet, she admits that it is early days before any reasoning can be determined for this finding. The trials have demonstrated that some patients respond well to the treatment of the DBS for MDD, while other patients show no response, and some patients feel worse than before the implantation. It is everybody's hope that increasingly more evidence is provided for the type of person that can and cannot undergo the procedure and for whom it is effective and for whom it is not. Nobody wishes to see live trials go ahead in this space, that render somebody worse off than what they began with. We need to be careful with bioethical decisions that affect real human beings. And yet in other cases patients outcry when a procedure is made available in Europe for example, and is only approved by the Food and Drug Administration some two decades later. There is a trade-off between safety and risk.

Much has been discussed regarding early experimentation of providing feedback to the brain via external electrical pulses as were showcased in experiments conducted by José Delgado. In one experiment, he implanted a raging bull with radiofrequency and was able to remote control it to come to a standstill by stimulating its brain. In other cases, he placed monkeys in cages and expose them to varying levels of electromagnetics. He thought his experimentation proved that we could help the brain in some way by providing to it direct feedback. In that same documentary was noted that the former Soviet Union had spent 30 years experimenting with the brain and mentally disturbed patients.

Much has been recounted about the potential to use deep brain stimulation techniques in defence. In 2012 tender for research, DARPA requested support for the development of implantable is for post-traumatic stress disorder and also memory enhancement for its ex-servicemen and women, and everyone else. Some headway has been happening with regard to this area of research, and many are proposing the artificial intelligence also play a role in this assemblage.

What to make of DBS for therapeutics versus DBS for enhancement? Is there a plumb line to be drawn or is the division between the two types of applications dotted? Can one stop science? Will we continue to tinker with the most vital organ in the brain creating applications like we've never thought of previously? Two examples of devices that measure brainwaves and allow for sorts to communicate with digital devices are Emotiv and Interaxon (MUSE). Imagine the support for disabled who could think about pouring themselves a cup of water, or bringing a water bottle to sip through closer to them, and how liberating this might be? At the same time it is clear that we are getting closer to understanding the inner workings of the brain, despite that we are still in the nascent stages. The brain project and the brain initiative are both propelling us into grand findings, even greater than those of the human genome project. The question then becomes if we can figure out where there are ways to stimulate the brain to help those suffering from chronic disease, then might we be able to reverse engineer a perfectly normal brain to the depths of dystonia, tremors, movement and speech issues?

Important links: http://edition.cnn.com/2016/03/07/politics/pentagon-developing-brain-implants-cyborgs/index.html

One of the classic cartoons I grew up with was the Transformers, a Hasbro animation. In one episode, the ultimate doom part one, that the decepticons higher Prof Arceville, to implant Chip's father against his will so that he can be used by the dark forces, in a remote control fashion powered by the chip. 

The Ultimate Doom (Hasbro, 1984): http://tfwiki.net/wiki/The_Ultimate_Doom,_Part_1. Full episode here.