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Poster C30, Thursday, November 9, 10:00 – 11:15 am, Harborview and Loch Raven Ballrooms

Examining gray matter differences in a single treatment non-responder with semantic variant primary progressive aphasia

Isabel Hubbard1, Stephanie Grassp2, Heather Dial2, Maria Luisa Mandelli1, Maria Luisa Gorno-Tempini1, Maya Henry1,2;1University of California San Francisco, 2University of Texas at Austin

Introduction: Semantic variant primary progressive aphasia (svPPA) is a neurodegenerative disorder characterized by a semantic deficit affecting naming and word comprehension (Gorno-Tempini, et al., 2011). Individuals with svPPA have benefited from interventions for naming that engage spared linguistic functions to promote word retrieval (e.g., Henry et al., 2013). Imaging studies have been used to monitor structural and functional changes from pre- to post-treatment in PPA (Beeson et al., 2011; Dressel et al., 2010). These analyses have documented neuroplasticity in the context of neurodegeneration for those responsive to treatment. No study, however, has identified neural factors that may contribute to failure to respond to treatment. In this study, we sought to explore structural imaging differences between responders and nonresponders to an established lexical retrieval treatment. Methods: Eight participants with svPPA underwent four to eight weeks of naming treatment (Henry et al., 2013). Effects sizes were calculated using d statistics in order to quantify the magnitude of change in naming performance and to identify participants who did not respond to treatment. One such participant (SE) was identified and voxel-based morphometry (VBM) was used to compare pre-treatment gray matter volumes in this participant relative to the group of svPPA treatment responders (n=7). The VBM analysis controlled for age and sex, with MMSE and total gray matter volume included as additional covariates in order to control for disease severity. Results: Effect sizes for the svPPA responder group ranged from 4.3-22.36 and SE was the only participant whose effect size (1.45) did not meet criterion for a “small” treatment effect (Beeson & Robey, 2006). On neuropsychological testing, SE showed poorer performance on the MMSE and a figure copy task at pre-treatment. VBM analysis of pre-treatment MRI scans revealed greater atrophy in bilateral prefrontal cortex in SE relative to the other participants. Atrophy was more pronounced in the left hemisphere, including portions of ventrolateral and dorsolateral prefrontal cortex. Conclusion: SE had greater bilateral prefrontal cortex atrophy compared to the responder group, suggesting that the integrity of gray matter in this region may be related to treatment outcomes. Two fMRI studies support this claim. Dressel and colleagues (2010) associated similar areas with successful response to treatment in one individual with svPPA. Comparing pre- and post-treatment fMRI using a naming task, they observed greater bilateral activation in middle and inferior frontal gyri at post-treatment. Beeson and colleagues (2011) found that, following successful naming treatment, one participant with logopenic variant PPA showed greater post-treatment activation in left dorsolateral prefrontal cortex. These regions are active in healthy controls during generative naming tasks (Meinzer, et al., 2009) and are implicated in lexical selection (Barde & Wagner, 2007; Warburton et al., 1996; Perani, 2003) and access to stored conceptual representations (Barde & Wagner, 2007). In conjunction with their established role in word retrieval, observation of pronounced atrophy in ventrolateral and dorsolateral prefrontal cortices in our single treatment non-responder provides preliminary evidence that cognitive processes supported by bilateral prefrontal cortex may be critical for response to naming treatment in svPPA.

Topic Area: Language Disorders

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