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.

Dufey M, Hurtado E, Fernandez HH, Manes F, Ibanez A.  Exploring the relationship between vagal tone and event-related potentials in response to an affective picture task. Social Neuroscience 2011

The present study is the first to investigate the relationship between vagal tone level and event-related potentials (ERPs) in adults. Numerous studies have shown a relationship between vagal tone and the individual differences between a variety of psychophysiological, affective, and social outcomes. This suggests that vagal tone can be related to how people process relevant affective social information at the brain level. This study aimed to assess whether the ERP response varies between high and low vagal tone groups, in the face of salient affective information. In the experimental cohort, two groups were separated according to their vagal tone level. ERPs were recorded while individuals performed an affective picture task that included positive, neutral, and negative emotional stimuli. Differences between the high and low vagal tone groups were observed at the early posterior negativity for both positive and negative valences, and at the late positive potential for all the categories. It can be concluded that differences between high and low vagal tone levels are related to differences in the ERPs at early, middle, and late latencies. The results are discussed with respect to the effect of differences between the vagal tone conditions on various stages of information-processing.

Sposato L, Riccio PM, Klein F.  Diagnosis and treatment of asymptomatic extracranial atherosclerotic carotid artery disease. Medicina 2011

The reported prevalence of asymptomatic atherosclerotic disease of the extracranial internal carotid artery is up to 12.5%. Carotid angioplasty has not yet proven safe and effective enough to prevent ischemic stroke in these patients. Randomized studies showed that carotid endarterectomy is superior to medical therapy in reducing the risk of ischemic stroke when performed by surgical teams with complication rates (stroke or death) of less than 3%. However, recruitment of these patients began more than 25 years ago, when the use of antiplatelet agents was lower than today, the treatment of hypertension was less effective than currently, and statins were not considered as key components of vascular prevention strategies. Optimizing the quality of medical treatment in recent decades has led to a significant reduction in stroke risk in patients not undergoing surgery. Based on these observations and with the exception of specific cases, medical therapy is the treatment of choice for patients with asymptomatic atherosclerotic disease of the extracranial carotid arteries.

Bekinschtein T, Manes F, Villarreal M, Owen A, Della-Maggiore V.  Functional imaging reveals movement preparatory activity in the vegetative State. Frontiers in Human Neuroscience 2011

The vegetative state (VS) is characterized by the absence of awareness of self or the environment and preserved autonomic functions. The diagnosis relies critically on the lack of consistent signs of purposeful behavior in response to external stimulation. Yet, given that patients with disorders of consciousness often exhibit fragmented movement patterns, voluntary actions may go unnoticed. Here we designed a simple motor paradigm that could potentially detect signs of purposeful behavior in VS patients with mild to severe brain damage by examining the neural correlates of motor preparation in response to verbal commands. Twenty-four patients who met the diagnostic criteria for VS were recruited for this study. Eleven of these patients showing preserved auditory evoked potentials underwent functional magnetic resonance imaging (fMRI) to test for basic speech processing. Five of these patients, who showed word related activity, were included in a second fMRI study aimed at detecting functional changes in premotor cortex elicited by specific verbal instructions to move either their left or their right hand. Despite the lack of overt muscle activity, two patients out of five activated the dorsal premotor cortex contralateral to the instructed hand, consistent with movement preparation. Our results may reflect residual voluntary processing in these two patients. We believe that the identification of positive results with fMRI using this simple task, may complement the clinical assessment by helping attain a more precise diagnosis in patients with disorders of consciousness.