Goldman SM, Kamel F, Ross GW, Bhudhikanok GS, Hoppin JA, Korrell M, Marras C, Meng C, Umbach DM, Kasten M, Chade AR, Comyns K, Richards MB, Sandler DP, Blair A, Langston JW, Tanner CM.  Genetic Modification of the Association of Paraquat and Parkinson’s Disease. Movement Disorders 2012

Paraquat is one of the most widely used herbicides worldwide. It produces a Parkinson´s disease (PD) model in rodents through redox cycling and oxidative stress (OS) and is associated with PD risk in humans. Glutathione transferases provide cellular protection against OS and could potentially modulate paraquat toxicity. We investigated PD risk associated with paraquat use in individuals with homozygous deletions of the genes encoding glutathione S-transferase M1 (GSTM1) or T1 (GSTT1). Eighty-seven PD subjects and 343 matched controls were recruited from the Agricultural Health Study, a study of licensed pesticide applicators and spouses in Iowa and North Carolina. PD was confirmed by in-person examination. Paraquat use and covariates were determined by interview. We genotyped subjects for homozygous deletions of GSTM1 (GSTM1*0) and GSTT1 (GSTT1*0) and tested interaction between paraquat use and genotype using logistic regression. Two hundred and twenty-three (52%) subjects had GSTM1*0, 95 (22%) had GSTT1*0, and 73 (17%; all men) used paraquat. After adjustment for potential confounders, there was no interaction with GSTM1. In contrast, GSTT1 genotype significantly modified the association between paraquat and PD. In men with functional GSTT1, the odds ratio (OR) for association of PD with paraquat use was 1.5 (95% confidence interval [CI]: 0.6–3.6); in men with GSTT1*0, the OR was 11.1 (95% CI: 3.0–44.6; P interaction: 0.027). Although replication is needed, our results suggest that PD risk from paraquat exposure might be particularly high in individuals lacking GSTT1. GSTT1*0 is common and could potentially identify a large subpopulation at high risk of PD from oxidative stressors such as paraquat.

Ibanez A, Riveros R, Hurtado E, Gleichgerrcht E, Urquina H, Herrera E, Amoruso L, Martin-Reyes M, Manes F.  The face and its emotion: Cortical Deficits in Structural Processing and Emotional Discrimination in Schizophrenic and Relatives. Psychiatry Research 2012

Previous studies have reported facial emotion recognition impairments in schizophrenic patients, as well as abnormalities in the N170 component of the event-related potential. Current research on schizophrenia highlights the importance of complexly-inherited brain-based deficits. In order to examine the N170 markers of face structural and emotional processing, DSM-IV diagnosed schizophrenia probands (n=13), unaffected first-degree relatives from multiplex families (n=13), and control subjects (n=13) matched by age, gender and educational level, performed a categorization task which involved words and faces with positive and negative valence. The N170 component, while present in relatives and control subjects, was reduced in patients, not only for faces, but also for face-word differences, suggesting a deficit in structural processing of stimuli. Control subjects showed N170 modulation according to the valence of facial stimuli. However, this discrimination effect was found to be reduced both in patients and relatives. This is the first report showing N170 valence deficits in relatives. Our results suggest a generalized deficit affecting the structural encoding of faces in patients, as well as the emotion discrimination both in patients and relatives. Finally, these findings lend support to the notion that cortical markers of facial discrimination can be validly considered as vulnerability markers.

Ibanez A, Melloni M, Huepe D, Rivera-Rei A, Canales-Johnson AF, Baker P, Moya A.  What event-related potentials (ERPs) bring to social neuroscience? Social Neuroscience 2012 10.1177/1352458514554054.

Social cognitive neuroscience is a recent interdisciplinary field that studies the neural basis of the social mind. Event-related potentials (ERPs) provide precise information about the time dynamics of the brain. In this study, we assess the role of ERPs in cognitive neuroscience, particularly in the emerging area of social neuroscience. First, we briefly introduce the technique of ERPs. Subsequently, we describe several ERP components (P1, N1, N170, vertex positive potential, early posterior negativity, N2, P2, P3, N400, N400-like, late positive complex, late positive potential, P600, error-related negativity, feedback error-related negativity, contingent negative variation, readiness potential, lateralized readiness potential, motor potential, re-afferent potential) that assess perceptual, cognitive, and motor processing. Then, we introduce ERP studies in social neuroscience on contextual effects on speech, emotional processing, empathy, and decision making. We provide an outline of ERPs’ relevance and applications in the field of social cognitive neuroscience. We also introduce important methodological issues that extend classical ERP research, such as intracranial recordings (iERP) and source location in dense arrays and simultaneous functional magnetic resonance imaging recordings. Further, this review discusses possible caveats of the ERP question assessment on neuroanatomical areas, biophysical origin, and methodological problems, and their relevance to explanatory pluralism and multilevel, contextual, and situated approaches to social neuroscience.

Wilson MA, Martinez Cuitiño M.  Semantic dementia without surface dyslexia in Spanish: Unimpaired reading with impaired semantics. Behavioural Neurology 2012 10.3758/s13415-013-0205-3

Surface dyslexia has been attributed to an overreliance on the sub-lexical route for reading. Typically, surface dyslexic patients commit regularisation errors when reading irregular words. Also, semantic dementia has often been associated with surface dyslexia, leading to some explanations of the reading impairment that stress the role of semantics in irregular word reading. Nevertheless, some patients have been reported with unimpaired ability to read irregular words, even though they show severe comprehension impairment. We present the case of M.B., the first Spanish-speaking semantic dementia patient to be reported who shows unimpaired reading of non-words, regular words, and – most strikingly – irregular loan words. M.B. has severely impaired comprehension of the same words he reads correctly (whether regular or irregular). We argue that M.B.’s pattern of performance shows that irregular words can be correctly read even with impaired semantic knowledge corresponding to those words.

Trujillo-Orrego N, Ibanez A, Pineda D Diagnostic validity of attention deficit/hyperactivity disorder: from phenomenology to neurobiology. Revista Neurológica 2012

The diagnostic criteria for the attention deficit/hyperactivity disorder (ADHD) were defined by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, fourth version. ADHD is a neuro-psychiatric disorder associated with impairments in everyday life and behavioral dysregulation (i.e. inattention, hyper-activity and impulsivity), and it has showed empirical evidence from clinical, pharmacological, and psychometric studies. Nevertheless, the role of neurobiological impairments in the presentation of the symptoms remains unclear. For this paper, the authors reviewed Spanish and English literature that support the neurobiological validity of the disorder, aimed to present evidence associated with its cognitive and behavioral phenotype (e.g. in: neuropsychology, electrophysiology, structural and functional magnetic resonance imaging, neurochemistry and genetics). Additionally, an integrative theoretical clinical and scientific proposal is presented. Finally, the introduction of neurobiological marker as part of the definitive diagnosis is suggested, as a started point for the identification of therapeutic targets.

Canales-Johnson AF, Lanfranco R, Vargas E, Ibanez A.  Neurobiología de la hipnosis y su contribución a la comprensión de la cognición y la conciencia. Anales de Psicología 2012

The growing interest for the scientific study of consciousness and the current development of neuroimaging tools have allowed to investigate the neuronal correlates of hypnosis and to expand its scope to assess normal and pathological neurocognitive phenomena. At an empirical level, theories that postulate hypnosis as a neurophysiological distinctive state of consciousness (´state theories´), and theories that claim that hypnosis would just represent different neurophysiological changes associated to specific suggestions without no change in the state of consciousness (´non-state theories´); have both been assessed. In this work, these two theories are critically reviewed, their main features are discussed and their neurophysiological evidence is described. A growing body of evidence supports that a hypnotic state of consciousness involves mainly the anterior cingulated cortex and the dorsolateral frontal cortex; as well as a pattern of attenuated cortical functional connectivity. Also, we concluded that hypnotic suggestions have allowed a better comprehension of a diversity of normal and pathological neuropsychological processes. Finally, we stated that the neurophysiologic evidence until now is still insufficient to solve the debate between state and non-state theorists.

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.