“Rewiring” neurons: how the brain copes with MS

Sophie was diagnosed with relapsing-remitting MS almost 20 years ago. With every relapse, or flare-up of her symptoms, Sophie noticed that she struggled to concentrate on simple tasks and remember new information, such as the name of someone she had just met. It wasn’t just her cognitive ability that took a hit; during one episode, Sophie nearly lost her ability to walk, and it would be many weeks before she began to recover and walk normally again. Over the past several years, Sophie has been receiving inpatient therapy at a neurorehabilitation clinic in the wake of each relapse, and since starting her therapy she has been able to bounce back more quickly after the onset of symptoms. To help with her cognitive difficulties, Sophie’s therapy involves memorization and problem-solving exercises that stimulate her mind and improve her ability to focus her attention and memorize details more effectively. When Sophie temporarily lost her ability to walk, she was put through an intensive physical therapy regimen that helped to restore her sense of balance and coordination in addition to strengthening her leg muscles.

Sophie’s situation is certainly not unique among people with MS, and in addition to disease-modifying drugs, rehabilitation plays a significant role in overall disease management. Furthermore, people with relapsing-remitting MS may experience periods of time between relapses with no apparent symptoms, despite evidence of nerve tissue damage on a radiological scan. This raises the question: how is the brain adapting to damage caused by MS in order to maintain its ability to function properly?


Part of the answer to this question lies in the phenomenon of neural plasticity, or neuroplasticity, which can be defined as the functional reorganization of pathways in the brain based on new experiences, such as changes in behaviour, the environment, or those brought about by injury. The brain is a staggeringly complex organ, with an estimated 86 billion neurons, or nerve cells, comprising an intricate web of both functionally distinct and overlapping circuits. A remarkable feature of the brain is its ability to “rewire” itself; that is, the capacity to create new connections between neurons or to rearrange existing ones to adapt to a range of new circumstances.

Although this post will focus on neuroplasticity in the context of MS, I can’t stress enough that neuroplasticity is very much a normal, everyday process that underlies learning and memory. Our brain contains intricate networks of neurons called cortical maps that are involved in processing information related to a specific function. For example, fine movement (motor) control of our fingers is represented and processed by a specific network of neurons in our cortex (outer layer of the brain). The brain of a person who is learning to play the piano will begin to functionally reorganize its cortical map dedicated to fine motor control of the fingers, perhaps by recruiting new or existing neurons to expand the cortical map, or by strengthening certain key connections between neurons. Similar processes take place in response to a wide range of behavioural adaptations, such as learning a new language or learning to ride a bike.

To help you visualize how your brain accomplishes this feat, think of your nerves like highways which billions of delivery cars carrying information use to travel around your nervous system every second. Now imagine that a natural disaster wipes out a few key roads in that highway network. In order to reach their destination, those delivery cars will need to take alternative paths, while at the same time, new highways are being built to handle the buildup of traffic. In much the same way, increasing neuroplasticity in the brain means building multiple complex highways and rerouting existing ones to enable the messages that control our body functions and sense our environment to be delivered quickly and efficiently.

The take-home message is that the brain is, both structurally and functionally, a highly dynamic organ, with its cortical maps and other pathways constantly undergoing a process of transformation. While neuroplasticity has captivated the minds of scientists for decades, it is only recently that the role of this phenomenon in MS has entered the spotlight.

To study neuroplasticity in the brain, scientists employ specialized imaging techniques, such as functional MRI (fMRI), combined with standard motor or sensory tasks that allow them to map the brains of patients in real-time and detect how certain regions “light up” on a scan during a specific task. For example, a patient may be asked to perform a simple motor task, such as tapping his or her index finger, or squeezing a tennis ball, while different cortical regions are monitored using fMRI to detect changes in activity. This information, in turn, can be compared between people with brain injury, such as those with MS, and healthy individuals to show how specific regions of the brain can effectively take over the function of other, damaged areas.

“Rewiring” the brain in MS

An apparent paradox in the field of MS research is that magnetic resonance imaging (MRI) studies often show the persistence or build-up of damage in the brains of those with relapsing-remitting MS, despite varying periods of time – called remissions – during which symptoms are absent. Many researchers believe that the process of remyelination, or repair of the damaged myelin sheath around nerves, cannot completely account for these remissions and tends to operate on a relatively longer timescale. A growing body of evidence reveals that neuroplasticity may be enabling the MS brain to compensate for damage to neurons in an effort to rapidly restore or maintain lost function. Such adaptive functional compensation is well documented in other forms of brain injury or neurological disease, such as stroke and Parkinson’s disease. One challenge facing scientists and clinicians alike is how to harness this innate adaptive capacity in the brains of people with MS to help manage their symptoms and speed up recovery. In the following few paragraphs, I will be profiling some exciting and promising developments in the field of neuroplasticity and MS.

To date, adaptive neuroplasticity has been extensively studied in the visual, cognitive, and motor systems in people with relapsing-remitting MS, and has provided important insights into the means by which the brain “rewires” its neurons to recover important functions during periods of remission. In a recent breakthrough in this field, Dr. Francesco Mori and colleagues published a study in Clinical Neurology demonstrating that neuroplasticity can predict recovery from an attack in people with relapsing-remitting MS. To quantify neuroplasticity, the researchers measured long-term potentiation (LTP) – the process by which the communication between two neurons is strengthened – in a particular region of the brain in response to a specific pattern of electrical stimulus. They found that patients with a higher LTP response, or greater neuroplasticity, also demonstrated improved recovery of their symptoms compared to patients exhibiting less neuroplasticity. Mori and colleagues argued that such a powerful marker that can predict a person’s clinical recovery could help physicians determine optimal treatment for individuals with MS based on their ability to cope with brain tissue injury.

A lingering question in the minds of MS researchers is whether the brain’s capacity for neuroplasticity becomes increasingly depleted in progressive forms of MS. Scientists have yet to reach a consensus on this issue: on the one hand, Tomassini and colleagues argue that adaptive neuroplasticity in the brain can persist despite progression of the disease, and that damage to “bottlenecks”, or critical brain pathways for which there are few alternatives, is the culprit for deteriorating symptoms. On the other hand, a study by Mori and colleagues demonstrated that people with the primary progressive course of MS had impaired brain neuroplasticity compared to those with the relapsing-remitting form. The upside of their study for people with progressive MS is that the researchers identified a molecule in the brain that is thought to promote neuroplasticity, and future studies will look at targeting this molecule with therapies to stimulate neuroplasticity and ultimately improve symptoms in people affected by progressive MS.

Harnessing the potential of neuroplasticity

The good news for people with MS is that treatments are currently available that can “coerce” the normal process of neuroplasticity into improving performance and optimizing functional recovery. Sophie, whom I introduced at the beginning of this post, would experience difficulties with her concentration and memory during a relapse episode, and found that she benefited immensely from exercises aimed at stimulating those abilities that were impaired. Indeed, cognitive rehabilitation therapies must be individually tailored to each person and to each relapse based on personalized assessments, and oftentimes will be staged in order to tackle basic functions like orientation and focus before moving on to memory and complex problem-solving.

Similarly, people with MS who experience impaired mobility have been shown to benefit from different forms of physical therapy, including standard rehabilitation, resistance strength training, and constraint-induced movement therapy. These and other strategies rely on a combination of combating muscle wasting caused by limb disuse, and stimulating the brain to reorganize the neural pathways responsible for controlling movement. Not only can physical therapy help people affected by MS to regain their muscle function, but recent evidence also suggests that physical activity, such as aerobic exercise, can help to combat cognitive decline. The link between exercise and improved cognitive performance has been mainly studied in healthy children, adults and the elderly. It remains to be seen whether people with MS who face challenges with learning and memory could also benefit from programs aimed at improving physical fitness.

As scientists and clinicians continue to learn more about neuroplasticity and discover ways to promote mental and physical recovery, the hope is that approaches for enhancing brain re-wiring, such as those used by Sophie, will be fine-tuned and used to promote recovery and enhance quality of life for people living with MS.

Categories Research

National vice-president, research, past MS researcher, and PhD in Cellular and Molecular Medicine from University of Ottawa. Leads the MS Society's research program to find the cure for MS and improve the quality of life for people affected by the disease.

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