Frontotemporal dementia as a neural system disease

Boccardi, Marina; Sabattoli, Francesca; Laakso, Mikko P.; Testa, Cristina; Rossi, Roberta; Beltramello, Alberto; Frisoni, Giovanni B.

doi:10.1016/j.neurobiolaging.2004.02.019

Cited by 125 publications

(95 citation statements)

References 38 publications

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“…34 -37 Reduced glucose metabolism has also been found in the cerebellar cortex 38 and cerebral atrophy in the anterior insula. 34 The atrophy found in PSP is similar to that found in FTD: frontal 39 -41 and temporal lobes, 41 caudate nuclei 39 -40,42 -45 and insula 46 seem to be affected. Glucose hypometabolism of atrophy, although one study did find atrophy in the head of the caudate nuclei.…”

Section: Discussionmentioning

confidence: 54%

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

et al. 2008

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The microtubule-associated protein Tau (MAPT) gene codes for the protein Tau that is involved in the pathogenesis of neurodegenerative diseases. Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD), whereas the H2 haplotype has been found to be related to familial FTD. We aimed to investigate the association between MAPT haplotype status and brain morphology in healthy adults. A total of 150 healthy subjects underwent 3D high-resolution magnetic resonance (MR). MR images were processed following an optimized protocol to perform the Voxel-based morphometry (VBM) comparisons of the gray matter (GM) in H1 carriers (n ¼ 141) in contrast to H2H2 homozygous (n ¼ 9), and H1H1 homozygous (n ¼ 85) in contrast to H2 carriers (n ¼ 65). The threshold for statistical significance was 0.005 uncorrected. Opposite comparisons were also carried out. The groups had similar demographic and cognitive features. Compared with H2H2, the H1 carriers showed up to 19% smaller GM volume in the head of the right caudate nucleus, in the right middle frontal gyrus, in the left insula and orbito-frontal cortex, and in the inferior temporal and inferior cerebellar lobes, bilaterally. Compared with all H2 carriers, H1H1 displayed lower GM in the same regions, but the effect was smaller (5%), possibly due to a dilution effect by H1 in the H2 carriers group. The data suggest that H1 haplotype is associated with a particular cerebral morphology that may increase the susceptibility of the healthy carriers to develop neurodegenerative diseases such as sporadic tauopathies.

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Section: Discussionmentioning

confidence: 54%

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

et al. 2008

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“…Previous cross-sectional neuroimaging studies have consistently shown that FTD is associated with atrophy or decreased metabolism in this region compared to controls or other dementias (Ishii et al, 1998;Garraux et al, 1999;Rosen et al, 2002;Varrone et al, 2002;Salmon et al, 2003;Boccardi et al, 2005;Franceschi et al, 2005;Jeong et al, 2005;Williams et al, 2005). The other regions that showed longitudinal loss of gray matter (the medial temporal, medial frontal, and insular cortices) are heavily anatomically interconnected with the anterior cingulate and with each other.…”

Section: Discussionmentioning

confidence: 93%

A tensor based morphometry study of longitudinal gray matter contraction in FTD

et al. 2007

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Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by progressive behavioural abnormalities and frontotemporal atrophy. Here we used tensor based morphometry (TBM) to identify regions of longitudinal progression of gray matter atrophy in FTD compared to controls. T1-weighted MRI images were acquired at presentation and 1-year follow-up from 12 patients with mild to moderate FTD and 12 healthy controls. Using TBM as implemented in SPM2, a voxel-wise estimation of regional tissue volume change was derived from the deformation field required to warp a subject's late to early anatomical images. A whole brain analysis was performed, in which a level of significance of p<0.05 corrected for multiple comparisons (family wise error-FWE) was accepted. Based on prior studies, a region of interest (ROI) analysis was also performed, including in the search area bilateral medial and orbital frontal regions, anterior cingulate gyrus, insula, amygdala and hippocampus. Within this ROI a level of significance of p<0.001 uncorrected was accepted. In the whole brain analysis, the anterior cingulate/paracingulate gyri were the only regions that showed significant atrophy change over 1 year. In the ROI analysis, the left ventromedial frontal cortex, right medial superior frontal gyrus, anterior insulae and left amygdala/ hippocampus showed significant longitudinal changes. In conclusion, limbic and paralimbic regions showed detectable gray matter contraction over 1 year in FTD, confirming the susceptibility of these regions to the disease and the consistency with their putative role in causing typical presenting behaviours. These results suggest that TBM might be useful in tracking progression of regional atrophy in FTD.

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“…51,52 This system is involved in a number of processes such as the evaluation of the motivational or emotional content of internal and external stimuli, error detection, response selection and decision-making, and subsequent regulation of context-dependent behaviors. 53 Recent neuroimaging studies suggest that patients with FTD show predominantly right frontal, anterior insular, and anterior cingulate deterioration, with pronounced orbitofrontal cortex atrophy. 51 Additionally, some studies have reported correlations between behavioral symptoms and brain structures, suggesting that the right orbitofrontal cortex regulates behavior together with a predominantly rightside network involving the insula and striatum.…”

Section: Scnm and Bvftdmentioning

confidence: 99%

Contextual social cognition and the behavioral variant of frontotemporal dementia

Ibáñez¹,

Manes²

2012

Neurology

293

260

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The significance of social situations is commonly context-embedded. Although the role of context has been extensively studied in basic sensory processing or simple stimulus-response settings, its relevance for social cognition is unknown. We propose the social context network model (SCNM), a fronto-insular-temporal network responsible for processing social contextual effects. The SCNM may 1) update the context and use it to make predictions, 2) coordinate internal and external milieus, and 3) consolidate context-target associative learning. We suggest the behavioral variant of frontotemporal dementia (bvFTD) as a specific disorder in which the reported deficits in social cognition (e.g., facial recognition, empathy, decisionmaking, figurative language, theory of mind) can be described as context impairments due to deficits in the SCNM. Disruption of orbitofrontal-amygdala circuit, as well as the frontal, temporal, and insular atrophy in bVFTD, suggests a relationship between context-sensitive social cognition and SCNM. In considering context as an intrinsic part of social cognition, we highlight the need for a situated cognition approach in social cognition research as opposed to an abstract, universal, and decontextualized approach. The assessment of context-dependent social cognition paradigms, the SCNM, and their possible application to neuropsychiatric disorders may provide new insight into bvFTD and other related frontal disorders. Context-dependence effects are pervasive in everyday cognition. When we perceive objects and colors, we always perceive these among other objects and colors. We listen and speak within other word streams, and every atom of meaning emerges from a background of meanings. We perceive facial emotion together with body language, the prosody, and cues from the situation, all of them merged to understand the precise emotional significance. Acting appropriately in social interactions requires the interpretation of explicit and implicit contextual clues that orient our responses toward being polite, to make a joke or point out an irony, to say or not say something. Cognitive science and neuroscience research have evidenced context-dependence effects in similar domains of visual perception, 1-3 emotion, 4 -7 language, 8 -14 and social cognition 15,16 in both normal and neuropsychiatric conditions. But what is context? Simply put, a contextual factor (X) is something that has an effect on a cognitive event and can be determined by observing how that event is affected when X is changed.17 However, this basic definition seems to miss the essence of contextual effects, which is best illustrated with a simple optical illusion. The Ebbinghaus illusion (figure 1A) depicts 2 identical central circles, surrounded by rings of circles. Despite the fact that they are the same size, one circle is perceived as small and the other as big. The contextual information available (the surrounding circles) creates the perception that the center circles are different sizes. Context seems to be more than...

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Frontotemporal dementia as a neural system disease

Cited by 125 publications

References 38 publications

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

H1 haplotype of the MAPT gene is associated with lower regional gray matter volume in healthy carriers

A tensor based morphometry study of longitudinal gray matter contraction in FTD

Contextual social cognition and the behavioral variant of frontotemporal dementia

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