Evans, H. | Search bioRxiv

bioRxiv2025

Pause characteristics of sentence production in Parkinson's disease: insights from sentence complexity and length

PurposeParkinsons disease (PD) affects forward flow of speech including fluency disruptions in 90% of individuals. One of the main parameters affecting flow and fluency of speech is pause behaviour. However, the precise language characteristics of pauses, including sentence complexity and length, and how they contribute to the fluency disruptions of PD are not fully understood. This study examined how sentence complexity and length affect pause behaviour in PD. MethodSeventy-one participants, comprising individuals with PD (n = 32) and neurotypical controls (n = 39), read a speech passage aloud. The number and duration of pauses, categorised by location (between, within sentences), sentence complexity (simple, complex), and sentence length (short, long) were analysed. Cognitive ability, assessed using the Montreal Cognitive Assessment (MoCA), and motor speech deficits (i.e., dysarthria) severity, assessed using a speech perceptual ranking, were evaluated and correlated with pause characteristics. ResultsIndividuals with PD produced significantly more pauses across all categories compared to controls. However, only between-sentence and long-sentence pauses were significantly longer in duration. Pause frequency and duration in both groups were higher in more complex and longer sentences. Significant negative correlations were found between MoCA scores and number of pauses. Significant positive correlations were observed between dysarthria severity and duration of pauses. ConclusionThese findings suggest that increased cognitive-linguistic demands--indexed by sentence complexity and length--may underlie pausing behaviour and contribute to fluency disruptions in individuals with PD. The results extend previous research by highlighting the potential cognitive-linguistic basis of motor speech dysfunction in PD.

neuroscience↗

bioRxiv2022

Metastatic infiltration of nervous tissue and periosteal nerve sprouting in multiple myeloma induced bone pain

Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly unknown. Using a syngeneic MM mouse model, we show that periosteal nerve sprouting of calcitonin-gene related protein (CGRP+) and growth associated protein 43 (GAP43+) fibres occurs concurrent to the onset of nociception and its blockade provides transient pain relief. MM patient samples also showed increased periosteal innervation. Mechanistically, we investigated MM induced gene expression changes in the dorsal root ganglia (DRG) innervating the MM-bearing bone and found alterations in pathways associated with cell cycle, immune response and neuronal signalling. The MM transcriptional signature was consistent with metastatic MM infiltration to the DRG, a never-before described feature of the disease that we further demonstrated histologically. In the DRG, MM cells caused loss of vascularization and neuronal injury, which may contribute to late-stage MIBP. Interestingly, the transcriptional signature of a MM patient was consistent with MM cell infiltration to the DRG. Overall, our results suggest that MM induces a plethora of peripheral nervous system alterations that may contribute to the failure of current analgesics and suggest neuroprotective drugs as appropriate strategies to treat early onset MIBP. Significance statementMultiple myeloma is a painful bone marrow cancer that significantly impairs the quality of life of the patients. Analgesic therapies for myeloma-induced bone pain (MIBP) are limited and often ineffective, and the mechanisms of MIBP remain unknown. In this manuscript, we describe cancer-induced periosteal nerve sprouting in a mouse model of MIBP, where we also encounter metastasis to the dorsal root ganglia (DRG), a never-before described feature of the disease. Concomitant to myeloma infiltration, the lumbar DRGs presented blood vessel damage and transcriptional alterations, which may mediate MIBP. Explorative studies on human tissue support our preclinical findings. Understanding the mechanisms of MIBP is crucial to develop targeted analgesic with better efficacy and fewer side effects for this patient population.

neuroscience↗