Objective: To explore the cortico-subcortical network related to rigidity.

Background: Rigidity of the upper limb is one of the cardinal symptoms in Parkinson’s disease (PD), impacting mobility and quality of life. We explore the concept of a rigidity network comprised of cortical and subcortical regions that are involved in motor control and sensorimotor integration, and examine how aberrant connectivity in this network contributes to rigidity.

Method: We recorded 256-channels EEG and simultaneous EMG from forearm and biceps muscles during voluntary elbow flexion in 27 people with PD (PwP, mean age: 65.6; range: 57-93) in the medication OFF state and 27 age- and sex-matched healthy controls (HC, mean age: 62.8; range: 40-83). We applied a unique approach of estimating the mode alignment between the EEG and EMG at the predominant frequency using first empirical mode decomposition followed by a Hilbert transformation and then identified the phase synchronization between the signals [1] to identify regions involved during movement. Directed connectivity between these regions was estimated as time-resolved partial directed coherence [2] involving a surrogate analysis to identify significant connections. Structural equation modelling allowed us to quantify the relationship between network connectivity and rigidity within PwP.

Results: The average predominant rigidity frequency for PwP was 23.45 ± 7.12 Hz for the biceps muscle. We found significant mode alignment to the EMG signal of sources at the contralateral motor cortex, premotor cortex, supplementary motor area, posterior parietal cortex, thalamus, cerebellum, and brainstem both in PwP and HC. The connectivity between subcortical and cortical regions within the identified network was significantly different between the groups. There was a significant relationship between the total connectivity of contralateral motor cortex and pre-motor cortex with rigidity, when including the connectivity of the cerebellum as a mediator.

Conclusion: We demonstrate a pre-existent rigidity network comprised of regions that are similarly engaged during an upper limb task in PwP and HC. Compared to bi-directional connections in HC, the connectivity from subcortical to cortical regions was mainly unidirectional in PwP. These results may pave the way for developing non-invasive, objective tools to monitor upper limb rigidity in real-time.

References: [1] Quinn AJ, Lopes-Dos-Santos V, Huang N, Liang WK, Juan CH, Yeh JR, Nobre AC, Dupret D, Woolrich MW. Within-cycle instantaneous frequency profiles report oscillatory waveform dynamics. J Neurophysiol. 2021 Oct 1;126(4):1190-1208. doi: 10.1152/jn.00201.2021.
[2] Muthuraman M, Raethjen J, Koirala N, Anwar AR, Mideksa KG, Elble R, Groppa S, Deuschl G. Cerebello-cortical network fingerprints differ between essential, Parkinson’s and mimicked tremors. Brain. 2018 Jun 1;141(6):1770-1781. doi: 10.1093/brain/awy098.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/quantification-of-an-upper-limb-rigidity-network-in-parkinson-disease/