Automated free speech analysis reveals distinct markers of Alzheimer's and frontotemporal dementia.

Dementia can disrupt how people experience and describe events as well as their own role in them. Alzheimer's disease (AD) compromises the processing of entities expressed by nouns, while behavioral variant frontotemporal dementia (bvFTD) entails a depersonalized perspective with increased third-person references. Yet, no study has examined whether these patterns can be captured in connected speech via natural language processing tools. To tackle such gaps, we asked 96 participants (32 AD patients, 32 bvFTD patients, 32 healthy controls) to narrate a typical day of their lives and calculated the proportion of nouns, verbs, and first- or third-person markers (via part-of-speech and morphological tagging). We also extracted objective properties (frequency, phonological neighborhood, length, semantic variability) from each content word. In our main study (with 21 AD patients, 21 bvFTD patients, and 21 healthy controls), we used inferential statistics and machine learning for group-level and subject-level discrimination. The above linguistic features were correlated with patients' scores in tests of general cognitive status and executive functions. We found that, compared with HCs, (i) AD (but not bvFTD) patients produced significantly fewer nouns, (ii) bvFTD (but not AD) patients used significantly more third-person markers, and (iii) both patient groups produced more frequent words. Machine learning analyses showed that these features identified individuals with AD and bvFTD (AUC = 0.71). A generalizability test, with a model trained on the entire main study sample and tested on hold-out samples (11 AD patients, 11 bvFTD patients, 11 healthy controls), showed even better performance, with AUCs of 0.76 and 0.83 for AD and bvFTD, respectively. No linguistic feature was significantly correlated with cognitive test scores in either patient group. These results suggest that specific cognitive traits of each disorder can be captured automatically in connected speech, favoring interpretability for enhanced syndrome characterization, diagnosis, and monitoring.

Decision-making under stress: A psychological and neurobiological integrative model.

Understanding the impact of stress on cognitive processes, particularly decision-making, is crucial as it underpins behaviors essential for survival. However, research in this domain has yielded disparate results, with inconsistencies evident across stress-induction paradigms and drug administration protocols designed to investigate specific stress pathways or neuromodulators. Building upon empirical studies, this research identifies a multifaceted matrix of variables contributing to the divergent findings. This matrix encompasses factors such as the temporal proximity between stressors and decision tasks, the nature of stressors and decision contexts, individual characteristics including psychobiological profiles and affective states at the time of decision-making and even cultural influences. In response to these complexities, we propose a comprehensive model that integrates these relevant factors and their intricate interplay to elucidate the mechanisms governing decision-making during stressful events. By synthesizing these insights, our model not only refines existing paradigms but also provides a framework for future study designs, offering avenues for theoretical advancements and translational developments in the field of stress's impact on cognitive functions. This research contributes to a deeper understanding of the nuanced relationship between stress and decision-making, ultimately advancing our knowledge of cognitive processes under challenging conditions.

Social concepts and the cerebellum: behavioural and functional connectivity signatures in cerebellar ataxic patients.

Neurocognitive research on social concepts underscores their reliance on fronto-temporo-limbic regions mediating broad socio-cognitive skills. Yet, the field has neglected another structure increasingly implicated in social cognition: the cerebellum. The present exploratory study examines this link combining a novel naturalistic text paradigm, a relevant atrophy model and functional magnetic resonance imaging. Fifteen cerebellar ataxia (CA) patients with focal cerebellar atrophy and 29 matched controls listened to a social text (highlighting interpersonal events) as well as a non-social text (focused on a single person's actions), and answered comprehension questionnaires. We compared behavioural outcomes between groups and examined their association with cerebellar connectivity. CA patients showed deficits in social text comprehension and normal scores in the non-social text. Also, social text outcomes in controls selectively correlated with connectivity between the cerebellum and key regions subserving multi-modal semantics and social cognition, including the superior and medial temporal gyri, the temporal pole and the insula. Conversely, brain-behaviour associations involving the cerebellum were abolished in the patients. Thus, cerebellar structures and connections seem involved in processing social concepts evoked by naturalistic discourse. Such findings invite new theoretical and translational developments integrating social neuroscience with embodied semantics. This article is part of the theme issue 'Concepts in interaction: social engagement and inner experiences'.

Behavioral tagging as a mechanism for aversive-memory formation under acute stress.

The behavioral tagging (BT) hypothesis postulates that a weak learning experience, which only induces short-term memory, may benefit from another event that provides plasticity-related proteins (PRPs) to establish a long-lasting memory. According to BT, the weak experience sets a transient learning tag at specific activated sites, and its temporal and spatial convergence with the PRPs allows the long-term memory (LTM) formation. In this work, rats were subjected to a weak inhibitory avoidance (IAw) training and we observed that acute stress (elevated platform, EP) experienced 1 hr before IAw promoted IA-LTM formation. This effect was dependent on glucocorticoid-receptor activity as well as protein synthesis in the dorsal hippocampus. However, the same stress has negative effects on IA-LTM formation when training is strong, probably by competing for necessary PRPs. Furthermore, our experiments showed that EP immediately after training did not impair the setting of the learning tag and even facilitated IA-LTM formation. These findings reveal different impacts of a given acute stressful experience on the formation of an aversive memory that could be explained by BT processes.

Rekindling Action Language: A Neuromodulatory Study on Parkinson's Disease Patients.

Impairments of action semantics (a cognitive domain that critically engages motor brain networks) are pervasive in early Parkinson's disease (PD). However, no study has examined whether action semantic skills in persons with this disease can be influenced by non-invasive neuromodulation. Here, we recruited 22 PD patients and performed a five-day randomized, blinded, sham-controlled study to assess whether anodal transcranial direct current stimulation (atDCS) over the primary motor cortex, combined with cognitive training, can boost action-concept processing. On day 1, participants completed a picture-word association (PWA) task involving action-verb and object-noun conditions. They were then randomly assigned to either an atDCS (n = 11, 2 mA for 20 m) or a sham tDCS (n = 11, 2 mA for 30 s) group and performed an online PWA practice over three days. On day 5, they repeated the initial protocol. Relative to sham tDCS, the atDCS group exhibited faster reaction times for action (as opposed to object) concepts in the post-stimulation test. This result was exclusive to the atDCS group and held irrespective of the subjects' cognitive, executive, and motor skills, further attesting to its specificity. Our findings suggest that action-concept deficits in PD are distinctively grounded in motor networks and might be countered by direct neuromodulation of such circuits. Moreover, they provide new evidence for neurosemantic models and inform a thriving agenda in the embodied cognition framework.

Spatial-Memory Formation After Spaced Learning Involves ERKs1/2 Activation Through a Behavioral-Tagging Process.

The superiority of spaced over massed learning is an established fact in the formation of long-term memories (LTM). Here we addressed the cellular processes and the temporal demands of this phenomenon using a weak spatial object recognition (wSOR) training, which induces short-term memories (STM) but not LTM. We observed SOR-LTM promotion when two identical wSOR training sessions were spaced by an inter-trial interval (ITI) ranging from 15 min to 7 h, consistently with spaced training. The promoting effect was dependent on neural activity, protein synthesis and ERKs1/2 activity in the hippocampus. Based on the "behavioral tagging" hypothesis, which postulates that learning induces a neural tag that requires proteins to induce LTM formation, we propose that retraining will mainly retag the sites initially labeled by the prior training. Thus, when weak, consecutive training sessions are experienced within an appropriate spacing, the intracellular mechanisms triggered by each session would add, thereby reaching the threshold for protein synthesis required for memory consolidation. Our results suggest in addition that ERKs1/2 kinases play a dual role in SOR-LTM formation after spaced learning, both inducing protein synthesis and setting the SOR learning-tag. Overall, our findings bring new light to the mechanisms underlying the promoting effect of spaced trials on LTM formation.

Spatial object recognition memory formation under acute stress.

Stress is known to have a critical impact on memory processes. In the present work, we focus on the effects of an acute stress event closely associated to an unrelated learning task. Here, we show that acute stress (elevated platform [EP] session) experienced 1 hr after a weak spatial object recognition (SOR) training, which only induces a short-term memory (STM), promoted the formation of SOR-long term memory (SOR-LTM) in rats. The effect induced by stress was dependent on the activation of glucocorticoid- and mineralocorticoid-receptors, brain-derived neurotrophic factor (BDNF) and protein synthesis in the dorsal hippocampus. In contrast, EP after a strong SOR impaired SOR-LTM probably by interfering with the use of necessary resources. Moreover, we show that the EP session before training induced anterograde interference, which it was not reversed by a subsequent exposure to an open field. Our findings provide novel insights into the impact of stress on LTM formation in rodents and they are discussed under the behavioral analogue of the synaptic tagging and capture hypothesis.

Memory consolidation and expression of object recognition are susceptible to retroactive interference.

With the aim of analyzing if object recognition long-term memory (OR-LTM) formation is susceptible to retroactive interference (RI), we submitted rats to sequential sample sessions using the same arena but changing the identity of a pair of objects placed in it. Separate groups of animals were tested in the arena in order to evaluate the LTM for these objects. Our results suggest that OR-LTM formation was retroactively interfered within a critical time window by the exploration of a new, but not familiar, object. This RI acted on the consolidation of the object explored in the first sample session because its OR-STM measured 3h after training was not affected, whereas the OR-LTM measured at 24h was impaired. This sample session also impaired the expression of OR memory when it took place before the test. Moreover, local inactivation of the dorsal Hippocampus (Hp) or the medial Prefrontal Cortex (mPFC) previous to the exploration of the second pair of objects impaired their consolidation restoring the LTM for the objects explored in the first session. This data suggests that both brain regions are involved in the processing of OR-memory and also that if those regions are engaged in another process before finishing the first consolidation process its LTM will be impaired by RI.