Gleichgerrcht E, Torralva T, Roca M, Szenkman D, Ibanez A, Richly P, Pose M, Manes F.  Decision making cognition in primary progressive aphasia. Behavioural Neurology 2012

We sought to investigate the decision making profile of Primary Progressive Aphasia (PPA) by assessing patients diagnosed with this disease (n = 10), patients diagnosed with behavioral variant frontotemporal dementia (bvFTD, n = 35), and matched controls (n = 14) using the Iowa Gambling Task, a widely used test that mimics real-life decision making. Participants were also evaluated with a complete neuropsychological battery. Patients with PPA were unable to adopt an advantageous strategy on the IGT, which resulted in a flat performance, different to that exhibited by both controls (who showed advantageous decision making) and bvFTD patients (who showed risk-appetitive behavior). The decision making profile of PPA patients was not associated with performance on language tasks and did not differ between sub-variants of the disease (namely, semantic dementia and progressive nonfluent aphasia). Investigating decision making in PPA is crucial both from a theoretical perspective, as it can shed light about the way in which language interacts with other cognitive functions, as well as a clinical standpoint, as it could lead to a more objective detection of impairments of decision making deficits in this condition.

Gleichgerrcht E, Young L.  Low Levels of Empathic Concern Predict Utilitarian Moral Judgment. PloS One 2013

Is it permissible to harm one to save many? Classic moral dilemmas are often defined by the conflict between a putatively rational response to maximize aggregate welfare (i.e., the utilitarian judgment) and an emotional aversion to harm (i.e., the non-utilitarian judgment). Here, we address two questions. First, what specific aspect of emotional responding is relevant for these judgments? Second, is this aspect of emotional responding selectively reduced in utilitarians or enhanced in non-utilitarians? The results reveal a key relationship between moral judgment and empathic concern in particular (i.e., feelings of warmth and compassion in response to someone in distress). Utilitarian participants showed significantly reduced empathic concern on an independent empathy measure. These findings therefore reveal diminished empathic concern in utilitarian moral judges.

Báez S, Herrera E, Villarin L, Theil D, González-Gadea ML, Gómez P, Mosquera M, Huepe D, Strejilevich S, Vigliecca NS,Matthäus F, Decety J, Manes F, Ibanez A.  Contextual social cognition impairments in schizophrenia and bipolar disorder. PloS One 2013

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.

Ibanez A, Aguado J, Báez S, Huepe D, R Ortega, Sigman M, Mikulan E, Lischinsky A, Torrente F, Cetkovich M, Torralva T, Bekinschtein T, Manes F.  From neural signatures of emotional modulation to social cognition: Individual differences in healthy volunteers and psychiatric participants. Social Cognitive and Affective Neurosciences 2013

It is commonly assumed thatearly emotional signals provide relevant informationfor social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures,and also to build a model which can predictthis association (a & b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing, and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gendermatched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the social cognition profile (SCP), as evidenced by a structural equation model (SEM) analysis. This is the first study to report anassociation model of brain markers of emotional processing and SCP.

Melloni M, Lopez V, Ibanez A. Empathy and contextual social cognition. Cognitive, Affective and Behavioral Neuroscience 2013

Empathy is a highly flexible and adaptive process that allows for the interplay of prosocial behavior in many different social contexts. Empathy appears to be a very situated cognitive process, embedded with specific contextual cues that trigger different automatic and controlled responses. In this review, we summarize relevant evidence regarding social context modulation of empathy for pain. Several contextual factors, such as stimulus reality and personal experience, affectively link with other factors, emotional cues, threat information, group membership, and attitudes toward others to influence the affective, sensorimotor, and cognitive processing of empathy. Thus, we propose that the frontoinsular-temporal network, the so-called social context network model (SCNM), is recruited during the contextual processing of empathy. This network would (1) update the contextual cues and use them to construct fast predictions (frontal regions), (2) coordinate the internal (body) and external milieus (insula), and (3) consolidate the context-target associative learning of empathic processes (temporal sites). Furthermore, we propose these context-dependent effects of empathy in the framework of the frontoinsular-temporal network and examine the behavioral and neural evidence of three neuropsychiatric conditions (Asperger syndrome, schizophrenia, and the behavioral variant of frontotemporal dementia), which simultaneously present with empathy and contextual integration impairments. We suggest potential advantages of a situated approach to empathy in the assessment of these neuropsychiatric disorders, as well as their relationship with the SCNM.

Sedeño L, Moya A, Baker P, Ibanez A.  Cognición social contexto-dependiente y redes frontotemporo-insulares. Revista de Psicología Social 2013

La cognición social es dependiente de la información sutil e implícita presente en el contexto durante interacciones sociales. Presentamos y describimos un modelo anatomofuncional, denominado SCNM (del inglés Social Context Network Model), que pretende explicar cómo se procesa el contexto en situaciones sociales. Además, muestra cómo diferentes alteraciones de sus redes subyacen a los déficits en cognición social de pacientes con demencia frontotemporal, lesiones fronto-insulares, enfermedades del neurodesarrollo y otros cuadros neuropsiquiátricos. Se presentan estudios precursores basados en el SCNM y se los contrapone al enfoque descontextualizado de abordajes clásicos en cognición social. El SCNM es un modelo teórico que provee un conjunto de hipótesis que permiten examinar y comprender mejor los procesos subyacentes a los déficits en cognición social. A nivel clínico, propone el desarrollo de herramientas más ecológicas que las tradicionales que permitirían una mejor detección y caracterización de distintas enfermedades neurológicas y psiquiátricas, como así también la implementación de ambientes en rehabilitación que imiten mejor las situaciones de la vida cotidiana

Cacioppo S, Couto JB, Bolmont M, Sedeño L, Frum C, Lewis JW, Manes F, Ibanez A, Cacioppo J.  Selective decision-making deficit in love following damage to the anterior insula. Current Trends in Neurology 2013 10.1093/cercor/bht197

Neuroimaging studies have found a correlation between activation in the anterior insula and love, and a correlation between activation in the posteriorinsula 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 anteriorinsula 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.

Struder B, Manes F, Humphreys G, Robbins TW.  Risk-Sensitive Decision-Making in Patients with Posterior Parietal and Ventromedial Prefrontal Cortex Injury. Cerebral Cortex 2013 10.1007/s00429-013-0510-1

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.

GT Grossberg, Manes F, RF Allegri, et al..  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 spectrums 2013 10.1371/journal.pone.0098769

Abstract 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.

Martinez Martin P, Chaudhuri RK, Rojo-Abuin JM, Rodriguez-Blazquez C, Alvarez-Sanchez M, Arakaki T, Bergareche-Yarza A, Chade AR, Garretto N, Gershanik O, Kurtis MM, Martinez-Castrillo JC, et al..  Assessing the non-motor symptoms of Parkinson’s disease: MDS-UPDRS and NMS Scale. European Journal of Neurology 2013

BACKGROUND AND PURPOSE: Although Parkinson’s disease (PD) is characterized by typical motor manifestations, non-motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Part I – Non-Motor Aspects of Experiences of Daily Living (nM-EDL) compared with the Non-Motor Symptoms Scale (NMSS). METHODS: To this purpose, 434 consecutive patients with PD were included in an international, observational, cross-sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin’s Concordance Correlation Coefficient (LCCC) and Bland-Altman plot. RESULTS: As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (0.60). The total score correlation of the MDS-UPDRS Part I with UPDRS Section 1 was high (0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60-64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland-Altman plot; LCCC 0.60 for severe patients). CONCLUSIONS: (i) MDS-UPDRS Part I (nM-EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant