Adolfo M. García

Your perspective and my benefit: multiple lesion models of self-other integration strategies during social bargaining

Recursive social decision-making requires the use of flexible, context-sensitive long-term strategies for negotiation. To succeed in social bargaining, participants own perspectives must be dynamically integrated with those of interactors to maximize self-benefits and adapt to the others preferences, respectively. This is a prerequisite to develop a successful long-term self-other integration strategy. While such form of strategic interaction is critical to social decision-making, little is known about its neurocognitive correlates. To bridge this gap, we analysed social bargaining behaviour in relation to its structural neural correlates, ongoing brain dynamics (oscillations and related source space), and functional connectivity signatures in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal stroke: behavioural variant frontotemporal dementia, Alzheimers disease, and frontal lesions. All groups showed preserved basic bargaining indexes. However, impaired self-other integration strategy was found in patients with behavioural variant frontotemporal dementia and frontal lesions, suggesting that social bargaining critically depends on the integrity of prefrontal regions. Also, associations between behavioural performance and data from voxel-based morphometry and voxel-based lesion-symptom mapping revealed a critical role of prefrontal regions in value integration and strategic decisions for self-other integration strategy. Furthermore, as shown by measures of brain dynamics and related sources during the task, the self-other integration strategy was predicted by brain anticipatory activity (alpha/beta oscillations with sources in frontotemporal regions) associated with expectations about others decisions. This pattern was reduced in all clinical groups, with greater impairments in behavioural variant frontotemporal dementia and frontal lesions than Alzheimers disease. Finally, connectivity analysis from functional magnetic resonance imaging evidenced a fronto-temporo-parietal network involved in successful self-other integration strategy, with selective compromise of long-distance connections in frontal disorders. In sum, this work provides unprecedented evidence of convergent behavioural and neurocognitive signatures of strategic social bargaining in different lesion models. Our findings offer new insights into the critical roles of prefrontal hubs and associated temporo-parietal networks for strategic social negotiation.

Feeling, learning from and being aware of inner states: interoceptive dimensions in neurodegeneration and stroke

Interoception is a complex process encompassing multiple dimensions, such as accuracy, learning and awareness. Here, we examined whether each of those dimensions relies on specialized neural regions distributed throughout the vast interoceptive network. To this end, we obtained relevant measures of cardiac interoception in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal brain damage: behavioural variant fronto-temporal dementia (bvFTD), Alzheimers disease (AD) and fronto-insular stroke. Neural correlates of the three dimensions were examined through structural and functional resting-state imaging, and online measurements of the heart-evoked potential (HEP). The three patient groups presented deficits in interoceptive accuracy, associated with insular damage, connectivity alterations and abnormal HEP modulations. Interoceptive learning was differentially impaired in AD patients, evidencing a key role of memory networks in this skill. Interoceptive awareness results showed that bvFTD and AD patients overestimated their performance; this pattern was related to abnormalities in anterior regions and associated networks sub-serving metacognitive processes, and probably linked to well-established insight deficits in dementia. Our findings indicate how damage to specific hubs in a broad fronto-temporo-insular network differentially compromises interoceptive dimensions, and how such disturbances affect widespread connections beyond those critical hubs. This is the first study in which a multiple lesion model reveals fine-grained alterations of body sensing, offering new theoretical insights into neuroanatomical foundations of interoceptive dimensions. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

A touch with words: Dynamic synergies between manual actions and language.

Manual actions are a hallmark of humanness. Their underlying neural circuitry gives rise to species-specific skills and interacts with language processes. In particular, multiple studies show that hand-related expressions - verbal units evoking manual activity - variously affect concurrent manual actions, yielding apparently controversial results (interference, facilitation, or null effects) in varied time windows. Through a systematic review of 108 experiments, we show that such effects are driven by several factors, such as the level of verbal processing, action complexity, and the time-lag between linguistic and motor processes. We reconcile key empirical patterns by introducing the Hand-Action-Network Dynamic Language Embodiment (HANDLE) model, an integrative framework based on neural coupling dynamics and predictive-coding principles. To conclude, we assess HANDLE against the backdrop of other action-cognition theories, illustrate its potential applications to understand high-level deficits in motor disorders, and discuss key challenges for further development. In sum, our work aligns with the pragmatic turn, moving away from passive and static representationalist perspectives to a more dynamic, enactive, and embodied conceptualization of cognitive processes.

Potent antimalarial 4-pyridones with improved physico-chemical properties.

Antimalarial 4-pyridones are a novel class of inhibitors of the plasmodial mitochondrial electron transport chain targeting Cytochrome bc1 (complex III). In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form. The strategy of introducing polar hydroxymethyl groups has enabled us to maintain the high levels of antimalarial potency observed for other more lipophilic analogues whilst improving the solubility and the oral bioavailability in pre-clinical species.

How language flows when movements don’t: An automated analysis of spontaneous discourse in Parkinson’s disease

To assess the impact of Parkinsons disease (PD) on spontaneous discourse, we conducted computerized analyses of brief monologues produced by 51 patients and 50 controls. We explored differences in semantic fields (via latent semantic analysis), grammatical choices (using part-of-speech tagging), and word-level repetitions (with graph embedding tools). Although overall output was quantitatively similar between groups, patients relied less heavily on action-related concepts and used more subordinate structures. Also, a classification tool operating on grammatical patterns identified monologues as pertaining to patients or controls with 75% accuracy. Finally, while the incidence of dysfluent word repetitions was similar between groups, it allowed inferring the patients level of motor impairment with 77% accuracy. Our results highlight the relevance of studying naturalistic discourse features to tap the integrity of neural (and, particularly, motor) networks, beyond the possibilities of standard token-level instruments.

Social neuroscience: undoing the schism between neurology and psychiatry

ABSTRACT Multiple disorders once jointly conceived as “nervous diseases” became segregated by the distinct institutional traditions forged in neurology and psychiatry. As a result, each field specialized in the study and treatment of a subset of such conditions. Here we propose new avenues for interdisciplinary interaction through a triangulation of both fields with social neuroscience. To this end, we review evidence from five relevant domains (facial emotion recognition, empathy, theory of mind, moral cognition, and social context assessment), highlighting their common disturbances across neurological and psychiatric conditions and discussing their multiple pathophysiological mechanisms. Our proposal is anchored in multidimensional evidence, including behavioral, neurocognitive, and genetic findings. From a clinical perspective, this work paves the way for dimensional and transdiagnostic approaches, new pharmacological treatments, and educational innovations rooted in a combined neuropsychiatric training. Research-wise, it fosters new models of the social brain and a novel platform to explore the interplay of cognitive and social functions. Finally, we identify new challenges for this synergistic framework.

The cerebellum and embodied semantics: evidence from a case of genetic ataxia due to STUB1 mutations

Fil: Garcia, Adolfo Martin. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundacion Ineco Rosario Sede del Incyt | Instituto de Neurologia Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundacion Ineco Rosario Sede del Incyt | Fundacion Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundacion Ineco Rosario Sede del Incyt; Argentina. Universidad Nacional de Cuyo; Argentina

Unspeakable motion: Selective action-verb impairments in Parkinson’s disease patients without mild cognitive impairment

&NA; Parkinsons disease (PD) patients show marked impairments in processing action verbs, and to a lesser extent, concrete (specially, manipulable) nouns. However, it is still unclear to what extent deficits in each of these categories are influenced by more general cognitive dysfunctions, and whether they are modulated by the words implied motility. To examine these issues, we evaluated 49 non‐demented PD patients and 49 healthy volunteers in an oral production task. The patients were divided into two groups depending on the presence or absence of mild cognitive impairment (PD‐MCI and PD‐nMCI, respectively). Participants named pictures of actions varying in motion content (low and high) and of objects varying in manipulability (low and high). The PD‐MCI group showed deficits across all four categories. However, PD‐nMCI patients exhibited a selective difficulty for high‐motion action verbs. This finding corroborates and refines previous results suggesting that disturbances of action‐related lexico‐semantic information in PD constitute a sui generis alteration manifested early in the course of the diseases physiopathology. Moreover, it suggests that the grounding of action verbs on motor circuits could depend on fine‐grained intracategorical semantic distinctions. HighlightsWe examined processing of action verbs and nouns in Parkinsons disease (PD).We assessed patients with and without mild cognitive impairment (PD‐MCI and PD‐nMCI).In PD‐MCI, deficits emerged for both action verbs and manipulable nouns.In PD‐nMCI, only action verbs with high motion content were disrupted.Action‐verb deficits may represent an early, sui generis alteration in PD.

Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer's Disease

Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimers disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250u200ams) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD.

Your misery is no longer my pleasure: Reduced schadenfreude in Huntington's disease families

Schadenfreude - pleasure at others misfortunes - has been systematically related to ventral striatum activity. This brain region is affected early in individuals with manifest and pre-manifest Huntingtons disease (HD). However, the experience of schadenfreude has not yet been investigated in HD. In this study, 21 manifest HD patients, 19 first-degree asymptomatic relatives, and 23 healthy controls performed an experimental task designed to trigger schadenfreude, envy (another social emotion acting as an affective control condition), and control situations. Both HD patients and first-degree relatives experienced lower schadenfreude in response to others misfortunes, with no group differences in ratings of envy and control conditions. These results offer unprecedented evidence of a highly specific impairment in reward processing, extending previous reports in manifest and pre-manifest HD individuals. Moreover, these findings suggest that early striatal impairments may be related to reduced feelings of schadenfreude. In sum, our work contributes to the understanding of emotional impairments in early stages of HD, while shedding light on their neural correlates.