DISRUPTED SYNCHRONY-NOISE BALANCE AS A SYSTEM-LEVEL SIGNATURE OF MOTOR CORTEX INSTABILITY IN PARKINSON’S DISEASE

Brain function relies on a delicate dynamic equilibrium that maintains perceptual stability while allowing behavioural flexibility. This equilibrium is typically interpreted at the cellular level as the balance between excitation and inhibition, which is prototypically disrupted in motor circuits in Parkinson’s disease (PD). However, the excitation-inhibition balance fails to capture system-level dynamics, where neural populations must coordinate and decorrelate across space and time. Here we propose as a governing principle of these dynamics the synchrony-noise balance (SynBa), representing the ratio between coordinated, low-dimensional population fluctuations (synchrony) and independent, high-dimensional fluctuations (noise). We investigated the synchrony-noise balance in the motor cortex of 77 PD patients and 42 healthy controls using multi-muscle TMS-EMG recordings across a battery of TMS protocols (including SICI, ICF, and SICF). Synchrony-noise balance was operationalized as the intra-hemispheric homogeneity in the fluctuations of motor-evoked potential (MEP) amplitude across muscles. Our results revealed that homogeneity was lower on the more affected side of PD patients compared to the less affected side and controls across all excitability protocols. The lower homogeneity on the more affected side was already evident in early, levodopa-naive patients. This alteration was mechanistically driven by excessive unstructured "noise", indicating that a shift toward disordered variance disrupted the local stability of motor networks. Clinically, this disruption correlated with the severity of postural tremor. These findings suggest that PD pathophysiology extends beyond alterations in excitability to a fundamental collapse of synchrony-noise balance, where excessive local noise compromises the system-level stability required for functional motor control.