Neurology

Stuck in a Loop of ‘Wrongness’: Brain Study Shows Roots of OCD

neurosciencestuff:

They clean their hands, many times in a row. They flip switches on
and off, over and over. They check — and re-check, then check again —
that they’ve turned the stove off.

No one knows exactly what drives people with obsessive-compulsive
disorder to do what they do, even when they’re fully aware that they
shouldn’t do it, and when it interferes with their ability to live a
normal life.

This lack of scientific understanding has a serious consequence —
experts say approximately half of all sufferers lack effective treatment
options.

But new research could
help guide future treatment to help more of them. In a study released
Thursday, researchers were able to pinpoint the specific brain areas and
processes linked to the repetitive behaviors common to patients with
OCD. Larger than any previous study, researchers studied brain scans
from hundreds of people with OCD, as well as the scans of people who did
not have the condition.

Put simply, the study suggests that the brains of OCD patients get
stuck in a loop of “wrongness” that prevents sufferers from stopping
behaviors even if they know they should.

Errors and stop signals  

Researchers from Michigan Medicine gathered together the largest-ever
pool of task-based functional brain scans and other data from OCD
studies around the world, and combined them for a new meta-analysis
published in Biological Psychiatry.

“These results show that, in OCD, the brain responds too much to
errors, and too little to stop signals, abnormalities that researchers
had suspected to play a crucial role in OCD, but that had not been
conclusively shown due to small numbers of participants in the
individual studies,” says Luke Norman, Ph.D., lead author of the new study and a postdoctoral research fellow in the U-M Department of Psychiatry.

“By combining data from 10 studies, and nearly 500 patients and
healthy volunteers, we could see how brain circuits long hypothesized to
be crucial to OCD are indeed involved in the disorder,” he says. “This
shows the power of doing this kind of research more collaboratively.”

New targets for therapy

Norman works with U-M psychiatry faculty members Kate Fitzgerald,
M.D., M.S., and Stephan Taylor, M.D. Fitzgerald co-directs the Pediatric Anxiety Disorders Program at Michigan Medicine, U-M’s academic medical center, and leads a clinical trial that is currently seeking teens and adults with OCD to test the ability of targeted therapy sessions to treat OCD symptoms.

“This analysis sets the stage for therapy targets in OCD, because it
shows that error processing and inhibitory control are both important
processes that are altered in people with the condition,” says
Fitzgerald.

“We know that patients often have insight into their behaviors, and
can detect that they’re doing something that doesn’t need to be done,”
she adds. “But these results show that the error signal probably isn’t
reaching the brain network that needs to be engaged in order for them to
stop doing it.”

Zeroing in on brain differences

In their paper, the U-M researchers focused on the cingulo-opercular
network — a collection of brain areas linked by highways of nerve
connections deep in the center of the brain. The area normally acts as a
monitor for errors or the potential need to stop an action, and gets
the decision-making areas at the front of the brain involved when it
senses something is “off.”

The pooled brain scan data used in the new paper was collected when
OCD patients and healthy people were asked to perform certain tasks
while lying in a powerful functional MRI scanner. In all, the new
analysis included scans and data from 484 children and adults, both
medicated and not.

Norman led the combining of the data in a carefully controlled way
that allowed for the inclusion of brain scan data from studies conducted
as far apart as the Netherlands, the United States and Australia.

It’s the first time a large-scale analysis has included data about
brain scans performed when participants with OCD had to respond to
errors during a brain scan, and when they had to stop themselves from
taking an action.

A consistent pattern emerged from the combined data: Compared with
healthy volunteers, people with OCD had far more activity in the
specific brain areas involved in recognizing that they were making an
error, but less activity in the areas that could help them stop.

Disconnected brakes

The researchers recognize that these differences aren’t the full
story — and they can’t tell from the available data if the differences
in activity are the cause, or the result, of having OCD.

But they suggest that OCD patients may have an “inefficient” linkage
between the brain system that links their ability to recognize errors
and the system that governs their ability to do something about those
errors. That could lead their overreaction to errors to overwhelm their
underpowered ability to tell themselves to stop.

“It’s like their foot is on the brake telling them to stop, but the
brake isn’t attached to the part of the wheel that can actually stop
them,” Fitzgerald says. “In cognitive behavioral therapy sessions for
OCD, we work to help patients identify, confront and resist their
compulsions, to increase communication between the ‘brake’ and the
wheels, until the wheels actually stop. But it only works in about half
of patients. Through findings like these, we hope we can make CBT more
effective, or guide new treatments.”

Translating the findings to clinical care

While OCD was once classified as an anxiety disorder — and patients
are often anxious about their behavior — it’s now seen as a separate
mental illness.

The anxiety that many OCD patients experience is now thought to be a
secondary effect of their condition, brought on by recognizing that they
are unable to control repetitive behaviors.

The U-M team will test techniques aimed at taming that drive, and preventing anxiety, in its clinical trial of CBT for OCD.
The study is currently seeking teens and adults up to age 45 who have
OCD, and healthy teens and adults who do not. It involves two brain
scans at U-M’s research fMRI facility, and 12 weeks of free therapy
between the first and last scan.  

Fitzgerald notes that rTMS (repetitive transcranial magnetic
stimulation), which was recently approved by the FDA to treat OCD,
targets some of the circuits that the U-M team has been working to
identify.

rTMS focuses magnetic fields on certain areas of the brain from
outside the skull. “If we know how brain regions interact together to
start and stop OCD symptoms, then we know where to target rTMS,” she
says.

For severe cases of OCD, brain surgery techniques have emerged in the
last decade as an option – and the new results are consistent with
their effects. In such cases, neurosurgeons either disconnect certain
brain areas from one another with tiny bursts of energy or cuts, or
insert a permanent probe that can stimulate activity in a particular
area.

The authors of the new paper call for neurosurgeons to consider the
new findings about the role of the brain areas involved in the
cingulo-opercular network in both inhibitory control and error
processing when deciding whether and where to intervene.

The bottom line for patients

The researchers also call for studies that use genetic tests and
repeated fMRI brain imaging of the same OCD patients over time, in
what’s called a longitudinal study. That could help researchers piece
apart the “chicken and egg” issue of whether the problems with error
processing and inhibitory control lie at the heart of OCD, or whether
they’re the effects of the symptoms of OCD.

In the meantime, Norman, Fitzgerald and Taylor hope that people who
currently have OCD, and parents of children with signs of the condition,
will take heart from the new findings. “We know that OCD is a
brain-based disorder, and we are gaining a better understanding of the
potential brain mechanisms that underlie symptoms, and that cause
patients to struggle to control their compulsive behaviors,” says
Norman.

Adds Fitzgerald, “This is not some deep dark problem of behavior –
OCD is a medical problem, and not anyone’s fault. With brain imaging we
can study it just like heart specialists study EKGs of their patients –
and we can use that information to improve care and the lives of people
with OCD.”

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