Damage to temporoparietal cortex is sufficient for impaired semantic control.

Semantic control allows us to focus semantic activation on currently relevant aspects of knowledge, even in the face of competition or when the required information is weakly encoded. Diverse cortical regions, including left prefrontal and posterior temporal cortex, are implicated in semantic control, however; the relative contribution of these regions is unclear. For the first time, we compared semantic aphasia (SA) patients with damage restricted to temporoparietal cortex (TPC; N = 8) to patients with infarcts encompassing prefrontal cortex (PF+; N = 22), to determine if prefrontal lesions are necessary for semantic control deficits. These SA groups were also compared with semantic dementia (SD; N = 10), characterised by degraded semantic representations. We asked whether TPC cases with semantic impairment show controlled retrieval deficits equivalent to PF+ cases or conceptual degradation similar to patients with SD. Independent of lesion location, the SA subgroups showed similarities, whereas SD patients showed a qualitatively distinct semantic impairment. Relative to SD, both TPC and PF+ SA subgroups: (1) showed few correlations in performance across tasks with differing control demands, but a strong relationship between tasks of similar difficulty; (2) exhibited attenuated effects of lexical frequency and concept familiarity, (3) showed evidence of poor semantic regulation in their verbal output - performance on picture naming was substantially improved when provided with a phonological cue, and (4) showed effects of control demands, such as retrieval difficulty, which were equivalent in severity across TPC and PF+ groups. These findings show that semantic impairment in SA is underpinned by damage to a distributed semantic control network, instantiated across anterior and posterior cortical areas.

Psychological and Mnemonic Benefits of Nostalgia for People with Dementia.

BACKGROUND: Studies with non-clinical populations show that nostalgia increases psychological resources, such as self-esteem and social connectedness. OBJECTIVES: Our objectives were to find out if the benefits of nostalgia in non-clinical populations generalize to people with dementia and if nostalgia facilitates recall of dementia-related information. METHODS: All three experiments recruited participants with mild or moderate levels of dementia. Experiment 1 tested whether nostalgia (compared to control) enhances psychological resources among 27 participants. Experiment 2 used music to induce nostalgia (compared to control) in 29 participants. Experiment 3 compared recall for self-referent dementia statements among 50 participants randomized to either a nostalgia or control condition. Findings across experiments were synthesized with integrative data analysis. RESULTS: Nostalgia (compared to control) significantly increased self-reported social connectedness, meaning in life, self-continuity, optimism, self-esteem, and positive (but not negative) affect (Experiments 1-3). Compared to controls, nostalgic participants also recalled significantly more self-referent dementia-related information (Experiment 3). CONCLUSION: This series of experiments extends social psychological research with non-clinical populations into dementia care, providing evidence that nostalgia significantly enhances psychological resources. The finding that nostalgia increased recall of self-referent statements about dementia suggests that this emotion lends participants the fortitude to face the threat posed by their illness. The finding has potentially important clinical implications both for the development of reminiscence therapy and for facilitating adjustment to a diagnosis of dementia.

The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction.

Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., , Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal 'hub' in combination with modality-specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time- and task-appropriate behaviour. Executive-semantic goal representations, largely supported by executive regions such as frontal and parietal cortex, are thought to allow the generation of non-dominant aspects of knowledge when these are appropriate for the task or context. Semantic aphasia (SA) patients have executive-semantic deficits, and these are correlated with general executive impairment. If the CSC proposal is correct, patients with executive impairment should not only exhibit impaired semantic cognition, but should also show characteristics that align with those observed in SA. This possibility remains largely untested, as patients selected on the basis that they show executive impairment (i.e., with 'dysexecutive syndrome') have not been extensively tested on tasks tapping semantic control and have not been previously compared with SA cases. We explored conceptual processing in 12 patients showing symptoms consistent with dysexecutive syndrome (DYS) and 24 SA patients, using a range of multimodal semantic assessments which manipulated control demands. Patients with executive impairments, despite not being selected to show semantic impairments, nevertheless showed parallel patterns to SA cases. They showed strong effects of distractor strength, cues and miscues, and probe-target distance, plus minimal effects of word frequency on comprehension (unlike semantic dementia patients with degradation of conceptual knowledge). This supports a component process account of semantic cognition in which retrieval is shaped by control processes, and confirms that deficits in SA patients reflect difficulty controlling semantic retrieval.

Vocabulary relearning in semantic dementia: Positive and negative consequences of increasing variability in the learning experience.

Anomia therapy typically aims to improve patients' communication ability through targeted practice in naming a set of particular items. For such interventions to be of maximum benefit, the use of trained (or relearned) vocabulary must generalise from the therapy setting into novel situations. We investigated relearning in three patients with semantic dementia, a condition that has been associated with poor generalisation of relearned vocabulary. We tested two manipulations designed to improve generalisation of relearned words by introducing greater variation into the learning experience. In the first study, we found that trained items were retained more successfully when they were presented in a variety of different sequences during learning. In the second study, we found that training items using a range of different pictured exemplars improved the patients' ability to generalise words to novel instances of the same object. However, in one patient this came at the cost of inappropriate over-generalisations, in which trained words were incorrectly used to name semantically or visually similar objects. We propose that more variable learning experiences benefit patients because they shift responsibility for learning away from the inflexible hippocampal learning system and towards the semantic system. The success of this approach therefore depends critically on the integrity of the semantic representations of the items being trained. Patients with naming impairments in the context of relatively mild comprehension deficits are most likely to benefit from this approach, while avoiding the negative consequences of over-generalisation.

Going beyond inferior prefrontal involvement in semantic control: evidence for the additional contribution of dorsal angular gyrus and posterior middle temporal cortex.

Semantic cognition requires a combination of semantic representations and executive control processes to direct activation in a task- and time-appropriate fashion [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132-2147, 2006]. We undertook a formal meta-analysis to investigate which regions within the large-scale semantic network are specifically associated with the executive component of semantic cognition. Previous studies have described in detail the role of left ventral pFC in semantic regulation. We examined 53 studies that contrasted semantic tasks with high > low executive requirements to determine whether cortical regions beyond the left pFC show the same response profile to executive semantic demands. Our findings revealed that right pFC, posterior middle temporal gyrus (pMTG) and dorsal angular gyrus (bordering intraparietal sulcus) were also consistently recruited by executively demanding semantic tasks, demonstrating patterns of activation that were highly similar to the left ventral pFC. These regions overlap with the lesions in aphasic patients who exhibit multimodal semantic impairment because of impaired regulatory control (semantic aphasia)-providing important convergence between functional neuroimaging and neuropsychological studies of semantic cognition. Activation in dorsal angular gyrus and left ventral pFC was consistent across all types of executive semantic manipulation, regardless of whether the task was receptive or expressive, whereas pMTG activation was only observed for manipulation of control demands within receptive tasks. Second, we contrasted executively demanding tasks tapping semantics and phonology. Our findings revealed substantial overlap between the two sets of contrasts within left ventral pFC, suggesting this region underpins domain-general control mechanisms. In contrast, we observed relative specialization for semantic control within pMTG as well as the most ventral aspects of left pFC (BA 47), consistent with our proposal of a distributed network underpinning semantic control.

Demonstrating the qualitative differences between semantic aphasia and semantic dementia: a novel exploration of nonverbal semantic processing.

Semantic dementia (SD) implicates the anterior temporal lobes (ATL) as a critical substrate for semantic memory. Multi-modal semantic impairment can also be a feature of post-stroke aphasia (referred to here as "semantic aphasia" or SA) where patients show impaired regulatory control accompanied by lesions to the frontal and/or temporo-parietal cortices, and thus the two patient groups demonstrate qualitatively different patterns of semantic impairment [1]. Previous comparisons of these two patient groups have tended to focus on verbal receptive tasks. Accordingly, this study investigated nonverbal receptive abilities via a comparison of reality decision judgements in SD and SA. Pictures of objects were presented alongside non-real distracters whose features were altered to make them more/less plausible for the semantic category. The results highlighted a number of critical differences between the two groups. Compared to SD patients, SA patients: (1) were relatively unimpaired on the two alternative forced choice (2AFC) decisions despite showing a comparable degree of semantic impairment on other assessments; (2) showed minimal effects of the plausibility manipulation; (3) were strongly influenced by variations in the regulatory requirements of tasks; and (4) exhibited a reversed effect of familiarity - i.e., better performance on less commonly encountered items. These results support a distinction between semantic impairments which arise from impaired regulatory processes (e.g., SA) versus those where degraded semantic knowledge is the causal factor (e.g., SD). SA patients performed relatively well because the task structure reduced the requirement for internally generated control. In contrast, SD patients performed poorly because their degraded knowledge did not allow the fine-grained distinctions required to complete the task.

A direct comparison of errorless and errorful therapy for object name relearning in Alzheimer's disease.

Developing rehabilitation techniques to combat cognitive decline is a key goal of healthcare strategies aimed at promoting increased longevity and better quality of life for individuals with Alzheimer's disease (AD). In AD, problems with episodic memory and word-finding greatly affect everyday life and, as such, these symptoms provide a clear clinical target for therapeutic interventions. Errorless learning (EL) has been proposed as a particularly effective technique for relearning in individuals with memory dysfunction, including AD. However, EL learning has rarely been directly contrasted with other more traditional trial-and-error techniques (errorful learning or EF) in individuals with AD, especially in the context of alleviating word-finding problems. In the current study, we directly contrasted the therapeutic gains of an EL learning paradigm (consisting of reading/repetition of object names) with an EF learning technique (comprised of phonemic/orthographic cueing) in eight mild to moderate AD patients with pronounced anomia. Both techniques were administered concurrently in sessions run twice a week over a five-week period. Therapeutic gains were assessed at one week and five weeks post-intervention using confrontation naming. Our results suggest that, both at the group and individual patient level, EL and EF techniques were equally effective. Correlational analyses of overall therapy gains and background assessments of patient neuropsychology revealed that individuals with better scores on measures of semantic memory, pre-intervention naming, and recognition memory demonstrated larger therapy gains. No individual patient showed a significant advantage for EL over EF learning, however, for patients that showed a numerical advantage in this direction. These results suggest that either EL or EF therapy can be used to alleviate word-finding problems in AD.

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.