Patients with Parkinson's disease (PD) have a wide and diverse range of motor and cognitive symptoms. The neural involvement and compensatory mechanisms might explain the differences in the behavioral manifestations among patients. Evaluation of the neurophysiological mechanisms may help to improve our understanding of the compensatory mechanisms and to inform the development of future therapeutic interventions.

100 PD patients underwent a Delphi assessment that included stimulation of six brain areas: left/right M1, dorso-lateral prefrontal cortex (DLPFC), and occipital cortex. Six measures were calculated to characterize the Delphi waveform of response: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) Short term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1, DLPFC, and occipital. K-means algorithm was used to define the clusters with the greatest possible distinction.

Two clusters of patients were generated based on Delphi output measures. 74 PD patients in cluster 1 demonstrated worse Delphi outcome compared to 26 PD patients in cluster 0. The PD patients in cluster 1 were older (t=3.570, p=0.005) and had worse motor symptoms based on higher UPDRS motor score (t=2.465, p=0.016) than the PD patients in cluster 0. Specifically, neck rigidity and left upper extremity rigidity were higher in cluster 1 compared to cluster 0. No differences in disease duration, total UPDRS, H&Y, and LEDD were found between the clusters.

These findings provide evidence that neurophysiological measures can distinguish between two groups of PD patients with distinct motor phenotype. Furthermore, they may pave the way for more efficient stratification tools for patients with high disease burden with likely faster progression.