Oscillopathies – Part Two: Expert Survey

(This is the second part of a series I am putting together on Oscillopathies. Click here for my introduction to the subject in part 1. It is also the third such expert survey I have done, click to read the other two on: Cell Replacement Therapy and Neuroimmunology.) 

Experts

Phillip Starr – Dr. Starr is the Dolores Cakebread Professor of Neurological Surgery, at the University of California, San Francisco. He did his neurosurgery residency at Brigham and Women’s Hospital, followed by a fellowship in movement disorders surgery at Emory University with Drs. Roy Bakay, Jerrold Vitek, and Mahlon Delong.   He was recruited to UCSF in 1998 by Dr. Mitch Berger, to launch a clinical and research program in deep brain stimulation. Dr. Starr and UCSF neurologist Dr. Jill Ostrem are the directors of a multidisciplinary clinic for comprehensive care of patients with movement disorders. Dr. Starr directs a fellowship training program in functional neurosurgery. His NIH funded research addresses: 1) Brain network abnormalities underlying motor and nonmotor features of movement disorders. 2) Mechanisms of therapeutic deep brain stimulation. 3) The use of totally implantable neural interfaces  for long term brain recording and adaptive DBS. 

Simon Little – Dr. Little is an Assistant Professor of Neurology at UCSF who specializes in the diagnosis and management of patients with movement disorders such as Parkinson’s disease, tremor, and dystonia. He has a particular interest in the use of deep brain stimulation therapies for the treatment of medically refractory movement symptoms. Dr. Little obtained his medical degrees at Cambridge University and University College London before training in neurology at St Georges university London and at the National Hospital of Neurology and Neurosurgery, UK. He then completed a PhD at Oxford University in experimental neurology, investigating personalized and responsive brain stimulation therapies for movement disorders. Following his work at Oxford University, he was appointed as a clinical lecturer at University College London, where he worked in Magnetoencephalography neuroimaging of movement networks.  At UCSF, Dr. Little manages clinical movement disorders and investigates new diagnostic and treatment approaches using brain recordings and stimulation therapies.  

Ro’ee Gilron – Dr. Gilron is the lead neuroscientist at Rune Labs where he helps industry and academic partners develop personalized therapies for neurodegenerative disorders. He completed his PhD in Cognitive Neuroscience at Tel Aviv University (TAU) where he studied action representation using neuroimaging. In addition he conducted research in the epilepsy monitoring unit with Itzhak Fried where he fell in love with clinical research. During his postdoc with Dr. Philip Starr at UCSF he helped develop adaptive DBS using chronic long term recordings in an experimental next generation deep brain stimulation device. When not in the lab you can find Roee abusing his Mountain Bike, or being abused by his 5 and 1 year old boys.

Alfonso Fasano – Dr. Fasano holds the Chair in Neuromodulation and Multi-Disciplinary Care at the University of Toronto and University Health Network. He is a Professor in the Department of Medicine (Division of Neurology) at the University of Toronto. He is a staff neurologist and co-director of the Surgical Program for Movement Disorders at Toronto Western Hospital, University Health Network. He is also a staff neurologist at the Hospital of Sick Children in Toronto and a Clinician Investigator at the Krembil Research Institute and KITE – Toronto Rehabilitation Hospital. He leads the Core E (closed-loop capabilities) of the CenteR for Advancing Neurotechnological Innovation to Application (CRANIA) and sits in the scientific advisory board of the Dystonia Medical Research Foundation and International Essential Tremor Foundation. He’s the chair of the Normal Pressure Hydrocephalus study group of and member of the study group on tremor of the International Parkinson Movement Disorders Society. Dr. Fasano received his medical degree from the Catholic University of Rome, Italy, in 2002 and became a neurologist in 2007. After a 2-year fellowship at the University of Kiel, Germany, he completed a PhD in neuroscience at the Catholic University of Rome.

Questions

What, if anything, is an oscillopathy?

Phillip Starr – A disorder in which populations of neurons are excessively synchronized, and the excessive synchronization occurs at specific frequencies.

Simon Little – An abnormal increase in brain waves in one area of the brain associated with clinical symptoms.

Ro’ee Gilron – Not sure this is an accepted term at all yet. But it’s a useful framework / lens to look at the (correlational) evidence we have so far that links excessive periodic oscillations in certain frequencies with signs and symptoms of an entire class of neurodegenerative disorders. This is the best review (from 2005! and newer review from 2019) that I know of on this topic. 

Alfonso Fasano – A fancier term to indicate a brain network problem, pretty obvious at this point. It’s a more neurophysiological way to describe networkpathy, another fancy term from a more anatomical standpoint

Are Parkinson’s diseases oscillopathies and would it be helpful if the field started to think of them as such?

Phillip Starr – Yes – physiologically PD is an oscillopathy and training of specialists is starting to underscore that.

Simon Little – Although Parkinson’s disease is an oscillopathy and it would be helpful if the field started to consider this in the pathophysiology – this is just one part of the story (starting with dopamine cells at the most basic level), so shouldn’t be considered as a complete account of what causes Parkinson’s.

Ro’ee Gilron – There is strong evidence that certain aspects of the disorder, in particular, motor aspects are strongly linked (check out figure 2) to oscillatory phenomena, and are good candidates for aDBS to better control motor phenomena of PD. In the non-motor, sleep, and autonomic domain the evidence is mixed.

Alfonso Fasano – Many brain disorders are such, probably epilepsy and the spreading depression seen in some conditions are the best examples. It won’t change how we approach PD.

Which other types of diseases are oscillopathies? 

Phillip Starr – Probably many; epilepsy is one, dystonia and tremor disorders like essential tremor are probably oscillopathies.

Simon Little – Essential tremor, Dystonia, Possibly Tourettes, OCD & Depression. 

Ro’ee Gilron – I’d argue that most neurological disorders that involve pathology in the brain may be reflected as abnormal oscillatory phenomena (either periodic or aperiodic). The causation/correlation or cause/effect issue is trickier to sort out. 

Does our brain intuit our own oscillations and how could we pick up on early signs of perturbations in them? 

Phillip Starr – Interesting… don’t think a brain can be self aware of its oscillatory status, unless they are in a research study in which the strength of the oscillation is translated to the position of a cursor on a computer screen, and the person can see the screen and examine how different thought patterns move the cursor.

Ro’ee Gilron – They likely manifest in behavior. For example, every time you move your arm there is a desynchronization in the beta phase in your motor cortex. This is directly tied to moving and is normal. In a similar fashion, abnormal movement is also reflected in oscillatory phenomena.  

Alfonso Fasano – Probably looking at fluctuations, any biological system start fluctuating more when in trouble.

Why do we have different names for the different frequencies of oscillations and is it helpful for us to continue using those names? 

Phillip Starr – Those ‘canonical” frequency bands like alpha, beta, etc. are historical, derived from the epilepsy world. That being said, they’re useful to use them as they are part of our common vocabulary.

Ro’ee Gilron – Probably for historical reasons. Good overview on Wikipedia page actually. Is it helpful – be the change you want to see 🙂 

Alfonso Fasano – It’s just a convention, very limited as it was coined almost a century ago (https://en.wikipedia.org/wiki/Hans_Berger).

If we had a perfect understanding of the oscillations of a human being and could accurately simulate each, could we recreate that person? 

Phillip Starr – Unlikely, since not all important brain activity is an oscillation.  Neurons often fire asynchronously, or synchronously but not in an oscillatory pattern, and many brain functions likely require non oscillatory activity too.

Ro’ee Gilron – Nope. The brain is a lot more complex than just it’s connectome or oscillations. We are not even remotely close to understanding and a lot of understanding is phenomenological in nature. 

 Alfonso Fasano – Nope, as we need also the accurate spatial distribution of those oscillations