Less locus coeruleus degeneration and its enhanced influence on neural circuit in Parkinson's tremor

Abstract

Objectives

The involvement of the locus coeruleus in Parkinson's tremor remains unclear. We aimed to decode the role of locus coeruleus in Parkinson's tremor.

Methods

We used MRI to examine 120 Parkinson's disease, including 48 tremor-dominant (TD) and 72 postural instability/gait disorder (PIGD), as well as 83 healthy controls. Neuromelanin-sensitive MRI accessed the contrast-to-noise ratio of locus coeruleus. Spectral dynamic causal modeling based on resting-state functional MRI accessed the effective connectivity from locus coeruleus to the cerebello-thalamo-cortical circuit. The pivotal nodes of cerebello-thalamo-cortical circuit included ventral intermediate nucleus, motor cortex, and cerebellum.

Results

Both TD and PIGD patients exhibited lower bilateral contrast-to-noise ratio of locus coeruleus than healthy controls. But TD patients had higher contrast-to-noise ratio of locus coeruleus than PIGD, accompanied by increased effective connectivity from locus coeruleus to cerebello-thalamo-cortical circuit than healthy controls and PIGD patients on the more-affected side (P < 0.003125, one-way analysis of covariance). The contrast-to-noise ratio of locus coeruleus and effective connectivity (e.g. locus coeruleus→motor cortex) positively correlated with rest tremor in TD patients (R = 0.47, P = 0.002; R = 0.427, P = 0.003, respectively).

Conclusions

TD patients exhibited less locus coeruleus degeneration than PIGD patients, alongside increased influence from locus coeruleus to the cerebello-thalamo-cortical circuit than healthy controls and PIGD patients. The structural/functional alterations of locus coeruleus are closely associated with rest tremor, suggesting the potential for tremor treatment targeting the locus coeruleus noradrenergic system.