Remembering 'zeal' but not 'thing':reverse frequency effects as a consequence of deregulated semantic processing

More efficient processing of high frequency (HF) words is a ubiquitous finding in healthy individuals, yet frequency effects are often small or absent in stroke aphasia. We propose that some patients fail to show the expected frequency effect because processing of HF words places strong demands on semantic control and regulation processes, counteracting the usual effect. This may occur because HF words appear in a wide range of linguistic contexts, each associated with distinct semantic information. This theory predicts that in extreme circumstances, patients with impaired semantic control should show an outright reversal of the normal frequency effect. To test this prediction, we tested two patients with impaired semantic control with a delayed repetition task that emphasised activation of semantic representations. By alternating HF and low frequency (LF) trials, we demonstrated a significant repetition advantage for LF words, principally because of perseverative errors in which patients produced the previous LF response in place of the HF target. These errors indicated that HF words were more weakly activated than LF words. We suggest that when presented with no contextual information, patients generate a weak and unstable pattern of semantic activation for HF words because information relating to many possible contexts and interpretations is activated. In contrast, LF words tend are associated with more stable patterns of activation because similar semantic information is activated whenever they are encountered

The degraded concept representation system in semantic dementia:damage to pan-modal hub, then visual spoke

The core clinical feature of semantic dementia is a progressive yet selective degradation of conceptual knowledge. Understanding the cognitive and neuroanatomical basis for this deficit is a key challenge for both clinical and basic science. Some researchers attribute the deficit to damage to pan-modal conceptual representations that are independent of any particular sensory-motor modality and are represented in the ventrolateral anterior temporal lobes. Others claim that damage to modality-specific visual feature representations in the occipitotemporal 'ventral stream' is responsible. In the present study, we tested the hypothesis that concept degradation in semantic dementia involves a combination of these pan-modal and modality-specific elements. We investigated factors influencing knowledge of object concepts by analysing 43 sets of picture-naming data from patients with semantic dementia. We found a strong influence of two pan-modal factors: highly familiar and typical items were named more accurately than less familiar/atypical items at all stages of the disorder. Items associated with rich sensory-motor information were also named more successfully at all stages, and this effect was present for sound/motion knowledge and tactile/action knowledge when these modalities were studied separately. However, there was no advantage for items rich in visual colour/form characteristics; instead, this factor had an increasingly negative impact in the later stages of the disorder. We propose that these results are best explained by a combination of (i) degradation of modality-independent conceptual representations, which is present throughout the disorder and is a consequence of atrophy focused on the ventrolateral anterior temporal lobes; and (ii) a later additional deficit for concepts that depend heavily on visual colour/form information, caused by the spreading of atrophy to posterior ventral temporal regions specialized for representing this information. This explanation is consistent with a graded hub-and-spoke model of conceptual knowledge, in which there is a gradual convergence of information along the temporal lobes, with visual attributes represented in the posterior cortex giving way to pan-modal representations in the anterior areas. © 2012 The Author

Explaining semantic short-term memory deficits:evidence for the critical role of semantic control

Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought and can occur as a result of mild disruption to semantic control processes, i.e., mechanisms that bias semantic processing towards task-relevant aspects of knowledge and away from irrelevant information. We tested three semantic STM patients with tasks that tapped four aspects of semantic control: (i) resolving ambiguity between word meanings, (ii) sensitivity to cues, (iii) ignoring irrelevant information and (iv) detecting weak semantic associations. All were impaired in conditions requiring more semantic control, irrespective of the STM demands of the task, suggesting a mild, but task-general, deficit in regulating semantic knowledge. This mild deficit has a disproportionate effect on STM tasks because they have high intrinsic control demands: in STM tasks, control is required to keep information active when it is no longer available in the environment and to manage competition between items held in memory simultaneously. By re-interpreting the core deficit in semantic STM patients in this way, we are able to explain their apparently selective impairment without the need for a specialised STM store. Instead, we argue that semantic STM patients occupy the mildest end of spectrum of semantic control disorders

Deficits of knowledge versus executive control in semantic cognition: Insights from cued naming

Deficits of semantic cognition in semantic dementia and in aphasia consequent on CVA (stroke) are qualitatively different. Patients with semantic dementia are characterised by progressive degradation of central semantic representations, whereas multimodal semantic deficits in stroke aphasia reflect impairment of executive processes that help to direct and control semantic activation in a task-appropriate fashion [Jefferies, E., & Lambon Ralph, M. A. (2006). Semantic impairment in stroke aphasia vs. semantic dementia: A case-series comparison. Brain 129, 2132-2147]. We explored interactions between these two aspects of semantic cognition by examining the effects of cumulative phonemic cueing on picture naming in case series of these two types of patient. The stroke aphasic patients with multimodal semantic deficits cued very readily and demonstrated near-perfect name retrieval when cumulative phonemic cues reached or exceeded the target name's uniqueness point. Therefore, knowledge of the picture names was largely intact for the aphasic patients, but they were unable to retrieve this information without cues that helped to direct activation towards the target response. Equivalent phonemic cues engendered significant but much more limited benefit to the semantic dementia patients: their naming was still severely impaired even when most of the word had been provided. In contrast to the pattern in the stroke aphasia group, successful cueing was mainly confined to the more familiar un-named pictures. We propose that this limited cueing effect in semantic dementia follows from the fact that concepts deteriorate in a graded fashion [Rogers, T. T., Lambon Ralph, M. A., Garrard, P., Bozeat, S., McClelland, J. L., & Hodges, J. R., et al. (2004). The structure and deterioration of semantic memory: A neuropsychological and computational investigation. Psychological Review 111, 205-235]. For partially degraded items, the residual conceptual knowledge may be insufficient to drive speech production to completion but these items might reach threshold when they are bolstered by cues. (C) 2007 Elsevier Ltd. All rights reserved

Preservation of episodic memory in semantic dementia:The importance of regions beyond the medial temporal lobes

Episodic memory impairment represents one of the hallmark clinical features of patients with Alzheimer's disease (AD) attributable to the degeneration of medial temporal and parietal regions of the brain. In contrast, a somewhat paradoxical profile of relatively intact episodic memory, particularly for non-verbal material, is observed in semantic dementia (SD), despite marked atrophy of the hippocampus. This retrospective study investigated the neural substrates of episodic memory retrieval in 20 patients with a diagnosis of SD and 21 disease-matched cases of AD and compared their performance to that of 35 age- and education-matched healthy older Controls. Participants completed the Rey Complex Figure and the memory subscale of the Addenbrooke's Cognitive Examination-Revised as indices of visual and verbal episodic recall, respectively. Relative to Controls, AD patients showed compromised memory performance on both visual and verbal memory tasks. In contrast, memory deficits in SD were modality-specific occurring exclusively on the verbal task. Controlling for semantic processing ameliorated these deficits in SD, while memory impairments persisted in AD. Voxel-based morphometry analyses revealed significant overlap in the neural correlates of verbal episodic memory in AD and SD with predominantly anteromedial regions, including the bilateral hippocampus, strongly implicated. Controlling for semantic processing negated this effect in SD, however, a distributed network of frontal, medial temporal, and parietal regions was implicated in AD. Our study corroborates the view that episodic memory deficits in SD arise very largely as a consequence of the conceptual loading of traditional tasks. We propose that the functional integrity of frontal and parietal regions enables new learning to occur in SD in the face of significant hippocampal and anteromedial temporal lobe pathology, underscoring the inherent complexity of the episodic memory circuitry

A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer's Disease

BACKGROUND: Apathy is a complex multidimensional syndrome frequently reported in Alzheimer's disease (AD) and is associated with impaired awareness. Here we present a psychometrically robust method to profile apathy in AD.  OBJECTIVES: To determine the validity and reliability of a multidimensional apathy measure, the Dimensional Apathy Scale (DAS), and explore the apathy subtype profile and its associations in AD.  METHODS: 102 people with AD and 55 healthy controls were recruited. Participants completed the DAS, the Apathy Evaluation Scale (AES), Geriatric Depression Short form (GDS-15), and Lawton Instrumental Activities of Daily Living (LIADL). Psychometric properties of the DAS were determined. AD-Control comparison was performed to explore group differences on the DAS. Latent Class Analysis (LCA) was used to explore the profile of apathy in AD.  RESULTS: The DAS had a good to excellent Cronbach's standardized alpha (self-rated = 0.85, informant/carer-rated = 0.93) and good convergent and divergent validity against standard apathy (AES) and depression (GDS-15) measures. Group comparison showed people with AD were significantly higher for all apathy subtypes than controls (p < 0.001), and lacking in awareness over all apathy subtype deficits. LCA showed three distinct AD subgroups, with 42.2% in the Executive-Initiation apathy, 28.4% in the Global apathy, and 29.4% in the Minimal apathy group.  CONCLUSIONS: The DAS is a psychometrically robust method of assessing multidimensional apathy in AD. The apathy profiles in AD are heterogeneous, with additional specific impairments relating to awareness dependent on apathy subtype

Distant from input : Evidence of regions within the default mode network supporting perceptually-decoupled and conceptually-guided cognition

The default mode network supports a variety of mental operations such as semantic processing, episodic memory retrieval, mental time travel and mind-wandering, yet the commonalities between these functions remains unclear. One possibility is that this system supports cognition that is independent of the immediate environment; alternatively or additionally, it might support higher-order conceptual representations that draw together multiple features. We tested these accounts using a novel paradigm that separately manipulated the availability of perceptual information to guide decision-making and the representational complexity of this information. Using task based imaging we established regions that respond when cognition combines both stimulus independence with multi-modal information. These included left and right angular gyri and the left middle temporal gyrus. Although these sites were within the default mode network, they showed a stronger response to demanding memory judgements than to an easier perceptual task, contrary to the view that they support automatic aspects of cognition. In a subsequent analysis, we showed that these regions were located at the extreme end of a macroscale gradient, which describes gradual transitions from sensorimotor to transmodal cortex. This shift in the focus of neural activity towards transmodal, default mode, regions might reflect a process of where the functional distance from specific sensory enables conceptually rich and detailed cognitive states to be generated in the absence of input

When objects lose their meaning: What happens to their use?

The 8 patients involved in this study were impaired on tests assessing knowledge of objects and on the demonstration of their use. The patients' success in object use was significantly correlated with their knowledge about the objects, providing further evidence that conceptual knowledge plays a key role in object use. Having a recipient present improved performance in the moderately impaired patients, suggesting that a certain level of conceptual knowledge must remain for the additional information to be beneficial. Although overall accuracy in using the target objects was not related to our measures of affordance, the specific aspects of use afforded by the objects' structures were relatively impervious to semantic impairment, suggesting a role for affordance information when object-specific knowledge is disrupted. The patients' familiarity with the objects was an important predictor of performance. Finally, despite good performance on tests of mechanical problem solving, the patients showed very little evidence of employing these skills in their interactions with real objects