“We are trying to discover the best targets in the brain and how to adjust the activity of malfunctioning brain circuits.”
Andres Lozano is Chair of Neurosurgery at the University of Toronto and a pioneer in the use of deep brain stimulation (DBS) to treat conditions such as Parkinson’s disease, depression, anorexia and Alzheimer’s. On May 8, he visits Lund to deliver the prestigious Segerfalk Lecture at the conclusion of Neuroscience Day. Throughout his career, professor Lozano has made significant contributions to the development and clinical application of both DBS and focused ultrasound for various neurological and motoric disorder. His research has resulted in over 850 publications, and he is ranked among the world’s most highly cited neurosurgeons.
How does DBS work, mechanistically?
“Think of deep brain stimulation as a dimmer switch. Sometimes you want to brighten things up; other times you want to diminish the intensity. DBS gives us that ability. We can target any circuit in the brain and increase the activity of underperforming areas – or decrease activity in overactive areas. We can fine-tune it by adjusting the level of electrical stimulation.”
There are various circuits in the brain that control movement, your mood, your memory. In some cases, these circuits are overactive– as in epilepsy or tremor – and need to be calmed. In others, such as Alzheimer's, large parts of the brain are underactive and need stimulation.
What are the biggest challenges expanding deep brain stimulation into clinical usage?
“Believe it or not: patient recruitment. The main challenge is getting psychiatrists to embrace the idea that psychiatric illnesses can be linked to circuit dysfunctions in the brain – and that local adjustments of these circuits can be beneficial. There's a stigma of surgery for psychiatric illness which is not yet overcome. That's why we're increasingly focusing on DBS and focused ultrasound – because they are reversible or less invasive. We need methods that are acceptable to the psychiatric community.”
“To me, the distinction between neurology and psychiatry is arbitrary. If there's a problem in a circuit that controls movement, we call it neurology – like in Parkinson’s. If it’s a mood circuit, and someone is depressed, we call it psychiatry. But it’s the same organ, the same brain – just different circuits being affected.”
When you do imaging of the brain, are the circuits larger than what you see light up?
“Yes, what you see light up in imaging, such as PET scans, is just one stop along the circuit. Think of it like the subway system: there are many stops along the route. We can access the circuit at many different locations. What you see lightning up on the imaging are some of these stations.”
You also work on focused ultrasound as a therapy – tell us!
“Ultrasound allows us to stimulate the brain noninvasively. Unlike older methods like magnetic stimulation, ultrasound offers a possibility to aim deep in the brain and stimulate deep targets in the brain. We're also using it to open the blood-brain barrier (BBB).”
The BBB is designed to protect the brain by keeping unwanted substances out – but it also prevents many drugs from entering. Focused ultrasound can temporarily open the BBB for. A few hours, creating a window during which medications or therapeutic agents that would normally be blocked can reach the brain.
“This also allows for molecules to leave the brain. In diseases like Alzheimer's or Parkinson's, there are accumulations of toxic proteins in the brain we would like to get rid of. We can also open the blood-brain barrier and give at the same time chemotherapy for tumors, or gene therapy for degenerative diseases, or antibodies to help clear molecules.”
Andres Lozano emphasizes the advantages of using focused ultrasound to open the blood-brain barrier.
“We can be very targeted and open the blood brain barrier selectively in just the specific area we want to reach. So, if you have a brain tumor you don't necessarily want to give medicine to the whole area, but only to the tumor. The main advance is the ability to, very selectively, target where the BBB is open and to control the amount of time that it remains open.”
“It can also be used as a method for making therapeutic lesions in the brain, destroying malfunctioning or overly active regions. Like in the cases of tremor: to destroy cells that cause tremor in the brain is done noninvasively through sound waves through the skull.”
You are also working on a brain machine interface with Neuralink?
“We are implanting electrodes into the brains of people that are completely paralyzed from the neck down. They can’t move their arms at all, and they are able to record signals from the motor area of the brain so that they can [TS1] activate a computer cursor – moving it and clicking. Our first patient is scheduled to be operated in April. “
Out of all these technologies you are working on, what do you think has the most transformative potential in the next 10 years?
“In terms of sheer numbers, treating psychiatric illnesses like depression would be the most significant. Millions of people suffer from depression. It's estimated that conventional treatments do not work on 20 percent of them – a group with a high suicide rate. It's a lethal condition. Depression is 30 to 40 times more common than Parkinson's disease.
Opening blood-brain barrier is a sort of a platform technology, which would be used across multiple disorders including tumors, Alzheimer's disease and depression. There are so many possible applications, but it is early in development.”
You have trained 96 fellows. What qualities define a great neurosurgeon and researcher?
“Curiosity, determination and perseverance – surrounding yourself with great colleagues.”
What initially drew you to the field?
“Curiosity. I was trying to understand how the brain works: how do we create memories? How is information encoded in the brain? These are fundamental questions on how the brain works and what makes us human.”
What has kept you motivated during the toughest moments?
“One thing is having a portfolio of ideas, rather than relying on just one. It's like investments – you need diversity, because some ideas will not work. I'm hoping that one of our four research lines will succeed. Sometimes we’re just wrong. But as Linus Pauling said, ´The way to have good ideas is to have many ideas´. It’s also important to know when to let go of something that is not working. That talent separates successful people from others.”
A particularly rewarding moment?
“We have gone to areas of the brain no one has ever been before. It's a little bit like traveling and mapping – like sailing around the world and landing on new territories. In our quest to identify new brain targets with therapeutic potential, we’ve had the chance to see what the neurons are doing in these unexplored areas – what they're saying and how they respond to stimuli. That has been incredibly exciting.”
Are there any breakthroughs in neurotechnology that you're particularly excited about?
“Focused ultrasound is very promising in terms of delivering therapies to a broad number of people. And the brain machine interface – while the number of individuals treated is not going to be as high – can be completely life-chanhing. These individuals can regain independence. Right now, we focus on recording or reading brain signals. In the future we’ll also be writing to the brain – enabling two-way communication between the outside worlds. So, in the future we envision that there will be a two-way communication between machines and the brain. That means the brain could download information and upload information.
Are ethical implications of these new techniques similar to those of pharmaceutical treatments – or different?
“There are differences. The risk profile is different: taking a pill versus having brain surgery. We are tackling illnesses in people that are vulnerable, people with psychiatric illness. But beyond treatment, there’s also the possibility of enhancement, such as improving memory. In the future, it may be possible to upgrade people who are already healthy. That has massive ethical implication. Who gets access to that?”
