Deep Brain Stimulation Used to Map Therapeutic Targets for Four Brain Disorders

Disrupted interactions between the frontal cortex and basal ganglia lie at the root of numerous disorders characterized by motor, cognitive, and affective dysfunction.

Previous research has shown direct electrical stimulation of the subthalamic nucleus, a small region in the basal ganglia that receives input from the entire frontal cortex, can help alleviate symptoms of a heterogeneous group of disorders, including Parkinson’s disease, dystonia, obsessive-compulsive disorder (OCD), and Tourette’s syndrome.

Using deep brain stimulation (DBS) as a research tool, Brigham and Women’s Hospital scientists have identified distinct neural circuits for these four disorders. They believe the resulting “maps” represent therapeutic targets that could inform stereotactic targeting in neurosurgery and possibly non-invasive neuromodulation at the cortical level.

Barbara Hollunder, of the Movement Disorders and Neuromodulation Unit in the Department of Neurology at Charité – Universitätsmedizin Berlin, Andreas Horn, MD, PhD, director of Deep Brain Stimulation Research at the Center for Brain Circuit Therapeutics in the Brigham Department of Neurology, and colleagues report these exciting advances in Nature Neuroscience.

Dysfunction Mapping

The researchers began with an international discovery cohort of 197 patients from seven centers who had been bilaterally implanted with subthalamic electrodes for DBS treatment of Parkinson’s (n=94), dystonia (n=70), OCD (n=19), or Tourette’s (n=14). All patients had neuroimaging and clinical information available.

By analyzing which connections had been modulated for optimal therapeutic response across these disorders, the team was able to segregate the frontal cortex and its connections with the subthalamic nucleus into distinct—although sometimes overlapping—dysfunctional territories:

  • Parkinson’s—Premotor regions and supplementary motor areas
  • Dystonia—Somatosensory and primary motor cortices
  • Tourette’s—Primary motor cortices and supplementary motor areas
  • OCD—Ventromedial prefrontal, dorsal anterior cingulate, dorsolateral prefrontal, and orbitofrontal cortices

Retrospective Model Validation

The optimal focal stimulation sites were validated using data from independent cohorts of 32 patients who had been treated with DBS for Parkinson’s and 35 patients treated for OCD.

Prospective Model Validation

In three patients, the Parkinson’s and OCD “maps” showed promise for fine-tuning DBS:

  • A 67-year-old man with a nine-year history of akinetic-rigid type Parkinson’s had DBS reprogrammed according to the dysfunction map; his symptom score on the Unified Parkinson’s Disease Rating Scale–Part III improved by 71%.
  • A 21-year-old woman with severe OCD had DBS reprogrammed; she showed 37% improvement on the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) at one month.
  • A 32-year-old man with a 14-year history of severe OCD was implanted with electrodes placed according to the results of this study; his Y-BOCS score was 77% improved at one month

Laying the Groundwork

The methodology used in this study is capable of mapping the human “dysfunctome”—a library of neural connections that may become disrupted and malfunctioning across different neurologic and psychiatric disorders.

By isolating circuits whose modulation provides the most substantial treatment benefit, it may be possible to determine whether one and the same—or multiple different—dysfunctional networks are implicated in disorders that manifest quite differently in phenotype.

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