Deregulated semantic cognition contributes to object-use deficits in Alzheimer's disease: A comparison with semantic aphasia and semantic dementia.

Executive control is impaired from the early stages of Alzheimer's Disease (AD) and this produces deregulated semantic cognition (Corbett, Jefferies, Burns, & Lambon Ralph, ; Perry, Watson, & Hodges, ). While control deficits should affect semantic retrieval across all modalities, previous studies have typically focused on verbal semantic tasks. Even when non-verbal semantic tasks have been used, these have typically employed simple picture-matching tasks, which may be influenced by abnormalities in covert naming. Therefore, in the present study, we examined 10 patients with AD on a battery of object-use tasks, in order to advance our understanding of the origins of non-verbal semantic deficits in this population. The AD patients' deficits were contrasted with previously published performance on the same tasks within two additional groups of patients, displaying either semantic degradation (semantic dementia) or deregulation of semantic retrieval (semantic aphasia; Corbett, Jefferies, Ehsan, & Lambon Ralph, ). While overall accuracy was comparable to the scores in both other groups, the AD patients' object-use impairment most closely resembled that observed in SA; they exhibited poorer performance on comprehension tasks that placed strong demands on executive control. A similar pattern was observed in the expressive domain: the AD and SA groups were relatively good at straightforward object use compared to executively demanding, mechanical puzzles. Error types also differed: while all patients omitted essential actions, the SA and AD groups' demonstrations also featured unrelated intrusions. An association between AD patients' object use and their scores on standard executive measures suggested that control deficits contributed to their non-verbal semantic deficits. Moreover, in a task specifically designed to manipulate executive demand, patients with AD (and SA) exhibited difficulty in thinking flexibly about the non-canonical uses of everyday objects, especially when distracted by semantically related objects. This study provides converging evidence for the notion that a failure of regulatory control contributes to multimodal semantic impairment in AD and uniquely demonstrates this pattern for the highly non-verbal domain of object use.

Unpicking the semantic impairment in Alzheimer's disease: qualitative changes with disease severity.

Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients' impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes--e.g., category fluency.

Deregulated semantic cognition follows prefrontal and temporo-parietal damage: evidence from the impact of task constraint on nonverbal object use.

Semantic cognition, which encompasses all conceptually based behavior, is dependent on the successful interaction of two key components: conceptual representations and regulatory control. Qualitatively distinct disorders of semantic knowledge follow damage to the different parts of this system. Previous studies have shown that patients with multimodal semantic impairment following CVA--a condition referred to as semantic aphasia (SA)--perform poorly on a range of conceptual tasks due to a failure of executive control following prefrontal and/or temporo-parietal infarction [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132-2147, 2006]. Although a deficit of core semantic control would be expected to impair all modalities in parallel, most research exploring this condition has focused on tasks in the verbal domain. In a novel exploration of semantic control in the nonverbal domain, therefore, we assessed eight patients with SA on two experiments that examined object use knowledge under different levels of task constraint. Patients exhibited three key characteristics of semantic deregulation: (a) difficulty using conceptual knowledge flexibly to support the noncanonical uses of everyday objects; (b) poor inhibition of semantically related distractor items; and (c) improved object use with the provision of more tightly constraining task conditions following verbal and pictorial cues. Our findings are consistent with the notion that a neural network incorporating the left inferior prefrontal and temporo-parietal areas (damaged in SA) underpins regulation of semantic activation across both verbal and nonverbal modalities.

Elucidating the nature of deregulated semantic cognition in semantic aphasia: evidence for the roles of prefrontal and temporo-parietal cortices.

Semantic cognition--semantically driven verbal and nonverbal behavior--is composed of at least two interactive principal components: conceptual representations and executive control processes that regulate and shape activation within the semantic system. Previous studies indicate that semantic dementia follows from a progressive yet specific degradation of conceptual knowledge. In contrast, multimodal semantic impairment in aphasic patients (semantic aphasia [SA]) reflects damage to the control component of semantic cognition [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132-2147, 2006]. The purpose of the present study was to examine the nature of the semantic control deficits in SA in detail for the first time. Seven patients with SA were tested on four comprehension and naming tasks that directly manipulated the requirement for executive control in different ways. In line with many theories of cognitive control, the SA patients demonstrated three core features of impaired control: (i) they exhibited poor on-line manipulation and exploration of semantic knowledge; (ii) they exhibited poor inhibition of strongly associated distractors; and (iii) they exhibited reduced ability to focus on or augment less dominant aspects of semantic information, although the knowledge itself remained and could be successfully cued by external constraints provided by the examiner. Our findings are consistent with the notion that the anterior temporal lobes are crucial for conceptual knowledge whereas the left prefrontal and temporo-parietal cortices, damaged in patients with SA, play a critical role in regulating semantic activation in a task-appropriate fashion.

Exploring multimodal semantic control impairments in semantic aphasia: evidence from naturalistic object use.

Semantic processing can break down in qualitatively distinct ways in different neuropsychological populations. Previous studies have shown that patients with multimodal semantic impairments following stroke - referred to as semantic aphasia (SA) - show deficits on a range of conceptual tasks due to a failure of semantic control processes in the context of prefrontal and/or temporoparietal infarction. Although a deficit of semantic control would be expected to impair performance in all modalities in parallel, most previous research in this patient group has focussed primarily on tasks employing words. This study explored the consequences of deregulated semantic cognition for an indisputably non-verbal task-naturalistic object use. Patients with SA performed more poorly than control participants on a range of everyday tasks assessed by the Naturalistic Action Test (NAT, Schwartz, M. F., Buxbaum, L. J., Ferraro, M., Veramonti, T., & Segal, M. (2002). Naturalistic action test. Thames Valley Test Company). Moreover, their scores on this assessment correlated with those obtained on language-based semantic tasks, suggesting that a common deficit could underlie the impairment in both modalities. As previously observed in the verbal domain, performance on the NAT was poorer when control processes were taxed by dual-task situations and the inclusion of semantically related distracting objects. A number of characteristics of the patients' action sequences were specifically indicative of deregulated semantic cognition. Their everyday action sequences were highly fragmented by a tendency to abandon subtasks before their completion and engage, instead, in extended periods of aimless "toying" with objects. The patient group also exhibited recurrent perseverative behaviour. These findings parallel the performance of a recurrent connectionist model of naturalistic action developed by Botvinick and Plaut [Botvinick, M. & Plaut, D. C. (2004). Doing without schema hierarchies: A recurrent connectionist approach to normal and impaired routine sequential action. Psychological Review, 111, 395-429], after the mechanism responsible for controlling action in a temporally sensitive manner was damaged. This study provides converging evidence for a failure of control processes underlying semantic memory impairment in SA, which is reflected not only in patients' performance on language-based tasks, but also in the non-verbal domain of naturalistic object use.

Different impairments of semantic cognition in semantic dementia and semantic aphasia: evidence from the non-verbal domain.

Disorders of semantic cognition in different neuropsychological conditions result from diverse areas of brain damage and may have different underlying causes. This study used a comparative case-series design to examine the hypothesis that relatively circumscribed bilateral atrophy of the anterior temporal lobe in semantic dementia (SD) produces a gradual degradation of core semantic representations, whilst a deficit of cognitive control produces multi-modal semantic impairment in a subset of patients with stroke aphasia following damage involving the left prefrontal cortex or regions in and around the temporoparietal area; this condition, which transcends traditional aphasia classifications, is referred to as 'semantic aphasia' (SA). There have been very few direct comparisons of these patient groups to date and these previous studies have focussed on verbal comprehension. This study used a battery of object-use tasks to extend this line of enquiry into the non-verbal domain for the first time. A group of seven SA patients were identified who failed both word and picture versions of a semantic association task. These patients were compared with eight SD cases. Both groups showed significant deficits in object use but these impairments were qualitatively different. Item familiarity correlated with performance on object-use tasks for the SD group, consistent with the view that core semantic representations are degrading in this condition. In contrast, the SA participants were insensitive to the familiarity of the objects. Further, while the SD patients performed consistently across tasks that tapped different aspects of knowledge and object use for the same items, the performance of the SA participants reflected the control requirements of the tasks. Single object use was relatively preserved in SA but performance on complex mechanical puzzles was substantially impaired. Similarly, the SA patients were able to complete straightforward item matching tasks, such as word-picture matching, but performed more poorly on associative picture-matching tasks, even when the tests involved the same items. The two groups of patients also showed a different pattern of errors in object use. SA patients made substantial numbers of erroneous intrusions in their demonstrations, such as inappropriate object movements. In contrast, response omissions were more common in SD. This study provides converging evidence for qualitatively different impairments of semantic cognition in SD and SA, and uniquely demonstrates this pattern in a non-verbal expressive domain-object use.