Researchers study the role of a new brain network in Parkinson's disease

It is a robust study, both in terms of the volume of data analysed (863 participants) and the approach used: neuroimaging of brain connectivity at rest and in response to different treatments. It reinforces the idea that Parkinson's disease does not only affect the “movement centre”, but also a broader neural circuit that coordinates action, motivation and bodily functions and therefore has both a “physical and mental” component. This could help explain well-known clinical observations, such as the fact that slow movements or gait freezing can disappear when lines of light are projected onto the floor to guide the steps or when the patient listens to music with a marked rhythm. In Parkinson's disease, they show that this cortical region (the SCAN network) appears to be hyperconnected to deep areas of the brain that we know are involved in the disease. In other words, the “wiring” between this network and these subcortical regions is overactive, with excessive communication.

Interestingly, when treatments are effective—whether levodopa medication or various neuromodulation techniques such as deep brain stimulation (DBS), transcranial magnetic stimulation (TMS) or focused ultrasound—this “excessive connection” tends to normalise or decrease. This fits with previous observations, but what is truly disruptive is that the study proposes a “common piece” capable of integrating motor and non-motor symptoms within the same framework and better guiding the targets to be used in therapeutic neuromodulation. In fact, in a small trial with TMS, stimulating an area of the SCAN network improved symptoms more than stimulating classic motor areas.

In a way, the study suggests a possible paradigm shift in both diagnosis—using hyperconnectivity as a marker—and in the treatment of Parkinson's disease through neuromodulation. It suggests that personalising the stimulation “target” (in DBS, TMS or ultrasound) could significantly improve outcomes. Even so, it is important to be cautious: at this point, it does not imply a cure or an immediate change in clinical practice. The practical message today is that this approach can help refine where to stimulate and design better clinical trials, but it does not yet change standard care protocols.

This study presents an ambitious analysis based on a large amount of neuroimaging data and different therapeutic approaches to Parkinson's disease. The authors propose that a recently described brain network in the primary motor cortex, related to the integration between cognition and action, could be significantly involved in the pathophysiology of the disease. The work is part of a growing line of research that attempts to understand Parkinson's disease as a disorder of brain networks and not just as an alteration of specific motor circuits.

However, it is important to interpret the results with caution, also from the point of view of the scientific narrative constructed by the article. The study follows a structure that is very common in this type of research: first, it reinterprets the disease from a conceptual construct that guides the reading of the results; then it identifies a “signature” in magnetic resonance imaging that is consistent with the construct; next, it shows that this signature changes with different treatments; and finally, it interprets these changes as a central mechanism of the disease. This type of narrative can be suggestive, but it does not always clearly distinguish between statistical correlation and biological causality. First, the “signature” in this case is based on correlations obtained using functional magnetic resonance imaging at rest, which are mathematical measures that do not allow direct inference of changes in the actual connectivity of the brain. Secondly, the experiment with transcranial magnetic stimulation, which provides the most direct causal and therapeutic evidence, is limited in size and presents possible technical confounding factors.

Therefore, although the study is undoubtedly very interesting and opens up new lines of research, it does not yet justify claiming that Parkinson's disease is a “somato-cognitive action network disorder”, as the title suggests, nor that this concept will “double” the effectiveness of treatments in clinical practice. Studies using other techniques will be necessary to confirm or refute the proposed hypothesis, as well as larger, independent trials with more rigorous designs before these ideas can be transferred to routine clinical practice.

This work is based on a very extensive database and robust neuroimaging and neuromodulation methods. The authors integrate data from nearly 900 individuals, combining resting-state functional magnetic resonance imaging (fMRI), direct electrophysiological recordings (ECoG), levodopa response tests, and various forms of neuromodulation (deep brain stimulation, transcranial magnetic stimulation (TMS), and focal ultrasound). This combination of techniques is particularly appropriate for investigating Parkinson's disease, as it is a disease that affects several brain circuits rather than a single region. Resting-state fMRI is a widely validated tool for studying altered functional networks in Parkinson's disease, and ECoG recordings during surgery provide direct validation, with high temporal resolution, of imaging findings. Furthermore, the use of clinical changes—improvement in symptoms—as a reference reinforces that the neurobiological measures analysed have real functional relevance.

Its main contribution, however, is not methodological but conceptual: it proposes that Parkinson's disease, which was already known to produce motor and non-motor symptoms, involves the alteration of a broader brain network, the so-called “somatocognitive action network”, which integrates movement, cognition and bodily functions. This idea fits well with previous clinical observations, such as the early presence of non-motor symptoms and the influence of cognitive factors on movement, but is now supported by direct experimental evidence.

It is important, however, to avoid exaggerated interpretations. Although the results suggest new targets for optimising therapies such as deep brain stimulation or TMS, many of the interventions tested, especially those involving transcranial magnetic stimulation and focal ultrasound, are based on small samples and studies conducted in one or a few centres, which limits their generalisability. The authors themselves acknowledge that, for example, the TMS trial is a pilot study and that its results need to be confirmed in larger multicentre trials, which is common in the early stages of clinical research. Secondly, although fMRI is a validated technique for studying brain networks in Parkinson's disease, it does not measure direct neuronal activity, but rather functional correlations. The study mitigates this limitation by combining fMRI with ECoG and clinical response to treatment, but even so, it cannot establish a definitive causal relationship between SCAN network hyperconnectivity and all Parkinson's symptoms. Furthermore, the study focuses mainly on motor and axial symptoms; the real impact on non-motor symptoms (cognition, mood, dysautonomia) remains largely unexplored.

This means that a change in standard clinical practice in Spain is not yet anticipated, but it does open up a promising avenue for better personalising treatments in the future. Furthermore, Parkinson's is a highly heterogeneous disease, and it is not yet clear whether this alteration of the SCAN network behaves the same in all clinical subtypes or at different stages of the disease. The key message for patients is that this is a step forward in understanding Parkinson's and how therapies could be refined, not an immediate cure or a technique ready for widespread use.

Although the most striking symptoms of Parkinson's disease (PD) are motor-related (rigidity, tremor, slow movements, etc.), it is a systemic disease that affects organs in the body (the digestive system and cardiac function), the sleep-wake cycle, behavioural planning and motivation, and cognitive functions. In line with these observations, it is known that in addition to the death of dopamine-producing neurons in the substantia nigra and the dysfunction of subcortical neural circuits that control movement, PD is associated with alterations in the cerebral cortex and, above all, in the interaction between the cortex and subcortical structures (such as the subthalamic nucleus, thalamus, substantia nigra, or globus pallidus). This paper describes how the dysfunction of motor cortex structures collectively known as the Somato-Cognitive Action Network (SCAN) could be involved in the pathophysiology of PD. Studying the state of interaction between the SCAN and subcortical structures could be highly relevant for diagnosis and treatment.

The SCAN is a neural structure identified a few years ago in the motor cortex which, unlike traditional motor areas (which send specific motor commands to the muscles of the hand, mouth, arms, etc.), does not perform direct motor functions. The SCAN integrates movement with the cognitive processes of planning and behavioural motivation, as well as the state of the body's organs. The study describes:

• That the connectivity between the SCAN and the subcortical motor structures mentioned in the previous paragraph (monitored in several patient cohorts using complex imaging techniques) is altered in Parkinson's disease patients (what they call hyperconnectivity in PD) and not in patients with other neurological conditions such as essential tremor, dystonia or amyotrophic lateral sclerosis.
• There is a relationship between the degree of SCAN-subcortical structure hyperconnectivity and the severity of patients' symptoms: greater hyperconnectivity in more severe patients.
• SCAN-subcortical structure hyperconnectivity decreases when patients undergo therapies that improve PD (such as levodopa administration or deep brain stimulation).
• The application of repetitive transcranial magnetic stimulation to the cortex of patients with PD to modulate the SCAN decreases SCAN-subcortical structure hyperconnectivity and improves the symptoms of the disease.

The study concludes by highlighting the importance of SCAN-subcortical structure connectivity in the pathophysiology of PD. It suggests that the measurement of this connectivity could be used as a diagnostic biomarker for PD. The measurement of SCAN-subcortical structure connectivity could also be used to optimise treatments (e.g., to better define the sites where deep brain stimulation should be applied). Finally, the modulation of SCAN-subcortical structure connectivity using non-invasive techniques (transcranial magnetic stimulation) could be used as a treatment for PD.

This is a very interesting but complex piece of work, which in my opinion is well done. The techniques for measuring SCAN-subcortical structure connectivity are difficult to set up in a normal healthcare centre, and I therefore do not believe that this article will change daily clinical practice in the short term. However, it does represent a significant advance in our understanding of how all the alterations present in Parkinson's patients are generated. From a more scientific point of view, I would have liked to see a more precise description of the concept of SCAN-subcortical structure hyperconnectivity, which is essential to the study.