Neurostimulation may herald a new treatment for depression
Depression is a growing problem in Canada and elsewhere, and one of the most important public health issues today, says the World Health Organization (WHO). The COVID-19 pandemic and the ensuing containment measures have had an impact on the mental health of Canadians and have created conditions that are associated with increased rates of suicide.
Unfortunately, front-line treatments for depression, such as psychotherapy and medication, remain ineffective for a large portion of patients receiving care.
However, a new type of treatment is promising: neurostimulation. Here, a technician in a clinic directs a magnetic coil and delivers a few hundred electromagnetic pulses to a specific area of the brain. Treatments are painless, involve no surgery or significant side-effects and take less than an hour a day. The results are impressive. But is this too good to be true?
As a professor of neuroscience in the department of biology at the University of Ottawa and an affiliated researcher at the Krembil Research Institute in Toronto, my research in nonlinear physics has led me to the incredible complexity and richness of biological systems, especially in neuroscience.
Using mathematics and the power of numerical computation, it is possible to better understand not only how the brain works at the cellular level but also how its vast network is organized and what may be lacking because in presence of diseases, such as depression. This can help identify new avenues for treatment and test their effectiveness through simulations. It’s a huge task that I’m working on in collaboration with an interdisciplinary team of researchers around the world.
The return of neuron stimulation
During the past decade, medical treatments involving neurostimulation, or cerebral electromagnetic stimulation, have resurfaced in neuroscience and psychiatry.
After the murky days of electroconvulsive therapy and other techniques, which had rather bad press, electrical or magnetic stimulation of neurons is attempting a comeback, using a much more sophisticated approach and much lower electrical currents. As a result, neurostimulation is becoming increasingly important in the treatment of depression, and its effectiveness seems to surpass that of medication in many patients.
Methods such as transcranial magnetic stimulation (TMS) are safe and painless alternatives to traditional pharmacological treatments. In addition, they have virtually no side-effects and offer new insights into the manipulation and control of cognitive processes.
Recent meta-analyses have identified positive and lasting effects of TMS neurostimulation treatments on patients with depression, some of whom experienced benefits up to one year after treatment.
These treatments are now approved by many regulatory agencies and the clinical use of neurostimulation is on the rise in many countries. In particular, portable TMS devices are in development and in the process of being approved by Health Canada for wider, accessible deployment. These devices would allow patients to treat themselves at home, without having to go to the clinic every day as is currently the case.
Intracranial neurostimulation. (Baburov/Wikimedia)
However, a major challenge remains: how to control brain activity accurately. What areas and types of magnetic signals should be used to relieve patients’ symptoms? For despite amazing results and promising advances, the mechanisms of neurostimulation remain poorly understood. Why?
TMS uses a coil to create a magnetic field that induces electric currents in the brain. Neurons are cells that communicate by means of repeated electrochemical impulses; the brain is an organ with essentially electrical functions. Magnetic fields can therefore influence the dialogue between different areas of the brain and — in theory — restore or balance their function.
The brain, composed of billions of neurons with continuously changing dynamics, is an incredibly complex network. Neurostimulation therefore poses quite a problem for researchers and clinicians, such as where to stimulate and how. The problem is so great that many advances are being made empirically using the trial-and-error method.
A mathematical calculation
Mathematics is involved in this interdisciplinary adventure. What if, through mathematical models of brain circuits, we could understand how stimulation influences neurons and how its effects propagate?
By integrating brain imaging data such as magnetic resonance and electroencephalograms, mathematics can be used to create numerical simulations to better understand the influence of neurostimulation on neuronal activity. It’s a promising approach that could indeed allow us to unravel the mystery of considering the brain as a pendulum!
To better understand, let’s go back a bit.
The activity of neurons in the brain is far from being random and irregular. On the contrary, the neurons in certain parts of the brain co-ordinate their activity and react at the same time. They synchronize. This synchronization of the neurons in the brain appears in the magnifying glass of medical imaging as waves, or very characteristic oscillations, which are also called brain rhythms.
Brain activity oscillates like a pendulum and this constant to-and-fro movement allows us to see neuronal processes in action. Like ripples on a pond, brain rhythms are dynamic, changing according to our cognitive states. They will be different during a sustained mental effort, during physical activity and during sleep or meditation.
Hope for tackling neurodegenerative diseases
Researchers believe that brain waves are involved in the majority of brain processes. It is also these same rhythms that seem to be lacking in many neurodegenerative diseases. They are absent, too strong or too slow.
What if we could control these rhythms with the help of neurostimulation? This is the emerging hypothesis put forward by some neurostimulation researchers. Using advanced mathematics and computer simulations, they want to understand how co-ordination between networked neurons can be influenced and to what extent electromagnetic stimulation can be used to control brain rhythms and to develop treatments for neurological disorders such as multiple sclerosis, Parkinson’s, schizophrenia and depression.
This research may lead to a better understanding of the role of these rhythms in brain function, the code used by neurons to communicate with each other and a better understanding of what is lacking in certain diseases. It may also allow us to use neurostimulation to increase the computational capacity of these neural networks, thereby increasing cognitive abilities and creativity. Science fiction? Maybe … but not completely.