A Canonical Neural Map and Its Deviations Shape Parkinson's Disease Phenotypes

Area of Science:

• Neuroscience
• Neurology
• Systems Neuroscience

Background:

• Parkinson's disease (PD) exhibits stereotyped network oscillations, particularly excessive beta activity.
• However, significant clinical heterogeneity exists among PD patients, with unclear links to beta oscillations.
• Existing literature shows inconsistencies regarding the clinical significance of beta oscillations in PD.

Purpose of the Study:

• To resolve the paradox of stereotyped oscillations and heterogeneous symptoms in Parkinson's disease.
• To define a "canonical spatio-spectral map" of network dysfunction in PD using intracranial recordings.
• To investigate how patient-specific deviations from this map correlate with clinical variability and motor symptom severity.

Main Methods:

• Multisite intracranial recordings from the motor cortex and basal ganglia in human PD patients.
• Definition of a "canonical spatio-spectral map" of network dysfunction.
• Analysis of inter-individual physiological variance and data-driven clustering to identify distinct clinical phenotypes.

Main Results:

• A robust, disease-specific "canonical spatio-spectral map" of network dysfunction in Parkinson's disease was identified.
• Patient-specific deviations from this common template were found to encode clinical variability.
• Regions with the highest inter-individual physiological variance significantly predicted motor symptom severity, revealing distinct clinical phenotypes.

Conclusions:

• Individual deviations from a normative pathological map in PD, often overlooked, correlate with clinical symptoms.
• A unified model of PD pathophysiology is proposed, linking the canonical beta signature to individual phenotypic diversity.
• This framework offers a quantitative blueprint for developing personalized, circuit-specific therapeutic strategies for Parkinson's disease.