Researchers in neurological and neurodegenerative diseases have shifted focus when it comes to how diseases are being diagnosed, asking how the brain is impacted, and how diseases like Parkinson’s disease spread over time across the brain’s neural network.
In earlier research, a paper published in the Journal of Nuclear Medicine in November of 2018, different neurodegenerative diseases show distinct patterns of regional involvement, and these patterns mirror the large-scale networks that exist in the healthy brain. This suggests that disease effects are not random but are shaped by how brain regions are linked. So, if you follow the logic laid out in the paper, this can help explain why the severity of each disease can be different for each patient, and why some people are affected in different ways than others, though how the disease spreads has been better understood.
Building on this idea, a recent paper published in Nature, titled “Parkinson’s disease as a somato-cognitive action network disorder(SCAN),” takes this network-based view even further. To simplify it a little, researchers are saying Parkinson’s isn’t just a disease that causes movement problems. Instead, it is a breakdown in the brain that impacts thinking, motivation, and the brain’s “get up and do something” communication system.
The 2018 study suggests that brain diseases don’t damage the brain but follow the “natural wiring” laid out in the brain and spreads along connected pathways, explaining why certain symptoms appear together and follow familiar pathways. The newer Nature study builds on this idea by showing how, in Parkinson’s disease, problems in one key brain network can affect both movement and thinking.
They call this system SCAN, a distributed brain network made up of interconnected regions. In normal, healthy individuals, this network coordinates how movements are prepared and executed, while also integrating thinking, motivation, and arousal, autonomic function, and internal body regulation.
When a disease like Parkinson’s develops, the brain’s network is disrupted. Because of this disruption, the symptoms patients experience, like tremor and stiffness, fatigue, low motivation, anxiety, and depression, are part of the effects of a hampered brain network that connects movement, thinking, emotion, and body regulation, rather than separate problems happening on their own. Researchers describe this as a disorder of a cortico–subcortical circuit, making Parkinson’s disease best understood as a brain network disorder.
One of the most striking findings in this study was that Parkinson’s treatments seem to work best by reducing abnormal brain activity across a network, rather than just targeting one specific brain structure. Deep Brain Stimulation (DBS) was most effective when aimed at areas strongly connected to SCAN, showing how improvements to the network help relieve symptoms.
In a small trial of 36 individuals divided into two groups of 18, the group that received Transcranial Magnetic Stimulation (TMS) versus those that had stimulation in other parts of the brain more than doubled symptom improvement. Focused Ultrasound and dopaminergic medications also provided much-needed benefits that matched changes in SCAN connectivity, pointing to this network as a central target for future therapies.
The two papers show how the understanding of neurodegenerative diseases is advancing and evolving the ideas of many other researchers who believe these diseases are moving along connected pathways and shaping how symptoms unfold over time explaing how damage may travel and shows what that damage looks like in a real disorder.
With Alzheimer’s patients, the neurodegenerative damage starts in the Hippocampus the part of the braint hat forms new memories, and from there it spreads through the brain’s natural wiring and connected pathways to areas that help store memories and help link thoughts, feelings, and experiences. Over time, those connections start to weaken. As these areas of the brain weaken, the effects of Alzheimer’s begin to grab hold, including confusion, getting lost, and changes in behavior and personality.
For Parkinson’s patients, it starts at the Substantia nigra, where the misfolding of alpha-synuclein proteins, a significant cause of the disease, occurs, and these proteins spread through the basal ganglia, the motor cortex, and the cerebellu which fine-tunes movement.
In ALS patients, the problems start in the Motor Cortex and spreads through the corticospinal tract, the main neurological pathway through which the body receives its instructions from. A direct pathway from the brain to the muscle. As the disease progresses over time, motor neurons die, and harmful clumps of TDP-43 build inside nerve cells, breaking down communication between the brain and muscle. Symptoms unfold this way because ALS follows the brain’s direct “wiring route” for movement from start to finish
Huntington’s Disease starts in the Striatum, an area of the brain that helps control movement, emotions, and decision-making, and then spreads through the Basal Gangila (which regulates both physical actions and behavior). As nerve cells die, a key part of the brain begins to shrink, and the brain has trouble controlling and filtering movement. The system that normally stops extra or unwanted motions becomes weaker, while “go” signals become too strong. This leads to involuntary, jerky movements and changes in mood and thinking. In simple terms, the brain loses its natural braking system for both movement and behavior.
All of these studies and descriptions of neurological diseases show patterns that suggest that brain diseases follow the brain’s wiring map. Starting at different points in the brain, they begin in different areas and then move through interconnected networks, shaping how symptoms appear and progress. Understanding these pathways may help doctors better predict disease course and design treatments that restore balance to entire brain systems, not just single brain regions.
In the paper, researchers state that,“ PD has traditionally been classified as a movement disorder on the basis of its most visible and debilitating symptoms, despite the well-recognized complex deficits in movement planning, coordination, and cognitive abilities.”
They go on to say, “Here, we provide evidence that the SCAN lies at the core of network dysfunction in PD. With this updated understanding, we propose that PD may be better conceptualized and treated as a SCAN disorder. While SCAN dysfunction is not exclusive to a single condition—as it could also arise from stroke or multiple sclerosis—our findings position PD as a paradigmatic instance of a SCAN disorder. This reclassification of PD shifts the focus from complex and diverse phenotypic symptoms to specific circuit pathologies, encouraging future research on the associations between network dysfunction and the various symptom domains of PD. Highlighting the SCAN dysfunction in PD should facilitate the optimization of existing therapies and the development of circuit-based neuromodulation treatments.”
The SCAN study fits into a growing scientific view that most brain diseases like Alzheimer’s, Huntington’s Disease, Parkinson’s, and ALS are network disorders, which is supported by many experts in the field of neurology. According to neurologist, Dr. Michael Okun, author of the best-selling book, Parkinson’s Plan on his LinkedIn page, “This paper opens the door to rethinking Parkinson’s as a disorder of action readiness and integration, not just movement execution. This is a big step forward for brain network science in Parkinson’s.”
In each case, the disease spreads through connected brain pathways rather than damaging random areas. The network that fails first will shape the symptoms that appear.
Unless noted, all media by Chris Denny/Adobe
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