Engineering the brain: the promise of neural engineering in medicine

In conversation with Dr. José Zariffa on how the field could address conditions from Alzheimer’s disease to vision loss

Engineering the brain: the promise of neural engineering in medicine

Much of the incredibly complicated human brain remains a mystery to scientists. Despite this complexity, there is new promise for technologies to treat neurological disorders.

A rapidly developing approach is neural engineering, which unites methods of neuroscience and engineering to investigate and repair neural networks.

The discipline has brought together researchers from a diverse array of scientific fields, including biology, chemistry, mathematics, computer science, and engineering. New devices and technologies have arisen from their efforts to help patients with neural disorders, such as epilepsy and Parkinson’s disease.

A new interdisciplinary area of science

Dr. José Zariffa, an associate professor at U of T’s Institute of Biomaterials & Biomedical Engineering, recently co-authored a review paper on the potential clinical applications of neural engineering.

In an interview with The Varsity, Zariffa said that he is mainly working on “decoding signals from the nervous system.” That is to say, his team has focused on analyzing messages sent from the brain to organs and membranes via electrical impulses to guide the development of medical devices.

Such a device could send impulses to a paralyzed muscle to make it contract or relax, which could help patients who have experienced a spinal injury or stroke.

If you were to track the activity of a nerve, you would notice many pathways entering it as “a mix of many different sources.” Zariffa’s team is currently investigating possible ways to separate those signals so that the messages sent to a pathway of interest can be isolated and used for specific medical purposes.

Current applications, promises, and challenges

In recent years, there has been renewed interest in potential applications of neural engineering — as evidenced by prominent enterprises such as the United States’ BRAIN Initiative — which has generated much momentum for the advancement of new technologies developed in the discipline.

The diversity of the possible applications of neural engineering is mind-blowing. For instance, neural technology can potentially reverse memory deterioration resulting from Alzheimer’s disease, restore lost or damaged eyesight, and even make prosthetic limbs move by thought.

Currently, deep brain stimulation, which involves implanting an electrode that sends signals to specific targets in the brain, is used to treat Parkinson’s disease and severe cases of obsessive-compulsive disorder and depression.

Another emerging trend which shows promise in neural engineering is the stimulation of the nervous system to treat various chronic diseases, ranging from epilepsy to conditions indirectly caused by a malfunctioning nervous system, such as hypertension and diabetes.

According to Zariffa, Toronto is a “hotbed” for neural engineering, as its strong pool of engineering and neuroscience research talent combined with a solid hospital network allow for the interdisciplinary research crucial for neural engineering to happen.

The recently-opened Center for Advancing Neurotechnological Innovation to Application launched by U of T and its affiliated University Health Network is an example of a Toronto-based initiative aiming to bring recent advances in neural engineering to clinical settings.

Zariffa’s own research focuses on developing technology to facilitate recovery from damage to the central nervous system resulting, for example, from spinal cord injury or stroke, which may help patients in their day-to-day lives.

Ethics of neural engineering

While a main objective of neural engineering is to develop devices for clinical applications, it is possible that the advances in this area will be used for non-medical purposes.

For instance, certain biotechnology companies are currently looking into ways to enhance the human brain’s processing abilities by creating brain-computer interfaces based on the most recent advances in artificial intelligence.

Such examples of human augmentation, including Elon Musk’s plan to create “human-AI hybrids” and people “upgrading” their bodies by implanting computer chips, are often sensationalized by media outlets.

Yet, according to Zariffa, modern science is still far from implementing such advances on a broader scale. The ethical considerations of the field, he noted, have not differed considerably from those in most areas of technological development.

Even without the sensationalism of the field, the growing applications of neural engineering remain vast and promising in treating medical disorders.

Women in STEM: Kath Intson

PhD candidate discusses research, using Instagram to spread diversity in science

Women in STEM: Kath Intson

Kath Intson is a PhD candidate at U of T’s Department of Pharmacology and a popular science communicator on Instagram, with the handle @weekday_neuroscientist. Her neuroscience research could lead to a better understanding of various neuropsychiatric disorders.

Intson’s doctoral research centres on neuropsychiatric disorders

The malfunction of a receptor for a neurotransmitter named glutamate has been linked to the development of neurological disorders, such as schizophrenia, autism, and Alzheimer’s disease.

Intson studies the effects of altering the ability of the glutamate receptor in mice, under the supervision of Professor Amy Ramsey. She specifically studies the NMDA receptor.

To function properly, the receptor requires a protein subunit called gluN1 to function, which is produced from the expression of the GRIN1 gene. By performing a technique called ‘gene knockdown,’ Intson can suppress the gene’s expression.

This suppression enables her to examine the effect of a malfunctioning gene on mice. The results of Intson’s research could help advance knowledge of human health, due to the similarities between the anatomy, physiology, and genetics of mice and humans.

Intson’s secondary project examines how environmental factors can influence organisms to develop characteristics associated with schizophrenia.

Paired together, these projects could enable Intson to better our understanding of schizophrenia, as the disorder is a result of both genetics and environmental factors

Representation and science communication 

Intson developed her Instagram account in response to snarky messages online from users skeptical that Intson is a PhD candidate.

In a social media post online, Intson explained that it’s normal for scientists to have a life outside of their research. “It doesn’t matter what I look like on Instagram,” she said to The Varsity, summarizing her post. “I can still be a scientist.”

The post garnered attention, which encouraged Intson to post more science-related content on her account.

With her Instagram account, Intson strives to represent a “voice in the diversity that is STEM.” The ability to communicate with her followers on Instagram is essential for this.

“I think I just love chatting with people more than anything,” Intson said. “And if something that I post can spark a conversation, then that’s the whole goal of the account.” 

According to Intson, Instagram science communicators are pushing the idea that there is no ‘one image’ of a scientist — something that Intson strongly supports. 

“I think it’s true that literally every single person that I pass on the street could be a scientist,” said Intson. “I don’t conjure that one image.”

Representation to Intson means that leadership positions across professions are represented by people of races, genders, and orientations proportional to the diversity of individuals in these fields.

Role models and the experiences of women in STEM 

Intson credits her women mentors for giving her confidence and “arming [her] with the tools that [she] needed to go forth and conquer.”

Understanding the career trajectories, challenges faced, and work put in by her mentors has been especially valuable for Intson. 

“Just seeing somebody who’s in that position as a woman has been very helpful for me,” she said.

How new technologies are transforming care for dementia patients

A conversation with Dr. Arlene Astell: using tech to improve the quality of life for aging population

How new technologies are transforming care for dementia patients

Dementia is taking a serious toll on Canada’s aging population: roughly 76,000 people are diagnosed with the condition every year. It is estimated that the number of Canadians living with dementia may even double over the next 20 years due to our growing senior demographic. 

Diagnosing, treating, and managing dementia brings many challenges for both those affected by it and their caregivers. Fortunately, the rapid growth of technology in recent years has sparked innovation which help tackle these issues. But lacklustre awareness and slow implementation of these technologies have limited their outreach.

Time is of the essence in dementia research. The surge in innovation, coupled with our aging population, means that we need to quickly change the way we treat dementia. 

What is dementia? 

Dementia is a medical term that covers a variety of syndromes affecting the brain. It can be caused by conditions such as Alzheimer’s, Parkinson’s, and head trauma. Patients affected by dementia experience memory loss, difficulties with problem solving and, in some cases, severe changes in mood.

Treating dementia can come with many challenges. However, technology can play a huge role in mitigating some of these obstacles.

Dr. Arlene Astell, an Ontario Shores Research Chair in Community Management of Dementia at U of T’s Medical Sciences Department, recently co-authored a paper summarizing developments on the diagnosis, treatment, and management of dementia.

The paper highlighted the multifaceted uses of technology in treating a syndrome like dementia.  

“Direct healthcare has very little to offer people once they have been diagnosed,” wrote Astell to The Varsity. While a range of medical interventions and services to support lifestyle management can be offered to patients with conditions such as diabetes and cancer, such is not the case with dementia.

“There are no disease-modifying therapies available,” continued Astell. Patients may only receive some medication for symptom management, which is not available for all types of dementia.

Most treatment plans for dementia largely rely on sending the patients “home to live as well as they can with support from family or friends.”

Improve treatment plans for dementia

Limitations of the current approach for treating dementia, according to Astell, lie in the way we treat the syndromes. Dementia has vast implications on a patient’s everyday life, which cannot be easily treated through traditional health care approaches. 

“Individuals with dementia need practical interventions and supports to compensate for their cognitive challenges,” she wrote. “By leveraging their retained abilities and enabling them to maintain independence for as long as possible.” 

Improving the ways in which we treat dementia can induce widespread benefits throughout the health care sector. Current methods for treating dementia are putting unnecessary strain on our hospital systems.

“We are seeing, for example, growing numbers of people with dementia filling acute hospital beds, which is leading to cancellation of planned surgeries due to [a] lack of recovery beds,” Astell noted.

Changing dementia treatment methods could also better ensure that patients with different conditions than dementia get the help they need more quickly. 

The role of technology in dementia treatment

Fortunately, many novel innovations for treating dementia are becoming more accessible with the rising use of smart home devices and wearable technology.

Prototypes, such as the Gloucester Smart House, have been developed to help dementia patients in their everyday lives. It comes programmed with bathing and cooking monitors, an automatic night light, and prompts that remind users when to take their medication. 

Since its introduction, smart home technology has grown rapidly. Newer systems use artificial intelligence, machine learning, and sensor technology to reduce reliance on caregiving and help patients with tasks such as dressing and cooking.

Researchers are hoping to use the easily-installed technology to run wide-scale clinical trials to understand its potential benefits on those with dementia. 

Developments in Global Positioning System (GPS) applications on smartphones and motion-enabled gaming can also be used to help maintain patients’ social and active lifestyles. Many GPS applications on smartphones can now detect whether the user is lost.

Such a feature is especially useful for dementia patients, who may rely heavily on the app to navigate. Helping users walk safely makes it easier for them to maintain an active lifestyle.

Many motion-based games have also been tested to improve cognitive and physical stimulation in those with dementia. These games, which can be used on tablets and consoles like the Kinect or Nintendo Wii, also enable patients to spend their leisure time with others without having to leave their homes.

The upshot is that technology can help dementia patients manage their symptoms daily. According to Astell, accessible technology has the potential to play a huge role in this stage.

“Providing technology to assist individuals to monitor how they are doing would empower them to self-manage their condition,” she wrote. “This could be in the form of an app or device that they interact with throughout the day as their companion for living with dementia.”

“We need to develop new kinds of services to provide this support, with digitally-enabled staff.” 

Moving forward 

Improving accessibility to these technologies remains a major challenge. “We currently do not have one place that people can access to find out what is available and what other people are using,” wrote Astell.

To address this issue, her research team has launched their AcTo Dementia website, which provides dementia-friendly gaming apps that have been reviewed for their suitability for patients affected by the syndrome. 

Astell is currently working on a new online resource to guide users on how to use smart home and motion-based technology to manage dementia. 

Yet another issue in the implementation of these technologies lies in research. Unlike traditional big pharma research, most dementia studies do not involve dementia patients. 

“It has focused either on families of people with dementia (as proxies) or care providers to address their needs in relation to dementia,” wrote Astell. Putting more focus on understanding dementia patients directly could broaden the care that is available for them. 

Technology-based dementia treatments are rapidly evolving. But its limited accessibility and slow implementation are preventing them from reaching patients who need it. Our traditional approach to treating dementia must keep up with the pace of innovation.

Unfortunately, dementia patients do not have the luxury of time. “We have accessible, affordable technologies at our fingertips that can revolutionise how we approach dementia,” wrote Astell.

“[We can] improve the lives of people who receive a diagnosis… and provide something useful and beneficial in the face of no effective medical treatments [for dementia patients].”

Women in STEM: Mehnaz Ahmed

Recent Master's graduate discusses representations in media and challenges of academia

Women in STEM: Mehnaz Ahmed

This year, Mehnaz Ahmed completed her Master of Science at U of T’s Department of Pharmacology and Toxicology. In addition to conducting scientific research, Ahmed has participated in Dove’s Project #ShowUs, an advocacy project that aims to better represent women and non-binary individuals by creating a library of stock photography for use in advertising and media, and was a mentor to undergraduate students like me. 

The hidden challenges of academia

As a graduate student, Ahmed investigated the relationship between the activity of an enzyme — named peripheral glutathione peroxidase — and the cognitive performance of individuals at an early stage of vascular dementia. Vascular dementia is a neurological disorder caused by impaired blood flow to the brain.

She described the challenges she faced as internal ones. “In essence doubting myself and wondering if I would ever be successful in research or in science overall,” she wrote in an email to me.

What helped her overcome these obstacles, she wrote, was changing her perspective: “redefining what success [means] to [her] in terms of establishing a certain work-life balance.”

But striking a work-life balance is a challenge on its own.

To reach this balance, she planned for “things to look forward to after a long period of working,” which helped prevent feelings of burnout or demotivation, which can stem from long-term work.

Having completed her Master’s degree, Ahmed is in the process of choosing a path that will enable her to pursue a fulfilling career.

She is motivated “to build a life that is worth living according to [her].” Ahmed also believes that “material items will [neither] make [her] happy at the end of the day,” nor contribute to her efforts to make positive change in the world.

Mentorship as a tool for growth

Ahmed was my Senior Peer Mentor in U of T’s “First in the Family” program, which connects first-generation university students to mentors, with the aim of easing the new students into university life. We eventually fostered a close friendship.

“[Being a mentor] gave me the validation that I had important knowledge to share and reminded me that I had overcome the same difficulties my mentees had and I was able to hopefully serve as a source of support,” wrote Ahmed.

Ahmed’s own mentor, Dr. Krista Lanctôt, a Senior Scientist at Sunnybrook Health Sciences Centre, played an important role in her development.

Ahmed noted that having a female supervisor and mentor is crucial as she “was able to see that conducting productive research was possible while still living a fulfilling life outside of the lab and juggling a family as well.”

“Don’t be so hard on yourself. You’re doing a lot better than you think.”

Dove created the Project #ShowUs initiative alongside Getty Images and Girlgaze to create a stock photo library of women and non-binary individuals.

Ahmed was photographed for the project by Alia Youssef, who had previously captured Ahmed’s image for Youssef’s “The Sisters Project,” which strives to dismantle discriminatory beliefs against Muslim women.

Participating in Project #ShowUs was important, wrote Ahmed, as it reinforces “the notion that these images of beauty in all forms must first start with appreciating the perspectives of women.”

The importance of a diverse representation of people in the media was noted by Ahmed, who added that “not all women and Muslim women are similar and they can often be painted with the same monolithic brush. The more representation there is, the more people will be comfortable being themselves.”

Ahmed added that the particular stereotype of Muslim women being reserved has sometimes been a challenge for her.

“There have been instances when I describe potential career trajectories [to others] where I can’t help but feel a tiny instance of being judged, in terms of not conforming to what others may perceive me as,” she wrote. This has sometimes created a pressure for her to perform to a certain standard, to challenge these expectations.

Ahmed’s advice for women pursuing STEM is to believe in yourself, be curious, and be resilient.

“Whatever is meant for you will not pass you.”

Discovery of special proteins in brain opens new pathway to treating depression

From MAO-A to B, protein discoveries may lead to a new types of antidepressants

Discovery of special proteins in brain opens new pathway to treating depression

Neuroscientists at the Centre for Addiction and Mental Health (CAMH) have found that patients with depression may have elevated levels of a particular protein in the brain, opening a pathway for developing a new type of antidepressant medication.

The research team, led by Dr. Jeffrey Meyer, the Head Scientist of the Neurochemical Imaging Program in Mood and Anxiety Disorders at CAMH, found that the MAO-B protein — short for monoamine oxidase B — was found in heightened levels in the prefrontal cortex area of the brains of depressed patients.

How Meyer’s research team first discovered the protein

The breakthrough of Meyer’s research team that led to this study was the discovery of elevated levels of the MAO-A protein in women who had recently delivered a baby.

Originally, researchers considered both MAO-A and MAO-B as the same protein, MAO, as they both break down the molecule tyrosine. However, medications developed to treat early postpartum depression – a mood disorder associated with childbirth – revealed that despite a 70 per cent overlap in the structures of the two proteins, the medications only affected the MAO-A enzyme.

Neuroscientists have therefore since considered MAO-A and MAO-B to be different types of chemicals.

The link between MAO-B levels and clinical depression

The recent study by Meyer’s research team evaluated images taken from the brains of 40 patients over a period of four years. Half of the volunteers had experienced episodes of major depression, while the remaining 20 were considered healthy controls.

Through positive emission tomography, a type of brain imaging, the researchers discovered that 50 per cent of the patients with depression had elevated levels of MAO-B compared to the healthy individuals.

The patients with depression were found to have, on average, a 26 per cent increase in the volume of MAO-B in the prefrontal cortex region compared to those without the condition. This region is primarily responsible for complex cognitive behaviour, personality regulation, decision-making, and moderating social behaviour and emotions.

The researchers also found a positive correlation between MAO-B levels and the duration of depressive episodes. That is, the longer the depressive episode, the higher the detected level of MAO-B in the prefrontal cortex and other brain regions.

While MAO-A breaks down serotonin, MAO-B promotes cell turnover by breaking down old and excess neurotransmitters, such as dopamine and norepinephrine, chemicals that are responsible for pleasure and reward.

Although this process is essential in maintaining a healthy brain, increased levels of MAO-B can lead to removing too much of the feel-good chemicals, which may lead to depression.

The limitations of current antidepressant medications

Although there are already antidepressants in the pharmaceutical market, they mainly only target serotonin. Meyer pointed out, in an email to The Varsity, that the current medications and treatment options are not effective for everyone with depression.

“While some people respond well to SSRI [selective serotonin reuptake inhibitors] medications half do not. A key problem is that there are subtypes of depression and we need to match treatments to the subtypes of depression better,” wrote Meyer.

There are already drugs on the market that inhibit MAO-B used for Alzheimer’s and Parkinson’s disease. The research team is looking for ways to direct them towards treating depression.

“There are medications purposed for other illness that shut down MAO-B and could be repurposed for depression,” wrote Meyer.

“With this study now in hand, published in what is traditionally the top psychiatric research journal, I am asking the companies that own the patent rights to these medications to use them for depression.”

How the discovery of MAO-B can lead to new antidepressant research

After the discovery of MAO-A, Meyer’s lab has made progress in developing a dietary supplement that would compensate for the sudden rise of MAO-A in early postpartum depression.

They are currently seeking to create a blood test that could detect monoamine type illnesses. This would help identify individuals who would respond better to MAO-targeted drugs as opposed to the usual antidepressant treatments.

“The main steps are to test medications in development and those available for use, (even if indicated for other illnesses) for their ability to shut down MAO-B. Then I would like to see if matching a medication that shuts down MAO-B to the subtype of depression with greater MAO-B would help increase the chance of cure,” wrote Meyer.

“We are also looking for low cost approaches to predict the subtype of clinical depression with the highest MAO-B level.”

Approximately 15 per cent of people are affected by depression at some point in their life and it is the main cause of disability around the  world.

Meyer wrote, “There is great reason for hope because we are increasingly understanding how the brain changes in clinical depression which is creating new opportunities for cures.”

How psychotherapy treats depression differently than antidepressants

A personal exploration into the science behind antidepressants and CBT

How psychotherapy treats depression differently than antidepressants

Content warning: discussions of depression and suicidal ideation.

The first time I walked through the door of my psychiatrist’s office, I was full of doubt. I had been feeling low for quite a while, and I had trouble believing that any treatment would truly help me feel better.

I had just completed my second year of university, and I felt broken and exhausted. A blend of burning out, experiencing depressive episodes, disengaging from pastimes I used to enjoy, and fantasizing about dying drove me to seek treatment at U of T’s Health & Wellness Centre.

As part of my initial assessment, which occurred over the course of several sessions, my psychiatrist asked me questions about practically every aspect of my life: recent events, medical history, sleep patterns, appetite, suicidal ideations, and more. After considering all my symptoms, she prescribed me Prozac, an antidepressant medication, and recommended cognitive behavioural therapy (CBT). Both are common treatments for depression.

I gave them both a try. I was fortunate to be able to see a therapist for CBT, which was covered by my family’s health insurance. At first, I was skeptical that it would work, but I decided to commit myself to at least a few sessions.

CBT, as I learned, is a short-term form of psychotherapy that helps people build skills for staying healthy. In essence, it helps people identify, question, and change distorted thoughts and beliefs they might have about themselves and the world. By recording their thoughts during upsetting situations, people examine how their unhelpful thoughts might contribute to problems like depression.

Research on how CBT compares to antidepressants

Dr. Zindel Segal, a U of T psychology professor and an expert in CBT, said in an interview with me that “when people are in certain mood states, they tend to have thoughts that are very compatible with those mood states. So, when someone’s feeling depressed, they’re more likely to feel hopeless, judge themselves, and be very critical.”

According to Segal, CBT provides a way of treating people’s thoughts and assumptions as hypotheses that can be tested, rather than as hard facts. “That can help people alleviate the impact that some of these thinking styles can have on their moods,” he elaborated.

For me, CBT was extremely challenging more so than any math or biochemistry course I have ever taken. Perceptions are simply hard to change. At the time, for example, I felt incredibly worthless and undeserving of love. In the face of this, CBT helped me stay objective and not always accept my perceptions as truth. Psychotherapy made me stand back from my thinking to consider situations from different viewpoints.

“In the face of [critical challenges], CBT helped me stay objective and not always take my perceptions as truth.”

However, distorted thoughts and beliefs are often not the only culprits of depression. Much is still unknown about the causes of depression, but researchers suspect that chemical imbalances in the brain play a role in maintaining low moods. Antidepressant medications are designed to address these chemical imbalances by boosting concentrations of neurotransmitters namely serotonin and norepinephrine in the brain.

At first, I was very reluctant to try antidepressant medication because I was wary of possible side-effects. However, my psychiatrist assured me that the starting dose was low, that I would be closely monitored, and that we could always adjust my treatment if the medication was not right for me. In the end, I experienced only minor side-effects and really benefited from the resulting stability in my mood.

The differences between CBT and antidepressants

So, what are the differences between CBT and antidepressants in treating depression, according to experts? Researchers like Segal, who recently co-authored a paper comparing the efficacy of CBT versus antidepressants, are working hard to answer this question.

Segal’s research team found that CBT and antidepressants target different symptoms of depression. Antidepressants were found to be best for treating symptoms specifically related to depressed mood, feelings of guilt, suicidal thoughts, and psychic anxiety.

On the contrary, CBT and antidepressants were equally effective in treating patients who struggled with other specific symptoms of depression, like changes in sleep and appetite. “This paper tries to address more of a symptom-to-patient matching approach so that people are getting antidepressants if they have a symptom profile that might be more responsive to the drug,” said Segal.

In my case, CBT and antidepressants were temporary treatments that helped me bounce back from a bout of depression and develop long-term skills in staying healthy. Each treatment helped me in different ways: CBT helped me build emotional resilience, whereas antidepressant medication gave me the extra energy to ‘get back on my feet’ and return to doing the things I love to do.

But whichever treatment people are prescribed, Segal stressed that depression is treatable. “Whether you have hypertension or depression, it is possible to get treatment.”

If you or someone you know is in distress, you can call:

  • Canada Suicide Prevention Service phone available 24/7 at 1-833-456-4566
  • Good 2 Talk Student Helpline at 1-866-925-5454
  • Ontario Mental Health Helpline at 1-866-531-2600
  • Gerstein Centre Crisis Line at 416-929-5200
  • U of T Health & Wellness Centre at 416-978-8030.

Warning signs of suicide include:

  • Talking about wanting to die
  • Looking for a way to kill oneself
  • Talking about feeling hopeless or having no purpose
  • Talking about feeling trapped or being in unbearable pain
  • Talking about being a burden to others
  • Increasing use of alcohol or drugs
  • Acting anxious, agitated, or recklessly
  • Sleeping too little or too much
  • Withdrawing or feeling isolated
  • Showing rage or talking about seeking revenge
  • Displaying extreme mood swings

The more of these signs a person shows, the greater the risk. If you suspect someone you know may be contemplating suicide, you should talk to them, according to the Canadian Association for Suicide Prevention.

The promise of ketamine in overcoming treatment-resistant depression

Therapeutic potential of ketamine discussed in review by U of T medical researchers

The promise of ketamine in overcoming treatment-resistant depression

Content warning: Discussions of suicide in the context of treating major depressive disorder.

Ketamine is a promising medication that brings hope to patients struggling with severe depression, offering potential therapeutic effects for those who are non-responsive to standard antidepressants.

The dissociative anesthetic is currently used by physicians and veterinarians to cause fast-acting insensitivity to pain during medical procedures. It is also used illicitly as a recreational drug, causing feelings of disconnection and relaxation among users.

Yet in controlled settings, ketamine also shows potential as a medication to help patients who are suffering from major depressive disorder. In April, a research review by U of T researchers found that ketamine offers significant effects as an antidepressant.

The lead author of the paper, Dr. Joshua Rosenblat, discussed the review’s findings with The Varsity. As a clinician-scientist in the Department of Psychiatry, Rosenblat is currently studying the antidepressant effects of ketamine.

He explained three major effects that differentiate ketamine from standard antidepressants: a different mechanism of action, a rapid onset of effects, and a response in patients who are not positively affected by commonly prescribed antidepressants.

Ketamine affects depression via a novel mechanism of action

For the past several decades, standard antidepressants have worked by affecting levels of serotonin, norepinephrine, and dopamine, explained Rosenblat.

In generalized terms, serotonin is a chemical messenger thought to regulate mood, while norepinephrine controls alertness and arousal. Dopamine affects attention and emotion.

But ketamine affects the brain differently. Rather than targeting these neurotransmitters, it instead changes levels of glutamate – the main excitatory messenger in the brain.

Ketamine’s unique mechanism of action could therefore explain why it may positively affect patients suffering from treatment-resistant depression, who do not respond to standard antidepressants.

Ketamine could provide a more rapid onset of affects, versus standard antidepressants

Ketamine also provides a rapid onset of effects. Standard antidepressants, said Rosenblat, usually take two months of prescribed usage to take effect.

He explained that with ketamine, alleviation of depressive symptoms can appear within two hours of consumption. This is especially promising as an option for patients suffering from suicidal thoughts.

A decrease in suicidal thoughts can plausibly reduce the number of suicidal attempts; however, Rosenblat noted that the evidence is currently too limited to make a conclusion. He explained that studies are lacking, as only a small percentage of patients affected by such thoughts attempt to commit suicide.

Ketamine could also be used for special applications. Depression is very common among patients facing terminal cancer, explained Rosenblat.

“If you were to start them on an antidepressant and they only have one month left to live, for example, [the patients may] only experience the side effects, and never get the benefits.”

Rosenblat is currently leading a clinical trial at Princess Margaret Hospital to research the use of ketamine for improving the final months of life for patients affected by terminal cancer.

The risks and drawbacks of ketamine as an antidepressant

While the prospect of applying ketamine for treating depression is promising, there are several discouraging factors to its application.

To start, ketamine carries the risk of substance abuse. While ketamine is not strongly addictive, said Rosenblat, recreational users of the drug can develop a dependence.

Ketamine may also be prohibitively expensive for potential patients, as it is not covered by OHIP. Furthermore, as a medicine that is only available for research study or private use, it cannot currently be prescribed by most physicians.

There are also limited studies on the rare side effects of ketamine. In the short-term, the main known side effects are disassociation, a daydream-like state, and nausea which may occur during the administration of ketamine.

“We don’t know what we don’t know,” said Rosenblat. It is unclear whether ketamine may cause rare, adverse reactions in some patients. Long-term side effects of ketamine are also unclear.

Rosenblat therefore does not encourage self-medication for U of T students suffering from mental health challenges, as ketamine is not sufficiently studied.

Only a “very small percentage” would likely positively benefit from ketamine, explained Rosenblat, compared to standard treatment options supported by a much wider body of research.

The future of ketamine research

Although ketamine is not fully studied and is currently only used in special situations, it still brings “a message of hope,” said Rosenblat.

While ketamine is still not approved as an antidepressant, the U.S. Food and Drug Administration has approved esketamine, a structurally similar compound, as a nasal spray antidepressant. This became the first antidepressant of its kind to be used in the United States.

While Rosenblat notes that much more future research needs to be done with ketamine, he agrees that preliminary results are “very promising.” With a new avenue of research in treating severe depression, the future of research in the field seems optimistic.

Talks with impact

The Canadian Association for Neuroscience held Public Lectures at the 10th Annual Canadian Neuroscience Meeting

Talks with impact

Rowan Stringer, a high school student from Ottawa, got her first concussion on a Friday in 2013. On the following Monday, she got her second concussion, and on the Wednesday, her third. On the following Sunday, these head injuries ended the life of the 17-year-old rugby player.

Dr. Charles Tator shared Rowan’s story with the audience members of the 2016 Canadian Association for Neuroscience (CAN) Public Lectures. As the first of several events, these lectures heralded the 10th Annual Canadian Neuroscience Meeting, a symposium showcasing the top Canadian research in this field.

Leading neuroscientists Dr. Margot Taylor, Director of Functional Neuroimaging and Diagnostic Imaging at The Hospital for Sick Children, and Dr. Charles Tator, a neurosurgeon at Toronto Western Hospital, were invited to the Peter Gilgan Centre for Research and Learning to speak about their work with innate and acquired brain injury, respectively.

Dr. Taylor introduced the magnetic resonance imaging (MRI) and magnetoencephalography (MEG) brain imaging techniques currently being used in her studies. Her work centres on developmental differences in the pediatric population, comparing typically developing (TD) children with children born preterm or who have Autism Spectrum Disorder (ASD).

“MEG and fMRI are complementary in understanding the neural mechanism of cognitive function,” explained Dr. Taylor. “The main advantage of MEG is that it gives timing information,” whereas fMRI allows the researcher to “determine what brain regions are involved with cognitive ability.” Using these neuroimaging methods, she found that atypical working memory brain processes are found in the ASD group.

In addition to investigating working memory, a component of short-term memory that allows information storage during mental activity, Dr. Taylor explored a concept called theory of mind (ToM) in children with ASD. ToM is the ability to understand that other people have different perspectives from oneself. “People have to inhibit their own belief to understand what others believe,” said Dr. Taylor. “It is considered a key deficit in autism and is called ‘mind-blindness.’”

ASD is an innate disorder of brain development. On the flip side of the coin, Dr. Tator spoke about his research, activism, and experience with acquired brain injuries as a neurosurgeon.

“A concussion is a brain injury. In fact, it is the most common brain injury,” said Dr. Tator. Although the exact mechanism is unknown, experts believe that rotational head acceleration — rather than the tearing or bruising of the brain — causes concussions. The brain moves within the skull. “That’s why helmets don’t work. Helmets do prevent other types of brain injury but they don’t prevent concussions.”

Another concern with concussions is in its diagnosis. “We do not have a good biomarker,” said Dr. Tator. Concussions today are still diagnosed clinically, meaning they are dependent on the amalgamation of a clinician’s judgement with a patient’s self-reported symptoms. This requires the patient to be compliant and truthful. “Imagine having a major disorder that can only be diagnosed with autopsy,” Dr. Tator posited. A purposeful effort to hide the injury can fool the examiner. “We still witness this regularly in professional sports,” said Dr. Tator, recalling hockey player Sidney Crosby’s melee with concussions.

Beyond the NHL, this issue has blighted many lives, including Rowan Stringer’s. She lost her life after ignoring several symptoms of concussion. “This case alone indicates that concussion is a public health concern,” said Dr. Tator. “We are playing catch-up in this field. It’s been a completely neglected field for a long time, but not anymore.”

As a prelude to the 10th Annual Canadian Neuroscience Meeting, these lectures sparked discussion of current research by the neuroscience community.