Journal: Nature
This study examines how a specific brain network—the somato-cognitive action network (SCAN)—relates to Parkinson’s disease (PD) symptoms and treatment response.
Key points:
- Conceptual focus: The SCAN is a large-scale network thought to coordinate arousal, internal organ states, whole-body motor plans, and behavioral motivation. The authors hypothesize that dysfunction of this network contributes to the broad motor and non-motor manifestations of PD.
- Dataset and methods:
- Large, multimodal clinical imaging dataset (n = 863) including patients with PD undergoing various treatments.
- Resting-state functional connectivity was used to map how deep-brain targets and cortical regions connect within brain networks.
- Additional cohorts were followed longitudinally with resting-state fMRI and electrocorticography to assess treatment effects on connectivity.
- Connectivity findings:
- The substantia nigra and all established PD deep-brain stimulation (DBS) targets—subthalamic nucleus, globus pallidus, and ventral intermediate thalamus—showed preferential functional connectivity to the SCAN rather than to classical, effector-specific motor regions.
- PD was specifically associated with hyperconnectivity between the SCAN and subcortical structures, suggesting an abnormal strengthening of this circuit as a core pathophysiologic feature.
- Treatment-related changes:
- Across six independent PD cohorts receiving DBS, repetitive transcranial magnetic stimulation (TMS), MRI-guided focused ultrasound (MRgFUS), or levodopa, effective treatments consistently reduced SCAN–subcortex hyperconnectivity.
- Electrocorticography confirmed that neuromodulation altering SCAN-related activity correlated with clinical benefit.
- Targeting strategy and efficacy:
- In TMS trials, using SCAN-based cortical targets instead of traditional effector-specific motor targets approximately doubled treatment efficacy.
- For MRgFUS, clinical improvements were greater when the lesion or ablation site was closer to a “SCAN sweet spot” within the thalamus.
- These findings suggest that both invasive (DBS, MRgFUS) and non-invasive (TMS) therapies may work best when they modulate functionally defined SCAN nodes rather than purely anatomical or primary motor regions.
- Clinical and translational implications:
- SCAN hyperconnectivity appears to be a central network abnormality in PD.
- Reduction of this hyperconnectivity may serve as a biomarker of successful neuromodulation or pharmacologic therapy.
- Intentionally targeting SCAN nodes—subcortical for surgical approaches and cortical for non-invasive neuromodulation—could optimize symptom control and potentially broaden therapeutic options for PD beyond classic motor-circuit-based approaches.