Research has used a wide range of techniques to understand the role of specific brain regions. The one that has provided the most information about the causal links between a brain region and its function has been to study when a brain region is missing or malfunctioning, i.e. a lesion.
You may have heard of some of these well-known studies. Phineas Gage, a 25-year-old railroad foreman, had an iron rod launched through the front of his skull, passing through his frontal lobe. He survived this accident and remarkably had no motor function or memory deficits. Although, his family noticed changes in his personality following the incident, which led to studies finding that the prefrontal cortex is involved in personality and social behaviours.
Another instance of lesion-induced scientific breakthroughs comes from the famous case of HM (or Henry Molaison), a 29-year-old man who was treated with an experimental surgery for his severe epilepsy that removed his medial temporal lobes (including his hippocampus and amygdala on both sides of his brain). Following the removal of his medial temporal lobes, his epilepsy was essentially cured. Although the side effects of removing these brain regions resulted in severe anterograde amnesia meaning he was unable to form new memories. This surgery laid the groundwork for many findings in understanding particular aspects of memory and its involvement with the medial temporal lobe.
While these lesions have taught us much about brain regions and their functions, it may seem extreme to wait until someone new has an iron rod launched into their brain to identify what function is associated with that region. Luckily, given our advances in science, we can make “virtual lesions” using non-invasive in an experimentally controlled setting. We can do this using a technique called transcranial magnetic stimulation or TMS. TMS can be used to identify the function of particular brain regions and treat malfunctioning brain regions.
TMS induces virtual lesions by transiently disrupting a particular and focal brain region, allowing researchers to make causal inferences about the function of that specific region. This is achieved using a device that looks like a small paddle (a.k.a. the coil). This device generates strong but harmless magnetic fields aimed at a particular part of your head that can pass through your skull and reach your brain.
Now, because neurons communicate with each other using electrical currents, when the magnetic fields from TMS hit your brain, it creates a small electrical current that can either activate or deactivate the neurons and impact how they communicate. Not only does this allow us to see what happens when the neurons are under-functioning or over-functioning, similar to how lesion studies taught us about behavioural function, but it can be used as a clinical treatment for disorders.
Currently, the most recognized use of TMS is for treatment-resistant depression (TRD; 1). The main goal of TMS for TRD is to increase the activity of the dorsal lateral prefrontal cortex (DLPFC). The DLPFC is notably less active in those with TRD. The hypoactivity of the DLPFC has not only been shown in brain scans (2) but when individuals with TRD start feeling better, there is increased activity in DLPFC (3), making it a target for treatment. Using TMS for TRD has shown significant clinical efficacy in clinical trials, making it an exciting treatment for this otherwise resistant disorder.
In addition to TRD, TMS has been used to treat Alzheimer's disease (AD). TMS for AD has been studied over the past 5–10 years, and the preliminary results are promising. In one study, they experimented with three groups of people with mild-to-moderate AD (4). They used a type of TMS that sends quick magnetic pulses (20 times per second) to the left and right parts of the DLPFC and found significant improvements in memory and executive functions. It's still early, but these studies give hope that TMS could be a helpful way to tackle AD.
One of the other more extensive areas of TMS treatment research is within stroke recovery. When someone has a stroke, their brain goes through many changes. These changes can make some parts of the brain less active where the stroke happened and more active in neighbouring brain regions, mainly caused by the parts of the brain that are not affected by the stroke trying to overcompensate.
TMS can help fix this imbalance after a stroke since it can over-activate or deactivate particular brain regions. So, TMS stroke rehabilitation strategies aim to restore the right balance in the brain after a stroke. They do this by making the affected side more active or deactivating the other side (5).
The list of potential TMS applications in neurology and psychiatry is lengthy and rapidly expanding month by month. For instance, new developments in addiction, obsessive-compulsive disorder, anorexia nervosa, schizophrenia, posttraumatic stress disorder, chronic pain, movement disorders, and migraine are all areas of developing research for TMS (6). While there is a lot of promise for TMS, the challenge going forward is identifying the variable effect of TMS between individuals and how much of the improvement is because of the treatment versus the placebo effect (where people feel better because they believe they're getting a real treatment).
Blog by Tanisse Epp
References:
1. Brunoni, A. R., Chaimani, A., Moffa, A. H., Razza, L. B., Gattaz, W. F., Daskalakis, Z. J., & Carvalho, A. F. (2017). Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes: a systematic review with network meta-analysis. JAMA psychiatry, 74(2), 143-152.
2. Fitzgerald, P. B., Oxley, T. J., Laird, A. R., Kulkarni, J., Egan, G. F., & Daskalakis, Z. J. (2006). An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression. Psychiatry Research: Neuroimaging, 148(1), 33-45.
3. Mayberg, H. S., Brannan, S. K., Tekell, J. L., Silva, J. A., Mahurin, R. K., McGinnis, S., & Jerabek, P. A. (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biological psychiatry, 48(8), 830-843.
4. Ahmed, M. A., Darwish, E. S., Khedr, E. M., El Serogy, Y. M., & Ali, A. M. (2012). Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer’s dementia. Journal of neurology, 259, 83-92.
5. Fregni, F., & Pascual-Leone, A. (2007). Technology insight: noninvasive brain stimulation in neurology—perspectives on the therapeutic potential of rTMS and tDCS. Nature clinical practice Neurology, 3(7), 383-393.
6. Burke, M. J., Fried, P. J., & Pascual-Leone, A. (2019). Transcranial magnetic stimulation: Neurophysiological and clinical applications. Handbook of clinical neurology, 163, 73-92.