Parkinson’s disease, a progressive neurological condition affecting over 10 million people worldwide, may stem from dysfunction within a specific brain network rather than being solely a movement disorder, according to new research. For decades, the disease has been primarily associated with motor deficits, but emerging evidence suggests a broader network disruption is at play.
An international research team, led by China’s Changping Laboratory and in collaboration with Washington University School of Medicine in St. Louis, has identified the somato-cognitive action network (SCAN) as a central driver of the disease. The findings, published on , in the journal Nature, challenge conventional understanding and open avenues for more targeted treatments.
The SCAN, first described in 2023 by researchers at Washington University, links thinking with movement. The new study reveals that in individuals with Parkinson’s, this network exhibits excessive connectivity with the subcortex – the part of the brain responsible for emotion, memory, and motor control. This “hyperconnectivity” disrupts not only movement but also cognitive and other bodily functions, contributing to the wide range of symptoms experienced by patients, including tremors, difficulty with movement, sleep problems, and cognitive decline.
“This work demonstrates that Parkinson’s is a SCAN disorder, and the data strongly suggest that if you target the SCAN in a personalized, precise manner you can treat Parkinson’s more successfully than was previously possible,” said co-author Nico U. Dosenbach, MD, PhD, the David M. & Tracy S. Holtzman Professor of Neurology at WashU Medicine.
Understanding the SCAN and its Role
The SCAN’s location within the motor cortex highlights its role in translating planned actions into physical movements and monitoring their execution. However, because Parkinson’s disease impacts functions beyond movement – including digestion, sleep, motivation, and cognitive processes – researchers investigated whether disruptions in the SCAN could explain the disease’s diverse symptom profile.
To explore this connection, the research team analyzed brain imaging data from over 800 participants across research centers in the United States and China. This group included individuals with Parkinson’s disease undergoing various therapies, including deep brain stimulation (DBS) and non-invasive treatments like transcranial magnetic stimulation (TMS), focused ultrasound stimulation, and medication. The analysis also included healthy volunteers and individuals with other movement disorders for comparison.
Targeting the SCAN with Non-Invasive Stimulation
The analysis consistently showed that treatments were most effective when they reduced the overconnection between the SCAN and the subcortex. Restoring a more balanced relationship between these brain regions helped normalize activity within the circuit responsible for planning and coordinating actions.
Researchers then developed a precision treatment system utilizing transcranial magnetic stimulation (TMS) to target the SCAN non-invasively with millimeter accuracy. In a clinical trial involving 18 patients, SCAN-targeted stimulation resulted in a 56% response rate after two weeks. In contrast, only 22% of 18 patients receiving stimulation to nearby brain regions showed improvement – a 2.5-fold increase in effectiveness.
“With non-invasive treatments, we could start treating with neuromodulation much earlier than is currently done with DBS,” because they don’t require brain surgery, Dosenbach explained.
Future Directions and Ongoing Research
While these findings represent a significant step forward, researchers emphasize the need for further investigation to fully understand how different parts of the SCAN contribute to specific Parkinson’s symptoms. Ongoing research aims to refine treatment strategies and personalize interventions based on individual patient needs.
Dosenbach plans to launch clinical trials through Turing Medical, a WashU Medicine startup he co-founded. These trials will evaluate a non-invasive therapy using surface electrode strips placed over SCAN regions to address gait problems in individuals with Parkinson’s disease. He also intends to explore low-intensity focused ultrasound as another non-invasive method for modulating SCAN activity using acoustic energy.
Current treatment options, such as long-term medications and invasive deep brain stimulation (DBS), can reduce symptoms but do not halt the disease’s progression or offer a cure. This new understanding of the SCAN’s role in Parkinson’s disease offers hope for more effective, targeted therapies that could potentially slow or even reverse the course of the illness.
