Mapping dysfunctional circuits in the brain by electrically stimulating areas deep within it could improve the treatment of four neurological disorders, research suggests.
The findings, in Nature Neuroscience, may help identify new targets and strategies for dystonia, Parkinson’s disease, Tourette Syndrome, and obsessive-compulsive disorder (OCD).
The researchers identified those circuits in the frontal cortex with the best responses to treatment with deep brain stimulation (DBS), helping them to understand areas of dysfunction in each disorder.
“Clinically, the identified circuits directly represent therapeutic targets that could inform stereotactic targeting in neurosurgery and potentially non-invasive neuromodulation at the cortical level,” reported Ningfei Li, PhD, from Charité–University Medicine Berlin in Germany, and colleagues.
DBS involves surgical implantation of electrodes in the brain to treat brain networks that are malfunctioning and manifest as neurological disorders.
It is commonly used in the subthalamic nucleus—a small structure below the thalamus—to treat Parkinson’s disease and is also being explored for dystonia, OCD, and Tourette’s.
However, it remains unclear which brain circuits need stimulation for the different conditions.
To investigate further, Li and the team studied data on 261 patients with Parkinson’s disease, dystonia, OCD, or Tourette Syndrome who had DBS electrodes implanted in the subthalamic nucleus.
The researchers found that interconnections of the subthalamic nucleus to the sensorimotor cortex were most important for treating dystonia while those linking to the primary motor cortex were most relevant for Tourette Syndrome.
Subthalamic nucleus connections to the supplementary motor area were most pertinent for Parkinson’s disease, while those to the ventromedial prefrontal and anterior cingulate cortices had the greatest consequences for OCD.
The researchers validated their findings in two additional, independent retrospective cohorts involving patients with Parkinson’s disease and OCD.
They also used their research prospectively to guide treatment in one patient with Parkinson’s disease and two with OCD.
All reported symptom reductions following individualized DBS treatment.
Li and fellow investigators say their methodology shows how successful neuromodulation could be used to outline and tune down what they term the “dysfunctome”—the set of connections that are disrupted in given brain disorders.
“In conclusion, our study demonstrates the potential of invasive brain stimulation as a ‘flashlight’ pointing from the subcortex onto the topography of the human ‘dysfunctome,’” they say.
