Abstract
The pathophysiology of primary progressive aphasias remains poorly understood. Here, we addressed this issue using activation fMRI in a cohort of 27 patients with primary progressive aphasia (nonfluent, semantic, and logopenic variants) versus 15 healthy controls. Participants listened passively to sequences of spoken syllables in which we manipulated 3-key auditory speech signal characteristics: temporal regularity, phonemic spectral structure, and pitch sequence entropy. Relative to healthy controls, nonfluent variant patients showed reduced activation of medial Heschl's gyrus in response to any auditory stimulation and reduced activation of anterior cingulate to temporal irregularity. Semantic variant patients had relatively reduced activation of caudate and anterior cingulate in response to increased entropy. Logopenic variant patients showed reduced activation of posterior superior temporal cortex to phonemic spectral structure. Taken together, our findings suggest that impaired processing of core speech signal attributes may drive particular progressive aphasia syndromes and could index a generic physiological mechanism of reduced computational efficiency relevant to all these syndromes, with implications for development of new biomarkers and therapeutic interventions.
Highlights
The primary progressive aphasias (PPAs) have collectively helped establish the paradigm of selective neural vulnerability to neurodegenerative pathologies (Mesulam, 1982; Mesulam et al, 2014)
Overlapping neuroanatomical and pathological substrates: nonfluent variant PPA (nfvPPA) principally targets a peri-Sylvian brain network and semantic variant PPA (svPPA) an anterior temporal lobe network and both syndromes are generally underpinned by non-Alzheimer proteinopathies in the frontotemporal lobar degeneration spectrum (Grossman, 2012; Hodges and Patterson, 2007; Rohrer et al, 2011); whereas logopenic variant PPA (lvPPA) targets a network centered on the temporo-parietal junction and is most often underpinned by Alzheimer pathology (Gorno-Tempini et al, 2008; Rabinovici et al, 2008; Rohrer et al, 2010)
Participant groups did not differ in gender, handedness, or educational attainment; the svPPA and lvPPA groups were on average significantly younger than the healthy control and nfvPPA groups (p < 0.05)
Summary
The primary progressive aphasias (PPAs) have collectively helped establish the paradigm of selective neural vulnerability to neurodegenerative pathologies (Mesulam, 1982; Mesulam et al, 2014) These disorders have been characterized as ‘language-led dementias’, comprising 3 canonical syndromes (Gorno-Tempini et al, 2011): nonfluent variant PPA (nfvPPA), presenting with impaired speech production and/or agrammatism; semantic variant PPA (svPPA), presenting with impaired single-word comprehension and vocabulary loss due to progressive erosion of semantic memory; and logopenic variant PPA (lvPPA), presenting with word-finding difficulty and impaired auditory verbal working memory.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
