TREATMENT-INDUCED CHANGES IN RESTING BRAIN ACTIVITY IN PRIMARY PROGRESSIVE APHASIA

Abstract

A growing literature supports the value of behavioral interventions to improve communication in primary progressive aphasia (PPA). The underlying neural mechanisms supporting these improvements, however, have not been well determined, particularly in non-fluent variant PPA (nfvPPA). One study, using task-based functional MRI, showed post-treatment recruitment of bilateral cortical and sub-cortical regions in a single nfvPPA case. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to investigate neural changes in 4 nfvPPA individuals after a successful course of Video-Implemented Script Training for Aphasia (VISTA). Participants included 4 right-handed individuals with nfvPPA and 40 age-matched controls. VISTA was administered over 4-6 weeks, with robust, positive outcomes (mean d = 14.68), for correct, intelligible scripted words. Pre-/post-treatment rsfMRI images were preprocessed using Data Processing Assistant for rsfMRI. Voxel-based morphometry was used to compare cortical volume in nfvPPA and control groups. A whole-brain voxel-wise analysis measured functional activity of each voxel using fractional amplitude of low frequency fluctuations (fALFF), with analysis limited to cortical voxels. Group comparisons (t-tests) with controls were performed using the REST toolbox. Results were corrected for multiple comparisons using False Discovery Rate (FDR) at p < 0.05. NfvPPA participants showed left perisylvian atrophy affecting inferior frontal, premotor and temporal areas. Pre-treatment rsfMRI revealed significantly decreased fALFF in left Broca's area, supramarginal gyrus, and polar superior temporal gyrus, and increased fALFF within the right inferior frontal gyrus pars orbitalis (IFG-orb). Pre/post-treatment comparisons revealed a significant increase in fALFF post-treatment in right insula, bilateral posterior inferior frontal gyri, and left posterior superior temporal, middle temporal, and supramarginal gyri. Increased fALFF in the right IFG-orb was no longer detected. Our findings revealed post-treatment fALFF changes in perisylvian regions which are involved in phonological, motoric, and grammatical processing. Increased brain activity was bi-hemispheric, indicating that post-treatment neural recruitment was within the affected hemisphere, with additional right insular compensatory changes. Decreased fALFF values in right IFG-orb may indicate downregulation of maladaptive activity. Behavioral improvements resulting from VISTA were supported by neural changes within the speech-language network, confirming the potential for significant neuroplasticity in the context of neurodegeneration.