Brain Stimulation to Treat OCD

Large-scale UHN-led study finds brain stimulation treatments may help people with severe OCD.

Image Caption: Obsessive compulsive disorder (OCD) affects 2–3% of people globally, yet is one of the leading causes of disability from mental health conditions. The need for new treatments is critical, particularly for those with severe manifestations of the disorder.

A new study from UHN’s Krembil Brain Institute (KBI) suggests that brain stimulation treatments, also called neuromodulation, may offer new hope for individuals living with severe obsessive-compulsive disorder (OCD). The findings of this meta-analysis, which combines results from many studies, suggest brain stimulation may help people better manage symptoms and improve quality of life.

OCD is a mental health condition characterized by intrusive, distressing thoughts (obsessions) and repetitive behaviours (compulsions) performed to reduce anxiety. These symptoms can take a serious toll and impair daily life. For 30–40% of patients, standard treatments fail to provide relief, and some do not respond even to additional medications used when first-line treatments do not work. This severe form of treatment resistance is known as treatment-refractory OCD.

As researchers learn more about how different parts of the brain communicate in OCD, new treatments have emerged that aim to treat the brain networks directly. These therapies, called neuromodulation, use controlled electrical or magnetic stimulation to adjust activity in specific areas of the brain. Until now, no study has comprehensively compared different brain-stimulating approaches, limiting understanding of which option is most effective.

The KBI team analyzed 142 studies involving 2,960 patients across four approaches: deep-brain stimulation (DBS), lesion-based surgery, transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS). DBS and lesion-based surgery are invasive, while tDCS and TMS are non-invasive.

Results showed that all techniques reduced OCD symptoms. While invasive approaches showed the strongest effects, non-invasive modalities still produced moderate improvements and may be a more accessible option for those with less severe symptoms. Researchers suggest invasive techniques perform better because they can more reliably and precisely target key communication areas deep in the brain, known as hubs.

"Our analysis points to the importance of considering how brain regions are connected when determining whether a region is an ideal candidate for neuromodulation, rather than its location alone," says KBI Assistant Scientist and senior author of the study, Dr. Jürgen Germann.

For people living with OCD for whom standard treatments have failed, this meta-analysis represents a step towards better symptom management and reduced disability as a result. The findings support the use of neuromodulation for severe OCD while also shedding light on the underlying brain circuitry and potential therapeutic targets. Future research that continues to focus on how brain networks function could help make brain stimulation treatments for OCD more precise and personalized.

Dr. Flavia Venetucci Gouveia, Scientist at The Hospital for Sick Children and Assistant Professor in the Department of Medical Biophysics at the University of Toronto, is the first author of this study.

Dr. Jürgen Germann, Assistant Scientist at UHN’s Krembil Brain Institute and Assistant Professor at the University of Toronto’s Institute of Biomedical Engineering, is the senior author of this study.

This work was supported by the Canadian Institutes of Health Research, Brain Canada Foundation, the Shireen and Edna Marcus Foundation, and UHN Foundation.

Dr. Andres Lozano is a co-founder of Functional Neuromodulation and a consultant for Boston Scientific, Medtronic and Abbott.

Gouveia FV, Elias GJB, Wong EHY, Yang A, Beyn M, Mesich A, Omere U, Iskin SA, Bai Y, Hu CK, Boutet A, Lozano AM, Germann J. Neuromodulation for treatment-resistant obsessive–compulsive disorder: a systematic review, meta-analysis and network analysis. Nat Mental Health. 2026 Apr 13. DOI: 10.1038/s44220-026-00586-9.

Research Spotlight

Read the latest bi-monthly newsletter that highlights advancements from UHN researchers.

Welcome to the latest issue of Research Spotlight. 

As Canada’s largest research hospital, UHN is a national and international source for discovery, education, and patient care. This newsletter highlights top research advancements from over 5,000 members of TeamUHN—a diverse group of trainees, staff, and principal investigators who conduct research at UHN. 

Stories in this month’s issue:  

• A Bridge Beyond Pacemakers: UHN team generates cardiac-like cells that could replace electronic pacemakers after AV block. 
• Advancing Care with Digital Lungs: Scientists develop digital twins of human lungs using Ex Vivo Lung Perfusion data.
• New Tool for Drug Discovery: Study identifies often-missed protein-binding molecules, accelerating drug discovery. 
• More Biomarkers Improve Detection: New diagnostic approach combining skin and blood tests could overhaul Parkinson disease care. 

Read these stories and more online here. To read previous issues, see the newsletter archive.  

Meet Dr. Jennifer Jones @PMResearch

From surviving to thriving: How research is reshaping life after cancer

Image Caption: Dr. Jennifer Jones is a Senior Scientist, Director of the Cancer Rehabilitation and Survivorship Program, and the Butterfield/Drew Chair in Cancer Survivorship Research at UHN’s Princess Margaret Cancer Centre.

More people are surviving cancer today than ever before, due to recent advancements in early detection and treatments.

However, survival is only part of the story. Cancer and its treatments often leave people with long-term effects such as fatigue, pain, weakness, memory problems, and emotional distress. These challenges can last months or years, making it hard to return to work, care for family, and enjoy everyday life.

 “Cancer changes everything,” says Dr. Jennifer Jones, Senior Scientist and Director of the Cancer Rehabilitation and Survivorship Program at UHN’s Princess Margaret Cancer Centre (PM).  “For many patients, the challenge isn’t just getting through treatment; it’s what comes after.”

A new model of care: Transforming life after cancer

Jennifer leads the Cancer Rehabilitation and Survivorship (CRS) Program at PM, which is one of the largest comprehensive programs of its kind worldwide.

Patients with cancer-related impairments and disability are referred to CRS to receive a full assessment, a personalized plan to address their needs, and sometimes 1:1 follow-up consults.

Patients who have several impairments and deconditioning are typically enrolled in the CaRE program, which supports patients with eight weeks of tailored progressive exercise training and self-management classes addressing common side effects such as fatigue, cognitive impairments, and dealing with difficult emotions.

The CaRE program can be delivered in person by a multidisciplinary CRS team in small groups at the ELLICSR Centre for Health, Wellness and Cancer Survivorship, which was funded by the Canadian Foundation for Innovation. The CaRE@ELLICSR program also places a focus on nutrition, providing hands-on cooking classes with a wellness chef and dietitian. A prospective study of CaRE@ELLICSR showed that it improved patients’ physical activity, upper body muscular strength, and cancer-related symptoms.

 “We see people regain strength, confidence, and control over their lives,” she says. “That’s what drives this work.”

CaRE@ELLICSR provides multi-dimensional rehabilitation care in group settings. Patients receive tailored exercise prescriptions, nutrition, and self-management classes to address their needs.

Research in a dynamic real-life situation

What sets the CRS program apart is how tightly care and research are connected.

Rather than treating research and clinical care as separate, Jennifer and her team have built an integrated model where each informs the other. Jennifer learned the model from her mentors, Dr. Gary Rodin, who founded the Department of Supportive Care at Princess Margaret, and Dr. Pamela Catton, former Director of Oncology Education and Cancer Survivorship at UHN.

When Dr. Catton passed away, Jennifer assumed the role of Director of the Cancer Rehabilitation and Survivorship Program. She carried on her legacy and their collective research that paved the way for the current program.

“What we study comes directly from what we see in the clinic,” she explains. “We identify the gaps, test solutions, and then bring those solutions right back into care.”

This approach has led to the rapid development and testing of new models like CaRE@Home, a virtual program designed to improve access. Early studies showed it is feasible, safe, and helps reduce disability. It is now being evaluated in a multi-centre Phase III trial funded through the Canadian Institutes of Health Research (CIHR) and the Canadian Cancer Society.

Other models of the CaRE program have been developed based on different patient needs: CaRE-Advanced Cancer, which was developed for people living with metastatic disease, helps patients maintain function, manage ongoing treatment effects, and sustain life roles. And CaRE-AYA was launched to address the specific needs of adolescents and young adults under 40.

Tailoring care for those who need it most

The same model is driving innovation for patients with more complex needs.

In 2019, Dr. Jonas Mattsson, Director of the Hans Messner Allogeneic Transplant Program at PM, contacted Jennifer to see how they could help patients undergoing allogeneic blood and marrow transplantation (allo-BMT) to be more active, so that they can better withstand and recover from transplantation. 

Together, the two teams developed CaRE-4-AlloBMT, which is a longitudinal rehab program delivered before transplant, during hospitalization, and then 6 months after transplant.

“AlloBMT patients face many physical challenges from previous cancer treatments and the transplant itself. Incorporating multidimensional rehabilitation from pre- to post-transplantation is the ideal clinical approach. This can provide both a preventive ‘buffering’ and a restorative supportive measure,” says Jennifer.

In a Phase II trial, CaRE-4-AlloBMT was found to be feasible, acceptable, and safe, with promising results related to improving physical function and disability. To build on this, the team is now conducting a larger Phase III trial funded through CIHR.

Jennifer is excited and optimistic about this study: “This is a proactive approach that can bring promising benefits to preserve and optimize physical function, address alloBMT-related morbidities, minimize dysfunction, and enhance quality of life.”

Changing the future of cancer recovery

For Jennifer, the ultimate goal extends beyond a single program.

“We have a responsibility to build the evidence around cancer rehabilitation,” she says. “If we can show these programs work, we can make the case for broader access so patients across Canada can receive the care they need.”

Through an integrated model of clinical care and research, her team is not only helping patients recover, but they are redefining what recovery after cancer can look like.

Reflecting on the important things in life

Through her work with patients, Dr. Jennifer Jones has gained a unique perspective on what truly matters in life.

She has seen how a cancer diagnosis reshapes priorities, shifting focus away from work, status, and material things, and toward family, relationships, and meaningful experiences.

“People often come out of cancer with a very different lens,” she says. “They think more about how they want to spend their time and who they want to spend it with.”

That perspective has shaped how she approaches her own life.

“I work hard, but when I leave work, I’m fully present with my family,” she says. “That balance is incredibly important to me.”

She and her family also try to live the same healthy, active lifestyle she encourages in her patients, something she sees not as an obligation, but as an investment in long-term well-being.

“Don’t wait for a health crisis to start making changes,” she says. “Small, consistent steps, staying active, prioritizing your mental health, and making time for the people in your life, can make a huge difference.”

It is a message that reflects both her research and her lived experience:

“More people are surviving cancer. The goal now is to live well, and that’s something we should all be thinking about.”

Meet PMResearch is a story series that features Princess Margaret researchers. It showcases the research of world-class scientists, as well as their passions and interests in career and life—from hobbies and avocations to career trajectories and life philosophies. The researchers that we select are relevant to advocacy/awareness initiatives or have recently received awards or published papers. We are also showcasing the diversity of our staff in keeping with UHN themes and priorities.

How the Body Remembers Inflammation

Researchers discover how repeated infections and stress can change blood stem cells over time.

Image Caption: Newly identified blood stem cells, called HSC inflammatory memory (HSC-iM) cells, are distinct from other blood stem cells in that they develop changes at the molecular level in response to inflammation that are maintained long term.

Stress from inflammation over long periods of time can drive the aging of blood cells and raise the risk of cancer. In a new study published in Nature, researchers at UHN’s Princess Margaret Cancer Centre (PM) and the University of Oxford have identified human blood stem cells (hematopoietic stem cells, HSCs) that can remember prior inflammation—a finding that could impact what is known about aging and the long-term effects of inflammation.

Mature blood cells are continuously replenished by bone marrow hematopoietic stem and progenitor cells—rare, self-renewing cells that develop into all blood cell types. Inflammation, caused by infections and other stressors over time, can contribute to an age-related decline in HSCs.

It is not fully known how daily blood production is coordinated with the maintenance of blood stem cells over a lifespan, especially in response to repeated episodes of inflammation. To understand how HSCs adapt and respond to inflammation, the research team, led by senior authors Drs. Stephanie Xie and John Dick from PM and Dr. Paresh Vyas from the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, generated specific lab models of inflammation to analyze human HSCs.

These models, called xenograft inflammation-recovery models, use human cells to study inflammation by exposing them to conditions that mimic inflammatory stress, such as those seen in sepsis or aging. These models are then analysed at the molecular and single-cell level.

The research team identified a distinct group of HSCs that differed at the level of how their genes work. These cells were termed HSC inflammatory memory cells (HSC-iM) as they could retain the memory of past inflammation. After exposure to inflammatory treatments, HSC-iM retained molecular changes that included long-lasting shifts in how the stem cells behaved and communicated. They also remained in a resting state and produced fewer blood cells than usual.

Indications of this inflammatory memory were also found in HSC samples from people recovering from COVID-19, individuals with sickle cell disease, older adults, and people with age-related blood cell changes—validating the results from the lab models.  

Interestingly, in situations where HSCs were impacted by a condition caused by age-related genetic mutations, called clonal hematopoiesis, the impact of inflammatory stress was reduced. HSC-iM with these changes were more likely to be activated and divide to mature into working blood cells. In other words, these mutations made the memory cells behave differently.

The molecular differences observed in HSC-iM were also passed down to immune cells that these stem cells matured into, shaping how those cells behave and react to inflammation later on.

Additionally, people whose circulating blood cells showed more of these long-lasting inflammatory patterns had a higher overall risk of death, linking these stem cell changes to real-world health outcomes and helping explain why inflammation affects people differently across a lifetime.

“These findings help explain why inflammatory experiences earlier in life may shape a person’s health decades later,” says Dr. Stephanie Xie, Scientist at UHN’s Princess Margaret Cancer Centre and corresponding author of the study. “It provides us with more tools to investigate how health outcomes due to aging and age-associated diseases can differ between individuals.”

Dr. Andy Zeng is the co-first author of the study and an MD/PhD candidate at UHN and the Temerty Faculty of Medicine at the University of Toronto.

Dr. Murtaza Nagree is the co-first author of the study and a Postdoctoral Researcher at UHN.

Dr. Niels Asger Jakobsen is the co-first author of the study and a Postdoctoral Research Scientist at the University of Oxford.

Dr. Paresh Vyas is the co-senior author of the study. He is a Professor of Haematology at the University of Oxford.

Dr. John Dick is the co-senior author of the study. He is a Senior Scientist at UHN’s Princess Margaret Cancer Centre, the Helga and Antonio De Gasperis Chair in Blood Cancer Stem Cell Research, a Professor in the Department of Molecular Genetics at the Temerty Faculty of Medicine at the University of Toronto, and University Professor, University of Toronto.

Dr. Stephanie Xie is the co-senior and corresponding author of the study. She is a Scientist at UHN’s Princess Margaret Cancer Centre and an Assistant Professor in the Department of Medical Biophysics at the Temerty Faculty of Medicine at University of Toronto.

This work was supported by the University of Toronto, the Medical Research Council, Leukaemia UK, Blood Cancer UK, the Government of Ontario, the International Development Research Centre, the Government of Canada, the Terry Fox Research Institute, Blood Cancer United, the Canadian Institutes for Health Research, the Canadian Cancer Society, the Medical Research Council (MRC) Molecular Haematology Unit at the University of Oxford, the NIHR Oxford Biomedical Research Centre, the Allan Slaight Breakthrough Fund, and The Princess Margaret Cancer Foundation.

Dr. John Dick receives royalties from Trillium Therapeutics Inc./Pfizer.

Zeng AGX, Nagree MS, Jakobsen NA, Shah S, Varesi A, Kang JRW, Murison A, Cheong JG, Turkalj S, Zhang X, Radtke FA, Abera TA, Lim INX, Jin L, Araújo J, Aguilar-Navarro AG, Parris D, McLeod J, Kim H, Lee HS, Zhang L, Boulanger M, Bader E, Gbeha E, Parkhurst CN, Wagenblast E, Flores-Figueroa E, Wang B, Schwartz GW, Shultz LD, Nam AS, Grimes HL, Josefowicz SZ, Awadalla P, Vyas P, Dick JE, Xie SZ. Human haematopoietic stem cells remember inflammatory stress. Nature. 2026 May 27; doi:10.1038/s41586-026-10522-7.

The Art of Transplant Experience

Exploring lived experience through art reveals deeper insights into organ transplantation.

Image Caption: The artwork created by participants illustrates how arts-based approaches can capture the emotional and lived experiences of organ transplantation. (Image courtesy of Dr. Suze Berkhout)

Examples of the visual field notes created by participants. (Images courtesy of Dr. Suze Berkhout) 

Surgical Research Excellence

UHN researcher awarded prestigious surgical research honour.

The Science Behind Safer Eating

Testing different food textures can support better care for people living with dysphagia.

Image Caption: Prof. Catriona Steele, senior author of the study, pictured here analyzing a videofluoroscopy recording. This technique allows clinicians to observe swallowing in real time and gain insights to better guide dysphagia care.