Salience Network Resting-State Activity

Abstract

dvances in functional neuroimaging have provided a window into the brain's intrinsic connectivity, leading to the discovery of the salience network (SLN), composed of the anterior cingulate, insula, striatum, and amygdala. The SLN is activated in healthy patients during tasks requiring attentional selection, task switching, and self-regulation of behavior 1 and is an important neural substrate in frontotemporal dementia (FTD), 2 with dysfunction confirmed on histopathology 3 and resting-state functional magnetic resonance (fMR) imaging. 1,2 Within the SLN, the insula has emerged as a nodal point of particular importance for frontolimbic function and dysfunction. 2 Supporting this assertion, insular atrophy is recognized as one of the earliest structural biomarkers in behavioral variant FTD (bvFTD) and semantic dementia, 3,4 with insular loss correlated with worsening be-havioral inventory scores 5 and progressive accumulation of FTDassociated pathologic inclusions within insular von Economo neurons and Fork cells. 6,7 Abnormal activity within intrinsic brain networks may be clinically relevant, indicative of neurodegenerative disease. 1,2 Resting-state fMR imaging may provide a noninvasive biomarker for the diagnosis and longitudinal monitoring of patients with FTD. However, it remains to be determined whether this emerging technique can be used to identify patterns of network disruption in patients before the development of changes on clinical examination or structural neuroimaging. We explored the ability of baseline resting-state connectivity measures to predict behavioral changes in participants with bvFTD and semantic dementia during 8 weeks. IMPORTANCE Noninvasive measures of activity within intrinsic brain networks may be clinically relevant, providing a marker of neurodegenerative disease and predicting clinical behaviors. OBJECTIVE To correlate baseline resting-state measures within the salience network and changes in behavior among patients with frontotemporal dementia. DESIGN Baseline resting-state functional magnetic resonance imaging data and longitudinal clinical measures were obtained from prospectively accrued patients during 8 weeks. SETTING Tertiary academic care center specializing in the assessment and management of patients with neurodegenerative disease. PARTICIPANTS Fifteen patients with clinically diagnosed frontotemporal dementia (5 behavioral variant and 10 semantic dementia). MAIN OUTCOMES AND MEASURES Baseline resting-state functional magnetic resonance imaging data measured within regions of interest were regressed on serial behavioral measures from prospectively accrued patients with frontotemporal dementia to determine the ability of baseline resting-state activity to account for changes in behavior. RESULTS Low-frequency fluctuations in the left insula significantly predicted changes in Frontal Behavioral Inventory scores (standard β = 0.51, P = .049), accounting for 28% of the change variance. The trend was driven by changes in measures of apathy independent of dementia severity. ...

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