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Why Deep Brain Stimulation Works for Some People and Not Others

Why does deep brain stimulation (DBS) work better for some people with neurologic and/or psychiatric illnesses than others? In a series of experiments involving functional MRI scans, investigators at Washington University School of Medicine in St. Louis found subcortical regions and cortical networks can be variable from person to person—and the current methods used for brain mapping before electrodes are implanted surgically for DBS may not account for those differences.

The findings are clinically relevant because surgeons implanting electrodes for DBS in patients with neurologic and psychiatric illnesses use anatomical mapping rather than a more precision-based functional mapping, said Deanna J. Greene, PhD, assistant professor of psychiatry and the first author of the report published online ahead of print on December 5 in Neuron. That could explain why the success of DBS is so variable, she said.

The ten study subjects were healthy men and women, including senior study author Nico U.F. Dosenbach, MD, PhD, an assistant professor at Washington University. The individuals were between 24- and 34-years-old. With ten hours of data on each of the subjects, the scientists had power to look at brain networks and regions on an individual level.

To test the hypothesis,  the researchers set out to measure how regions communicate with each other and to understand the relationship between cortical networks and subcortical regions. The researchers brought the subjects into the fMRI scanner a dozen times and measured brain activity while they were in a resting state. (They didn't do any particular task. They just stayed still, awake, and kept their eyes open. They were looking at a black screen with a small white plus sign.) In subsequent studies, they asked participants to do a series of more classical fMRI tasks, asking them to move their left and right hand. These task-activation maps were only used to validate specific parts of the resting-state maps.

The team looked at the connectivity of subcortical regions, primarily the basal ganglia and the thalamus, and cortical network, and identified individual differences that suggest variability from person to person.  "In individuals, we found that parts of the subcortex and different brain networks work together," Dr. Greene said, referring to these as network integration zones. For example, the motor integration zones—networks that process motor information and cognitive control—converge in the same place in all ten individuals they tested. But when they looked at fMRI activity in the globus pallidus, the cortical networks that converged varied across the study subjects.

Dr. Dosenbach explained that they identified one very interesting integration zone in the ventral intermediate nucleus of the thalamus that showed integration of motor and executive control networks. "When we showed it to our colleagues—neurologist Scott Norris, MD, and Jarod Roland, MD—we learned that that very spot we'd identified on our individual-specific maps was the site for DBS treatment in essential tremor. And that it is effective in 90 percent of patients. This was a critical realization because the motor integration zone in the thalamus is in the exact same spatial location in every one of our subjects."

The scientists looked at other DBS target sites as well and learned that a common DBS site in the globus pallidus is only 40 percent effective. "When we checked our functional network maps, we found that the globus pallidus DBS target site had a range of different functional network representations, consistent with the hypothesis that DBS in that location is less effective because targeting the same spatial coordinate will actually hit different functional networks in that location in different people."

He added that these realizations have led them to propose that the DBS field "should generate patient-specific functional maps of the thalamus and basal ganglia to place DBS leads in a patient-specific, rather than a one-size-fits-all approach."

The researchers are now designing another series of studies to test their hypothesis in patients with neurological conditions heading into DBS surgery.

Link Up to More Information:

Greene DJ, Marek S, Gordon EM, et al. Integrative and network-specific connectivity of the basal ganglia and thalamus defined in individuals. Neuron 2020; Epub 2019 Dec 5.

Gordon EM, Laumann TO, Gilmore AW, et al. Precision functional mapping of individual human brains. Neuron 2017;95(4):791–807.