Selective perterbations of language network connectivity in primary progressive aphasia

Abstract: "Background:As shown in our previous study, the underlying mechanismof primary progressive aphasia may be due to alterednetwork connectivity rather than failure of specific nodes (Bonakdarpouret al., 2017). The purpose of the current investigation wasto look further into the anatomical organization of altered functionalconnectivity in patients with different forms of PPA. Additionally,the anatomy of disrupted connectivity in these patientsmay add new insights into the organization of the languagenetwork. Methods:Magnetic resonance imaging data were analyzedfor cortical morphometry and resting state functional connectivityin 28 PPA patients and 33 controls. Thirteen patients had semanticPPA (PPA-S), characterized by impaired word comprehension, and15 had non-semantic PPA (PPA-NS), characterized by impairedgrammar and repetition. Strengths of pairwise connectivity in fivepreselected language network nodes [pars triangularis and opercularisof the inferior frontal gyrus (IFGt and IFGo), middle temporalgyrus (MTG), supramarginal gyrus (SM), and anterior temporallobe (ATL)] and their homologous counterparts were analyzedfor group comparisons and correlation with measures of grammar,repetition, and comprehension. Effects of cortical volume werefactored out in all analyses. Results:Both PPA groups had decreasedIFGt-MTG connectivity. There were also group-specific connectivityimpairments of the IFGo-SM pair in PPA-NS and the IFGt-ATLand MTG-ATL pairs in PPA-S. No significant alterations were seenin the homologous connections. After factoring out the effects ofatrophy, significant decreases remained in the IFGo-SM connectionin PPA-NS and the MTG-ATL connection in PPA-S. Performanceon grammar and repetition correlated with strength of the IFGt-MTG and IFGo-SM connections, and performance on comprehensioncorrelated with connectivity of the left IFGt-ATL node pair.The correlations of repetition impairment remained significant aftercorrection for atrophy. Conclusions: Our results show that the languageimpairments in PPA are mediated at least in part through perturbationsof functional connectivity within concordantcomponents of the language network. The impaired connectivitymay reflect not only the loss of neurons but also the dysfunction of residual neurons. These findings have potential practical implications,especially since physiologic disturbances that precedeneuronal death may be modulated by targeted neurostimulationand neuroprotective treatments."