Atrophy of hippocampal subfields and amygdala nuclei in subjects with mild cognitive impairment progressing to Alzheimer's disease.

The hippocampus and amygdala are the first brain regions to show early signs of Alzheimer's Disease (AD) pathology. AD is preceded by a prodromal stage known as Mild Cognitive Impairment (MCI), a crucial crossroad in the clinical progression of the disease. The topographical development of AD has been the subject of extended investigation. However, it is still largely unknown how the transition from MCI to AD affects specific hippocampal and amygdala subregions. The present study is set to answer that question. We analyzed data from 223 subjects: 75 healthy controls, 52 individuals with MCI, and 96 AD patients obtained from the ADNI. The MCI group was further divided into two subgroups depending on whether individuals in the 48 months following the diagnosis either remained stable (N = 21) or progressed to AD (N = 31). A MANCOVA test evaluated group differences in the volume of distinct amygdala and hippocampal subregions obtained from magnetic resonance images. Subsequently, a stepwise linear discriminant analysis (LDA) determined which combination of magnetic resonance imaging parameters was most effective in predicting the conversion from MCI to AD. The predictive performance was assessed through a Receiver Operating Characteristic analysis. AD patients displayed widespread subregional atrophy. MCI individuals who progressed to AD showed selective atrophy of the hippocampal subiculum and tail compared to stable MCI individuals, who were undistinguishable from healthy controls. Converter MCI showed atrophy of the amygdala's accessory basal, central, and cortical nuclei. The LDA identified the hippocampal subiculum and the amygdala's lateral and accessory basal nuclei as significant predictors of MCI conversion to AD. The analysis returned a sensitivity value of 0.78 and a specificity value of 0.62. These findings highlight the importance of targeted assessments of distinct amygdala and hippocampus subregions to help dissect the clinical and pathophysiological development of the MCI to AD transition.

Neuroimaging evidence supporting a dual-network architecture for the control of visuospatial attention in the human brain: a mini review.

Neuroimaging studies conducted in the last three decades have distinguished two frontoparietal networks responsible for the control of visuospatial attention. The present review summarizes recent findings on the neurophysiological mechanisms implemented in both networks and describes the evolution from a model centered on the distinction between top-down and bottom-up attention to a model that emphasizes the dynamic interplay between the two networks based on attentional demands. The role of the dorsal attention network (DAN) in attentional orienting, by boosting behavioral performance, has been investigated with multiple experimental approaches. This research effort allowed us to trace a distinction between DAN regions involved in shifting vs. maintenance of attention, gather evidence for the modulatory influence exerted by the DAN over sensory cortices, and identify the electrophysiological correlates of the orienting function. Simultaneously, other studies have contributed to reframing our understanding of the functions of the ventral attention network (VAN) and its relevance for behavior. The VAN is not simply involved in bottom-up attentional capture but interacts with the DAN during reorienting to behaviorally relevant targets, exhibiting a general resetting function. Further studies have confirmed the selective rightward asymmetry of the VAN, proposed a functional dissociation along the anteroposterior axis, and suggested hypotheses about its emergence during the evolution of the primate brain. Finally, novel models of network interactions explain the expression of complex attentional functions and the emergence and restorations of symptoms characterizing unilateral spatial neglect. These latter studies emphasize the importance of considering patterns of network interactions for understanding the consequences of brain lesions.

Long-term memory for movie details: selective decay for verbal information at one week.

Mnemonic representations of complex events are multidimensional, incorporating information about objects and characters, their interactions and their spatial-temporal context. The present study investigated the degree to which detailed verbal information (i.e., dialogues), as well as semantic and spatiotemporal (i.e., "what", "where", and "when") elements of episodic memories for movies, are forgotten over the course of a week. Moreover, we tested whether the amount of dimension-specific forgetting differed as a function of the participant's age. In a mixed design, younger and middle-aged participants were asked to watch a ∼90 min movie and provide yes/no answers to detailed questions about different dimensions of the presented material after 1, 3 days, and 1 week. The results indicate that memory decay mainly affects the verbal dimension, both in terms of response accuracy and confidence. Instead, detailed information about objects/characters' features and spatiotemporal context seems to be relatively preserved, despite a general decrease in response confidence. Furthermore, younger adults were in general more accurate and confident than middle-aged participants, although, again, the verbal dimension exhibited a significant age-related difference. We propose that this selective forgetting depends on the progressive advantage of visual compared to auditory/verbal information in memory for complex events.

Effects of a narrative template on memory for the time of movie scenes: automatic reshaping is independent of consolidation.

Memory for time is influenced by reconstructive processes, but the underlying mechanisms remain unclear. The present study investigated whether the effect of schematic prior knowledge on temporal memory for movie scenes, produced by the incomplete presentation (cut) of the movie at encoding, is modulated by cut position, retention interval, and task repetition. In a timeline positioning task, participants were asked to indicate when short video clips extracted from a previously encoded movie occurred on a horizontal timeline that represented the video duration. In line with previous findings, removing the final part of the movie resulted in a systematic underestimation of clips' position as a function of their proximity to the missing part. Further experiments demonstrate that the direction of this automatic effect depends on which part of the movie is deleted from the encoding session, consistent with the inferential structure of the schema, and does not depend on consolidation nor reconsolidation processes, at least within the present experimental conditions. We propose that the observed bias depends on the automatic influence of reconstructive processes on judgments about the time of occurrence, based on prior schematic knowledge.

Foot-related/walking macro-affordances are implicitly activated and preferentially guided by the framing distance of the environmental layout.

As classically captured in the notion of affordance, the natural environment presents animals with multiple opportunities for action and locomotion appears as the privileged form of action to cover distance in the extrapersonal space/environment. We have recently described a facilitation effect, known as "macro-affordance", for the execution of walking-related actions in response to distant vs. near objects/locations in the extrapersonal space. However, since the manipulation of distance was coextensive to landmark-objects contained in the environment and to the environmental layout per se, the relative contribution of these two factors remains undetermined. In addition, since the effect was originally described in the context of an incidental priming paradigm, it is still unknown whether it was specifically associated with an implicit coding of environmental distance. Here, across three experiments, we examined the degree to which the "macro-affordance" effect reflects (i) the encoding of environmental vs. landmark-objects' distance, (ii) the involvement of an implicit vs. controlled system, (iii) a foot-effector specificity. The results showed that the "macro-affordance" effect is more efficiently triggered by the framing distance of the environmental layout (far/wide/panoramic vs. near/close/restricted) rather than of isolated landmark-objects in the environment and that it only emerges when the distance dimension is implicitly processed within the incidental priming paradigm. The results additionally suggested a specificity of the effect for foot- vs. hand-related actions. The present findings suggest that macro-affordances reflect an implicit coding of spatial features of the environmental layout and viewer-environment relationships that preferentially guide a walking-related exploration of the spatial environment.

Empowering episodic memory through a model-based egocentric navigational training.

Recent works have proposed that spatial mechanisms in the hippocampal-entorhinal system might have originally developed to represent distances and positions in the physical space and successively evolved to represent experience and memory in the mental space (Bellmund et al. 2018; Bottini and Doeller 2020). Within this phylogenetic continuity hypothesis (Buzsáki and Moser 2013), mechanisms supporting episodic and semantic memory would have evolved from egocentric and allocentric spatial navigation mechanisms, respectively. Recent studies have described a specific relationship between human performance in egocentric navigation and episodic memory (Committeri et al. 2020; Fragueiro et al. 2021), representing the first behavioral support to this hypothesis. Here, we tested the causal relationship among egocentric navigation and both episodic and semantic components of declarative memory. We conducted two experiments on healthy young adults: in the first experiment, participants were submitted to a navigational training based on path integration, while in the second experiment, participants completed a control training based on visual-perceptual learning. Performance in a set of memory tasks assessing episodic, semantic and short-term memory was compared among the pre- vs. post-training sessions. The results indicated a significant improvement of the episodic memory but not of the semantic or the short-term memory performance following the navigational training. In addition, no modulations of performance across the three memory tasks were observed following the control perceptual training. Our findings provide brand-new evidence of a potential causal association between mechanisms of egocentric navigation and episodic memory, thereby further supporting the phylogenetic continuity hypothesis between navigation and memory mechanisms as well as offering new insights about possible clinical applications of navigational trainings for memory functions/dysfunctions.

Magnetoencephalographic spectral fingerprints differentiate evidence accumulation from saccadic motor preparation in perceptual decision-making.

The understanding of the neurobiological basis of perceptual decision-making has been profoundly shaped by studies in the monkey brain in tandem with mathematical models, providing the basis for the formulation of an intentional account of decision-making. Although much progress has been made in human studies, a characterization of the neural underpinnings of an integrative mechanism, where evidence accumulation and the selection and execution of responses are carried out by the same system, remains challenging. Here, by employing magnetoencephalographic recording in combination with an experimental protocol that measures saccadic response and leverages a systematic modulation of evidence levels, we obtained a spectral dissociation between evidence accumulation mechanisms and motor preparation within the same brain region. Specifically, we show that within the dorsomedial parietal cortex alpha power modulation reflects the amount of sensory evidence available while beta power modulations reflect motor preparation, putatively representing the human homolog of the saccadic-related LIP region.

Alpha rhythm modulations in the intraparietal sulcus reflect decision signals during item recognition.

Theoretical work and empirical observations suggest a contribution of regions along the intraparietal sulcus to the process of evidence accumulation during episodic memory retrieval. In the present study, we recorded magnetoencephalographic signals in a group of healthy human participants to test whether the pattern of oscillatory modulations in the lateral parietal lobe is consistent with the mnemonic accumulator hypothesis. To this aim, the dynamic properties and the spatial distribution of MEG oscillatory power modulations were investigated during an item recognition task in which the amount of evidence for old vs. new memory decisions was manipulated across three levels. A data-driven approach was employed to identify brain nodes where oscillatory activity was sensitive to both retrieval success and the amount of evidence for old decisions. The analysis identified three nodes in the left lateral parietal lobe where the event-related desynchronization (ERD) in the alpha frequency band showed both effects. Further analyses revealed that the alpha ERD in the intraparietal sulcus, but not in other parietal nodes: i. showed modulation of duration in response to the amount of evidence for both old and new decisions, ii. was behaviorally significant, and iii. more accurately tracked the subjective memory judgment rather than the objective memory status. The present findings provide support for a recent anatomical-functional model of the parietal involvement in episodic memory retrieval and suggest that the alpha ERD in the intraparietal sulcus might represent a neural signature of the evidence accumulation process during simple memory-based decisions.

Sensory-Motor Modulations of EEG Event-Related Potentials Reflect Walking-Related Macro-Affordances.

One fundamental principle of the brain functional organization is the elaboration of sensory information for the specification of action plans that are most appropriate for interaction with the environment. Using an incidental go/no-go priming paradigm, we have previously shown a facilitation effect for the execution of a walking-related action in response to far vs. near objects/locations in the extrapersonal space, and this effect has been called "macro-affordance" to reflect the role of locomotion in the coverage of extrapersonal distance. Here, we investigated the neurophysiological underpinnings of such an effect by recording scalp electroencephalography (EEG) from 30 human participants during the same paradigm. The results of a whole-brain analysis indicated a significant modulation of the event-related potentials (ERPs) both during prime and target stimulus presentation. Specifically, consistent with a mechanism of action anticipation and automatic activation of affordances, a stronger ERP was observed in response to prime images framing the environment from a far vs. near distance, and this modulation was localized in dorso-medial motor regions. In addition, an inversion of polarity for far vs. near conditions was observed during the subsequent target period in dorso-medial parietal regions associated with spatially directed foot-related actions. These findings were interpreted within the framework of embodied models of brain functioning as arising from a mechanism of motor-anticipation and subsequent prediction error which was guided by the preferential affordance relationship between the distant large-scale environment and locomotion. More in general, our findings reveal a sensory-motor mechanism for the processing of walking-related environmental affordances.

Effects of Individual Discount Rate and Uncertainty Perception on Compliance with Containment Measures during the COVID-19 Pandemic.

Anti-contagion measures restricting individual freedom, such as social distancing and wearing a mask, are crucial to contain the COVID-19 pandemic. Decision-making patterns and attitudes about uncertainty can highly influence the adherence to these restrictive measures. Here we investigated the relationship between risky behavior and individual preferences for immediate vs. delayed reward, as indexed by temporal discounting (TD), as well as the association between these measures and confidence in the future, perceived risk and confidence in the containment measures. These measures were collected through an online survey administered on 353 participants at the end of the more restrictive phase of the first Italian lockdown. The results showed an unexpected inverse relationship between the individual pattern of choice preferences and risky behavior, with an overall greater adherence to containment measures in more discounter participants. These findings were interpreted in terms of a reframing process in which behaviors aimed at protecting oneself from contagion turn into immediate gains rather than losses. Interestingly, an excessive confidence in a better future was correlated with a higher tendency to assume risky behavior, thereby highlighting the downside of an overly and blindly optimistic view.

Travel in the Physical and Mental Space: A Behavioral Assessment of the Phylogenetic Continuity Hypothesis Between Egocentric Navigation and Episodic Memory.

Based on the neuro-functional association between navigation in the physical and the mental space at the level of the hippocampal-entorhinal system, Buzsáki and Moser (2013) have hypothesized a phylogenetic continuity between spatial navigation and declarative memory functions. According to this proposal, mechanisms of episodic and semantic memory would have evolved from mechanisms of self-based and map-based navigation in the physical space, respectively. Using classic versions of path integration and item recognition tasks in human subjects, we have recently described a correlation and a predictive relationship between abilities in egocentric navigation and episodic memory. Here we aim at confirming and extending this association to the dynamic component of sequential updating in the physical (egocentric navigation) and mental (episodic memory) space, and at investigating the relationship of these self-centered abilities with semantic memory. To this aim, we developed three new experimental tasks in which the dynamic component of updating information is particularly emphasized in the spatial, the temporal, and the semantic domain. The contribution of visual short-term memory to the three tasks was also controlled by including an additional task. The results confirmed the existence of a direct and predictive relationship between self-based spatial navigation and episodic memory. We also found a significant association between egocentric navigation and semantic memory, but this relationship was explained by short-term memory abilities and was mediated by episodic memory functions. Our results support the hypothesis of an evolutionary link between mechanisms that allow spatial navigation in the physical space and time travel in the mental space.

Reconstructive nature of temporal memory for movie scenes.

Remembering when events took place is a key component of episodic memory. Using a sensitive behavioral measure, the present study investigates whether spontaneous event segmentation and script-based prior knowledge affect memory for the time of movie scenes. In three experiments, different groups of participants were asked to indicate when short video clips extracted from a previously encoded movie occurred on a horizontal timeline that represented the video duration. When participants encoded the entire movie, they were more precise at judging the temporal occurrence of clips extracted from the beginning and the end of the film compared to its middle part, but also at judging clips that were closer to event boundaries. Removing the final part of the movie from the encoding session resulted in a systematic bias in memory for time. Specifically, participants increasingly underestimated the time of occurrence of the video clips as a function of their proximity to the missing part of the movie. An additional experiment indicated that such an underestimation effect generalizes to different audio-visual material and does not necessarily reflect poor temporal memory. By showing that memories are moved in time to make room for missing information, the present study demonstrates that narrative time can be adapted to fit a standard template regardless of what has been effectively encoded, in line with reconstructive theories of memory.

Automatic coding of environmental distance for walking-related locomotion in the foot-related sensory-motor system: A TMS study on macro-affordances.

We have recently described a facilitation effect for the execution of a walking-related action in response to distant objects/locations in the extrapersonal space. Based on the parallelism with the well-known effect of "micro-affordance", observed during the execution of functionally appropriate hand-related actions towards manipulable objects, we have referred to this effect in terms of "macro-affordance". Here we used transcranical magnetic stimulation (TMS) to investigate whether a foot-related region located in the human dorsal precuneate cortex plays a causal role in the generation and maintenance of such behavioral effect. This question was addressed by comparing the magnitude of the facilitation effect during an incidental go/no-go task, i.e. advantage for walking-related actions to pictures framing an environment from a far vs. near distance, during three different TMS conditions. The three TMS conditions were collected in all subjects in a randomized order and included stimulation of: i. a foot-related region in the anterior precuneus, ii. a control region in the middle intraparietal sulcus (mIPS), and iii. a sham condition. Enrollment in the TMS protocol was based on analysis of individual performance during a preliminary session conducted using a sham stimulation. TMS was administered at a low frequency range before the beginning of each condition. The results showed that stimulation of the foot-related region in the anterior precuneus produced a significant reduction of the walking-related facilitation effect as compared to both stimulation of the active-control region and the non-active sham stimulation. These findings suggest that the foot-related sensory-motor system directly participates in the process of extraction of the spatial features (i.e. distance) from an environmental scene that are useful for locomotion. More in general, these findings support an automatic coding of environmental affordance or "macro-affordances" in the walking-related sensory-motor system.

Egocentric Navigation Abilities Predict Episodic Memory Performance.

The medial temporal lobe supports both navigation and declarative memory. On this basis, a theory of phylogenetic continuity has been proposed according to which episodic and semantic memories have evolved from egocentric (e.g., path integration) and allocentric (e.g., map-based) navigation in the physical world, respectively. Here, we explored the behavioral significance of this neurophysiological model by investigating the relationship between the performance of healthy individuals on a path integration and an episodic memory task. We investigated the path integration performance through a proprioceptive Triangle Completion Task and assessed episodic memory through a picture recognition task. We evaluated the specificity of the association between performance in these two tasks by including in the study design a verbal semantic memory task. We also controlled for the effect of attention and working memory and tested the robustness of the results by including alternative versions of the path integration and semantic memory tasks. We found a significant positive correlation between the performance on the path integration the episodic, but not semantic, memory tasks. This pattern of correlation was not explained by general cognitive abilities and persisted also when considering a visual path integration task and a non-verbal semantic memory task. Importantly, a cross-validation analysis showed that participants' egocentric navigation abilities reliably predicted episodic memory performance. Altogether, our findings support the hypothesis of a phylogenetic continuity between egocentric navigation and episodic memory and pave the way for future research on the potential causal role of egocentric navigation on multiple forms of episodic memory.

Properties and temporal dynamics of choice- and action-predictive signals during item recognition decisions.

Decision-making is in the service of action regardless of whether the decision concerns perceptual information, goods or memories. Compared to recent advances in the neurobiology of perceptual or value-based decisions, however, the neural bases supporting the sampling of evidence in long-term memory, and the transformation of memory-based decisions into appropriate actions, are still poorly understood. In the present fMRI study, we used multivariate pattern analysis to investigate the temporal dynamics of choice- and action-predictive signals during an item recognition task that manipulated the association between memory choices (old/new) and motor responses (eye/hand) across subjects. Choice-predictive activity was mainly observed in striatal, lateral prefrontal and lateral parietal regions, was sensitive to the amount of decision evidence and showed a rapid increase after stimulus onset, followed by a fast decay. Action-predictive signals were found in primary sensory motor, premotor and occipito-parietal regions, were generally observed at the end of the decision phase and were not modulated by decision evidence. These findings suggest that a memory decision variable, potentially represented in a fronto-striato-parietal network, is not directly transformed into an action plan as often observed in perceptual decisions. Regions exhibiting choice predictive activity, and especially the striatum, however, also showed a second peak of decision-related activity that, unlike pure choice- or action-predictive signals, depended on the particular choice-response association. This second peak of activity in the striatum might represent the neural signature of the transformation of a memory decision into an appropriate motor response based on the specific choice-response association.

Cognitive dynamics of intertemporal choice in gambling disorder.

Gambling Disorder (GD) is a behavioral addiction characterized by the persistence of recurrent gambling behaviors despite serious adverse consequences. One of the key features of GD is a marked inability to delay gratification and an overall impairment of decision-making mechanisms. Indeed, in intertemporal choice (ITC) tasks, GD patients usually display a marked tendency to prefer smaller-sooner over larger-later rewards (temporal discounting, TD). However, ITC represents a highly verbal/explicit measure, and as such it might not be sensitive to implicit decision biases. Here we sought to uncover the implicit mechanisms underlying the ITC impairment in GD by employing the process-tracing method of mouse kinematics. To this aim, we collected and analyzed ITCs and kinematics measures from 24 GD patients and 23 matched healthy control participants (HC). In line with the relevant literature, the results showed that GD patients discounted future rewards more steeply compared to HCs. Additionally, the results of kinematics analyses showed that patients were characterized by a strong bias toward the immediate option, which was associated with straight-line trajectories. Conversely, the delayed option was selected with edge-curved trajectories, indicating a bias toward the immediate option which was revised in later stages of processing. Interestingly, kinematics indices were also found to be predictive of individual discounting preferences (i.e., discount rates) across the two groups. Taken together, these results suggest that kinematics indices, by revealing hidden and implicit patterns of attraction toward the unselected choice option, may represent reliable behavioral markers of TD in gambling disorder.

Walking-related locomotion is facilitated by the perception of distant targets in the extrapersonal space.

The Gibsonian notion of affordance has been massively employed in cognitive sciences to characterize the tight interdependence between hand-related actions, manipulable objects and peripersonal space. A behavioural facilitation effect, indeed, is observed for grasping actions directed to objects located in the 'reachable' peripersonal space. Relevantly, this relationship is supported by dedicated neural systems in the brain. The original notion of affordance, however, was directly inspired by real-time interactions between animals and their extended natural environment. Consistently, also the extrapersonal space representation can be significantly modulated by action-related factors, and the brain contains dedicated systems for the representation of topographical space and navigation. Here we examined whether a facilitation effect could be also described for a walking-related action in the far extrapersonal space. To this aim, we employed a go/no-go paradigm requiring subjects to execute a footstep ahead in response to pictures of a virtual reality environment containing objects located at different distances (near, far) and eccentricities (central, peripheral). A walking-related, facilitation effect for distant extrapersonal locations was found, suggesting an automatic trigger of walking by positions that preferentially guide spatial exploration. Based on the parallelism with the literature on micro-affordances, we propose that this effect can be described in terms of "macro-affordances".

Concreteness and emotional valence of episodic future thinking (EFT) independently affect the dynamics of intertemporal decisions.

During intertemporal decisions, the value of future rewards decreases as a function of the delay of its receipt (temporal discounting, TD). Since high discount rates have been associated with a series of problematic behaviours and clinical conditions, current research has focused on possible modulators of TD. Specifically, a reduction of individual discount rates has been shown during episodic future thinking (EFT), wherein time intervals are anchored to personal future events. However, it is not entirely clear whether this effect is mediated by a change in the representation of future events (i.e., from abstract to concrete) or by a positive-emotion modulation. Here, we investigated this issue by manipulating the valence of the EFT (i.e., using negative, neutral and positive episodic tags), and by collecting explicit and implicit measures of behaviour. The results showed a significant reduction of TD in all the three emotional conditions compared to the baseline, with differences among them, thus suggesting the existence of a cumulative effect of the concreteness and affective components of the EFT. The analyses of implicit measures additionally revealed that this effect was mediated by a simultaneous increase/decrease of attraction toward the delayed/immediate alternative. Finally, these effects appeared to be modulated by participants' baseline discounting preferences. These findings provide important insights on clinical applications in reward-related disorders.

Choice-predictive activity in parietal cortex during source memory decisions.

Neurobiological research has classically focused on perceptual decision-making, although many real-life decisions are based on information that is not currently available but stored in long-term memory. Previous studies have suggested that the lateral parietal cortex encodes decision-related signals during item recognition judgments. In the present fMRI study, we employed a parametric manipulation of evidence for source memory judgments and tested several hypotheses concerning memory decision signals in parietal cortex. As expected, the mean BOLD signal in several parietal regions was modulated by decision evidence. An analysis of the locally distributed pattern of activity, moreover, identified a parietal cluster showing significant choice-predictive activity even at the lowest level of decision evidence, with decoding accuracy that increased as a function of evidence. Decoding patterns were consistent across subjects as shown by a leave-one-subject-out classification analysis. Finally, we found that the pattern of choice-predictive activity in parietal lobe was temporally correlated with that observed in medial temporal regions traditionally associated with long-term memory functions. The present findings are consistent with a general role of lateral parietal regions located around the intraparietal sulcus in representing a decision variable for memory-based decisions.

Can you change my preferences? Effect of social influence on intertemporal choice behavior.

The present study presents a novel social observation paradigm to examine whether temporal discounting (TD) can be modulated in a specific direction. In particular, after estimating a baseline discount rate, we exposed subjects to a pattern of choice that was opposite to their baseline preferences, i.e., subjects preferring immediate over delayed rewards were exposed to a farsighted pattern of behavior and vice-versa. The results showed a significant decrease of the discount rate in the discounter group and an increase in the farsighted group. The effect was mainly guided by a modification of the subjective values at short time delays and was stronger in subjects with extreme, compared to mild, baseline preferences. Importantly, the magnitude and direction of the effect predicted the baseline preferences. These findings have potentially very relevant implications for the prevention and treatment of clinical conditions, such as addition-related disorders, characterized by severe impairments of decision-making mechanisms.