Objective: Aim of this study is to describe specific alterations in comprehending syntactically complex sentences in patients with Lewy body diseases (LBDs) that already have mild cognitive impairment (MCI-LB patients) as compared to healthy controls (HC) and identify the neural underpinnings of these deficits using functional connectivity analysis of the language network (domain-specific areas) divided into dorsal and ventral pathways.

Background: LBDs consist of two major clinical entities – Parkinson’s disease (PD) and dementia with Lewy bodies. The vast majority of patients with LBDs already have MCI at the time of the diagnosis. Language dysfunctions in patients with MCI-LB are often unrecognized and negatively affect the patient’s quality of life. We previously found that Slovak patients with PD without MCI already have problems with sentence reading comprehension with altered task-dependent functional connectivity¹.

Method: A total of 25 MCI-LB patients and 25 HC performed task-fMRI Test of Sentence Comprehension (ToSC). Functional connectivity was analyzed using psychophysiological interaction (PPI) method. We used five peak coordinates (ROIs) for the ventral and the dorsal language pathways, according to previously published work². For PPI analyses between ROIs, we reported results with statistical significance threshold set to p˂0.05 with FDR correction.

Results: MCI-LB patients had lower ToSC scores than HC (MCI-LB: 74.7±15.7, HC: 88.5±9.0, p<0.001) and their PPI analysis revealed reduced connectivity particularly in the dorsal pathway during noncanonical (syntactically more complex) sentence processing. Specifically, we have seen that connectivity between anterior part of the superior temporal gyrus and the language areas in the frontal lobule was lower in MCI-LB patients than in HC during noncanonical condition.

Conclusion: Taken together, MCI-LB patients showed impaired sentence comprehension related to decreased dorsal language network connectivity. Specific changes in frontotemporal connectivity in LBDs might be a promising indicator of cognitive impairment in these a-synucleinopathies.

References: 1 Novakova, L. et al. Language impairment in Parkinson’s disease: fMRI study of sentence reading comprehension. Front. Aging Neurosci. 15, 1117473 (2023).
2 Saur, D. et al. Ventral and dorsal pathways for language. Proc. Natl. Acad. Sci. U.S.A. 105, 18035–18040 (2008).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ventral-and-dorsal-language-pathways-in-patients-with-lewy-bodies-an-fmri-study-of-syntactic-sentence-processing/