Slide Slam P3
Disruption of inter-hemispheric, homotopic functional connectivity in post-stroke and progressive aphasia
Yuan Tao1, Celia Litovsky1, Kyrana Tsapkini2, Brenda Rapp1; 1Department of Cognitive Science, Johns Hopkins University, 2Department of Neurology, Johns Hopkins School of Medicine
A large number of studies have reported strong, synchronized neural activity both at rest and during task performance between homologous regions of the left and right hemispheres. While the function/s of homotopic functional connectivity (FC) are not well-understood, the degree of synchronization has been associated with performance on cognitive tasks and has been reported to be disrupted in a number of brain disorders (see Jin et al., 2020, for a review). Siegel et al. (2016) reported that reduced homotopic functional connectivity was a key feature subsequent to stroke, a finding confirmed by Tao & Rapp (2020). In this research we examined the extent to which homotopic FC patterns reflect disruption to underlying gray and/or white matter structures in post-stroke aphasia (PSA) and primary progressive aphasia (PPA). Methods: We examined resting-state fMRI in 18 individuals with PSA, 18 with non-fluent PPA, and 14 age-matched healthy controls (HC). PSA and PPA groups were matched in age, education, gender and damage epicenter (left inferior frontal lobe). Functional connectivity between the 43 pairs of homologous cortical regions from the AAL atlas were calculated for each participant. First, we evaluated group differences in the average homotopic connectivity strength across all the homologous pairs. Then the connectivity strengths of each homologue pair were compared, with results FDR corrected for multiple comparisons. Results: In terms of average homotopic FC, the PSA group exhibited significantly lower average values than the HCs (p=0.0023), while the PPA group exhibited significantly higher homotopic FC than the HCs (p=0.0011). In terms of individual homotopic connections, we found that for the PSA group, abnormally diminished homotopic FC was concentrated in perisylvian regions (e.g., insula, STG) while for the PPA group, abnormally elevated homotopic FC was concentrated in frontal areas and cingulate cortex. Summary: One hypothesis is that the disruptions to homotopic functional connectivity observed following neural injury are the direct result of structural damage to the gray and white matter substrates specifically involved in the communication between homologous regions. However, we report findings that represent a challenge to this hypothesis. We found that despite having very similar lesion epicenters and damage distributions, post-stroke and progressive aphasia groups exhibited opposite patterns of homotopic disruption relative to healthy controls, with PSA exhibiting significantly reduced homotopic FC, while individuals with PPA exhibited significantly increased homotopic FC. In addition, the specific distribution of disruption across homotopic regions was mostly non-overlapping for the two groups. These findings provide important constraints on hypotheses and form the basis for further investigation regarding the structural and/or functional origins of homotopic FC disruption and the role that these strong inter-hemispheric relationships play in language processing.