A neuroanatomical and cognitive model of impaired social behaviour in frontotemporal dementia

Abstract

Impaired social cognition is a core deficit in frontotemporal dementia (FTD). It is most commonly associated with the behavioural-variant of FTD, with atrophy of the orbitofrontal and ventromedial prefrontal cortex. Social cognitive changes are also common in semantic dementia, with atrophy centred on the anterior temporal lobes. The impairment of social behaviour in FTD has typically been attributed to damage to the orbitofrontal cortex and/or temporal poles and/or the uncinate fasciculus that connects them. However, the relative contributions of each region are unresolved. In this Review, we present a unified neurocognitive model of controlled social behaviour that not only explains the observed impairment of social behaviours in FTD, but also assimilates both consistent and potentially contradictory findings from other patient groups, comparative neurology and normative cognitive neuroscience. We propose that impaired social behaviour results from damage to two cognitively- and anatomically-distinct components. The first component is social-semantic knowledge, a part of the general semantic-conceptual system supported by the anterior temporal lobes bilaterally. The second component is social control, supported by the orbitofrontal cortex, medial frontal cortex and ventrolateral frontal cortex, which interacts with social-semantic knowledge to guide and shape social behaviour.

Overlapping Neural Correlates Underpin Theory of Mind and Semantic Cognition: Evidence from a Meta-Analysis of 344 Functional Neuroimaging Studies

“…How tightly coupled are theory of mind and semantic processes? We argue our findings, together with prior patient (Binney, Henry, et al, 2016; Ding et al, 2020; Edwards-Lee et al, 1997; Snowden et al, 2018), animal (Klüver & Bucy, 1937) and neuroscientific studies involving healthy populations (Balgova et al, 2022; Diveica et al, 2021), suggest the underlying systems are closely linked (also see Binney & Ramsey, 2020; Olson et al, 2013; Rouse et al, 2024). One possibility is that theory of mind can be considered a case of semantic processes, rather than something distinct, and this means it would operate upon the same basic principles (and neural underpinnings; Binney & Ramsey, 2020).…”

“…Then one must infer their likely mental state, particularly given their identity/role (e.g., the bereaved next of kin), and generate a context-appropriate social response (e.g., in this case, suppression of smiling or laughter). Now imagine the possible consequences of having impaired semantic knowledge (e.g., in semantic dementia, Rouse et al, 2024). Failure to correctly recognise the identity and/or the actions of the agent could lead to a misattribution of mental state, and/or socially inappropriate behaviour.…”

“…Conceptual knowledge critically underpins our capacity to recognise and interact with objects, words, people, and events in our environment (Patterson et al, 2007; Lambon Ralph et al, 2017), and Binney and Ramsey (2020) have argued that it should play a pivotal role in social cognition given that social interaction is, at its core, a process of meaningful exchange between persons. Support for this hypothesis has long existed within neuropsychological and comparative neuroscience literature, where there appears to be a tight coupling of general semantic deficits and social impairments (Bertoux et al, 2020; Irish et al, 2014; Klüver & Bucy, 1937; Miller et al, 2012; Souter et al, 2021; for a review see Olson et al, 2013 and Rouse et al, 2024). Evidence at the level of whole-brain networks has yet to be conclusively obtained.…”

Distributed and convergent representations of tools in human parietal and anterior temporal regions revealed by fMRI-RSA

“…The absence of the ATLs from models of praxis (and previously language) probably reflects the neuropsychological origins of the classical models which were founded on the study of patients after MCA stroke. The middle-to-inferior aspects of the ATLs are in the watershed between the MCA and PCA (Lambon Ralph et al, 2017; Phan et al, 2005; Zhao et al, 2020), and thus unlikely to be damaged after embolic stroke (and even less likely to produce bilateral ATL damage, which is the atrophy distribution in semantic dementia: Ding et al, 2020; Rouse et al, 2024). The RSA results fit precisely with previous investigations of ATL and IPL using TMS (Ishibashi et al, 2011: Pobric et al, 2010) and most directly with past explorations of tool knowledge and use in SD patients, which showed parallel degradation of semantic knowledge of tools (as a part of their generalised semantic deficits) and impaired object use (Bozeat et al, 2000; 2002; Coccia et al, 2004; Hodges et al, 1999; 2000).…”