# Network changes associated with right anterior temporal lobe atrophy: insight into unique symptoms

## TL;DR

This study explores how brain network changes in a rare form of dementia are linked to specific symptoms like emotional deficits and compulsive behaviors.

## Contribution

The study identifies distinct functional connectivity patterns in right-sided brain networks associated with unique clinical features of semantic behavioural variant frontotemporal dementia.

## Key findings

- Reduced connectivity in the right ventral network correlates with socioemotional-semantic deficits.
- Increased connectivity in the right dorsal network correlates with hyper-focus on specific interests.
- Symptoms arise from interactions between damaged and intact brain networks.

## Abstract

Semantic behavioural variant (also referred to as right temporal) frontotemporal dementia is a newly described syndrome associated with predominant right anterior temporal lobe atrophy and a distinctive combination of behavioural 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 increases (e.g. hyper-fluency) in cognitive and behavioural processes in the left-sided semantic progressive aphasia, less is known about these phenomena in the right-sided semantic behavioural 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 behavioural variant. We hypothesized that socioemotional-semantic deficits would be associated with reduced connectivity in the right ventral semantic network, while heightened behavioural 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 functional MRI data and cognitive scores from 22 individuals with semantic behavioural 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 behavioural measurements, controlling for global atrophy. Compared to the control group, individuals with semantic behavioural variant exhibited reduced connectivity in the right 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 higher 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 predominant anterior temporal lobe atrophy, greater expression of behaviours such as hyper-focus is 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 behavioural variant frontotemporal dementia.

Ulugut and Mandelli et al. used functional brain imaging and clinical data to investigate rare right-lateralized frontotemporal dementia. They found network disruptions linked to socio-emotional deficits and compulsive narrow interests. Results suggest symptoms emerge from dynamic interactions between damaged and intact neural circuits, not from injury to single, isolated brain regions.

Graphical Abstract