A collaborative international research effort has identified a key brain network, dubbed the somato-cognitive action network (SCAN), as central to the development and progression of Parkinson’s disease. The findings, published today, , in the journal Nature, challenge long-held understandings of the neurological basis of the debilitating condition and offer a potential pathway towards more effective, precision-targeted treatments.
Parkinson’s disease, a progressive neurological disorder, affects more than 1 million people in the United States and over 10 million globally. Characterized by symptoms including tremors, movement difficulties, sleep disturbances, and cognitive impairments, the disease currently lacks a cure and existing treatments – including long-term medication and invasive deep brain stimulation (DBS) – primarily focus on symptom management.
The study, led by China’s Changping Laboratory in collaboration with Washington University School of Medicine in St. Louis and other institutions, demonstrates that Parkinson’s disease is not simply a movement disorder, but rather a disorder of the SCAN. This network, first described in 2023, resides within the motor cortex – the part of the brain controlling body movements – and is responsible for translating action plans into movements and processing feedback on their execution.
Researchers discovered that the SCAN is abnormally hyperconnected to key regions associated with Parkinson’s disease. This disrupted wiring, they believe, impacts not only motor function but also related cognitive and bodily functions. The team found that targeting this network with a non-invasive therapy called transcranial magnetic stimulation (TMS) yielded significantly improved outcomes in a small group of patients.
In a clinical trial, 18 patients receiving TMS targeted at the SCAN demonstrated a 56% response rate after two weeks, compared to a 22% response rate in a control group of 18 patients who received TMS in surrounding brain areas. This represents a 2.5-fold increase in efficacy, according to the published research.
“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 Nico U. Dosenbach, MD, PhD, the David M. & Tracy S. Holtzman Professor of Neurology at WashU Medicine. “Changing the activity within SCAN could slow or reverse the progression of the disease, not just treat the symptoms.”
The research team analyzed brain imaging data from over 800 participants, including individuals with Parkinson’s disease undergoing various treatments – DBS, TMS, focused ultrasound stimulation, and medication – from institutions in both the United States and China. Analysis revealed that the disease is characterized by hyperconnectivity between the SCAN and the subcortex, the brain region responsible for emotions, memory, and motor control.
Importantly, the study found that the efficacy of existing therapies, including DBS, TMS, and focused ultrasound, was enhanced when treatments were focused on reducing this hyperconnectivity between the SCAN and the subcortex. The substantia nigra, a brain region affected in Parkinson’s, and all current DBS targets (subthalamic nucleus, globus pallidus, and ventral intermediate thalamus) are selectively connected to the SCAN, rather than to specific motor regions.
“For decades, Parkinson’s has been associated primarily with motor deficits and the basal ganglia,” explained Hesheng Liu, the study’s lead author. “Our work demonstrates that the disease originates in dysfunction of a much broader neuronal network. The SCAN is hyperconnected to key regions associated with Parkinson’s disease, and this abnormal wiring disrupts not only movement but also related cognitive and bodily functions.”
The researchers have developed a new precision treatment system capable of targeting the SCAN non-invasively with millimeter accuracy. This system utilizes TMS to deliver magnetic pulses to the brain, offering a potentially less invasive alternative to DBS, which requires surgical implantation of electrodes.
The findings represent a significant shift in the understanding of Parkinson’s disease, moving away from a focus solely on motor symptoms and towards a more holistic view of the condition as a disorder of brain network connectivity. Further research will be needed to validate these findings in larger patient populations and to optimize SCAN-targeted therapies for widespread clinical use. However, the initial results offer a promising new avenue for the treatment of this debilitating disease.
