Researchers at the University of Florida perform deep brain stimulation on a patient with Alzheimer’s disease (Credit: University of Florida)

Unlocking the Brain with New Stimulation Technologies

In some of the more obscure corners of the online tech community, you may have heard predictions that the human brain will be able to connect directly to the internet by 2030. Although these predictions still feel a lot like sci-fi, advances in brain related technology have already moved us far closer to that goal than almost anyone realizes. New technologies are constantly improving our knowledge about brain function and there are many neurotechnology innovations happening right now that genuinely affect how people live for the better. 15 years ago, when I was at university, the popular theories on the brain were that specific regions of the brain were aligned to certain functions and behaviours. This theory has since been shown to be too simple. New sophisticated brain mapping technologies have shifted the focus to connectivity between brain regions. We still have so much to learn.

Kate Hoy is a neurotech researcher in this space. She is awesome. I was lucky enough to spend some time with her recently and gain insight into some of her pioneering research in brain stimulation. She’s a Senior Research Fellow and NHMRC Career Development Fellow at the Monash Alfred Psychiatry Research Centre in Melbourne, and her work utilises the latest research in brain function and applies brain stimulation technologies to help people with cognitive impairments, such as schizophrenia, live more productive and resilient lives. She explains how.

As a child, did you know what you wanted to be when you grew up?

I was the youngest of four and I loved to read, in fact, I really wanted to be a writer. I remember I used to get in trouble because Mum would come up to my bedroom where she would find me under the covers with a book at 11 o’clock at night and would say ‘Go to bed!’. My Dad got me interested in fantasy with Raymond E. Feist books which were a little bit ‘sciencey.’ I was always interested in stories with those kinds of ideas.

When I got into high school I really enjoyed psychology and biology. As I went through university I became interested in behaviour, mental health and mental illness but from the angle of what was happening in the brain and how this linked to behaviour. I was particularly interested in schizophrenia, it was an illness that was so debilitating but also one which we knew so little about. That’s still the case today. There were so many questions about what actually caused schizophrenia and I think those questions really contribute to the stigma around it because we can’t say definitively that this is the area of the brain or this is the part of the DNA code that causes your illness. This really interested me so I did my Honours and then a doctorate on the topic of schizophrenia.

What kinds of things do you research?

Broadly speaking my research is around developing new treatments for cognitive impairment with a focus on schizophrenia. People with schizophrenia often experience difficulty with working memory and attention. These impairments, even more so than the voices that they hear, really impact their ability to complete daily tasks such as grocery shopping. At the moment treatments are limited. Medication is available as one form of treatment, and although it can help with the voices in some cases, it doesn’t really do much for cognitive symptoms. Cognitive training has some mild effects but not enough to genuinely improve people’s lives.

This lack of progress has led me to focus on brain stimulation techniques to target what we believe underlies each symptom and is something that hasn’t been done before. The brain stimulation technology we are using is called transcranial Direct Current Stimulation (tDCS), which is a really gentle electrical stimulation that makes brain cells more or less likely to fire. To find out if this treatment has any effect we completed a proof of concept study that found with just 20 minutes of electrical stimulation to the area of the brain that is involved in working memory, the patient experiences a significant improvement. This effect lasts up to approximately 40 minutes, which is really promising. Now we are looking to roll this out into longer stimulation sessions (similar to the more established brain stimulation treatment methods used for depression) to determine if we can make the improvement last and if it contributes to our ultimate goal, which is better outcomes in their daily lives.

We have developed a broader program looking at other significant cognitive impairments such as traumatic brain injury. In these cases people have had a severe knock to the head and have developed attention and memory problems. We are also about to start a study using Transcranial Magnetic Stimulation (TMS) on mild to moderate Alzheimer’s disease to see if we can improve the symptoms in the early stages. Each study will target stimulation to the specific impairment in each disorder.

What inspired you to get into this area of research?

My doctorate was in clinical neuropsychology which makes me a neuropsychologist by training. I worked clinically for a short period of time but it wasn’t for me. We would see patients with cognitive impairments that were severely impacting their lives and there was little we could do for them. There was a lot of externally-focused treatments (such as keeping diaries etc) and I became frustrated with the lack of innovation in treatment development. It was almost like we were saying that what underlies cognitive impairment is so complicated that trying to develop a specific treatment is too hard. Don’t get me wrong, it is hard! However with advances in technology and the outcomes we were seeing elsewhere with brain stimulation, it seemed to me that there had to be a way forward. So I moved out of clinical to work on finding treatments that could one day be used clinically.

How would you describe the different forms of brain stimulation?

Transcranial Magnetic Stimulation (TMS) is delivered via a figure of eight coil that is attached to a machine and held over the area of the brain that you want to stimulate. A magnetic stimulus (termed a ‘pulse’) is generated and passes into the brain via the coil. This induces an electrical field in the brain which causes brain cells to fire. If you give TMS at a high frequency (i.e. greater than one pulse per second) you will increase brain activity, if you give at low frequency (i.e. less than one pulse per second) it can decrease brain activity. The patient is completely awake during treatment and does feel it, it’s often described as like a tapping on the head. We also use the technology to understand how the healthy brain works, connection pathways and how the brain regions communicate.

Transcranial Magnetic Stimulation (TMS) in action. (Photo credit: Monash University)

If you were treating depression with magnetic stimulation, the patients would receive daily treatments to increase brain activity for 20 minutes five times a week for about four weeks. This results in a lasting change in approximately 50% of patients’ mood. We can infer a lot about the best treatment approach for people with cognitive impairments due to the work in depression.

Transcranial Direct Current Stimulation (tDCS) is another form of brain stimulation, which uses very low levels of electrical stimulation. Two electrodes are placed on the head, generally an anode and a cathode. Electrical current flows between the electrodes, with the majority of stimulation occurring at the site of the electrodes. This is a much more subtle way of stimulating the brain than the magnetic stimulation as the neurons don’t fire, the treatment simply makes the neurons more or less likely to activate, effectively lowering or increasing the threshold and enhancing the brain’s natural firing pattern.

Both of these forms of stimulation (TMS and tDCS) have effects on the specific areas of the brain that you apply them to but they are also able to modulate networks throughout the brain. This makes them promising treatments for illnesses such as schizophrenia, depression and dementia, which we now understand as disorders of brain networks.

What is the most surprising or interesting research case you have worked on?

The findings where the data doesn’t show what you expected are always the ones that mean the most. In one study we were looking at the effect of gentle electrical stimulation (tDCS) on memory in healthy people; we compared sham (‘fake’) stimulation with a low and a high dose of tDCS. My hypothesis was that the higher the dose the better would be the performance and I couldn’t have been more wrong. The findings showed that the sham stimulation did nothing (as predicted), the low dose improved performance significantly, and the high dose behaved most similar to the sham stimulation.

This puzzled us so we brainstormed the findings and came back to the idea of homeostasis, where you can push the healthy brain a little but if you push it too much it will ‘push back’. Essentially, there are only limited gains in brain function that can be achieved in the healthy brain. That finding, which was from an Honours project, that I had initially worried was uninterpretable, resulted in a publication, two current PhD projects, and set me off on a different path with this aspect of my research.

How have you seen this field change in the last 15 years?

Our understanding of the brain has changed a lot in the last 15 years, which is driving a lot of the science that we are doing now. We used to think that certain brain regions were responsible for specific outcomes whereas now we know that it’s not that simple. We know this because of the incredible technological advances in how we are able to look at the brain. Magnetic Resonance Imaging (MRI) technologies have uncovered the brain for us in a way that has hugely changed our understanding.

There is a relatively new analysis of MRI called Diffusion Tensor Imaging (DTI) that has appeared in the last 5–10 years that images the white matter connections in the brain (as opposed to the grey matter traditionally seen). All regions in the brain are connected by an intricate network of fibres and DTI allows us to image them. Combine this with analysis of the electrical activity in the brain and we are beginning to see the many connected regions that are involved in completing a task.

There is also a relatively new area of research called Connectomics which uses very advanced imaging techniques, graph theory and mathematics to define how nodes in the brain are connected and how this differs in specific brain disorders. For example, it was not that long ago we thought we needed to target certain regions to treat depression but now with these advances in technology and techniques we can see that it is actually a complex interdependent network. We can see how this network is dysfunctional in patients with depression, some parts are overactive and some underactive, which has informed us on how to target brain stimulation treatments more accurately.

Expanding our understanding is critical because previously we have been treating patients with medication without much knowledge about the specific ways that the medication caused improvements. Now we can start our understanding from the networks that are not functioning correctly and determine the correct treatment and then apply that therapy. This turns traditional treatment methods on their head and is letting the innovation in tools drive the innovation in treatment.

There are very few truly innovative changes in psychiatry in the last fifty years but brain stimulation (such as TMS and tDCS) is definitely one of them. There are now around ten different types of brain stimulation techniques that are being investigated so ultimately patients will have a much wider choice about the type of treatment they want. They could try medication or they could try one of the brain stimulation treatments. This is important because no single treatment is going to work for everybody so you need to have a wide variety available and they need to be targeted to that person’s particular symptomology.

Where do you see this technology and industry going?

I think what the industry needs is a bit more innovation in the techniques, for example, there are techniques now being developed where the stimulation mimics or interacts with natural brain activity, enhancing natural patterns, such as transcranial Alternating Current Stimulation (tACS) or Theta Burst Stimulation (TBS).

Another important area of development is personalising treatments to get the most benefit for the individual. There are many different ways to apply magnetic stimulation (frequencies, areas of the brain for example) and different people will most likely respond to different configurations of treatment. This is where determining the predictors of success for different treatments is so important so we can assess the patient and immediately provide them the best advice for their own personalised course of treatment.

Another innovation is the potential in making the treatment more accessible. One idea is providing the technology for home-use for patients, although, we are a fair way away from this. If the technology was available at home then should the patient’s symptoms return they could have another course without having to come into the centre every day. There is a lot of regulation and considerations for this to occur but this is where it is heading.

An interesting development has been the DIY community, who are using this technology on their own healthy brains to increase speed and cognition. I have concerns with this approach as this technology doesn’t have much evidence and there are safety considerations. Data consistently shows us that using these brain stimulation technologies in the healthy population might improve your processing speed a little but likely no more that when the brain is in its optimal state. This is because the brain is so incredibly good at keeping itself at the right levels of processing through its homeostatic response. If you give your brain too much stimulation it will bring the levels back down to what it needs. Conversely we see almost the exact opposite in patient groups where there is an impairment in that brain activity, as there is a problem with the natural state of brain activity these changes are accepted more readily.

What is the most rewarding part of the work you do?

The most rewarding part is working towards something that might actually improve patients’ lives. When you have a patient say that they feel better or their lives are easier, this is encouraging. You can’t help but aspire to increasing the evidence base and rolling this solution out wider to positively impact more lives. This is why we do what we do.

Also, I get paid to think of things I want to know and find them out, it’s a really good job.

What is the most challenging part of the work you do?

The most challenging part is everything around the research, or in other words, trying to get the money to follow your ideas. There is no shortage of really good ideas in this field, the reason they are not all being done is simply because there is not enough money to do them with. There is a lot to do in developing these treatments, a lot of questions to ask, a lot more evidence to gather. This means finding the money and time to ask and research these questions.

What advice would you give someone wanting to get into your line of work?

The best piece of advice that I can give them is that persistence and hard work is easily as important as natural talent. You will get negative feedback but you must be resilient and persist. People look at PhDs as an incredible intellectual achievement, which it is, but it is as much about being able to just keep going and getting to the end.

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