A study that combined electrical stimulation of the brain with advanced imaging has shown how correcting misfiring neural circuits can lessen the symptoms of a common psychiatric disorder.
A brain-pacemaker helped put out-of-sync brain circuits back on track in patients with extreme forms of obsessive-compulsive disorder (OCD), reported researchers in yesterday’s Nature Neuroscience. The work could help improve treatment of severe OCD and even lead to other, less invasive new forms of treatment.
Obsessive-compulsive disorder is a psychiatric condition that causes patients to have obsessive thoughts that are often tied to repetitive compulsive behaviors. Neuropsychiatrists Martijn Figee and Damiaan Denys at the Academic Medical Center in Amsterdam and their colleagues used functional magnetic resonance imaging, or fMRI, to monitor changes in blood flow in the brain, a proxy for neural activity, in both healthy patients and while treating patients with severe cases of OCD disorder with deep-brain stimulation.
Benjamin Greenberg, a psychiatrist at Brown University who uses deep brain stimulation to treat intractable OCD in his patients, who was not involved in the project, says the study was a “tour de force”: “To do fMRI in patients who have deep-brain stimulation electrodes implanted in their brains takes a huge amount of very painstaking work to make sure you can do it safely,” he says. The MRI technology uses strong magnetic fields and radio frequency pulses, both of which could disrupt the stimulator’s battery or “even worse, heat up the brain around the electrode,” says Figee. But by using a magnetic coil that only surrounds the patient’s head, turning the stimulator off briefly during the scan, and taking some other safety measures, researchers could detect the neural changes in the treated patients.
The study showed that OCD patients had less activity than healthy participants in a brain region called the nucleus accumbens, which is involved in motivational processes and automatic behaviors, says Figee. But the disorder actually seems to be tied to connectivity between the nucleus accumbens and the frontal cortex, which helps an individual decide whether or not to do something. Communication between these regions was actually higher in the OCD patients when their stimulators were off; when the stimulators were on, the connectivity lowered.
“It is both a local and a global effect,” says Figee. “In OCD, when patients are engaged in unhealthy behaviors, they can’t do anything else, they are continuously washing their hands at the cost of all other normal behaviors, for example.” There is continuous cross talk and excessive connectivity between the frontal cortex and the nucleus accumbens, and this is what deep-brain stimulation seems to break, he says, by overriding disease-linked oscillations between the two brain regions.
The results fit in with what many hypothesize happens with deep-brain stimulation, says Figee. “For a while, the scientific community speculated that this resynchronization of a whole brain circuit should underlie the therapeutic effects, but we could never prove it,” he says. “Now we know that it is indeed network changes and synchronization that we are looking at.”
The findings “could lead to methods that would help us diagnose people using signatures of brain activity as well as methods that might help us monitor treatments ranging from medication to behavioral therapies to deep-brain stimulation,” says Greenberg.
It might also lead to smarter brain stimulating devices. “In some ways the pacemakers that we use for the brain are not as smart as the ones we use for the heart,” says Greenberg. “If you have an implanted defibrillator for the heart you can detect abnormal activity and turn the device on just to interrupt that. But in the brain, we are still learning what the abnormal activity is that we want to affect. This is a step toward understanding what we might be trying to sense, and then we might be able to interrupt it,” he says.
The next step, says Figee, will be to see if he and his colleagues can use the brain activity measures to determine if a patient’s deep-brain stimulator is working properly. An implant has several electrodes, and it can take a lot of trial and error to learn which should be active and at which pulse settings for each patient. “We still don’t really know what we do; sometimes people respond, sometimes they don’t, sometimes it takes weeks or a year trying all kinds of settings,” he says. Using the brain scanning tools in the clinic may be years away, but it is possible, says Figee. “This may help us focus on the brain synchronization that we should aim for,” he says.
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