When Is Irony Effortful?

International audienc

Irony

International audienc

Cognitive and Neuroanatomic Accounts of Referential Communication in Focal Dementia

The primary function of language is to communicate-that is, to make individuals reach a state of mutual understanding about a particular thought or idea. Accordingly, daily communication is truly a task of social coordination. Indeed, successful interactions require individuals to (1) track and adopt a partner's perspective and (2) continuously shift between the numerous elements relevant to the exchange. Here, we use a referential communication task to study the contributions of perspective taking and executive function to effective communication in nonaphasic human patients with behavioral variant frontotemporal dementia (bvFTD). Similar to previous work, the task was to identify a target object, embedded among an array of competitors, for an interlocutor. Results indicate that bvFTD patients are impaired relative to control subjects in selecting the optimal, precise response. Neuropsychological testing related this performance to mental set shifting, but not to working memory or inhibition. Follow-up analyses indicated that some bvFTD patients perform equally well as control subjects, while a second, clinically matched patient group performs significantly worse. Importantly, the neuropsychological profiles of these subgroups differed only in set shifting. Finally, structural MRI analyses related patient impairment to gray matter disease in orbitofrontal, medial prefrontal, and dorsolateral prefrontal cortex, all regions previously implicated in social cognition and overlapping those related to set shifting. Complementary white matter analyses implicated uncinate fasciculus, which carries projections between orbitofrontal and temporal cortices. Together, these findings demonstrate that impaired referential communication in bvFTD is cognitively related to set shifting, and anatomically related to a social-executive network including prefrontal cortices and uncinate fasciculus

The atrophy pattern in Alzheimer-related PPA is more widespread than that of the frontotemporal lobar degeneration associated variants

Objective: The three recognized variants of primary progressive aphasia (PPA) are associated with different loci of degeneration—left posterior perisylvian in logopenic variant (lvPPA), left frontal operculum in non-fluent variant (nfvPPA), and left rostroventral-temporal in semantic variant (svPPA). Meanwhile, it has become apparent that patients with lvPPA, in which Alzheimer pathology is the norm, frequently have more extensive language deficits—namely semantic and grammatical problems—than is captured in the strict diagnostic recommendations for this variant. We hypothesized that this may be because the degeneration in AD-related PPA typically extends beyond the left posterior perisylvian region. Methods: Magnetic resonance images from 25 PPA patients (9AD-related PPA, 10 svPPA, 6 nfvPPA) and a healthy control cohort were used to calculate cortical thickness in three regions of interest (ROIs). The three ROIs being the left-hemispheric loci of maximal reported degeneration for each of the three variants of PPA. Results: Consistent with past studies, the most severe cortical thinning was in the posterior perisylvian ROI in AD-related PPA; the ventral temporal ROI in svPPA; and the frontal opercular ROI in nfvPPA. Significant cortical thinning in AD-related PPA, however, was evident in all three ROIs. In contrast, thinning in svPPA and nfvPPA was largely restricted to their known peak loci of degeneration. Conclusions: Although cortical degeneration in AD-related PPA is maximal in the left posterior perisylvian region, it extends more diffusely throughout the left hemisphere language network offering a plausible explanation for why the linguistic profile of lvPPA so often includes additional semantic and grammatic deficits

Measures of cortical microstructure are linked to amyloid pathology in Alzheimer's disease

Markers of downstream events are a key component of clinical trials of disease-modifying therapies for Alzheimer's disease. Morphological metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect amyloid-beta (Aβ)- related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes and to test their associations with multiple aspects of the Alzheimer's disease pathological cascade, including both Aβ and tau accumulation, astrocytic activation and cognitive deficits. We applied the mean apparent diffusion propagator model to diffusion MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. Participants were stratified in Aβ-negative/tau-negative, Aβ-positive/tau-negative and Aβ-positive/tau-positive based on Aβ- and tau-PET uptake. Cortical regional values of diffusion MRI metrics and cortical thickness were compared across groups. Associations between regional values of diffusion MRI metrics and both Aβ- and tau-PET uptake were also investigated along with the association with plasma level of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation (available in 292 participants). Mean squared displacement revealed widespread microstructural differences already between Aβ-negative/tau-negative and Aβ-positive/tau-negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation. In contrast, differences in cortical thickness were clearly more limited. Mean squared displacement was also correlated with both Aβ- and tau-PET uptake even independently from one another and from cortical thickness. Further, the same metric exhibited significantly stronger correlations with PET uptake than cortical thickness (P < 0.05). Mean squared displacement was also positively correlated with GFAP with a pattern that resembles Aβ accumulation, and GFAP partially mediated the association between Aβ accumulation and mean squared displacement. Further, impairments in executive functions were significantly more associated with mean squared displacement values extracted from a meta-region of interest encompassing regions accumulating Aβ early in the disease process, than with cortical thickness (P < 0.05). Similarly, impairments in memory functions were significantly more associated with mean squared displacement values extracted from a temporal meta-region of interest than with cortical thickness (P < 0.05). Metrics of cortical microstructural alteration derived from diffusion MRI are highly sensitive to multiple aspects of the Alzheimer's disease pathological cascade. Of particular interest is the link with both Aβ-PET and GFAP, suggesting diffusion MRI might reflects microstructural changes related to the astrocytic response to Aβ aggregation. Therefore, metrics of cortical diffusion might be important outcome measures in anti-Aβ treatments clinical trials for detecting drug-induced changes in cortical microstructure

The mean diffusion propagator model revealed cortical microstructural changes associated with both amyloid-β and tau pathology and astroglial activation

Background: Markers of downstream events are a key component of clinical trials of disease-modifying therapies for Alzheimer’s disease (AD). Morphometric metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect Aβ-related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes that could complement morphometric macrostructural measures. Method: We applied the mean apparent diffusion propagator model (MAP-MRI) to diffusion MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. MAP-MRI extends diffusion tensor imaging and provides metrics sensitive to subtle changes in the cortex. Participants were stratified in Aβ-negative/tau-negative, Aβ-positive/tau-negative, and Aβ-positive/tau-positive based on Aβ- and tau-PET uptake. Cortical regional values of both MAP-MRI metrics and CT were compared across groups. Associations between regional values of MAP-MRI metrics and both Aβ- and tau-PET uptake were also investigated as well as the association between MAP-MRI metrics and plasma level of GFAP, a marker of astroglial activation (available in 292 participants). Result: Mean square displacement (MSD) from MAP-MRI revealed widespread microstructural differences already between Aβ-negative/tau-negative and Aβ-positive/tau-negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation. In contrast, differences in cortical thickness appeared to be more limited (figure 1). MSD was also highly correlated with both Aβ- and tau-PET uptake even independently from one another (figure 2). Regional MSD values were associated with GFAP with a pattern that resemble Aβ accumulation, and GFAP partially mediated the association between Aβ and MSD. A sensitivity analysis controlling for cortical thickness revealed that the associations between MSD and Aβ-PET, tau-PET and GFAP were largely independent from macrostructural changes (figures 2-3). Conclusion: Metrics of cortical microstructural alteration derived from MAP-MRI are highly sensitive to multiple aspects of the AD pathological cascade. Of particular interest is the link between MSD, Aβ-PET and GFAP which suggests MSD might reflects microstructural changes related to the astrocytic response to Aβ aggregation. Therefore, MSD could help monitoring the response to anti-Aβ treatments in clinical trials

What’s behind a P600? Integration Operations during Irony Processing

The combined knowledge of word meanings and grammatical rules does not allow a listener to grasp the intended meaning of a speaker’s utterance. Pragmatic inferences on the part of the listener are also required. The present work focuses on the processing of ironic utterances (imagine a slow day being described as ‘‘really productive’’) because these clearly require the listener to go beyond the linguistic code. Such utterances are advantageous experimentally because they can serve as their own controls in the form of literal sentences (now imagine an active day being described as ‘‘really productive’’) as we employ techniques from electrophysiology (EEG). Importantly, the results confirm previous ERP findings showing that irony processing elicits an enhancement of the P600 component (Regel et al., 2011). More original are the findings drawn from Time Frequency Analysis (TFA) and especially the increase of power in the gamma band in the 280–400 time-window, which points to an integration among different streams of information relatively early in the comprehension of an irony. This represents a departure from traditional accounts of language processing which generally view pragmatic inferences as late-arriving. We propose that these results indicate that unification operations between the linguistic code and contextual information play a critical role throughout the course of irony processing and earlier than previousl