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Canada Pacemaker for the brain: An inside look at an experimental PTSD treatment

Medical charts plot the course where electrodes will be driven six centimetres into patient Serena Kelly's brain at Sunnybrook Health Sciences Centre in Toronto. She is part of a trial in which post-traumatic stress disorder is treated by deep stimulation of the brain.

Photography by Melissa Tait/The Globe and Mail

Roughly one in three patients with post-traumatic stress disorder do not respond to the standard treatments of drugs and psychotherapy. But a team of researchers in Toronto believes deep brain stimulation, which is sometimes described as a pacemaker for the brain, may hold the key to their relief.

Earlier this month, surgeons at Sunnybrook Health Sciences Centre implanted a pacemaker-like device in their first PTSD patient, launching a pioneering trial of deep brain stimulation for treating the complex disorder. The procedure involves drilling dime-sized holes in the patient’s skull and inserting two electrodes, which are powered by a battery pack implanted under the collarbone. By adjusting the electric pulses emitted by the electrodes, the researchers aim to regulate a brain circuit, called the limbic circuit, which involves multiple areas of the brain associated with PTSD symptoms.

Deep brain stimulation has been used for around 20 years to treat Parkinson’s disease, as well as a range of other conditions, from epilepsy to major depression. But the experimental use of it for PTSD reflects a recent shift in the understanding of the mental illness, which affects an estimated one in 10 Canadians at some point in their lives and involves multiple symptoms, from depression and anger to flashbacks and intrusive thoughts.

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In the past decade, researchers and doctors have begun moving away from viewing PTSD and multiple other conditions, including addiction and anorexia nervosa, as clusters of symptoms. Instead, they now see them as circuit disorders of the brain, says principal investigator Dr. Nir Lipsman, a neurosurgeon and scientist at Sunnybrook.

Dysfunctional brain circuits in PTSD are believed to overlap with the circuits and brain structures involved in other disorders, such as depression and anxiety disorder, he explains.

This new understanding paves the way for potentially treating an entire network by stimulating a very specific point in a circuit, rather than trying to target individual brain structures linked to the various symptoms.

Using deep brain stimulation, "if you can home in on a specific structure that you know has been implicated [in PTSD], you can potentially involve the entire circuit,” Dr. Lipsman explains.

DEEP BRAIN STIMULATION FOR PTSD

The tips of the electrodes, or leads, are inserted about

6 cm into the brain in an area called the subgenual

cingulate, which is involved in mood and anxiety

disorders. By stimulating this specific point in a brain

circuit, called the limbic circuit, researchers hope

to regulate dysfunctional brain signals across multiple

brain structures associated with PTSD symptoms.

The electrical impulses

are carried via an

insulated wire under

the skin of the scalp,

neck and shoulder.

A battery pack implanted under the collarbone

provides constant current stimulation.

LIMBIC SYSTEM

Amygdala

(fear and anxiety)

Medial prefrontal cortex

(decision making and

mood processing)

Hippocampus

(learning and memory)

Subgenual cingulate

(emotion)

and nucleus accumbens

(targeted for addiction

and depression)

TRISH McALASTER / THE GLOBE AND MAIL

DEEP BRAIN STIMULATION FOR PTSD

The tips of the electrodes, or leads, are inserted about

6 cm into the brain in an area called the subgenual

cingulate, which is involved in mood and anxiety

disorders. By stimulating this specific point in a brain

circuit, called the limbic circuit, researchers hope

to regulate dysfunctional brain signals across multiple

brain structures associated with PTSD symptoms.

The electrical impulses

are carried via an

insulated wire under

the skin of the scalp,

neck and shoulder.

A battery pack implanted under the collarbone

provides constant current stimulation.

LIMBIC SYSTEM

Amygdala

(fear and anxiety)

Medial prefrontal cortex

(decision making and

mood processing)

Hippocampus

(learning and memory)

Subgenual cingulate

(emotion)

and nucleus accumbens

(targeted for addiction

and depression)

TRISH McALASTER / THE GLOBE AND MAIL

DEEP BRAIN STIMULATION FOR PTSD

The tips of the electrodes, or leads,

are inserted about 6 cm into the brain

in an area called the subgenual cingulate,

which is involved in mood and anxiety

disorders. By stimulating this specific

point in a brain circuit, called the limbic

circuit, researchers hope to regulate

dysfunctional brain signals across

multiple brain structures associated

with PTSD symptoms.

The electrical impulses are carried via

an insulated wire under the skin

of the scalp, neck and shoulder.

A battery pack implanted

under the collarbone

provides constant

current stimulation.

LIMBIC SYSTEM

Amygdala

(fear and anxiety)

Medial prefrontal cortex

(decision making and

mood processing)

Hippocampus

(learning and memory)

Subgenual cingulate

(emotion)

and nucleus accumbens

(targeted for addiction

and depression)

TRISH McALASTER / THE GLOBE AND MAIL

While it’s possible this approach may be effective for certain, very treatment-resistant patients, “we have to keep in mind that’s a very invasive procedure,” says PTSD expert Dr. Ruth Lanius, a professor of psychiatry at the University of Western Ontario’s Schulich School of Medicine and Dentistry, who is not involved in the Sunnybrook trial.

Although deep brain stimulation is considered safe, there are risks of complications from the surgery, such as infection and, in very rare cases, stroke due to bleeding and even death. Side effects of the stimulation, which tend to be reversible or temporary, can include changes in mood, personality or behaviour, and seizures.

Currently, the standard treatments for PTSD include medications, such as antidepressants and atypical (also known as second-generation) anti-psychotics and therapy, Dr. Lanius says.

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Serena Kelly, 47, and her husband Ron, left, listen to surgical resident Dr. Benjamin Davidson, right, before she is prepped for deep brain stimulation at Sunnybrook.

For those who find no relief from these standard treatments, PTSD can be consuming. Serena Kelly, 47, for instance, has lost count of all the treatments she has tried over the past 20 years. Medications failed to help. And while a type of therapy called cognitive processing therapy allowed her to recognize distorted thoughts, it did not prevent her from becoming instantly overwhelmed by fear and distress whenever she encountered a smell, sight or sound that reminded her of a traumatic incident.

For Ms. Kelly, who developed PTSD after multiple traumas, including abuse and the death of her daughter, day-to-day life is filled with such triggers. She freezes in terror, her chest tightens, she hyperventilates and it can take around half an hour before she can resume whatever she was doing. At night, intrusive images invade her thoughts when she closes her eyes.

Her search for help led her to agree to become the first patient in the Sunnybrook trial. Under anaesthetic on Feb. 7, Ms. Kelly lay awake on the operating table as doctors guided two electrodes into the subgenual cingulate of her brain, an area known to be tied to mood and anxiety disorders. As they activated the electrodes and adjusted their settings, they asked Ms. Kelly a series of questions to gauge how she was feeling to ensure there were no adverse side effects.

Ms. Kelly says she could feel a heightened sense of awareness when the electrodes were turned on in the operating room, though she says it was was difficult to tell whether she felt any better. “It was just a feeling of being very alert and awake.”

In the coming weeks, the research team will examine the effects of the deep brain stimulation, and will make adjustments to the direction and frequency of the electric pulses to try to tailor the treatment for Ms. Kelly. For this first phase of the trial, the researchers intend to replicate the procedure on four other patients to ensure the safety and feasibility of the treatment. Subsequent phases will investigate its efficacy.

Regardless of whether deep brain stimulation is effective for her, Ms. Kelly says her participation in the trial will help researchers better understand her condition. “At this point, I can’t not try,” she says. “I’m not living. I’m surviving.”




In pictures: Serena Kelly’s journey

(Warning: Contains some graphic content)



Before surgery, Dr. Nir Lipsman and resident Dr. Benjamin Davidson place a head frame on Ms. Kelly. It will keep her completely still during the procedure – which will take place while she is still awake.

Melissa Tait/The Globe and Mail

She is given a variety of brain scans ahead of the surgery, so the doctors can carefully plan the path the electrodes will take. They are aiming for the ubgenual cingulate, an area connected with mood and anxiety disorders.

This is an X-ray view of the electrode that will go into Ms. Kelly's brain.

The electrodes, about six centimetres long, come in eight segments.

Melissa Tait/The Globe and Mail

Dr. Nir Lipsman makes a guide on her skull.

Once the electrodes are inside her brain, a technician controls the current on a tablet under Dr. Lipsman's direction.

Dr. Lipsman leans in to ask Ms. Kelly questions about her emotional and physical awareness. She says she could feel a heightened sense of awareness when the electrodes were turned on in the operating room, though it was hard for her to say if she felt better or not.

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