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The neurocognitive bases of social cognition have been framed in terms of representing others’ actions through the mirror system and their mental states via the mentalizing network. Alongside representing another person’s actions or mental states, however, social cognitive processing is also shaped by their (mis)match with one’s own corresponding states. Here, we addressed the distinction between representing others’ states through the action observation or mentalizing networks (i.e. representational processing) and detecting the extent to which such states align with one’s own ones (i.e. relational processing, mediated by social conflict). We took a meta-analytic approach to unveil the neural bases of both relational and representational processing by focusing on previously reported brain activations from functional magnetic resonance imaging studies using false-belief and action observation tasks. Our findings suggest that relational processing for belief and action states involves, respectively, the left and right temporo-parietal junction, likely contributing to self-other differentiation. Moreover, distinct sectors of the posterior fronto-medial cortex support social conflict processing for belief and action, possibly through the inhibition of conflictual representations. These data might pave the way for further studies addressing social conflict as an important component of normal and pathological processing, and inform the design of rehabilitative treatments for social deficits.

Increased decision latency in alcohol use disorder (AUD) has been generally explained in terms of psychomotor slowing. Recent results suggest that AUD patients’ slowed decision-making might rather reflect alterations in the neural circuitry underlying the engagement of controlled processing by salient stimuli. We addressed this hypothesis by testing a relationship between decision latency at the Cambridge Gambling Task (CGT) and intrinsic brain activity in 22 individuals with AUD and 19 matched controls. CGT deliberation time was related to two complementary facets of resting-state fMRI activity, i.e. coherence and intensity, representing early biomarkers of functional changes in the intrinsic brain architecture. For both metrics, we assessed a multiple regression (to test a relationship with deliberation time in the whole sample), and an interaction analysis (to test a significantly different relationship with decision latency across groups). AUD patients’ slowed deliberation time (p

The development of alcohol habits is considered a form of maladaptive reinforced learning, with sustained alcohol use resulting in the strengthening of associative links between consumption and either rewarding, or the lack of aversive, experiences. Despite recent efforts in characterizing decision-making skills in alcohol-use-disorder (AUD), it is still unknown whether impaired behavioural learning in AUD patients reflects a defective processing and anticipation of choice-related, cognitively mediated, emotions such as regret or relief for what might have been under a different choice. We administered a Wheel-of-Fortune (WoF) task to 26 AUD patients and 19 healthy controls, to investigate possible alterations in adjusting choices to the magnitude of experienced regret/relief, and in other facets of decision-making performance such as choice latency. AUD patients displayed both longer deliberation time than healthy controls, and impaired adaptations to previous outcome-related negative emotions. Although further evidence is needed to unveil the cognitive mechanisms underlying AUD patients’ abnormal choice, the present results highlight important implications for the clinical practice, e.g. in terms of cognitive treatments aiming to shape faulty perceptions about negative emotions associated with excessive alcohol exposure.

The COVID-19 pandemic and the measures to counteract it have highlighted the role of individual differences in evaluating and reacting to emergencies, and the challenges inherent in promoting precautionary behaviours. We aimed to explore the psychological and cognitive factors modulating behaviour and intentions during the national lockdown in Italy. We administered an online questionnaire (N = 244) that included tests for assessing personality traits (Temperament and Character Inventory; Locus of Control of Behaviour) and moral judgment (Moral Foundations Questionnaire), alongside behavioural economics tasks addressing different facets of risk attitude (loss aversion, risk aversion and delay discounting). We then assessed the extent to which individual variations in these dimensions modulated participants’ compliance with the lockdown norms. When assessing their joint contribution via multiple regressions, lockdown adherence was mostly predicted by internal locus of control, psycho-economic dimensions suggestive of long-sighted and loss-averse attitudes, as well as personality traits related to cautionary behaviour, such as harm avoidance, and the authority moral concern. These findings show that a multi-domain assessment of the factors underlying personal intentions, and thus driving compliance with government measures, can help predict individuals’ actions during health emergencies. This evidence points to factors that should be considered when developing interventions and communication strategies to promote precautionary behaviours.

In this article we argue that in order to understand failure or success in adapting to environmental change, we should better understand why people hesitate to pursue novel choices. This article asks: what forces hinder individuals’ exploration choices of different alternatives, and hence their ability to learn from them? To answer this question, this article looks to the cognitive sciences to identify a set of plausible mechanisms that hinder people’s tendency to explore. So far, “exploration” has been studied as a relatively monolithic behavior. Instead, we propose that exploration can be characterized in terms of some distinctive forces behind it. On one hand, agents experience “attachment” to choices that proved successful in the past, and hence comfort when sticking with them. On the other hand, they also experience concerns about less familiar options, as they lack knowledge about “distant” choices that have not been tried for a long time, or ever. We propose that high attachment is related to anxiety, and high distance to fear. Both these negative affective states hinder exploration. We find and discuss preliminary and tentative evidence of this effect.

The COVID-19 pandemic is known to increase older adults’ vulnerability to adverse outcomes. Alongside increased physical frailty, anxiety symptoms associated with the risk of SARS-CoV-2 contagion appear to represent its most prominent ‘sequelae’. The attentional and linguistic resources required for decoding virus-related information may also influence the perceived threat of contagion. However, the possible role of neuropsychogeriatric factors on the latter dimension has never been assessed in a longitudinal study on the older population. To fill this gap, 50 healthy cognitively preserved older adults underwent a neuropsychological and physical frailty assessment before the pandemic (T0). Subsequently, they agreed to be interviewed and re-assessed during the lockdown (T1) and immediately after it (T2) through a longitudinal one-year study. Perceived threat of SARS-CoV-2 at T2 was predicted both by baseline anxiety and frailty scores, and by decreased performance in information processing speed and language comprehension tests. While confirming the joint role of frailty and anxiety, a moderation/interaction model showed that each of them was sufficient, at its highest level, to support the maximum degree of perceived threat of contagion. The contribution of neuropsychological factors to perceived threat of SARS-CoV-2 highlights their importance of tailoring information campaigns addressed to older people.

While the discussion on the foundations of social understanding mainly revolves around the notions of empathy, affective mentalizing, and cognitive mentalizing, their degree of overlap versus specificity is still unclear. We took a meta‐analytic approach to unveil the neural bases of cognitive mentalizing, affective mentalizing, and empathy, both in healthy individuals and pathological conditions characterized by social deficits such as schizophrenia and autism. We observed partially overlapping networks for cognitive and affective mentalizing in the medial prefrontal, posterior cingulate, and lateral temporal cortex, while empathy mainly engaged fronto‐insular, somatosensory, and anterior cingulate cortex. Adjacent process‐specific regions in the posterior lateral temporal, ventrolateral, and dorsomedial prefrontal cortex might underpin a transition from abstract representations of cognitive mental states detached from sensory facets to emotionally‐charged representations of affective mental states. Altered mentalizing‐related activity involved distinct sectors of the posterior lateral temporal cortex in schizophrenia and autism, while only the latter group displayed abnormal empathy related activity in the amygdala. These data might inform the design of rehabilitative treatments for social cognitive deficits., The relationship between affective Theory of Mind (ToM), cognitive ToM, and empathy is still unclear. We addressed this issue via coordinate‐based meta‐analyses of previous fMRI data. Empathy and mentalizing engaged frontoinsular and classical ToM nodes, respectively. Adjacent regions might underpin graded transitions between ToM and mentalizing. Autistic and schizophrenic patients displayed specific patterns of altered activity.

Previous inconsistencies on the effects of implicitly processing positively - vs. negatively - connotated emotional words might reflect the influence of uncontrolled psycholinguistic dimensions, and/or social facets inherent in putative “emotional” stimuli. Based on the relevance of social features in semantic cognition, we developed a socio-emotional Stroop task to assess the influence of social vs. individual (non-social) emotional content, besides negative vs. positive valence, on implicit word processing. The effect of these variables was evaluated in terms of performance and RTs, alongside associated brain activity/connectivity. We matched conditions for several psycholinguistic variables, and assessed a modulation of brain activity/connectivity by trial-wise RT, to characterize the maximum of condition- and subject-specific variability. RTs were tracked by insular and anterior cingulate activations likely reflecting implicit attention to stimuli, interfering with task-performance based on condition-specific processing of their subjective salience. Slower performance for negative than neutral/positive words was tracked by left-hemispheric structures processing negative stimuli and emotions, such as fronto-insular cortex, while the lack of specific activations for positively-connotated words supported their marginal facilitatory effect. The speeding/slowing effects of processing positive/negative individual emotional stimuli were enhanced by social words, reflecting in specific activations of the right anterior temporal and orbitofrontal cortex, respectively. RTs to social positive and negative words modulated connectivity from these regions to fronto-striatal and sensorimotor structures, respectively, likely promoting approach vs. avoidance dispositions shaping their facilitatory vs. inhibitory effect. These results might help assessing the neural correlates of impaired social cognition and emotional regulation, and the effects of rehabilitative interventions.

The new contemporary multi-city needs the landscape as a proactive eco-systemic infrastructure in order to rethink the whole food system, from the design of public spaces to domestic spaces. In this direction, Creative Food Cycles (CFC) is an EU project that, according to the Sustainable Development Goals (SDGs), addresses the topic of food as a cross-cutting factor and powerful accelerator toward the co-design of sustainability in cities. Design culture today has begun to question and innovate production, distribution, and recycling models of food cycles. In the post-consumption and disposal phase illustrated herein, making the most of food means conceiving waste as a resource for the creation of new sustainable materials or prototypes. The concept of food waste and food losses has been shown to be not only a topic at the center of the debate but also a powerful tool for raising awareness of sustainable development at the community level. The CFC actions shown here were developed with the objective of persuading consumers to change their behaviors, while at the same time exploring cultural and social perceptions. With the aim of making cities more sustainable, this paper describes tools to engage different stakeholders, such as architects, product designers, and citizens, from a cultural point of view. The ongoing research has turned in the end into an educational campaign and an open platform where prototypes, new materials, and products are developed as inspiration for change.

Highlights • Alcohol User Disorder (AUD) entails widespread white-matter (WM) alterations. • WM alterations underlie the typical profile of executive impairment in AUD. • Executive profile in AUD is related to WM tracts connecting large-scale networks. • Altered large-scale structural connections may promote maladaptive behavior in AUD., Alcohol Use Disorders (AUD) is associated with negative consequences on global functioning, likely reflecting chronic changes in brain morphology and connectivity. Previous attempts to characterize cognitive impairment in AUD addressed patients’ performance in single domains, without considering their cognitive profile as a whole. While altered cognitive performance likely reflects abnormal white-matter microstructural properties, to date no study has directly addressed the relationship between a proxy of patients’ cognitive profile and microstructural damage. To fill this gap we aimed to characterize the microstructural damage pattern, and its relationship with cognitive profile, in treatment-seeking AUD patients. Twenty-two AUD patients and 18 healthy controls underwent a multimodal MRI protocol including diffusion tensor imaging (DTI), alongside a comprehensive neurocognitive assessment. We used a principal component analysis (PCA) to identify superordinate components maximally explaining variability in cognitive performance, and whole-brain voxelwise analyses to unveil the neural correlates of AUD patients’ cognitive impairment in terms of different white-matter microstructural features, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). PCA revealed a basic executive component, significantly impaired in AUD patients, associated with tasks tapping visuo-motor processing speed, attention and working-memory. Within a widespread pattern of white-matter damage in patients, we found diverse types of relationship linking WM microstructure and executive performance: (i) in the whole sample, we observed a linear relationship involving MD/RD metrics within both ‘superficial’ white-matter systems mediating connectivity within large-scale brain networks, and deeper systems modulating their reciprocal connections; (ii) in AUD patients vs. controls, a performance-by-group interaction highlighted a MD/AD pattern involving two frontal white-matter systems, including the genu of corpus callosum and cingulum bundle, mediating structural connectivity among central executive, salience and default mode networks. Alterations of prefrontal white-matter pathways are suggestive of abnormal structural connectivity in AUD, whereby a defective interplay among large-scale networks underpins patients’ executive dysfunction. These findings highlight different directions for future basic and translational research aiming to tailor novel rehabilitation strategies and assess their functional outcomes.

The neural bases of cognitive impairment(s) in alcohol use disorders (AUDs) might reflect either a global brain damage underlying different neuro-cognitive alterations, or the involvement of specific regions mostly affected by alcohol neuro-toxic effects. While voxel-based-morphometry (VBM) studies have shown a distributed atrophic pattern in fronto-limbic and cerebellar structures, the lack of comprehensive neuro-cognitive assessments prevents previous studies from drawing robust inferences on the specificity of the association between neuro-structural and cognitive impairments in AUDs. To fill this gap, we addressed the neuro-structural bases of cognitive impairment in AUDs, by coupling VBM with an in-depth neuropsychological assessment. VBM results highlighted a diffuse pattern of grey matter reduction in patients, involving the key-nodes of the meso-cortico-limbic (striatum, hippocampus, medial prefrontal cortex), salience (insular and dorsal anterior cingulate cortex) and executive (inferior frontal cortex) networks. Grey matter density in the insular and anterior cingulate sectors of the salience network, significantly decreased in patients, explained almost half of variability in their defective attentional and working-memory performance. The multiple cognitive and neurological impairments observed in AUDs might thus reflect a specific executive deficit associated with the selective damage of a salience-based neural mechanism enhancing access to cognitive resources required for controlled cognition and behaviour.

Obstructive sleep apnea (OSA) is characterized by the frequent presence of neuro-cognitive impairment. Recent studies associate cognitive dysfunction with altered resting-state brain connectivity between key nodes of the executive and default-mode networks, two anti-correlated functional networks whose strength of activation increases or decreases with cognitive activity, respectively. To date no study has investigated a relationship between cognitive impairment in OSA and brain connectivity during an active working-memory challenge. We thus investigated the effect of OSA on working-memory performance and underlying brain connectivity. OSA patients and matched healthy controls underwent functional magnetic resonance imaging (fMRI) scanning while performing a 2-back working-memory task. Standard fMRI analyses highlighted the brain regions activated at increasing levels of working-memory load, which were used as seeds in connectivity analyses. The latter were based on a multiregional Psycho-Physiological-Interaction (PPI) approach, to unveil group differences in effective connectivity underlying working-memory performance. Compared with controls, in OSA patients normal working-memory performance reflected in: a) reduced interhemispheric effective connectivity between the frontal “executive” nodes of the working-memory network, and b) increased right-hemispheric connectivity among regions mediating the “salience-based” switch from the default resting-state mode to the effortful cognitive activity associated with the executive network. The strength of such connections was correlated, at increasing task-demands, with executive (Stroop test) and memory (Digit Span test) performance in neuro-cognitive evaluations. The analysis of effective connectivity changes during a working-memory challenge provides a complementary window, compared with resting-state studies, on the mechanisms supporting preserved performance despite functional and structural brain modifications in OSA., Highlights • Sleep apnea (OSA) is frequently characterized by neuro-cognitive impairment. • We addressed brain connectivity underlying working-memory (WM) in OSA. • Normal WM reflected in reduced interhemispheric connectivity in the executive network. • Normal WM reflected in increased connectivity between salience and default networks. • Brain connectivity highlights compensatory mechanisms supporting performance in OSA.

Background: Alzheimer’s Disease (AD) is a multifactorial disorder driven by genetic and modifiable lifestyle risk factors. Lifestyle primary prevention initiatives may reduce the prevalence and incidence of dementia in older adults. Objectives: The E.Mu.N.I study is a randomized controlled trial investigating the effect of multilevel non-pharmacologic interventions on cognitive performances (primary outcome) and structural and vascular brain MRI markers (secondary outcome), as well as markers of brain functional connectivity change (exploratory outcome), in older adults with subjective memory decline (SMD). Here, we present the study design and the baseline features of the sample. Methods: Cognitively intact older adults with SMD, enrolled between February 2016 and June 2017, were randomly assigned to one of the 3 interventions for 1 year: Active Control Intervention (ACI), i.e., educational lessons; Partial Intervention (PI), i.e., homotaurine administration (100 mg/die) and lessons on the Mediterranean diet; Multilevel Intervention (MI), i.e., PI plus computerized cognitive training and physical exercise training. Results: One-hundred and twenty-eight eligible participants were enrolled (66% female; age: 68 ± 5 years). Eighty-two percent of the sample was composed of volunteers with SMD from the community. Participants were randomly allocated to the interventions as follows: ACI (N = 40), PI (N = 44), MI (N = 44). No significant differences among groups emerged on socio-demographic, clinical–neuropsychological variables and MRI markers at baseline. Conclusions: The outcomes obtained from the E.Mu.N.I. study will clarify the efficacy of multilevel non-pharmacologic interventions on cognitive and neuroimaging markers in SMD individuals. This is a crucial step forward for the development of cost-effective non-pharmacologic primary prevention initiatives for AD.

Objectives Recent literature proved that social cognition impairments may characterize the neuropsychological profile of Multiple Sclerosis (MS) patients. However, little is still known about moral cognition in MS. In this study, we evaluated non-social, social, and moral cognitive performances in 45 relapsing-remitting MS patients. Methods Patients underwent the Brief International Cognitive Assessment for Multiple Sclerosis battery, the Cognitive Estimation and Stroop tasks, the Ekman-60 Faces test, the Reading the Mind in the Eye and Story-based Empathy task. Additionally, a task of moral dilemmas including both "instrumental" and "incidental" conditions was administered to patients. Forty-five age-, gender- and education-matched healthy control subjects (HC) were enrolled for comparisons. Results The majority of patients (i.e., 77.6%) showed deficits at non-social tasks, particularly in the executive domains. A subset of MS sample (i.e., 24%) presented with emotion recognition and socio-affective processing impairments. Overall, MS patients showed comparable levels of moral judgment with respect to HC. The rate of yes/no response in resolution of moral dilemmas and scores of attribution of emotional valence were comparable between groups. Nevertheless, lower moral permissibility and emotional arousal, particularly for the instrumental dilemmas, characterized the MS profile. Significant correlations between the attribution of emotional valence to moral actions and mentalizing scores emerged. Conclusions Our findings expand current literature on MS supporting not only deficits in executive and socio-emotional domains but also low levels of permissibility of immoral actions and emotional detachment in the moral judgment process.

While the action observation and mentalizing networks are considered to play complementary roles in understanding others' goals and intentions, they might be concurrently engaged when processing social interactions. We assessed this hypothesis via three activation-likelihood-estimation meta-analyses of neuroimaging studies on the neural processing of: (a) social interactions, (b) individual actions by the action observation network, and (c) mental states by the mentalizing network. Conjunction analyses and direct comparisons unveiled overlapping and specific regions among the resulting maps. We report quantitative meta-analytic evidence for a "social interaction network" including key nodes of the action observation and mentalizing networks. An action-social interaction-mentalizing gradient of activity along the posterior temporal cortex highlighted a hierarchical processing of interactions, from visuomotor analyses decoding individual and shared intentions to in-depth inferences on actors' intentional states. The medial prefrontal cortex, possibly in conjunction with the amygdala, might provide additional information concerning the affective valence of the interaction. This evidence suggests that the functional architecture underlying the neural processing of interactions involves the joint involvement of the action observation and mentalizing networks. These data might inform the design of rehabilitative treatments for social cognition disorders in pathological conditions, and the assessment of their outcome in randomized controlled trials.

Social cognition refers to a set of processes, ranging from perception to decision-making, underlying the ability to decode others’ intentions and behaviors to plan actions fitting with social and moral, besides individual and economic considerations. Its centrality in everyday life reflects the neural complexity of social processing and the ubiquity of social cognitive deficits in different pathological conditions. Social cognitive processes can be clustered in three domains associated with (a) perceptual processing of social information such as faces and emotional expressions (social perception), (b) grasping others’ cognitive or affective states (social understanding), and (c) planning behaviors taking into consideration others’, in addition to one’s own, goals (social decision-making). We review these domains from the lens of cognitive neuroscience, i.e., in terms of the brain areas mediating the role of such processes in the ability to make sense of others’ behavior and plan socially appropriate actions. The increasing evidence on the “social brain” obtained from healthy young individuals nowadays constitutes the baseline for detecting changes in social cognitive skills associated with physiological aging or pathological conditions. In the latter case, impairments in one or more of the abovementioned domains represent a prominent concern, or even a core facet, of neurological (e.g., acquired brain injury or neurodegenerative diseases), psychiatric (e.g., schizophrenia), and developmental (e.g., autism) disorders. To pave the way for the other papers of this issue, addressing the social cognitive deficits associated with severe acquired brain injury, we will briefly discuss the available evidence on the status of social cognition in normal aging and its breakdown in neurodegenerative disorders. Although the assessment and treatment of such impairments is a relatively novel sector in neurorehabilitation, the evidence summarized here strongly suggests that the development of remediation procedures for social cognitive skills will represent a future field of translational research in clinical neuroscience.

Decoding the meaning of others’ actions, a crucial step for social cognition, involves different neural mechanisms. While the “mirror” and “mentalizing” systems have been associated with, respectively, the processing of biological actions versus more abstract information, their respective contribution to intention understanding is debated. Processing social interactions seems to recruit both neural systems, with a different weight depending on cues emphasizing either shared action goals or shared mental states. We have previously shown that observing cooperative and affective social interactions elicits stronger activity in key nodes of, respectively, the mirror (left posterior superior temporal sulcus (pSTS), superior parietal cortex (SPL), and ventral/dorsal premotor cortex (vPMC/dPMC)) and mentalizing (ventromedial prefrontal cortex (vmPFC)) systems. To unveil their causal organization, we investigated the effective connectivity underlying the observation of human social interactions expressing increasing cooperativity (involving left pSTS, SPL, and vPMC) versus affectivity (vmPFC) via dynamic causal modeling in 36 healthy human subjects. We found strong evidence for a model including the pSTS and vPMC as input nodes for the observed interactions. The extrinsic connectivity of this model undergoes oppositely valenced modulations, with cooperativity promoting positive modulations of connectivity between pSTS and both SPL (forward) and vPMC (mainly backward), and affectivity promoting reciprocal positive modulations of connectivity between pSTS and vmPFC (mainly backward). Alongside fMRI data, such divergent effective connectivity suggests that different dimensions underlying the processing of social interactions recruit distinct, although strongly interconnected, neural pathways associated with, respectively, the bottom–up visuomotor processing of motor intentions, and the top–down attribution of affective/mental states.

Innovative decision-making entails the balance of exploitative and explorative choices, and has been linked to the efficiency of executive functioning, including working-memory and attentional skills, associated with fronto-parietal networks. Based on the notion that such skills can be improved by cognitive training, we assessed whether a cognitive training enhancing basic executive skills might also improve the ability to manage the exploration-exploitation trade-off and its financial consequences, and whether any improvement in training-related performance would be reflected in neurostructural changes within fronto-parietal networks. Eighteen subjects participated in a baseline assessment, a training period and a follow-up measurement, while a matched group of 18 subjects did not undertake the training program. A subgroup of subjects underwent a multimodal MRI study to explore training-related changes in grey-matter volume and white-matter microstructure. After training, increased efficiency of innovative decision-making, related to the improvement of executive control skills, reflected neurostructural changes involving the right fronto-polar cortex and left superior longitudinal fasciculus. The quality of innovative decision-making can be improved by ad-hoc cognitive training procedures focused on executive skills, promoting neurostructural changes in fronto-parietal networks. The manifold implications involve both managerial and rehabilitative settings concerned with the quality of choices in normal and pathological conditions, respectively.

Theory of Mind (ToM), the process by which an individual imputes mental states to himself and others, is presently considered as a multidimensional cognitive domain, with two main facets (i.e., cognitive and affective ToM) accounting, respectively, for the ability to under- stand others' intention (intention attribution-IA) and emotions (emotion attribution-EA). Despite the large amount of literature investigating the behavioural and neural bases of mentalizing abilities in neurological con- ditions, there is still a lack of validated neuropsycholog- ical tools specifically designed to assess such skills. Here, we report the normative data of the Story-Based Empathy Task (SET), a non-verbal test developed for the assess- ment of intention and emotion attribution in the neu- rodegenerative conditions characterized by the impairment of social-emotional abilities. It is an easy-to- administer task including 18 stimuli, sub-grouped into two experimental conditions assessing, respectively, the ability to infer others' intentions (SET-IA) and emotions (SET- EA), compared to a control condition of causal inference (SET-CI). Normative data were collected in 136 Italian subjects pooled across subgroups homogenous for age (range 20-79 years), sex, and education (at least 5 years). The results show a detrimental effect of age and a ben- eficial effect of education on both the global score and each subscale, for which we provide correction grids. This new task could be a useful tool to investigate both affective and cognitive aspects of ToM in the course of disorders of socio-emotional behaviour, such as the fronto-temporal dementia spectrum.

The continuum hypothesis linking the behavioral variant of frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) is supported by clinical, pathological, genetic, and neuroimaging evidence. In the present multimodal magnetic resonance study, we characterized the site and extent of shared neurostructural changes in gray and white matter in 20 bvFTD and 19 ALS patients without dementia. We found an overlap of macrostructural and microstructural damage in both patient groups compared with healthy controls, involving the right orbital and the bilateral anterior cingulate cortices, the corticospinal tract and corpus callosum. The quantification of gray and white matter damage within the areas of shared alterations highlighted a higher degree of atrophy in orbitofrontal and frontomedial regions in patients with more severe executive and/or behavioral symptoms, and a higher degree of degeneration in the motor pathway in patients with more severe motor neuron disorders. Our finding provides additional evidence confirming the FTD-ALS continuum hypothesis and supports the notion of a bimodal but convergent pattern of neurostructural changes characterizing bvFTD and ALS.

Background Limbic encephalitis (LE) is characterized by an acute or subacute onset with memory impairments, confusional state, behavioral disorders, variably associated with seizures and dystonic movements. It is due to inflammatory processes that selectively affect the medial temporal lobe structures. Voltage-gate potassium channel (VGKC) autoantibodies are frequently observed. In this study, we assessed at the individual level FDG-PET brain metabolic dysfunctions and neuropsychological profiles in three autoimmune LE cases seropositive for neuronal VGKC-complex autoantibodies. Materials and methods LGI1 and CASPR2 potassium channel complex autoantibody subtyping was performed. Cognitive abilities were evaluated with an in-depth neuropsychological battery focused on episodic memory and affective recognition/processing skills. FDG-PET data were analyzed at single-subject level according to a standardized and validated voxel-based Statistical Parametric Mapping (SPM) method. Results Patients showed severe episodic memory and fear recognition deficits at the neuropsychological assessment. No disorder of mentalizing processing was present. Variable patterns of increases and decreases of brain glucose metabolism emerged in the limbic structures, highlighting the pathology-driven selective vulnerability of this system. Additional involvement of cortical and subcortical regions, particularly in the sensorimotor system and basal ganglia, was found. Conclusions Episodic memory and fear recognition deficits characterize the cognitive profile of LE. Commonalities and differences may occur in the brain metabolic patterns. Single-subject voxel-based analysis of FDG-PET imaging could be useful in the early detection of the metabolic correlates of cognitive and non-cognitive deficits characterizing LE condition.

Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control.