Multivariate word properties in fluency tasks reveal markers of Alzheimer’s dementia

Version of Record online: 12 October 2023INTRODUCTION Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease-specific semantic memory patterns. Here, we leveraged automated word-property analysis to capture neurocognitive markers of AD vis-à-vis behavioral variant frontotemporal dementia (bvFTD). METHODS Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group-level discrimination, patient-level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns. RESULTS Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group- and subject-level discrimination only in AD, also predicting executive outcomes. Disease-specific cortical thickness patterns were predicted by frequency in both disorders. Default-mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD. DISCUSSION Word-property analysis of fluency can boost AD characterization and diagnosis. Highlights We report novel word-property analyses of verbal fluency in AD and bvFTD. Standard valid response counts captured deficits and brain patterns in both groups. Specific word properties (e.g., frequency, granularity) were altered only in AD. Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD. Word-property analysis of fluency can boost AD characterization and diagnosis.National Institutes of Health, National Institutes of Aging, Grant/Award Numbers: R01AG057234, R01AG075775; ANID: FONDECYT Regular, Grant/Award Numbers: 1210176, 1210195, 1220995; FONDAP, Grant/Award Number: 15150012; PIA/ANILLOS, Grant/Award Number: ACT210096; FONDEF, Grant/Award Number: ID20I10152; GBHI, Alzheimer’s Association, and Alzheimer’s Society: Alzheimer’s Association GBHI, Grant/Award Number: ALZ UK-22-865742; Alzheimer’s Association, Grant/Award Number: SG-20-725707; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile, Grant/Award Number: #BL-SRGP2021-01; Programa Interdisciplinario de Investigación Experimental en Comunicación y Cognición (PIIECC), Facultad de Humanidades, USACH; Takeda, Grant/Award Number: CW2680521; Rainwater Charitable Foundation; Tau Consortium; European Commission: H2020-MSCA-IF-GFMULTI-LAND, Grant/Award Number: 10102581

Emotional descriptions increase accidental harm punishment and its cortico-limbic signatures during moral judgment in autism

Abstract Individuals with autism spectrum disorder (ASD) present difficulties in integrating mental state information in complex moral tasks. Yet, ASD research has not examined whether this process is influenced by emotions, let alone while capturing its neural bases. We investigated how language-induced emotions modulate intent-based moral judgment in ASD. In a fMRI task, 30 adults with ASD and 27 neurotypical controls read vignettes whose protagonists commit harm either accidentally or intentionally, and then decided how much punishment the protagonist deserved. Emotional content was manipulated across scenarios through the use of graphic language (designed to trigger arousing negative responses) vs. plain (just-the-facts, emotionless) language. Off-line functional connectivity correlates of task performance were also analyzed. In ASD, emotional (graphic) descriptions amplified punishment ratings of accidental harms, associated with increased activity in fronto-temporo-limbic, precentral, and postcentral/supramarginal regions (critical for emotional and empathic processes), and reduced connectivity among the orbitofrontal cortex and the angular gyrus (involved in mentalizing). Language manipulation did not influence intentional harm processing in ASD. In conclusion, in arousing and ambiguous social situations that lack intentionality clues (i.e. graphic accidental harm scenarios), individuals with ASD would misuse their emotional responses as the main source of information to guide their moral decisions. Conversely, in face of explicit harmful intentions, they would be able to compensate their socioemotional alterations and assign punishment through non-emotional pathways. Despite limitations, such as the small sample size and low ecological validity of the task, results of the present study proved reliable and have relevant theoretical and translational implications

Emotional descriptions increase accidental harm punishment and its cortico-limbic signatures during moral judgment in autism

Individuals with autism spectrum disorder (ASD) present difficulties in integrating mental state information in complex moral tasks. Yet, ASD research has not examined whether this process is influenced by emotions, let alone while capturing its neural bases. We investigated how language-induced emotions modulate intent-based moral judgment in ASD. In a fMRI task, 30 adults with ASD and 27 neurotypical controls read vignettes whose protagonists commit harm either accidentally or intentionally, and then decided how much punishment the protagonist deserved. Emotional content was manipulated across scenarios through the use of graphic language (designed to trigger arousing negative responses) vs. plain (just-the-facts, emotionless) language. Off-line functional connectivity correlates of task performance were also analyzed. In ASD, emotional (graphic) descriptions amplified punishment ratings of accidental harms, associated with increased activity in fronto-temporo-limbic, precentral, and postcentral/supramarginal regions (critical for emotional and empathic processes), and reduced connectivity among the orbitofrontal cortex and the angular gyrus (involved in mentalizing). Language manipulation did not influence intentional harm processing in ASD. In conclusion, in arousing and ambiguous social situations that lack intentionality clues (i.e. graphic accidental harm scenarios), individuals with ASD would misuse their emotional responses as the main source of information to guide their moral decisions. Conversely, in face of explicit harmful intentions, they would be able to compensate their socioemotional alterations and assign punishment through non-emotional pathways. Despite limitations, such as the small sample size and low ecological validity of the task, results of the present study proved reliable and have relevant theoretical and translational implications.Fil: Fittipaldi, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. Universidad Adolfo Ibañez; Chile. University of California; Estados UnidosFil: Armony, Jorge Lazaro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. McGill University; CanadáFil: García, Adolfo Martín. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Migeot, Joaquín. Universidad Adolfo Ibañez; ChileFil: Cadaveira, Matías. No especifíca;Fil: Ibañez, Agustin Mariano. Universidad de San Andrés; Argentina. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baez, Sandra. Universidad de los Andes; Colombi

Metacognition of emotion recognition across neurodegenerative diseases

Metacognition (monitoring) of emotion recognition is fundamental for social interactions. Correct recognition of and confidence in the emotional meaning inferred from others' faces are fundamental for guiding and adjusting interpersonal behavior. Yet, although emotion recognition impairments are well documented across neurodegenerative diseases, the role of metacognition in this domain remains poorly understood. Here, we evaluate multimodal neurocognitive markers of metacognition in 83 subjects, encompassing patients with behavioral variant frontotemporal dementia [bvFTD, n = 18], Alzheimer's disease [AD, n = 27], and demographically-matched controls (n = 38). Participants performed a classical facial emotion recognition task and, after each trial, they rated their confidence in their performance. We examined two measures of metacognition: (i) calibration: how well confidence tracks accuracy; and (ii) a metacognitive index (MI) capturing the magnitude of the difference between confidence and accuracy. Then, whole-brain grey matter volume and fMRI-derived resting-state functional connectivity were analyzed to track associations with metacognition. Results showed that metacognition deficits were linked to basic emotion recognition. Metacognition of negative emotions was compromised in patients, especially disgust in bvFTD as well as sadness in AD. Metacognition impairments were associated with reduced volume of fronto-temporo-insular and subcortical areas in bvFTD and fronto-parietal regions in AD. Metacognition deficits were associated with disconnection of large-scale fronto-posterior networks for both groups. This study reveals a link between emotion recognition and metacognition in neurodegenerative diseases. The characterization of metacognitive impairments in bvFTD and AD would be relevant for understanding patients' daily life changes in social behavior.Fil: García Cordero, Indira Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Migeot, Joaquín. Universidad Adolfo Ibañez; ChileFil: Fittipaldi, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Aquino, Alexia. Universidad de San Andrés; ArgentinaFil: Gonzalez Campo, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. Universidad Nacional de Cuyo. Facultad de Educación Elemental y Especial; Argentina. Universidad de Santiago de Chile. Facultad de Humanidades; Chile. University of California; Estados UnidosFil: Ibáñez, Santiago Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. Universidad Adolfo Ibañez; Chile. University of California; Estados Unido

Neurocognitive correlates of semantic memory navigation in Parkinson’s disease

Abstract Cognitive studies on Parkinson’s disease (PD) reveal abnormal semantic processing. Most research, however, fails to indicate which conceptual properties are most affected and capture patients’ neurocognitive profiles. Here, we asked persons with PD, healthy controls, and individuals with behavioral variant frontotemporal dementia (bvFTD, as a disease control group) to read concepts (e.g., ‘sun’) and list their features (e.g., hot). Responses were analyzed in terms of ten word properties (including concreteness, imageability, and semantic variability), used for group-level comparisons, subject-level classification, and brain-behavior correlations. PD (but not bvFTD) patients produced more concrete and imageable words than controls, both patterns being associated with overall cognitive status. PD and bvFTD patients showed reduced semantic variability, an anomaly which predicted semantic inhibition outcomes. Word-property patterns robustly classified PD (but not bvFTD) patients and correlated with disease-specific hypoconnectivity along the sensorimotor and salience networks. Fine-grained semantic assessments, then, can reveal distinct neurocognitive signatures of PD