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.

Huepe D, Riveros R, Manes F, Couto JB, Hurtado E, Cetkovich M, Escobar J, Vergara V, Parrao T, Ibanez A.  The relationship of clinical, cognitive and social measures in schizophrenia: a preliminary finding combining measures in probands and relatives. Behavioural Neurology 2012 10.3389/fnhum.2014.00547

This study examines performance of schizophrenia patients, unaffected relatives and controls in social cognition, cognitive and psychiatric scales looking for possible markers of vulnerability in schizophrenia. Performance of schizophrenia patients from multiplex families, first-degree relatives, and matched controls was compared and, subsequently, discriminant analysis method was used for identifying the best predictors for group membership. By using Multigroup Discriminant Analyses on the three groups, the best predictors were PANSS, Premorbid Adjustment Scale, Faux Pas test, and a face/emotion categorizing task. This model obtained 82% correct global classification, suggesting that the combination of psychiatric scales and neuropsychological/social cognition tasks are the best approach for characterizing this disease. Although preliminary, our results suggest that social cognition tasks are robust markers of schizophrenia family impairments, and that combining clinical, social and neuropsychological measures is the best approach to asses patients and relatives vulnerability.

Mendiz OA, Sposato L, Fabbro N, Lev GA, Calle A, Valdivieso L, Fava CM, Klein F, Torralva T, Gleichgerrcht E, Manes F. Improvement of Executive Function after Unilateral Carotid Artery Stenting for Severe Asymptomatic Stenosis. Journal of Neurosurgery 2012

OBJECT: Executive functions are crucial for organizing and integrating cognitive processes. While some studies have assessed the effect of carotid artery stenting (CAS) on cognitive functioning, results have been conflicting. The object of this study was to assess the effect of CAS on cognitive status, with special interest on executive functions, among patients with severe asymptomatic internal carotid artery (ICA) stenosis. METHODS: The authors prospectively assessed the neuropsychological status of 20 patients with unilateral asymptomatic extracranial ICA stenosis of 60% or more by using a comprehensive assessment battery focused on executive functions before and after CAS. Individual raw scores on neuropsychological tests were converted into z scores by normalizing for age, sex, and years of education. The authors compared baseline and 3-month postoperative neuropsychological scores by using Wilcoxon signed-rank tests. RESULTS: The mean preoperative cognitive performance was within normal ranges on all variables. All patients underwent a successful CAS procedure. Executive function scores improved after CAS, relative to baseline performance as follows: set shifting (Trail-Making Test Part B: -0.75 ± 1.43 vs -1.2 ± 1.48, p = 0.003) and processing speed (digit symbol coding: -0.66 ± 0.85 vs -0.97 ± 0.82, p = 0.035; and symbol search: -0.24 ± 1.32 vs -0.56 ± 0.77, p = 0.049). The benefit of CAS for working memory was marginally significant (digit span backward: -0.41 ± 0.61 vs -0.58 ± 0.76, p = 0.052). Both verbal (immediate Rey Auditory Verbal Learning Test: 0.35 ± 1.04 vs -0.22 ± 0.82, p = 0.011) and visual (delayed Rey-Osterrieth Complex Figure: 0.27 ± 1.26 vs -0.22 ± 1.01, p = 0.024) memory improved after CAS. CONCLUSIONS: The authors found a beneficial effect on executive function and memory 3 months after CAS among their prospective cohort of consecutive patients with unilateral and asymptomatic ICA stenosis of 60% or more.

Martino D, Strejilevich S, Manes F.  Neurocognitive functioning in early-onset and late-onset older patients with euthymic bipolar disorder. International Journal of Geriatric Psychiatry 2012

OBJECTIVE: Most neurocognitive studies have not taken into account the fact that older patients with bipolar disorder (BD) are a heterogeneous population. The main goal of this study was to compare neurocognitive performance and extrapyramidal symptoms in older patients with early-onset BD (EO-BD) and late-onset BD (LO-BD).METHODS: Euthymic older patients with EO-BD (n=20), LO-BD (n=20), and healthy controls (n=20) were evaluated with traditional clinical instruments and measures of exposure to psychotropic drugs, as well as extrapyramidal symptoms. All subjects completed an extensive neuropsychological battery.RESULTS: Patients with EO-BD showed poorer performance than healthy controls in two measures of verbal memory and two measures of executive functions, whereas patients with LO-BD exhibited lower performance scores than healthy controls in almost all of the measures assessed. Impairments in the LO-BD group included even neurocognitive domains typically spared in mixed-age patients. Additionally, there was a trend toward displaying higher extrapyramidal symptoms in the LO-BD group compared with both EO-BD and healthy control groups. In both patient groups, psychosocial functioning was related with executive dysfunction and extrapyramidal symptoms.CONCLUSIONS: Patients with LO-BD may have more extensive and severe cognitive impairments, as well as higher vulnerability to extrapyramidal symptoms, compared with patients with EO-BD. Cognitive-motor disturbances may help to explain impairments in daily functioning among older patients with EO-BD and LO-BD during remission.

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.

Melloni M, Urbistondo C, Sedeño L, Gelormini C, Kichic R, Ibanez A.  The Extended Fronto-Striatal Model of Obsessive Compulsive Disorder: Convergence from Event-Related Potentials, Neuropsychology and Neuroimaging. Frontiers in Human Neuroscience 2012

In this work, we explored convergent evidence supporting the fronto-striatal model of obsessive-compulsive disorder (FSMOCD) and the contribution of event-related potential (ERP) studies to this model. First, we considered minor modifications to the FSMOCD model based on neuroimaging and neuropsychological data. We noted the brain areas most affected in this disorder -anterior cingulate cortex (ACC), basal ganglia (BG) and orbito-frontal cortex (OFC)- and their related cognitive functions, such as monitoring and inhibition. Then, we assessed the ERPs that are directly related to the FSMOCD, including the error-related negativity (ERN), N200 and P600. Several OCD studies present enhanced ERN and N2 responses during conflict tasks as well as an enhanced P600 during working memory tasks. Evidence from ERP studies (especially regarding ERN and N200 amplitude enhancement), neuroimaging and neuropsychological findings suggests abnormal activity in the OFC, ACC and BG in OCD patients. Moreover, additional findings from these analyses suggest dorsolateral prefrontal and parietal cortex involvement, which might be related to executive function deficits. Thus, these convergent results suggest the existence of a self-monitoring imbalance involving inhibitory deficits and executive dysfunctions. OCD patients present an impaired ability to monitor, control, and inhibit intrusive thoughts, urges, feelings and behaviors. In the current model, this imbalance is triggered by an excitatory role of the BG (associated with cognitive or motor actions without volitional control) and inhibitory activity of the OFC as well as excessive monitoring of the ACC to block excitatory impulses. This imbalance would interact with the reduced activation of the parietal-DLPC network, leading to executive dysfunction. ERP research may provide further insight regarding the temporal dynamics of action monitoring and executive functioning in OCD.