title: Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia.
abstract: BACKGROUND
  bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated.
  
  
  OBJECTIVE
  To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD).
  
  
  METHODS
  We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy.
  
  
  RESULTS
  Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks.
  
  
  CONCLUSIONS
  Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms.
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; In Vivo Human Molecular and Structural Neuroimaging, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Caminiti
authors.affiliation: Cognitive Neuroscience Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy ; NETS Center, Istituto Universitario di Studi Superiori (IUSS), Pavia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Canessa
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; In Vivo Human Molecular and Structural Neuroimaging, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy ; Nuclear Medicine Department, San Raffaele Hospital, Milan, Italy ; Clinical Neuroscience Department, San Raffaele Hospital, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerami
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; Cognitive Neuroscience Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dodich
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; Cognitive Neuroscience Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Crespi
authors.affiliation: Clinical Neuroscience Department, San Raffaele Hospital, Milan, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Iannaccone
authors.affiliation: Clinical Neuroscience Department, San Raffaele Hospital, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; Neuroradiology - CERMAC, San Raffaele Hospital, Milan, Italy ; Functional Neuroradiology Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Cognitive Neuroscience Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy ; NETS Center, Istituto Universitario di Studi Superiori (IUSS), Pavia, Italy.
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Cappa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000378:metabolism*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D025341:Principal Component Analysis; D012146:Rest; D056345:Theory of Mind / Q000502:physiology*
chemical_list: D010100:Oxygen
keywords: AD, Alzheimer's disease; Affective mentalizing; BOLD, blood-oxygen-level-dependent; Behavioral variant of frontotemporal dementia; CI, causal inferences; Default mode network; EA, emotion attribution; Executive functioning network; FDR, false discovery rate; FTLD, frontotemporal lobar degeneration; GM, gray matter; IA, intention attribution; MANCOVAN, multivariate analysis of covariance; MMSE, Mini-Mental State Examination; PCA, principal component analysis; RSNs, resting-state networks; Resting state functional MRI; SET, story-based empathy task; SPM, statistical parametric mapping; ToM, theory of mind; VBM, voxel based morphometry; aDMN, anterior default mode network; bvFTD, behavioral variant of frontotemporal dementia; gICA, group independent component analysis; pDMN, posterior default mode network; rs-fMRI, resting-state fMRI