Knowing "what for," but not "where": Dissociation between functional and contextual tool knowledge in healthy individuals and patients with dementia.

OBJECTIVE: Semantic tool knowledge underlies the ability to perform activities of daily living. Models of apraxia have emphasized the role of functional knowledge about the action performed with tools (e.g., a hammer and a mallet allow a "hammering" action), and contextual knowledge informing individuals about where to find tools in the social space (e.g., a hammer and a mallet can be found in a workshop). The goal of this study was to test whether contextual or functional knowledge, would be central in the organization of tool knowledge. It was assumed that contextual knowledge would be more salient than functional knowledge for healthy controls and that patients with dementia would show impaired contextual knowledge. METHODS: We created an original, open-ended categorization task with ambiguity, in which the same familiar tools could be matched on either contextual or functional criteria. RESULTS: In our findings, healthy controls prioritized a contextual, over a functional criterion. Patients with dementia had normal visual categorization skills (as demonstrated by an original picture categorization task), yet they made less contextual, but more functional associations than healthy controls. CONCLUSION: The findings support a dissociation between functional knowledge ("what for") on the one hand, and contextual knowledge ("where") on the other hand. While functional knowledge may be distributed across semantic and action-related factors, contextual knowledge may actually be the name of higher-order social norms applied to tool knowledge. These findings may encourage researchers to test both functional and contextual knowledge to diagnose semantic deficits and to use open-ended categorization tests.

Nonspecific Effects of Normal Aging on Taxonomic and Thematic Semantic Processing.

OBJECTIVE: This study aimed to assess the effect of normal aging on the processing of taxonomic and thematic semantic relations. METHOD: We used the Visual-World-Paradigm coupled with eye-movement recording. We compared performance of healthy younger and older adults on a word-to-picture matching task in which participants had to identify each target among semantically related (taxonomic or thematic) and unrelated distractors. RESULTS: Younger and older participants exhibited similar patterns of gaze fixations in the two semantic conditions. The effect of aging took the form of an overall reduction in sensitivity to semantic competitors, with no difference between the taxonomic and thematic conditions. Moreover, comparison of the proportions of fixations between the younger and older participants indicated that targets were identified equally quickly in both age groups. This was not the case when mouse-click reaction times were analyzed. CONCLUSIONS: Findings argue in favor of nonspecific effects of normal aging on semantic processing that similarly affect taxonomic and thematic processing. There are important clinical implications, as pathological aging has been repeatedly shown to selectively affect either taxonomic or thematic relations. Measuring eye-movements in a semantic task is also an interesting approach in the elderly, as these seem to be less impacted by aging than other motor responses.

When affect overlaps with concept: emotion recognition in semantic variant of primary progressive aphasia.

The most recent theories of emotions have postulated that their expression and recognition depend on acquired conceptual knowledge. In other words, the conceptual knowledge derived from prior experiences guide our ability to make sense of such emotions. However, clear evidence is still lacking to contradict more traditional theories, considering emotions as innate, distinct and universal physiological states. In addition, whether valence processing (i.e. recognition of the pleasant/unpleasant character of emotions) also relies on semantic knowledge is yet to be determined. To investigate the contribution of semantic knowledge to facial emotion recognition and valence processing, we conducted a behavioural and neuroimaging study in 20 controls and 16 patients with the semantic variant of primary progressive aphasia, a neurodegenerative disease that is prototypical of semantic memory impairment, and in which an emotion recognition deficit has already been described. We assessed participants' knowledge of emotion concepts and recognition of 10 basic (e.g. anger) or self-conscious (e.g. embarrassment) facial emotional expressions presented both statically (images) and dynamically (videos). All participants also underwent a brain MRI. Group comparisons revealed deficits in both emotion concept knowledge and emotion recognition in patients, independently of type of emotion and presentation. These measures were significantly correlated with each other in patients and with semantic fluency in patients and controls. Neuroimaging analyses showed that both emotion recognition and emotion conceptual knowledge were correlated with reduced grey matter density in similar areas within frontal ventral, temporal, insular and striatal regions, together with white fibre degeneration in tracts connecting frontal regions with each other as well as with temporal regions. We then performed a qualitative analysis of responses made during the facial emotion recognition task, by delineating valence errors (when one emotion was mistaken for another of a different valence), from other errors made during the emotion recognition test. We found that patients made more valence errors. The number of valence errors correlated with emotion conceptual knowledge as well as with reduced grey matter volume in brain regions already retrieved to correlate with this score. Specificity analyses allowed us to conclude that this cognitive relationship and anatomical overlap were not mediated by a general effect of disease severity. Our findings suggest that semantic knowledge guides the recognition of emotions and is also involved in valence processing. Our study supports a constructionist view of emotion recognition and valence processing, and could help to refine current theories on the interweaving of semantic knowledge and emotion processing.

MEM&SO protocol: understanding the determinants of social learning in neurodegenerative diseases.

BACKGROUND: People with neurodegenerative diseases may have difficulty learning new information, owing to their cognitive impairments. Teaching them techniques for learning in social contexts could alleviate this difficulty. The present study will examine the performances of patients with Alzheimer's disease and patients with the semantic variant of primary progressive aphasia on a memory test administered in three social contexts. The protocol will make it possible to identify determinants of social interactions, social abilities, cognition, and personality that can explain the potentially beneficial effect of social context on learning in these patients. METHODS: Thirty dyads (patient with primary memory impairment who meets criteria for Alzheimer's disease paired with caregiver), 16 dyads (patient meeting criteria for semantic variant of primary progressive aphasia paired with caregiver), and 46 dyads (healthy controls with no cognitive complaints) will be recruited. A nonverbal memory test (social memory task) will be administered to each dyad in three different social contexts (presence-only, observation, collaboration). Patients and healthy controls will also undergo a neuropsychological assessment to measure social (interactions and abilities), cognitive and personality aspects. Patients will be compared with controls on differential social scores calculated between the presence-only and collaboration contexts, and between the presence-only and observation contexts. A multiple comparative case study will be conducted to identify social, cognitive and personality variables that potentially explain the differential scores in the collaboration and observation contexts. DISCUSSION: For the first time, memory will be assessed in patients with Alzheimer's disease and patients with the semantic variant of primary progressive aphasia in three different contexts (presence-only, observation, collaboration). The multiple comparative case study will make it possible to identify the determinants of memory performance in the social context, in order to create the most beneficial learning context for individual patients, according to their profile. TRIAL REGISTRATION: This study was approved by the Ile de France XI institutional review board (2022-A00198-35), and registered on ClinicalTrials.gov (no. NCT05800028), on April 27, 2023.

Daily life activities in patients with Alzheimer's disease or semantic dementia: Multitasking assessment.

The aim of the present study was to compare patients with mild to moderate Alzheimer's disease (AD) or semantic dementia (SD) on their cognitive processes and the severity of their daily life activity impairments. Three types of tasks were administered to patients (SD = 15; AD = 31) and 30 healthy controls (HC): 1) informant-based scales and questionnaires, 2) a neuropsychological assessment exploring executive functions, episodic and semantic memory, and 3) a new original test featuring multi-step naturalistic actions and multitasking: the Sequential Daily Life Multitasking (SDLM). We predicted that patients with AD would mainly exhibit task perplexity, associated with episodic and executive deficits on the SDLM, while the behavior of patients with SD would mostly be characterized by object perplexity, associated with semantic memory deficits. Results showed that patients with AD or SD were impaired across all neuropsychological tests, particularly episodic memory in AD and semantic memory in SD. General performance on the SDLM also appeared dramatically impaired in both patient groups, and correlated with results of questionnaires about instrumental activities and memory impairments. However, specific qualitative measurements on the SDLM did not allow us to pinpoint different patterns of errors and behavior in patients with AD versus SD. We suggest that the inability of patients in both groups to perform the SDLM may derive from a constellation of disorders or else from more subtle impairment of cognitive and conative processes that requires further exploration.

Overreliance on thematic knowledge in semantic dementia: Evidence from an eye-tracking paradigm.

OBJECTIVE: The present study explored two types of semantic relationships in semantic dementia (SD), that rely on functionally and neuroanatomically distinct semantic systems (taxonomic vs. thematic). METHOD: We used the visual world paradigm coupled with eye-movement recordings, to gain an implicit, fine-grained and dynamic measure of semantic processing. Nine patients with SD and 15 healthy controls performed a simple word-to-picture matching task in which they had to identify each target among semantically related (taxonomic or thematic) competitors and unrelated distractors. RESULTS: We demonstrated different patterns of gaze fixations between patients with SD and controls: while patients with SD and controls were similarly sensitive to competition from taxonomically related pictures, patients with SD were far more sensitive than controls to thematically related competitors before identifying the targets. Moreover, most of the confusion errors made by patients with SD involved taxonomic distractors rather than thematic ones. CONCLUSIONS: We interpreted these findings as reflecting a semantic disequilibrium in SD, with increasing overreliance on thematic knowledge as taxonomic knowledge gradually deteriorates. We concluded that thematic relationships constitute a set of residual semantic knowledge and that their exaggerated activation in SD might certainly deserve further explorations to determine their specific role in this disease and notably, their influence on patients' abilities to deal with daily living activities. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Identification of taxonomic and thematic relationships: Do the two semantic systems have the same status in semantic dementia?

Introduction: Disequilibrium between the taxonomic and thematic semantic systems was previously hypothesized in participants with semantic dementia (SD), without rigorously assessing their ability to identify the two types of semantic relationships. Therefore, the aim of the present study was to directly compare the ability of 10 participants with SD, 10 participants with Alzheimer's disease (AD), and 20 controls to identify thematic versus taxonomic relationships. Methods: Participants performed an explicit forced-choice picture-matching task in which they had to determine which of two pictures of choice was semantically related to the target picture. Target pictures could display natural or artifact objects. Each target was presented once with a taxonomically related picture and once with a thematically related picture. Results: Analyses of correct thematic and taxonomic matches as a function of target domain showed that the performance of the two groups of patients differed in the taxonomic conditions but not in the thematic conditions, demonstrating a relative preservation of thematic knowledge in SD. Additional correlation analyses further indicated that the particular status of thematic relationships in SD was even stronger for artifact concepts. Conclusions: Results provide evidence of the heterogeneous nature of semantic knowledge disruption in SD, and could be regarded as being consistent with the existence of two neuroanatomically and functionally distinct semantic systems. Results further stress the relevance of performing a more detailed and complete assessment of semantic performance in participants with SD, in order to capture the impaired but also preserved aspects of their knowledge.

The - weak - role of memory in tool use: Evidence from neurodegenerative diseases.

OBJECTIVE: Although tool use disorders are frequent in neurodegenerative diseases, the question of which cognitive mechanisms are at stake is still under debate. Memory-based hypotheses (i.e., the semantic knowledge hypothesis and the manipulation knowledge hypothesis) posit that tool use relies solely on stored information about either tools or gestures whereas a reasoning-based hypothesis (i.e., the technical-semantic hypothesis) suggests that loss of semantic knowledge can be partially compensated by technical reasoning about the physical properties of tools and objects. METHOD: These three hypotheses were tested by comparing performance of 30 healthy controls, 30 patients with Alzheimer's disease and 13 patients with semantic dementia in gesture production tasks (i.e., pantomime of tool use, single tool use, real tool use) and tool or gesture recognition tasks (i.e., functional and contextual matching, recognition of tool manipulation). Individual, item-based patterns of performance were analyzed to answer the following question: Could participants demonstrate the use of tools about which they had lost knowledge? With this aim in mind, "validation" and "rebuttal" frequencies were calculated based on each prediction. RESULTS: Predictions from the technical-semantic hypothesis were more frequently observed than memory-based predictions. A number of patients were able to use and demonstrate the use of tools for which they had lost either semantic or manipulation knowledge (or both). CONCLUSIONS: These data lead to question the role of different types of memory in tool use. The hypothesis of stored, tool-specific knowledge does not predict accurately clinical performances at the individual level. This may lead to explore the influence of either additional memory systems (e.g., personal/impersonal memory) or other modes of reasoning (e.g., theory of mind) on tool use skills.

What semantic dementia teaches us about the functional organization of the left posterior fusiform gyrus.

After demonstrating the relative preservation of fruit and vegetable knowledge in patients with semantic dementia (SD), we sought to identify the neural substrate of this unusual category effect. Nineteen patients with SD performed a semantic sorting task and underwent a morphometric 3T MRI scan. The grey-matter volumes of five regions within the temporal lobe were bilaterally computed, as well as those of two recently described areas (FG1 and FG2) within the posterior fusiform gyrus. In contrast to the other semantic categories we tested, fruit and vegetable scores were only predicted by left FG1 volume. We therefore found a specific relationship between the volume of a subregion within the left posterior fusiform gyrus and performance on fruits and vegetables in SD. We argue that the left FG1 is a convergence zone for the features that might be critical to successfully sort fruits and vegetables. We also discuss evidence for a functional specialization of the fusiform gyrus along two axes (lateral medial and longitudinal), depending on the nature of the concepts and on the level of processing complexity required by the ongoing task.

Distinct neural substrates of affective and cognitive theory of mind impairment in semantic dementia.

Using structural MRI, we investigated the brain substrates of both affective and cognitive theory of mind (ToM) in 19 patients with semantic dementia. We also ran intrinsic connectivity analyses to identify the networks to which the substrates belong and whether they are functionally disturbed in semantic dementia. In line with previous studies, we observed a ToM impairment in patients with semantic dementia even when semantic memory was regressed out. Our results also highlighted different neural bases according to the nature (affective or cognitive) of the representations being inferred. The affective ToM deficit was associated with atrophy in the amygdala, suggesting the involvement of emotion-processing deficits in this impairment. By contrast, cognitive ToM performances were correlated with the volume of medial prefrontal and parietal regions, as well as the right frontal operculum. Intrinsic connectivity analyses revealed decreased functional connectivity, mainly between midline cortical regions and temporal regions. They also showed that left medial temporal regions were functionally isolated, a further possible hindrance to normal social cognitive functioning in semantic dementia. Overall, this study addressed for the first time the neuroanatomical substrates of both cognitive and affective ToM disruption in semantic dementia, highlighting disturbed connectivity within the networks that sustain these abilities.

Tool use disorders in neurodegenerative diseases: Roles of semantic memory and technical reasoning.

In the field of apraxia, it has been suggested that the ability to use tools and objects in daily life depends not only on semantic knowledge about tool function and context of use but also on technical reasoning about mechanical properties of tools and objects. The aim of the present work was to assess tool use abilities regarding these hypotheses in patients with neurodegenerative diseases and reduced autonomy. Performance of patients with Alzheimer's disease (AD) (n = 31), semantic dementia (SD) (n = 16) and corticobasal syndrome (CBS) (n = 7) was compared to that of healthy control participants (n = 31) in familiar tool use tasks, functional/contextual associations and mechanical problem solving (MPS). A conversion method was applied to data in order to avoid ceiling effects. Tool use disorders were found in all patient groups but the underlying reasons were different. Patients with SD had difficulties in imagining and selecting familiar tools due to the semantic loss but they performed in normal range in MPS tasks. Interestingly, they performed better with only one tool and its corresponding object, which is interpreted as a partial compensation of semantic loss by spared technical reasoning. Patients with CBS exhibited the reverse pattern, that is, MPS deficits without semantic loss. However, additional qualitative research is needed to disentangle the relative contributions of motor and technical reasoning deficits to this pattern. Both of these profiles were found in patients with AD. For all that, these patients did not commit the same errors as stroke patients with left brain-damage documented in previous works. Several hypotheses are proposed to account for the specificity of tool use disorders in neurodegenerative diseases, and recommendations are provided to caregivers.

When the zebra loses its stripes but is still in the savannah: results from a semantic priming paradigm in semantic dementia.

Studies using semantic priming paradigms to measure the integrity of the features underlying concepts in semantic dementia (SD) reported differential impairment, in that functional features appeared to be more robust to brain damage than other features, such as perceptual ones. However, these prior studies were single case reports and the inclusion of too many heterogeneous features under the "functional features" heading casts doubts on their apparent preservation. To verify the robustness of functional features compared with perceptual ones, we carried out a group study where we deliberately restricted the exploration of semantic features to two clearly defined types of attribute: visuoperceptual ("visual") versus contextual-functional ("contextual"). We administered an implicit lexical-decision priming task to 8 SD patients and 31 healthy matched controls, at baseline. Four of the patients underwent a follow-up assessment at one year. For controls, we found a significant priming effect in the visual condition, but not in the contextual one, whereas the SD group exhibited the reverse pattern of performances. The follow-up data provided evidence of the robustness of the dissociation between priming performances in the two attribute conditions. The fact that a particular priming effect was observed in the SD patients but not in controls could be regarded as a sign of semantic disequilibrium. Since perceptual features have been shown to be a core determinant of similarity-based/taxonomic relationships, whereas complementary-based/thematic processing relies mainly on contextual relationships, we interpreted our findings in terms of the differential recruitment of one of the two systems of semantic relationships (taxonomic vs. thematic). Moreover, these two distinct and parallel systems have previously been reported to coexist - and compete - in healthy adults. We thus argue that controls automatically drew on similarity-based/taxonomic relationships, leading to a significant priming effect for visual features but not for contextual ones. By contrast, their impaired perceptual features forced the SD patients to resort to the system of thematic relationships.

Relative category-specific preservation in semantic dementia? Evidence from 35 cases.

Category-specific deficits have rarely been reported in semantic dementia (SD). To our knowledge, only four previous studies have documented category-specific deficits, and these have focused on the living versus non-living things contrast rather than on more fine-grained semantic categories. This study aimed to determine whether a category-specific effect could be highlighted by a semantic sorting task administered to 35 SD patients once at baseline and again after 2 years and to 10 Alzheimer's disease patients (AD). We found a relative preservation of fruit and vegetables only in SD. This relative preservation of fruit and vegetables could be considered with regard to the importance of color knowledge in their discrimination. Indeed, color knowledge retrieval is known to depend on the left posterior fusiform gyrus which is relatively spared in SD. Finally, according to predictions of semantic memory models, our findings best fitted the Devlin and Gonnerman's computational account.