RESUMO
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.
Assuntos
Demência Frontotemporal , Comportamento Social , Humanos , Demência Frontotemporal/patologia , Demência Frontotemporal/psicologia , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/fisiopatologia , Cognição Social , Cognição/fisiologiaRESUMO
Clinical variants of Alzheimer's disease and frontotemporal lobar degeneration display a spectrum of cognitive-behavioural changes varying between individuals and over time. Understanding the landscape of these graded individual-/group-level longitudinal variations is critical for precise phenotyping; however, this remains challenging to model. Addressing this challenge, we leverage the National Alzheimer's Coordinating Center database to derive a unified geometric framework of graded longitudinal phenotypic variation in Alzheimer's disease and frontotemporal lobar degeneration. We included three time-point, cognitive-behavioural and clinical data from 390 typical, atypical and intermediate Alzheimer's disease and frontotemporal lobar degeneration variants (114 typical Alzheimer's disease; 107 behavioural variant frontotemporal dementia; 42 motor variants of frontotemporal lobar degeneration; and 103 primary progressive aphasia patients). On this data, we applied advanced data-science approaches to derive low-dimensional geometric spaces capturing core features underpinning clinical progression of Alzheimer's disease and frontotemporal lobar degeneration syndromes. To do so, we first used principal component analysis to derive six axes of graded longitudinal phenotypic variation capturing patient-specific movement along and across these axes. Then, we distilled these axes into a visualisable 2D manifold of longitudinal phenotypic variation using Uniform Manifold Approximation and Projection. Both geometries together enabled the assimilation and inter-relation of paradigmatic and mixed cases, capturing dynamic individual trajectories, and linking syndromic variability to neuropathology and key clinical end-points such as survival. Through these low-dimensional geometries, we show that (i) specific syndromes (Alzheimer's disease and primary progressive aphasia) converge over time into a de-differentiated pooled phenotype, while others (frontotemporal dementia variants) diverge to look different from this generic phenotype; (ii) phenotypic diversification is predicted by simultaneous progression along multiple axes, varying in a graded manner between individuals and syndromes; and (iii) movement along specific principal axes predicts survival at 36 months in a syndrome-specific manner and in individual pathological groupings. The resultant mapping of dynamics underlying cognitive-behavioural evolution potentially holds paradigm-changing implications to predicting phenotypic diversification and phenotype-neurobiological mapping in Alzheimer's disease and frontotemporal lobar degeneration.
RESUMO
The functional importance of the anterior temporal lobes (ATLs) has come to prominence in two active, albeit unconnected literatures-(i) face recognition and (ii) semantic memory. To generate a unified account of the ATLs, we tested the predictions from each literature and examined the effects of bilateral versus unilateral ATL damage on face recognition, person knowledge, and semantic memory. Sixteen people with bilateral ATL atrophy from semantic dementia (SD), 17 people with unilateral ATL resection for temporal lobe epilepsy (TLE; left = 10, right = 7), and 14 controls completed tasks assessing perceptual face matching, person knowledge and general semantic memory. People with SD were impaired across all semantic tasks, including person knowledge. Despite commensurate total ATL damage, unilateral resection generated mild impairments, with minimal differences between left- and right-ATL resection. Face matching performance was largely preserved but slightly reduced in SD and right TLE. All groups displayed the familiarity effect in face matching; however, it was reduced in SD and right TLE and was aligned with the level of item-specific semantic knowledge in all participants. We propose a neurocognitive framework whereby the ATLs underpin a resilient bilateral representation system that supports semantic memory, person knowledge and face recognition.
Assuntos
Epilepsia do Lobo Temporal , Reconhecimento Facial , Semântica , Lobo Temporal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Lobo Temporal/cirurgia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adulto , Reconhecimento Facial/fisiologia , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/fisiopatologia , Reconhecimento Psicológico/fisiologia , Lateralidade Funcional/fisiologia , Testes Neuropsicológicos , Memória/fisiologia , Idoso , FaceRESUMO
Semantic dementia (SD) is characterized by progressive impairment in conceptual knowledge due to anterior temporal lobe (ATL) neurodegeneration. Extended neuropsychological assessments can quantitatively demonstrate the semantic impairment, but this graded loss of knowledge can also be readily observed in the qualitative observation of patients' recall of single concepts. Here, we present the results of a simple task of object drawing-from-name, by patients with SD (N = 19), who have isolated atrophy of the ATL bilaterally. Both cross-sectionally and longitudinally, patient drawings demonstrated a pattern of degradation in which rare and distinctive features (such as the hump on a camel) were lost earliest in disease course, and there was an increase in the intrusion of prototypical features (such as the typical small ears of most mammals on an elephant) with more advanced disease. Crucially, patient drawings showed a continuum of conceptual knowledge loss rather than a binary 'present' or 'absent' state. Overall, we demonstrate that qualitative evaluation of line drawings of animals and objects provides fascinating insights into the transmodal semantic deficit in SD. Our results are consistent with a distributed-plus-hub model of semantic memory. The graded nature of the deficit in semantic performance observed in our subset of longitudinally observed patients suggests that the temporal lobe binds feature-based semantic attributes in its central convergence zone.
RESUMO
Semantic Dementia (SD) is a neurodegenerative disease characterised by progressive deterioration of semantic knowledge, resulting in diminished understanding of concepts, whether encountered in verbal or non-verbal form. Over the past three decades, a number of studies employing a range of treatment techniques and learning methods have examined whether patients with SD can relearn previously known concepts or learn and retain new information. In this article, we review this research, addressing two main questions: a) Can aspects of semantic knowledge that are 'lost' due to degeneration be re-acquired? b) How much do other memory systems (working and episodic memory) interact with and depend on semantic memory? Several studies demonstrate successful relearning of previously known words and concepts in SD, particularly after regular, prolonged practice; but this success tends to diminish once practice ceases, and furthermore often fails to generalise to other instances of the same object/concept. This pattern suggests that, with impaired semantic knowledge, learning relies to an abnormal extent on perceptual factors, making it difficult to abstract away from the specific visual or other perceptual format in which a given concept has been trained. Furthermore, the impact of semantic 'status' of a word or object on both working and episodic memory indicates pervasive interaction of these other memory systems with conceptual knowledge.
Assuntos
Demência Frontotemporal , Doenças Neurodegenerativas , Humanos , Demência Frontotemporal/complicações , Aprendizagem , Memória , Rememoração Mental , Semântica , Testes NeuropsicológicosRESUMO
BACKGROUND: Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants. METHODS: Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes). RESULTS: Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations. CONCLUSIONS: Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.