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What is neuromodulation?

At the Harquail Centre for Neuromodulation, the focus of this rapidly evolving field is on the ability to influence brain circuitry to stop, start and interrupt the systems at the root of the most common and challenging brain disorders. This can be accomplished using a variety of neuromodulation treatments which are led by the expertise of our world-leading researchers and clinical teams who strive beyond excellence in providing treatment options and care to patients.

Repetitive Transcranial Magnetic Stimulation (rTMS)

Repetitive transcranial magnetic stimulation (rTMS) involves applying magnetic pulses to specific areas of the brain, altering electrical activity. By directing this stimulation to particular regions that may be underactive or overactive in certain mental illnesses, such as depression, and with repeated stimulation over time, networks in the brain may eventually be altered. Although rTMS is currently only clinically approved for treating Major Depressive Disorder (MDD), it is under investigation for many other psychiatric and neurological disorders, including: Bipolar Disorder, Obsessive Compulsive Disorder and Post-Traumatic Stress Disorder.

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What are potential benefits of rTMS?

The therapeutic benefits of rTMS have been explored extensively over the past several decades, for numerous psychiatric diseases. In general, approximately 40-60% of individuals with Major Depressive Disorder (MDD) who are not responding to medication and other treatment options, achieve a “response” with rTMS, defined as at least a 50% reduction in their symptoms.

Although rTMS is currently only clinically approved for treating Major Depressive Disorder, it is under investigation for many other psychiatric and neurological disorders, including: Bipolar Disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress Disorder, Panic Disorder, Generalized Anxiety Disorder, Schizophrenia, Tourette syndrome, Eating Disorders, movement disorders, dementia, and chronic pain. Studies have shown promising results for many of these illnesses, but investigations are ongoing.

Am I eligible for rTMS?

rTMS has been approved by Health Canada and the United States Food and Drug Administration (FDA) for the treatment of Major Depressive Disorder (MDD).Your evaluating physician will assess eligibility prior to the treatment.

rTMS is not safe in patients with any metallic or magnetic implants in their head, pacemakers, and a history of seizures or epilepsy. Increased sickness is associated with current pregnancy, recent brain surgery, recent stroke, and/or certain other medical and neurological illnesses.

What happens during an rTMS treatment?

rTMS requires minimal preparation prior to the procedure. Before the first treatment, a patient’s motor threshold will be determined by measuring thumb contractions to a series of simulation tests. The motor threshold level helps to determine the proper dose for the rTMS treatment.

The rTMS coil is placed on the scalp for optimal treatment. .During the treatment you are asked to wear ear plugs to minimize the effect of the sound of the device. You are awake during the procedure and the technician is present at all times. The stimulation can be manually terminated at any point during this process.

How long does rTMS take?

rTMS treatment for Major Depressive Disorder vary in duration from 3 to 37.5minutes.

What are the potential risks of rTMS?

All procedures carry risk. rTMS has been approved by Health Canada and the United States Food and Drug Administration (FDA) for the treatment of Major Depressive Disorder (MDD )that has not responded to 1 antidepressant medication. For the majority of people, there are no serious risks associated with rTMS. The most common side-effects are short-term headache, pain or discomfort to the scalp. Some people have also experienced temporary muscle twitchingand ringing in the ears after rTMS. All side-effects usually resolve within 24 hours.

There is a small risk of inducing hypomania; an abnormal state of elevated or euphoric mood, disinhibition, irritation, or high energy. ) There is also a small risk of thoughts of self harm. Seizures are another risk, but this risk is extremely low. Risk factors for a seizure with rTMS include a family or personal history of seizures.

What are some alternative treatments to rTMS?

Electroconvulsive therapy (ECT), also known as electroshock therapy, has been used to treat many psychiatric disorders since being developed in the 1930s. ECT is an approved treatment for Major Depressive Disorder and involves electrically inducing a seizure in a controlled environment, under anesthesia. ECT appears to have more robust antidepressant properties however, it may be associated with more side effects than rTMS.

ECT can cause deficits in memory, attention, concentration, or intellectual dysfunction, none of which are known side-effects of rTMS. Unlike ECT, rTMS does not require anesthesia or sedation.The main disadvantage of rTMS is that it requires numerous, regularly scheduled outpatient hospital visits (typically 5 days per week for 4-6 weeks), which may be difficult for some people.Health Quality Ontario has concluded that rTMS is an effective option for individuals uncomfortable with undergoing ECT.

Other potential alternatives include: transcranial direct current stimulation (tDCS), focused ultrasound (FUS), or deep brain stimulation (DBS).

Transcranial Direct Current Stimulation (tDCS)

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that involves passing a low, continuous electrical current through specific parts of the brain. Depending on the type of stimulation used, the resting activity in that part of the brain can either be increased or decreased.

tDCSis an experimental treatment and has not yet been approved by Health Canada for clinical use in psychiatric illnesses.

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What are potential benefits of tDCS?

Transcranial Direct Current Stimulation (tDCS) is a minimally invasive technique in treating emotional difficulties. tDSC is still under investigation but early studies have shown it is generally well tolerated with few side-effects being reported the majority of the evidence for tDCS is in the treatment of depressive symptoms.

Am I eligible for tDCS?

It is important to consult with and be assessed by your physician prior to any treatment procedure. As tDCS involves the application of an electric current, patients who have metallic implants (e.g. cochlear implants, pacemakers, devices in the head or brain, etc.) may not be eligible.

What happens during a tDCS treatment?

tDCS requires minimal preparation prior to the procedure. Based on the intended target, your physician will choose specific points on your scalp to place electrodes. The stimulator will then be configured and activated, proceeding through three phases.

The first phase involves a “ramp-up”, where the system will slowly increase the current, while testing to ensure that the electrodes are adequately prepared and placed. If the first phase passes, the system will then administer a continuous stimulation. Finally, the stimulation will “ramp-down” and terminate. The stimulation can be manually terminated at any point during this process.

How long does tDCS take?

tDCS treatment for Major Depressive Disorder can vary in duration from 20 to 40 minutes.

What are some potential benefits of DBS?

Deep Brain Stimulation (DBS) is one ofthe most effective treatments for multiple psychiatric diseases including: Major Depressive Disorder, Obsessive Compulsive Disorder, and Anorexia Nervosa. It is a neurosurgical procedure in which electrodes are implanted in the brain to influence the activity of dysfunctional circuits. The benefits and risks of DBS treatment continues to be investigated.

Am I eligible for DBS?

DBS is typically reserved for severe cases which are resistant to traditional treatment options. Candidates are evaluated and the required criteria is dependent on specific symptoms or disorders. We currently have research trials investigating the safety and feasibility of Deep Brain Stimulation (DBS) in patients with treatment-resistant Post-Traumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD).

For more information on these studies, please visit the Projects page.

What happens during a DBS treatment?

On the day of the procedure, patients will have a stereotactic frame attached to their head to ensure it remains still during the operation, and help the clinical team precisely target the appropriate area of the brain. This is followed by MRI and/or CT scans.

The neurosurgeon will numb parts of the patient’s scalp, and make an incision. Two small holes, approximately the size of a nickel, will be made in the skull . The electrodes will be placed through these holes to reach the target tissue, using images of your brain for guidance. The surgeon will then electrically stimulate the electrodes, and test how the brain reacts. When the precise target is located, the electrodes are implanted in the brain. An extension wire is then passed under the skin of the head and neck, to a battery pack, implanted under the skin beneath the collarbone. The battery provides constant electrical stimulation to the brain.

After the operation, patients will be monitored overnight, and can expect to go home 1-2 days after the surgery.

Patients will be given instructions regarding the activation of the DBS system. Patients are required to attend a series of follow-up appointments after the operation, for health updates and to check the device.

How long does DBS treatment last?

The DBS treatment procedure takes about 4 hours.

What are the potential risks of DBS?

All procedures carry risk. DBS has several risks associated that are associated with any neurosurgical procedure such as damage to the brain, hemorrhage and infection, stroke, cardiac problems, seizures, pain (e.g. headaches) and nausea.

Some other side effects include: unexpected mood changes or worsening of depression or mania, problems with vision, speech, balance, or walking. Abnormal sensations (e.g. numbness or tingling), cognitive changes, such as issues with memories, concentration, judgement, along with muscle tightness or pain are also possible side effects.

What are some alternative treatments to DBS?

Alternatives to DBS include: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), or focused ultrasound (FUS).

All procedures carry risk. tDCS remains an experimental treatment and has not yet been approved by Health Canada for clinical use in psychiatric illnesses. Clinical trials continue to test the safety and effectiveness of this novel treatment.

tDCS is generally well-tolerated and pateints report few adverse effects. The most commonly reported side-effect oftDCSis a tingling sensation under the electrodes, during and shortly after the treatment. A small proportion of these individuals describe the sensation as mildly uncomfortable.

Tiredness is another common sideeffect which can occur during the stimulation and occasionally persist afterwards. Less than 10% of patients have reported minor headaches, but they have consistently responsive to over-the-counter medications.

It is possible for tDCS to inadvertently induce a seizure. There have been a few reported cases of hypomania (an abnormal state of persistently elevated or euphoric mood, disinhibition, irritation, or high energy) triggered by tDCS.

What are some alternative treatments to tDCS?

Potential alternatives to tDCS include: repetitive transcranial magnetic stimulation (rTMS), focused ultrasound (FUS), or deep brain stimulation (DBS).

Deep brain stimulation (DBS)

DBS is a neurosurgical procedure that involves the administration of small amounts of electricity to disrupt abnormal activity of brain structures associated with disease symptoms. It involves inserting thin electrodes into deep brain structures and electrically stimulating them in a controllable and ultimately reversible manner. The electrodes are connected to an internal pulse generator that is implanted in the upper chest region, below your collarbone.

Currently, we are investigating the use of DBS in treating treatment-resistant Post-Traumatic Stress Disorder (PTSD). We are also investigating the use of DBS in treating treatment-resistant Alcohol Use Disorder (AUD).

For more information about these trials, please visit »

Focused Ultrasound (FUS)

Focused Ultrasound (FUS) uses high-intensity and low-intensity ultrasound waves to perform scalpel-free neurosurgery. Focused ultrasound is an incision-free, image-guided technology that targets specific areas of the brain using high frequency ultrasound waves that pass through the scalp and skull. Thousands of ultrasound waves, when converged on a single point, can heat up and cause a lesion to a very small portion of brain tissue. Targeting is highly precise, with millimeter-level accuracy, and done using Magnetic Resonance Imaging (MRI).

Currently, our North American first, clinical trials are investigating the use of FUS in treating treatment-resistant Obsessive Compulsive Disorder (OCD) and Major Depressive Disorder (MDD).

Low-intensity ultrasound waves are being investigated in trials using focused ultrasound to open the blood-brain barrier (BBB), which is a protective wrap around the brain that prevents dangerous compounds from entering the brain. However, the BBB also blocks potential treatments, such as medications, antibodies or chemotherapy agents from entering as well.

In a first in the world clinical trial our researchers have demonstrated safe and non-invasive ways to open the blood-brain barrier in patients with Alzheimer’s disease. MRI-guided low frequency sound waves can target blood vessels in the brain causing microscopic bubbles that have been injected into the bloodstream, to vibrate, which opens up the BBB.

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What are the potential benefits of FUS?

Focused ultrasound (FUS) may treat some neurodegenerative diseases and psychiatric symptoms that are resistant to medical management and other therapies.FUS does not require an incision or radiation treatment.

FUS was successfully tested in a world first trial at Sunnybrook and other medical centres for use with patients with essential tremor, which led to Health Canada and FDA approval in 2016.

The safety and efficacy of FUS inAlzheimer’s Disease, Major Depressive Disorder (MDD), Obsessive Compulsive Disorder and Amyotrophic Lateral Sclerosis (ALS) continues to be investigated through clinical trials. The Harquail Centre for Neuromodulation is at the forefront of research and discovery to provide the latest medical and technological expertise to patients.

Am I eligible for FUS?

Eligibility for FUS treatment or participation in a clinical trial for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), brain tumours, Major Depressive Disorder, Obsessive Compulsive Disorder and Essential Tremor is dependent upon the specific disorder, age requirements for the trial, score(s) on various rating scales and/or country of residence.

To learn more about our Focused Ultrasound clinical trial visit the Projects page.

What happens during a FUS treatment?

FUS is a non-surgical procedure that eliminates skin incisions, drilling and removing the skull, or passage of probes through the brain. Patients are usually awake throughout the entire procedure and carefully monitored by the medical team which includes a neurosurgeon, physicist, anesthesiologist, neurologist, psychiatrist, and FUS technician,

Preparation for the treatment will require you to come to the hospital several weeks prior to treatment day for pre-operative testing that includes imaging (e.g. MRI, CT), blood work, neuropsychological assessment and a pre-assessment visit with the anesthesia clinic

On the morning of a FUS procedure, a stereotactic frame is attached to the patient’s head with local anesthetic. This ensures the head remains completely still during the procedure. With the head frame on, the patient lies down in the MRI scanner and a FUS helmet is connected. The helmet contains transducers which deliver ultrasound waves to the target.At very high frequencies, ultrasound energy can be focused with precision to targets as small as one millimeter, and generate high temperatures creating lesions at a desired focal point.During the procedure, patients remain in constant active contact with the treatment team, who will be observing the procedure.

How long will FUS take?

FUS treatment time typically takes approximately 3–4 hours. Following the procedure, patients stay at the hospital for 1 day overnightand are discharged home the next day, following aMRI scan. The surgical and medical teams closely monitor each patient’s post-treatment recovery and longer term outcome.

What are the potential risks of FUS?

All procedures carry risk. The main risks of Focused Ultrasound include: bleeding and swelling of the tissue in and around the area of the targeted brain region. Other risks include hemorrhage or stroke, or even death although the likelihood of these is very small (1%). Minor risks include discomfort with pin site during stereotactic frame placement, discomfort with lying in a supine position for a long time, pain, headaches and swelling of the face post-procedure.

What are some alternative treatments to FUS?

Other options include: radiofrequency (RF) ablation which requires surgical insertion of a probe into the brain region, gamma knife radiosurgery (GKRS), a non-invasive procedure that involves targetingmultiple sources of radiation to a specific area. Another alternative treatment is deep brain stimulation (DBS) which involves the insertion of electrodes into the symptom-generating structures on both sides of the brain and connecting the electrodes to a ‘pacemaker’ battery in the chest

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) may also be considered as alternatives to FUS treatment.