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author:("Manes, fecund")
1.  Selective decision-making deficit in love following damage to the anterior insula 
Neuroimaging studies have found a correlation between activation in the anterior insula and love, and a correlation between activation in the posterior insula and lust. The present control-case study describes a neurological male patient, with a rare, circumscribed lesion in the anterior insula, whom we tested using a decision task that required he judge whether each of a series of attractive individuals could be the object of his love or lust. The patient, in contrast with neurologically typical participants matched on age, gender, and ethnicity, performed normally when making decisions about lust but showed a selective deficit when making decisions about love. These results provide the first clinical evidence indicating that the anterior insula may play an instrumental role in love but not lust more generally. These data support the notion of a posterior-to-anterior insular gradient, from sensorimotor to abstract representations, in the evaluation of anticipatory rewards in interpersonal relationships.
PMCID: PMC4222039  PMID: 25382944
anterior insula; stroke; neurology; pair-bonding; love; sexual desire; social neuroscience
2.  Selective impairment of cognitive empathy for moral judgment in adults with high functioning autism 
Faced with a moral dilemma, conflict arises between a cognitive controlled response aimed at maximizing welfare, i.e. the utilitarian judgment, and an emotional aversion to harm, i.e. the deontological judgment. In the present study, we investigated moral judgment in adult individuals with high functioning autism/Asperger syndrome (HFA/AS), a clinical population characterized by impairments in prosocial emotions and social cognition. In Experiment 1, we compared the response patterns of HFA/AS participants and neurotypical controls to moral dilemmas with low and high emotional saliency. We found that HFA/AS participants more frequently delivered the utilitarian judgment. Their perception of appropriateness of moral transgression was similar to that of controls, but HFA/AS participants reported decreased levels of emotional reaction to the dilemma. In Experiment 2, we explored the way in which demographic, clinical and social cognition variables including emotional and cognitive aspects of empathy and theory of mind influenced moral judgment. We found that utilitarian HFA/AS participants showed a decreased ability to infer other people’s thoughts and to understand their intentions, as measured both by performance on neuropsychological tests and through dispositional measures. We conclude that greater prevalence of utilitarianism in HFA/AS is associated with difficulties in specific aspects of social cognition.
doi:10.1093/scan/nss067
PMCID: PMC3791066  PMID: 22689217
utilitarianism; moral judgment; social cognition; emotion; Asperger syndrome
3.  How Do You Feel when You Can't Feel Your Body? Interoception, Functional Connectivity and Emotional Processing in Depersonalization-Derealization Disorder 
PLoS ONE  2014;9(6):e98769.
Depersonalization-Derealization Disorder (DD) typically manifests as a disruption of body self-awareness. Interoception −defined as the cognitive processing of body signals− has been extensively considered as a key processing for body self-awareness. In consequence, the purpose of this study was to investigate whether there are systematic differences in interoception between a patient with DD and controls that might explain the disembodiment symptoms suffered in this disease. To assess interoception, we utilized a heartbeat detection task and measures of functional connectivity derived from fMRI networks in interoceptive/exteroceptivo/mind-wandering states. Additionally, we evaluated empathic abilities to test the association between interoception and emotional experience. The results showed patient's impaired performance in the heartbeat detection task when compared to controls. Furthermore, regarding functional connectivity, we found a lower global brain connectivity of the patient relative to controls only in the interoceptive state. He also presented a particular pattern of impairments in affective empathy. To our knowledge, this is the first experimental research that assesses the relationship between interoception and DD combining behavioral and neurobiological measures. Our results suggest that altered neural mechanisms and cognitive processes regarding body signaling might be engaged in DD phenomenology. Moreover, our study contributes experimental data to the comprehension of brain-body interactions and the emergence of self-awareness and emotional feelings.
doi:10.1371/journal.pone.0098769
PMCID: PMC4072534  PMID: 24967634
4.  The relationship between executive functions and fluid intelligence in schizophrenia 
An enduring question is unity vs. separability of executive deficits resulting from impaired frontal lobe function. In previous studies, we have asked how executive deficits link to a conventional measure of fluid intelligence, obtained either by standard tests of novel problem-solving, or by averaging performance in a battery of novel tasks. For some classical executive tasks, such as the Wisconsin Card Sorting Test (WCST), Verbal Fluency, and Trail Making Test B (TMTB), frontal deficits are entirely explained by fluid intelligence. However, on a second set of executive tasks, including tests of multitasking and decision making, deficits exceed those predicted by fluid intelligence loss. In this paper we discuss how these results shed light on the diverse clinical phenomenology observed in frontal dysfunction, and present new data on a group of 15 schizophrenic patients and 14 controls. Subjects were assessed with a range of executive tests and with a general cognitive battery used to derive a measure of fluid intelligence. Group performance was compared and fluid intelligence was introduced as a covariate. In line with our previous results, significant patient-control differences in classical executive tests were removed when fluid intelligence was introduced as a covariate. However, for tests of multitasking and decision making, deficits remained. We relate our findings to those of previous factor analytic studies describing a single principal component, which accounts for much of the variance of schizophrenic patients' cognitive performance. We propose that this general factor reflects low fluid intelligence capacity, which accounts for much but not all cognitive impairment in this patient group. Partialling out the general effects of fluid intelligence, we propose, may clarify the role of additional, more specific cognitive impairments in conditions such as schizophrenia.
doi:10.3389/fnbeh.2014.00046
PMCID: PMC3932409  PMID: 24605092
executive function; fluid intelligence; schizophrenia; frontal lobe; multitasking; decision making
5.  Motor–Language Coupling in Huntington’s Disease Families 
Traditionally, Huntington’s disease (HD) has been known as a movement disorder, characterized by motor, psychiatric, and cognitive impairments. Recent studies have shown that motor and action–language processes are neurally associated. The cognitive mechanisms underlying this interaction have been investigated through the action compatibility effect (ACE) paradigm, which induces a contextual coupling of ongoing motor actions and verbal processing. The present study is the first to use the ACE paradigm to evaluate action–word processing in HD patients (HDP) and their families. Specifically, we tested three groups: HDP, healthy first-degree relatives (HDR), and non-relative healthy controls. The results showed that ACE was abolished in HDP as well as HDR, but not in controls. Furthermore, we found that the processing deficits were primarily linguistic, given that they did not correlate executive function measurements. Our overall results underscore the role of cortico-basal ganglia circuits in action–word processing and indicate that the ACE task is a sensitive and robust early biomarker of HD and familial vulnerability.
doi:10.3389/fnagi.2014.00122
PMCID: PMC4054328  PMID: 24971062
Huntington’s disease; action–language; ACE; KDT; motor–language coupling; familial vulnerability
6.  Inter-individual cognitive variability in children with Asperger's syndrome 
Multiple studies have tried to establish the distinctive profile of individuals with Asperger's syndrome (AS). However, recent reports suggest that adults with AS feature heterogeneous cognitive profiles. The present study explores inter-individual variability in children with AS through group comparison and multiple case series analysis. All participants completed an extended battery including measures of fluid and crystallized intelligence, executive functions, theory of mind, and classical neuropsychological tests. Significant group differences were found in theory of mind and other domains related to global information processing. However, the AS group showed high inter-individual variability (both sub- and supra-normal performance) on most cognitive tasks. Furthermore, high fluid intelligence correlated with less general cognitive impairment, high cognitive flexibility, and speed of motor processing. In light of these findings, we propose that children with AS are characterized by a distinct, uneven pattern of cognitive strengths and weaknesses.
doi:10.3389/fnhum.2014.00575
PMCID: PMC4117184  PMID: 25132817
individual variability; fluid intelligence; theory of mind; executive functions; Asperger's syndrome
7.  Methodological Considerations Regarding Cognitive Interventions in Dementia 
doi:10.3389/fnagi.2014.00212
PMCID: PMC4131264  PMID: 25165450
cognitive intervention; dementia; methods development; pre/post measurement; cognition; neuropsychology; neuroscience
8.  Primary empathy deficits in frontotemporal dementia 
Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.
doi:10.3389/fnagi.2014.00262
PMCID: PMC4193328  PMID: 25346685
behavioral variant of frontotemporal dementia; empathy; empathic concern; social cognition; executive functions; moral judgment
9.  Emotion recognition and cognitive empathy deficits in adolescent offenders revealed by context-sensitive tasks 
Emotion recognition and empathy abilities require the integration of contextual information in real-life scenarios. Previous reports have explored these domains in adolescent offenders (AOs) but have not used tasks that replicate everyday situations. In this study we included ecological measures with different levels of contextual dependence to evaluate emotion recognition and empathy in AOs relative to non-offenders, controlling for the effect of demographic variables. We also explored the influence of fluid intelligence (FI) and executive functions (EFs) in the prediction of relevant deficits in these domains. Our results showed that AOs exhibit deficits in context-sensitive measures of emotion recognition and cognitive empathy. Difficulties in these tasks were neither explained by demographic variables nor predicted by FI or EFs. However, performance on measures that included simpler stimuli or could be solved by explicit knowledge was either only partially affected by demographic variables or preserved in AOs. These findings indicate that AOs show contextual social-cognition impairments which are relatively independent of basic cognitive functioning and demographic variables.
doi:10.3389/fnhum.2014.00850
PMCID: PMC4204464  PMID: 25374529
offenders; adolescence; delinquency; social cognition; contextual processing; ecological tasks
10.  Preliminary evidence about the effects of meditation on interoceptive sensitivity and social cognition 
Background
Interoception refers to the conscious perception of body signals. Mindfulness is a meditation practice that encourages individuals to focus on their internal experiences such as bodily sensations, thoughts, and emotions. In this study, we selected a behavioral measure of interoceptive sensitivity (heartbeat detection task, HBD) to compare the effect of meditation practice on interoceptive sensitivity among long term practitioners (LTP), short term meditators (STM, subjects that completed a Mindfulness-Based Stress Reduction (MBSR) program) and controls (non-meditators). All participants were examined with a battery of different tasks including mood state, executive function and social cognition tests (emotion recognition, empathy and theory of mind).
Findings
Compared to controls, both meditators’ groups showed lower levels of anxiety and depression, but no improvement in executive function or social cognition performance was observed (except for lower scores compared to controls only in the personal distress dimension of empathy). More importantly, meditators’ performance did not differ from that of nonmeditators regarding cardiac interoceptive sensitivity.
Conclusion
Results suggest no influence of meditation practice in cardiac interoception and in most related social cognition measures. These negative results could be partially due to the fact that awareness of heartbeat sensations is not emphasized during mindfulness/vipassana meditation and may not be the best index of the awareness supported by the practice of meditation.
doi:10.1186/1744-9081-9-47
PMCID: PMC3878404  PMID: 24365106
Interoception; Meditation; Mindfulness; Social cognition; Heartbeat detection task
11.  Risk-Sensitive Decision-Making in Patients with Posterior Parietal and Ventromedial Prefrontal Cortex Injury 
Successful choice under risk requires the integration of information about outcome probabilities and values and implicates a brain network including the ventromedial prefrontal cortex (vmPFC) and posterior parietal cortex (pPAR). Damage to the vmPFC is linked to poor decision-making and increased risk-taking. Electrophysiological and neuroimaging data implicate the pPAR in the processing of reward probability during choice, but the causal contribution of this area has not been established. We compared patients with lesions to the pPAR (n = 13), vmPFC (n = 13), and healthy volunteers (n = 22) on the Roulette Betting Task, a measure of risk-sensitive decision-making. Both lesion groups were impaired in adjusting their bets to the probability of winning. This impairment was correlated with the extent of pPAR, but not vmPFC, damage. In addition, the vmPFC group chose higher bets than healthy controls overall, an effect that correlated with lesion volume in the medial orbitofrontal cortex. Both lesion groups earned fewer points than healthy controls. The groups did not differ on 2 tasks assessing probabilistic reasoning outside of a risk-reward context. Our results demonstrate the causal involvement of both the pPAR and vmPFC in risk-sensitive choice and indicate distinguishable roles of these areas in probability processing and risk appetite.
doi:10.1093/cercor/bht197
PMCID: PMC4259274  PMID: 23926113
decision-making; lesion study; posterior parietal cortex; risk; ventromedial prefrontal cortex
12.  Attachment Patterns Trigger Differential Neural Signature of Emotional Processing in Adolescents 
PLoS ONE  2013;8(8):e70247.
Background
Research suggests that individuals with different attachment patterns process social information differently, especially in terms of facial emotion recognition. However, few studies have explored social information processes in adolescents. This study examined the behavioral and ERP correlates of emotional processing in adolescents with different attachment orientations (insecure attachment group and secure attachment group; IAG and SAG, respectively). This study also explored the association of these correlates to individual neuropsychological profiles.
Methodology/Principal Findings
We used a modified version of the dual valence task (DVT), in which participants classify stimuli (faces and words) according to emotional valence (positive or negative). Results showed that the IAG performed significantly worse than SAG on tests of executive function (EF attention, processing speed, visuospatial abilities and cognitive flexibility). In the behavioral DVT, the IAG presented lower performance and accuracy. The IAG also exhibited slower RTs for stimuli with negative valence. Compared to the SAG, the IAG showed a negative bias for faces; a larger P1 and attenuated N170 component over the right hemisphere was observed. A negative bias was also observed in the IAG for word stimuli, which was demonstrated by comparing the N170 amplitude of the IAG with the valence of the SAG. Finally, the amplitude of the N170 elicited by the facial stimuli correlated with EF in both groups (and negative valence with EF in the IAG).
Conclusions/Significance
Our results suggest that individuals with different attachment patterns process key emotional information and corresponding EF differently. This is evidenced by an early modulation of ERP components’ amplitudes, which are correlated with behavioral and neuropsychological effects. In brief, attachments patterns appear to impact multiple domains, such as emotional processing and EFs.
doi:10.1371/journal.pone.0070247
PMCID: PMC3733979  PMID: 23940552
13.  The Safety, Tolerability, and Efficacy of Once-Daily Memantine (28 mg): A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients with Moderate-to-Severe Alzheimer’s Disease Taking Cholinesterase Inhibitors 
CNS Drugs  2013;27(6):469-478.
Introduction
Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer’s disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors.
Methods
In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3–14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS–ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran–Mantel–Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations.
Results
A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS–ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %).
Conclusion
Extended-release memantine was efficacious, safe, and well tolerated in this population.
Electronic supplementary material
The online version of this article (doi:10.1007/s40263-013-0077-7) contains supplementary material, which is available to authorized users.
doi:10.1007/s40263-013-0077-7
PMCID: PMC3680656  PMID: 23733403
14.  Contextual social cognition and the behavioral variant of frontotemporal dementia 
Neurology  2012;78(17):1354-1362.
The significance of social situations is commonly context-embedded. Although the role of context has been extensively studied in basic sensory processing or simple stimulus-response settings, its relevance for social cognition is unknown. We propose the social context network model (SCNM), a fronto-insular-temporal network responsible for processing social contextual effects. The SCNM may 1) update the context and use it to make predictions, 2) coordinate internal and external milieus, and 3) consolidate context-target associative learning. We suggest the behavioral variant of frontotemporal dementia (bvFTD) as a specific disorder in which the reported deficits in social cognition (e.g., facial recognition, empathy, decision-making, figurative language, theory of mind) can be described as context impairments due to deficits in the SCNM. Disruption of orbitofrontal-amygdala circuit, as well as the frontal, temporal, and insular atrophy in bVFTD, suggests a relationship between context-sensitive social cognition and SCNM. In considering context as an intrinsic part of social cognition, we highlight the need for a situated cognition approach in social cognition research as opposed to an abstract, universal, and decontextualized approach. The assessment of context-dependent social cognition paradigms, the SCNM, and their possible application to neuropsychiatric disorders may provide new insight into bvFTD and other related frontal disorders.
doi:10.1212/WNL.0b013e3182518375
PMCID: PMC3335455  PMID: 22529204
15.  Contextual Social Cognition Impairments in Schizophrenia and Bipolar Disorder 
PLoS ONE  2013;8(3):e57664.
Background
The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations.
Methodology/Principal Findings
This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge) that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients’ depression levels were negatively correlated with performance on empathy tasks.
Conclusions/Significance
Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.
doi:10.1371/journal.pone.0057664
PMCID: PMC3592887  PMID: 23520477
16.  Intelligence and executive functions in frontotemporal dementia 
Neuropsychologia  2013;51(4):725-730.
Recently (Roca et al. (2010), we used the relationship with general intelligence (Spearman’s g) to define two sets of frontal lobe or “executive” tests. For one group, including Wisconsin card sorting and verbal fluency, reduction in g entirely explained the deficits found in frontal patients. For another group, including tests of social cognition and multitasking, frontal deficits remained even after correction for g. Preliminary evidence suggested a link of the latter tasks to more anterior frontal regions. Here we develop this distinction in the context of behavioural-variant frontotemporal dementia (bvFTD), a disorder which progressively affects frontal lobe cortices. In bvFTD, some executive tests, including tests of social cognition and multitasking, decline from the early stage of the disease, while others, including classical executive tests such as Wisconsin card sorting, verbal fluency or Trail Making Test part B, show deficits only later on. Here we show that, while deficits in the classical executive tests are entirely explained by g, deficits in the social cognition and multitasking tests are not. The results suggest a relatively selective cognitive deficit at mild stages of the disease, followed by more widespread cognitive decline well predicted by g.
Highlights
► A progressive loss of general intelligence (g) can be found in patients with FTD. ► Advanced FTD classical executive deficits can be entirely explained by loss of g. ► Early social cognition and multitasking deficits exceed the ones predicted from g. ► Assessment in FTD should encompass g, multitasking and social cognition.
doi:10.1016/j.neuropsychologia.2013.01.008
PMCID: PMC3610016  PMID: 23347963
Frontotemporal dementia; Fluid intelligence; Executive functions; Theory of mind; Multitasking
17.  N400 ERPs for actions: building meaning in context 
Converging neuroscientific evidence suggests the existence of close links between language and sensorimotor cognition. Accordingly, during the comprehension of meaningful actions, our brain would recruit semantic-related operations similar to those associated with the processing of language information. Consistent with this view, electrophysiological findings show that the N400 component, traditionally linked to the semantic processing of linguistic material, can also be elicited by action-related material. This review outlines recent data from N400 studies that examine the understanding of action events. We focus on three specific domains, including everyday action comprehension, co-speech gesture integration, and the semantics involved in motor planning and execution. Based on the reviewed findings, we suggest that both negativities (the N400 and the action-N400) reflect a common neurocognitive mechanism involved in the construction of meaning through the expectancies created by previous experiences and current contextual information. To shed light on how this process is instantiated in the brain, a testable contextual fronto-temporo-parietal model is proposed.
doi:10.3389/fnhum.2013.00057
PMCID: PMC3586681  PMID: 23459873
N400; action comprehension; action meaning; language; contextual integration; fronto-temporo-parietal network
18.  Organization of brain networks governed by long-range connections index autistic traits in the general population 
Background
The dimensional approach to autism spectrum disorder (ASD) considers ASD as the extreme of a dimension traversing through the entire population. We explored the potential utility of electroencephalography (EEG) functional connectivity as a biomarker. We hypothesized that individual differences in autistic traits of typical subjects would involve a long-range connectivity diminution within the delta band.
Methods
Resting-state EEG functional connectivity was measured for 74 neurotypical subjects. All participants also provided a questionnaire (Social Responsiveness Scale, SRS) that was completed by an informant who knows the participant in social settings. We conducted multivariate regression between the SRS score and functional connectivity in all EEG frequency bands. We explored modulations of network graph metrics characterizing the optimality of a network using the SRS score.
Results
Our results show a decay in functional connectivity mainly within the delta and theta bands (the lower part of the EEG spectrum) associated with an increasing number of autistic traits. When inspecting the impact of autistic traits on the global organization of the functional network, we found that the optimal properties of the network are inversely related to the number of autistic traits, suggesting that the autistic dimension, throughout the entire population, modulates the efficiency of functional brain networks.
Conclusions
EEG functional connectivity at low frequencies and its associated network properties may be associated with some autistic traits in the general population.
doi:10.1186/1866-1955-5-16
PMCID: PMC3698083  PMID: 23806204
Autism spectrum disorders; Electroencephalography; Autistic traits; Synchronization likelihood; Small world; Long-range connections
19.  Structural neuroimaging of social cognition in progressive non-fluent aphasia and behavioral variant of frontotemporal dementia 
Social cognition impairments are pervasive in the frontotemporal dementias (FTD). These deficits would be triggered by (a) basic emotion and face recognition processes as well as by (b) higher level social cognition (e.g., theory of mind, ToM). Both emotional processing and social cognition impairments have been previously reported in the behavioral variant of FTD (bvFTD) and also in other versions of FTDs, including primary progressive aphasia. However, no neuroanatomic comparison between different FTD variants has been performed. We report selective behavioral impairments of face recognition, emotion recognition, and ToM in patients with bvFTD and progressive non-fluent aphasia (PNFA) when compared to controls. Voxel-based morphometry (VBM) shows a classical impairment of mainly orbitofrontal (OFC), anterior cingulate (ACC), insula and lateral temporal cortices in patients. Comparative analysis of regional gray matter related to social cognition deficits (VBM) reveals a differential pattern of fronto-insulo-temporal atrophy in bvFTD and an insulo-temporal involvement in PNFA group. Results suggest that in spite of similar social cognition impairments reported in bvFTD and PNFA, the former represents an inherent ToM affectation whereas in the PNFA these deficits could be related to more basic processes of face and emotion recognition. These results are interpreted in the frame of the fronto-insulo-temporal social context network model (SCNM).
doi:10.3389/fnhum.2013.00467
PMCID: PMC3744869  PMID: 23966929
PNFA; bvFTD; theory of mind; voxel-based morphometry; social context network model; fronto-insulo-temporal network
20.  Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome 
Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.
doi:10.3389/fnagi.2013.00080
PMCID: PMC3840614  PMID: 24324434
Cockayne syndrome; ERCC8; social cognition; cognitive profile; executive functions; VBM; early-onset neurodegeneration
21.  P300 and Neuropsychological Assessment in Mild Cognitive Impairment and Alzheimer Dementia 
Only a small proportion of individuals with Mild Cognitive Impairment (MCI) will convert to dementia. Methods currently available to identify risk for conversion do not combine enough sensitivity and specificity, which is even more problematic in low-educated populations. Current guidelines suggest the use of combined markers for dementia to enhance the prediction accuracy of assessment methods. The present study adhered to this proposal and investigated the sensitivity and specificity of the electrophysiological component P300 and standard neuropsychological tests to assess patients with Alzheimer’s disease (AD) and MCI recruited from a low-income country. The neuropsychological battery comprised tests of memory, attention, language, praxis, and executive functions. The P300 was recorded using a classical visual odd-ball paradigm. Three variables were found to achieve sensitivity and specificity values above 80% (Immediate and Delayed recall of word list – CERAD – and the latency of P300) for both MCI and AD. When they entered the model together (i.e., combined approach) the sensitivity for MCI increased to 96% and the specificity remained high (80%). Our preliminary findings suggest that the combined use of sensitive neuropsychological tasks and the analysis of the P300 may offer a very useful method for the preclinical assessment of AD, particularly in populations with low socioeconomic and educational levels. Our results provide a platform and justification to employ more resources to convert P300 and related parameters into a biological marker for AD.
doi:10.3389/fneur.2012.00172
PMCID: PMC3514532  PMID: 23227021
Alzheimer’s disease; mild cognitive impairment; event related potentials; P300; neuropsychology; early detection; preclinical markers
22.  Neural Processing of Emotional Facial and Semantic Expressions in Euthymic Bipolar Disorder (BD) and Its Association with Theory of Mind (ToM) 
PLoS ONE  2012;7(10):e46877.
Background
Adults with bipolar disorder (BD) have cognitive impairments that affect face processing and social cognition. However, it remains unknown whether these deficits in euthymic BD have impaired brain markers of emotional processing.
Methodology/Principal Findings
We recruited twenty six participants, 13 controls subjects with an equal number of euthymic BD participants. We used an event-related potential (ERP) assessment of a dual valence task (DVT), in which faces (angry and happy), words (pleasant and unpleasant), and face-word simultaneous combinations are presented to test the effects of the stimulus type (face vs word) and valence (positive vs. negative). All participants received clinical, neuropsychological and social cognition evaluations. ERP analysis revealed that both groups showed N170 modulation of stimulus type effects (face > word). BD patients exhibited reduced and enhanced N170 to facial and semantic valence, respectively. The neural source estimation of N170 was a posterior section of the fusiform gyrus (FG), including the face fusiform area (FFA). Neural generators of N170 for faces (FG and FFA) were reduced in BD. In these patients, N170 modulation was associated with social cognition (theory of mind).
Conclusions/Significance
This is the first report of euthymic BD exhibiting abnormal N170 emotional discrimination associated with theory of mind impairments.
doi:10.1371/journal.pone.0046877
PMCID: PMC3466207  PMID: 23056505
23.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia 
Brain  2011;134(9):2456-2477.
Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.
doi:10.1093/brain/awr179
PMCID: PMC3170532  PMID: 21810890
behavioural variant frontotemporal dementia; diagnostic criteria; frontotemporal lobar degeneration; FTD; pathology
24.  The emerging impact of social neuroscience on neuropsychiatry and clinical neuroscience 
Social Neuroscience  2011;6(5-6):415-419.
doi:10.1080/17470919.2011.624806
PMCID: PMC3373960  PMID: 21970720
25.  The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD) 
PLoS ONE  2012;7(5):e37306.
Background
Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD.
Methodology/Principal Findings
We used the Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR) and a rapid-decision gambling task (RDGT) which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3) in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT); however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN) and insensitivity to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3) was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD.
Conclusions/Significance
Our data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems.
doi:10.1371/journal.pone.0037306
PMCID: PMC3356275  PMID: 22624011

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