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Dissociation between structural and functional longitudinal changes in Primary Progressive Aphasia

Poster E59 in Poster Session E, Saturday, October 8, 3:15 - 5:00 pm EDT, Millennium Hall

Yuan Tao¹, Brenda Rapp¹, Kyrana Tsapkini²; ¹Johns Hopkins University, ²Johns Hopkins School of Medicine

Introduction Primary Progressive Aphasia (PPA) is a neurodegenerative disease with prominent progressive left-lateralized gray matter atrophy. However, changes in functional and white-matter structural connectivity have been less investigated. Previously in a cross-sectional study, we reported that lower structural connectivity (SC) between homotopic regions was associated with elevated homotopic functional connectivity (FC) (Tao et al., 2022). Here with longitudinal data, we examined how white-matter structural and functional connectivity are affected by tDCS-augmented behavioral language treatment that occurred in the context of continuing gray matter degeneration. Methods Thirty-seven PPA participants (17 non-fluent, 14 logopenic, 6 semantic) were recruited for a clinical trial (NCT02606422) and received the same multi-week treatment protocol. They underwent MRI scanning at least 6 months apart, prior to and after treatment. For each participant and time-point, we calculated functional and structural connectivity measured by resting-state fMRI and DTI, as well as gray matter volumes with VBM analysis. Using the AAL atlas (Rolls et al., 2020), we calculated the functional and structural connectivity strength between 43 pairs of cortical homologous regions (i.e., homotopic FC and SC). Longitudinal changes between the two time-points were evaluated with paired t-tests. Results Consistent with our previous findings, at baseline, homotopic FC values were elevated while SC values were depressed relative to healthy controls in frontal regions. With regard to structural changes, we found evidence of continuing degeneration with significant decreases in gray matter volume in areas typically atrophic in PPA, as well as significantly decreased homotopic SC volumes concentrated in the medial frontal regions (FDR alpha<0.1). In contrast, homotopic FC showed evidence of normalization from baseline to follow-up (t=0.24, p=0.0233). Furthermore, the longitudinal FC and SC changes were not correlated (r=0.04, p=0.42). Conclusions Subsequent to tDCS-augment behavioral language intervention, we found normalization of homotopic functional connectivity that occurred along with behavioral improvement. The fact that the structural and functional homotopic connectivity changes were uncorrelated suggests that the functional changes reflect dynamic reorganization despite continuing structural decline. Factors underlying the functional connectivity changes (e.g., disease stage, treatment effect) in PPA will be discussed.

Topic Areas: Disorders: Acquired, Language Therapy