Network changes associated with right anterior temporal lobe atrophy: insight into unique symptoms
Authors: Ulugut Hulya , Mandelli Maria Luisa , Gilioli Anna , Ezzes Zoe , Pillai Janhavi , Baquirin David , Wallman-Jones Amie , Gerenza Amanda , Palser Eleanor R. , Scheffler Aaron , Battistella Giovanni , Cobigo Yann , Rosen Howard J. , Miller Zachary , Younes Kyan , Miller Bruce L , Kramer Joel H. , Seeley William W. , Sturm Virginia E. , Rankin Katherine P. , Gorno-Tempini Maria Luisa 
Published: February 2025

AbstractSemantic behavioral variant (also referred to as right temporal) frontotemporal dementia is a newly described syndrome associated with focal right anterior temporal lobe atrophy and a distinctive combination of behavioral and semantic changes. It is considered the right-sided counterpart of semantic variant primary progressive aphasia, with which it has overlapping neuropathological and cognitive mechanisms. Although more is known about how brain network alterations relate to both losses (e.g., word comprehension deficits) and gains (e.g., hyper-fluency) in cognitive and behavioral processes in the left-sided semantic progressive aphasia, less is known about these phenomena in the right-sided semantic behavioral variant. In this study, we investigated functional connectivity within the right counterparts of established ventral and dorsal cortical speech and language networks and their relationship to specific clinical manifestations in individuals with the semantic behavioral variant. We hypothesized that socioemotional-semantic deficits would be associated with reduced connectivity in the right ventral semantic network, while heightened behavioral manifestations, such as hyper-focus on specific interests (also referred to as rigidity), would be associated with increased connectivity in the right dorsal network. Using seed-based intrinsic connectivity analyses of fMRI data and cognitive scores from 22 individuals with semantic behavioral variant frontotemporal dementia and 48 cognitively normal individuals, we measured intrinsic connectivity strength in networks anchored in the right anterior middle temporal gyrus (ventral network) and in the right opercular inferior frontal gyrus (dorsal network). Functional connectivity values were then correlated with cognitive and behavioral measurements, controlling for global atrophy. Compared to the control group, individuals with semantic behavioral variant exhibited reduced connectivity in the ventral network (t= 2.7,P= 0.003), which was associated with socioemotional-semantic deficits (r= 0.47,P= 0.03), as measured by standardized tests. Conversely, increased functional connectivity was observed in the spared right dorsal network (t= 4.26,P< 0.001), which correlated with heightened scores for hyper-focus on fixed interests, as measured by retrospective ratings of medical notes (r= 0.63,P= 0.002). Together with previous evidence, these findings suggest that in individuals with focal anterior temporal lobe atrophy, enhanced behaviors such as hyper-focus and hyper-fluency are associated with altered functional dynamics within networks that remain relatively spared by the disease process. This highlights the complex interplay between damaged and spared networks in shaping the clinical manifestations of semantic behavioral variant frontotemporal dementia.