Torralva T, Gleichgerrcht E, Roca M, Ibanez A, Marenco V, Rattazzi A, Manes F Impaired theory of mind but intact decision-making in Asperger syndrome: Implications for the relationship between these cognitive domains. Psychiatry Research 2012

The relationship between decision making and theory of mind (TOM) has been hardly investigated in patients with Asperger Syndrome (AS). Here, we show that the AS group (n=25) exhibited deficits on a complex TOM task, yet were unimpaired in a decision-making test. No association was found between these two domains.

Manes F, Báez S, Couto JB, Herrera E, Trujillo-Orrego N, Cardona JF, Ibanez A.  Psychiatric Conditions That Can Mimic Early Behavioral Variant Frontotemporal Dementia: The Importance of the New Diagnostic Criteria. Current Psychiatry Reports 2012

Psychiatric Conditions That Can Mimic Early Behavioral Variant Frontotemporal Dementia: The Importance of the New Diagnostic Criteria. Autores Manes F, Báez S, Couto JB, Herrera E, Trujillo-Orrego N, Cardona JF, Ibanez A.  Año 2012 Journal  Manes F, Báez S, Couto JB, Herrera E, Trujillo-Orrego N, Cardona JF, Ibanez A.  Volumen 14(5): 450-452 Abstract   Otra información  La publicación trata sobre la importancia de los nuevos criterios en … Leer más

Ibanez A, Manes F.  Contextual social cognition and the behavioral variant of frontotemporal dementia. Neurology 2012

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.

Ibanez A, Urquina H, Petroni A, Báez S, Lopez V, do Nascimento M, Herrera E, Guex R, Hurtado E, Blenkmann A, Beltrachini L, Gelormini C, Sigman M, Lischinsky A, Torralva T, Torrente F, Cetkovich M, Manes F.  Neural processing of emotional facial and semantic expressions in euthymic bipolar disorder (BD) and its association with theory of mind (ToM). PloS One 2012

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.

Ibanez A, Cetkovich M, Petroni A, Urquina H, Báez S, González-Gadea ML, Kamienkowski JE, Torralva T, Torrente F,Strejilevich S, Teitelbaum J, Hurtado E, Melloni L, Lischinsky A, Sigman M, Manes F.  The neural basis of decision-making and reward processing in adults with euthymic bipolar disorder or attention-deficit/hyperactivity disorder (ADHD). PloS One 2012 10.5498/wjp.v4.i3.56

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.

Roca M, Manes F, Chade AR, Gleichgerrcht E, Gershanik O, Gómez Arévalo G, Torralva T, Duncan J.  The relationship between executive functions and fluid intelligence in Parkinson’s disease. Psychological Medicine 2012 10.1001/jamaneurol.2014.347

BACKGROUND: We recently demonstrated that decline in fluid intelligence is a substantial contributor to frontal deficits. For some classical ‘executive’ tasks, such as the Wisconsin Card Sorting Test (WCST) and Verbal Fluency, frontal deficits were entirely explained by fluid intelligence. However, on a second set of frontal tasks, deficits remained even after statistically controlling for this factor. These tasks included tests of theory of mind and multitasking. As frontal dysfunction is the most frequent cognitive deficit observed in early Parkinson’s disease (PD), the present study aimed to determine the role of fluid intelligence in such deficits.MethodWe assessed patients with PD (n=32) and control subjects (n=22) with the aforementioned frontal tests and with a test of fluid intelligence. Group performance was compared and fluid intelligence was introduced as a covariate to determine its role in frontal deficits shown by PD patients. RESULTS: In line with our previous results, scores on the WCST and Verbal Fluency were closely linked to fluid intelligence. Significant patient-control differences were eliminated or at least substantially reduced once fluid intelligence was introduced as a covariate. However, for tasks of theory of mind and multitasking, deficits remained even after fluid intelligence was statistically controlled. CONCLUSIONS: The present results suggest that clinical assessment of neuropsychological deficits in PD should include tests of fluid intelligence, together with one or more specific tasks that allow for the assessment of residual frontal deficits associated with theory of mind and multitasking.

Báez S, Rattazzi A, González-Gadea ML, Torralva T, Vigliecca NS, Decety J, Manes F, Ibanez A Integrating intention and context: assessing social cognition in adults with Asperger syndrome. Frontiers in Human Neuroscience 2012

Deficits in social cognition are an evident clinical feature of the Asperger syndrome (AS). Although many daily life problems of adults with AS are related to social cognition impairments, few studies have conducted comprehensive research in this area. The current study examined multiple domains of social cognition in adults with AS assessing the executive functions (EF) and exploring the intra and inter-individual variability. Fifteen adults diagnosed with AS and 15 matched healthy controls completed a battery of social cognition tasks. This battery included measures of emotion recognition, theory of mind, empathy, moral judgment, social norms knowledge and self-monitoring behavior in social settings. We controlled for the effect of EF and explored the individual variability. The results indicated that adults with AS had a fundamental deficit in several domains of social cognition. We also found high variability in the social cognition tasks. In these tasks, AS participants obtained mostly subnormal performance. Executive functions did not seem to play a major role in the social cognition impairments. Our results suggest that adults with AS present a pattern of social cognition deficits characterized by the decreased ability to implicitly encode and integrate contextual information in order to access to the social meaning. Nevertheless, when social information is explicitly presented or the situation can be navigated with abstract rules, performance is improved. Our findings have implications for the diagnosis and treatment of individuals with AS as well as for the neurocognitive models of this syndrome.

Pontello N, Gleichgerrcht E, Manes F, Sinay V.  Criptococosis meníngea en inmunosuprimidos: rol del síndrome in?amatorio de reconstitución inmune. Neurología 2012

El síndrome inflamatorio de reconstitución inmune (SIRI) es una complicación poco frecuente pero grave que aumenta la morbimortalidad de algunos pacientes en los que su sistema inmune comienza a recuperarse tras la disminución del tratamiento inmunosupresor y reacciona contra una infección oportunista adquirida previamente. Dicha respuesta inflamatoria es excesiva y produce un deterioro paradójico del estado clínico del paciente, a pesar de estar recibiendo adecuado tratamiento infeccioso.
Presentamos el caso de una mujer de 67 años, inmunosuprimida por un trasplante hepatorrenal, que consulta por cuadro de deterioro general con disminución de la ingesta, tendencia al sueño y cefalea. Se diagnostica criptococosis meníngea e inicia tratamiento antifúngico adecuado con una respuesta inicial favorable. Tras dos meses experimenta una recaída de sus síntomas, agregando mayor compromiso neurológico. El caso clínico plantea las posibles causas de dicho empeoramiento, remarcando la importancia de considerar al SIRI.

Gleichgerrcht E, Torralva T, Rattazzi A, Marenco V, Roca M, Manes F.  Selective impairment of cognitive empathy for moral judgment in adults with high functioning autism. Social Cognitive and Affective Neurosciences 2012 10.1371/journal.pone.0070247

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.

Easton JD, Lopes R, Dra. Cecilia Bahit, Wojdyla D, Wranger C, Wallentin L, Alings M, Goto S, Lewis B, Rosenqvist M, Hanna M, Mohan P, Alexander J, Diener HC.  Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurology 2012

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. METHODS: Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. FINDINGS: Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. INTERPRETATION: The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. FUNDING: Bristol-Myers Squibb and Pfizer.