Sposato L, Klein F, Jáuregui A, Ferrúa M, Klin P, Zamora R, Riccio PM, Rabinstein A.  Newly diagnosed atrial fibrillation after acute ischemic stroke and transient ischemic attack: importance of immediate and prolonged continuous cardiac monitoring. Journal of Stroke and Cerebrovascular Diseases 2012

Atrial fibrillation (AF) is the major cause of cardioembolic stroke. It often remains occult when asymptomatic and paroxysmal. We hypothesized that the detection of AF after acute ischemic stroke (AIS) or transient ischemic attack (TIA) could be improved by using continuous cardiac monitoring (CCM) immediately after admission. We sought to determine the detection rate of AF by immediate in-hospital CCM after cryptogenic and noncryptogenic AIS or TIA in patients without a previous diagnosis of AF. We retrospectively studied a cohort of 155 patients with cryptogenic and noncryptogenic AIS or TIA without known AF. We compared the detection rates of newly diagnosed AF (NDAF) in patients admitted to areas with CCM and those never admitted to these areas. We developed a multiple logistic regression model for identifying predictors of NDAF. We characterized NDAF episodes and analyzed how the availability of CCM data changed secondary prevention strategies. We detected NDAF in 21 patients (13.5%). Diagnostic rates of NDAF in patients who underwent CCM and those who did not undergo CCM were 18.2% and 2.2%, respectively (P = .005). The median time from admission to recognition of NDAF was 2.0 days. Most NDAFs were paroxysmal (95.2%) and lasted less than 1 hour (85.7%). Diabetes mellitus and infarct size were predictors of NDAF. Detection of NDAF prompted the initiation of anticoagulation therapy in 8.2% of the patients admitted to areas with CCM availability. Our findings suggest that immediate and prolonged CCM significantly improves the detection of NDAF after cryptogenic and noncryptogenic AIS or TIA, and that diabetes mellitus and infarct size are significantly associated with NDAF.

González-Gadea ML, Báez S, Torralva T, Castellanos FX, Rattazzi A, Bein V, Rogg K, Manes F, Ibanez A.  Cognitive variability in adults with ADHD and AS: Disentangling the roles of executive functions and social cognition. Research in Developmental Disabilities 2012

Attention-deficit/hyperactivity disorder (ADHD) and Asperger’s Syndrome (AS) share a heterogeneous cognitive profile. Studies assessing executive functions (EF) and social cognition in both groups have found preserved and impaired performances. These inconsistent findings would be partially explained by the cognitive variability reported in these disorders. First, the present study explored the inter-individual variability in EF and social cognition in both patient groups. Second, we compared differential characteristics and commonalities in the cognitive profiles of EF and social cognition between ADHD, AS and control adults. We assessed 22 patients with ADHD, 23 adults with AS and 21 matched typically developing subjects using different measures of EF (working memory, cognitive flexibility and multitasking) and social cognition (theory of mind and decision-making). Group comparisons and multiple case series analyses (MCSA) were conducted. The between-group comparisons showed an EF deficit in working memory in ADHD and a theory of mind (ToM) impairment in AS. The MCSA evidenced that, compared to controls, ADHD patients had a higher inter-individual variability in EF, while individuals with AS had a more heterogeneous profile in social cognition tasks compared to both groups. Finally, the AS and ADHD groups presented higher task-related variability compared to controls and shared a common heterogeneous profile in EF. This is the first study to compare variability in EF and social cognition profiles of ADHD and AS. We propose that heterogeneity in EF performance is a link between ADHD and AS which may explain the overlap of symptomatology between both diagnoses. In addition, patients with AS seem to show a unique heterogeneous profile in ToM which may explain the low probability of finding AS symptoms in patients with ADHD.

Torralva T, Strejilevich S, Gleichgerrcht E, Roca M, Martino D, Cetkovich M, Manes F.  Deficits in tasks of executive functioning tha mimic real-lifescenarios in Bipolar Disorder. Bipolar Disorders 2012

BACKGROUND: A growing body of evidence suggests that patients with bipolar disorder (BD) have cognitive impairments even during euthymic periods. The main cognitive domains affected are verbal memory, attention, and executive function. Nevertheless, some studies suggest that at least a subgroup of euthymic patients demonstrates intact executive functioning in classic neuropsychological tests, which could be due to the lack of real-life, or ecological validity. OBJECTIVE: In this study, we highlight the usefulness of incorporating more ecological tests of executive function in assessment batteries in order to detect specific cognitive deficits in BD patients with otherwise normal performance in standard executive tests. METHODS: Nineteen euthymic BD patients and 15 healthy controls completed a standard neuropsychological battery assessment and two experimental tasks (the Multiple Errands Test-Hospital Version and the Hotel Task) to measure executive functioning in highly demanding cognitive settings that mimic real-life scenarios. RESULTS: No significant differences were found between the groups’ demographic variables. We found, as predicted, that the group of euthymic BD patients who had control-comparable performance in classic executive tasks showed important deficits in more ecological tasks of executive functioning of the type that mimic real-life scenarios. CONCLUSIONS: Together, these data suggest that the inclusion of ecological tests in the assessment of BD patients can contribute to providing a more realistic cognitive profile of this patient population, which will undoubtedly allow for a better design of therapeutic and rehabilitation strategies that can help patients to minimize impact in real-life settings.

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.