Disrupted functional connectivity in primary progressive apraxia of speech

Hugo Botha, Rene L. Utianski, Jennifer Lynn Whitwell, Joseph R. Duffy, Heather Clark, Edythe A. Strand, Mary Margaret Machulda, Nirubol Tosakulwong, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack, Keith Anthony Josephs, David T Jones

Research output: Contribution to journalArticle

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Abstract

Apraxia of speech is a motor speech disorder thought to result from impaired planning or programming of articulatory movements. It can be the initial or only manifestation of a degenerative disease, termed primary progressive apraxia of speech (PPAOS). The aim of this study was to use task-free functional magnetic resonance imaging (fMRI) to assess large-scale brain network pathophysiology in PPAOS. Twenty-two PPAOS participants were identified from a prospective cohort of degenerative speech and language disorders patients. All participants had a comprehensive, standardized evaluation including an evaluation by a speech-language pathologist, examination by a behavioral neurologist and a multimodal imaging protocol which included a task-free fMRI sequence. PPAOS participants were age and sex matched to amyloid-negative, cognitively normal participants with a 1:2 ratio. We chose a set of hypothesis driven, predefined intrinsic connectivity networks (ICNs) from a large, out of sample independent component analysis and then used them to initialize a spatiotemporal dual regression to estimate participant level connectivity within these ICNs. Specifically, we evaluated connectivity within the speech and language, face and hand sensorimotor, left working memory, salience, superior parietal, supramarginal, insular and deep gray ICNs in a multivariate manner. The spatial maps for each ICN were then compared between PPAOS and control participants. We used clinical measures of apraxia of speech severity to assess for clinical-connectivity correlations for regions found to differ between PPAOS and control participants. Compared to controls, PPAOS participants had reduced connectivity of the right supplementary motor area and left posterior temporal gyrus to the rest of the speech and language ICN. The connectivity of the right supplementary motor area correlated negatively with an articulatory error score. PPAOS participants also had reduced connectivity of the left supplementary motor area to the face sensorimotor ICN, between the left lateral prefrontal cortex and the salience ICN and between the left temporal-occipital junction and the left working memory ICN. The latter connectivity correlated with the apraxia of speech severity rating scale, although the finding did not survive correction for multiple comparisons. Increased connectivity was noted in PPAOS participants between the dorsal posterior cingulate and the left working memory ICN. Our results support the importance of the supplementary motor area in the pathophysiology of PPAOS, which appears to be disconnected from speech and language regions. Supplementary motor area connectivity may serve as a biomarker of degenerative apraxia of speech severity.

Original languageEnglish (US)
Pages (from-to)617-629
Number of pages13
JournalNeuroImage: Clinical
Volume18
DOIs
StatePublished - Jan 1 2018

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Apraxias
Motor Cortex
Language
Short-Term Memory
Speech Disorders
Multimodal Imaging
Magnetic Resonance Imaging
Language Disorders

Keywords

  • Apraxia of speech
  • Functional connectivity
  • Intrinsic connectivity networks

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Disrupted functional connectivity in primary progressive apraxia of speech. / Botha, Hugo; Utianski, Rene L.; Whitwell, Jennifer Lynn; Duffy, Joseph R.; Clark, Heather; Strand, Edythe A.; Machulda, Mary Margaret; Tosakulwong, Nirubol; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.; Josephs, Keith Anthony; Jones, David T.

In: NeuroImage: Clinical, Vol. 18, 01.01.2018, p. 617-629.

Research output: Contribution to journalArticle

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