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Resting-State Connectivity and Language Impairments in Primary Progressive Aphasia: A Comparative Study of lvPPA and nfvPPA
Poster Session D, Saturday, October 26, 10:30 am - 12:00 pm, Great Hall 3 and 4
Michèle Masson-Trottier1, Jessie Gallegos1, Alexandros Afthinos1, Sophia Norvillas1, Cesia Diaz1, Kyrana Tsapkini1; 1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, (MD), USA
Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by language deficits [1]. There are three main variants: semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA). These variants have distinct clinical profiles, atrophy patterns, and underlying pathology. Diagnosing lvPPA and nfvPPA can be challenging, especially in early stages of disease due to overlapping symptoms. According to the consensus diagnosis criteria, sentence repetition impairment is a key differentiator between these two variants, which is more pronounced in lvPPA [1]. Resting-state functional connectivity (rsFC) is a neuroimaging method that measures the temporal correlation of spontaneous brain activity while a person is at rest. This method has been increasingly used to understand the neural underpinnings of various behavioral impairments in neurological conditions [2, 3]. This study aims to identify the rsFC underpinnings of repetition impairments in nfvPPA and lvPPA, which could further be used as differential diagnostic criteria. We examined 37 participants with PPA (24 lvPPA, 13 nfvPPA). Participants were matched for age, time post-onset, overall severity, and language severity, and they underwent neurocognitive assessments and imaging including a rsfMRI scan. MRI preprocessing and rsFC analysis were conducted using the CONN toolbox [4]. We examined ROI-to-ROI connectivity between 91 cortical regions based on the Harvard-Oxford and AAL atlases and the NACC sentence repetition scores. Both groups performed equally on the sentence repetition task (p=0.986). In the lvPPA group, higher inter-cluster rsFC between a phonological processing cluster (bilateral insular cortex, central operculum, Heschl's gyrus, and planum temporale) and a semantic processing cluster (bilateral temporal pole, temporo-occipital middle temporal gyrus (MTG), frontal orbital cortex, and the right anterior and posterior MTG) was associated with better repetition. In the nfvPPA individuals, higher inter-cluster rsFC between a speech motor planning cluster (bilateral central opercular cortex and bilateral parietal operculum) and a phonological working memory cluster (bilateral anterior supramarginal gyrus (SMG) and the right frontal operculum) was associated with better performance in repetition. Different neural correlates for repetition were identified in lvPPA and nfvPPA, reflecting their distinct impairment profiles. In individuals with lvPPA, the increased parieto-temporal connectivity between the phonological processing and the semantic processing clusters associated with better repetition may support more efficient transfer and integration of auditory, phonological, and higher-level semantic information. In nfvPPA, increased fronto-parietal connectivity between the speech motor planning and the phonological working memory clusters may support better motor planning and phonological processing integration. In lvPPA, enhanced parieto-temporal connectivity could represent either a specific compensatory mechanism for repetition abilities, despite underlying neurodegeneration, or a lvPPA disease mechanism. Similarly, in nfvPPA, enhanced fronto-parietal connectivity might represent a different compensatory mechanism, specific for nfvPPA, for repetition abilities despite the neurodegenerative speech production impairments, or a nfvPPA disease mechanism. Leveraging rsFC analysis, this study elucidates distinct connectivity patterns associated with repetition deficits in these two PPA variants. These findings provide insights that could aid differential diagnosis and inform the development of therapeutic strategies targeting functional connectivity, such as neuromodulation. References 1. Gorno-Tempini 2011 https://doi.org/10.1212/WNL.0b013e31821103e6 2. Chaudhary, 2022 https://doi.org/10.1177/15333175221082834 3. Tao 2023 https://doi.org/10.3389/fnagi.2021.681043 4. Nieto-Castanon 2022 https://doi.org/10.56441/hilbertpress.2246.5840
Topic Areas: Disorders: Acquired,