Struder B, Manes F, Humphreys G, Robbins TW.  Risk-Sensitive Decision-Making in Patients with Posterior Parietal and Ventromedial Prefrontal Cortex Injury. Cerebral Cortex 2013 10.1007/s00429-013-0510-1

Successful choice under risk requires the integration of information about outcome probabilities and values and implicates a brain network including the ventromedial prefrontal cortex (vmPFC) and posterior parietal cortex (pPAR). Damage to the vmPFC is linked to poor decision-making and increased risk-taking. Electrophysiological and neuroimaging data implicate the pPAR in the processing of reward probability during choice, but the causal contribution of this area has not been established. We compared patients with lesions to the pPAR (n = 13), vmPFC (n = 13), and healthy volunteers (n = 22) on the Roulette Betting Task, a measure of risk-sensitive decision-making. Both lesion groups were impaired in adjusting their bets to the probability of winning. This impairment was correlated with the extent of pPAR, but not vmPFC, damage. In addition, the vmPFC group chose higher bets than healthy controls overall, an effect that correlated with lesion volume in the medial orbitofrontal cortex. Both lesion groups earned fewer points than healthy controls. The groups did not differ on 2 tasks assessing probabilistic reasoning outside of a risk-reward context. Our results demonstrate the causal involvement of both the pPAR and vmPFC in risk-sensitive choice and indicate distinguishable roles of these areas in probability processing and risk appetite.

GT Grossberg, Manes F, RF Allegri, et al..  The Safety, Tolerability, and Efficacy of Once-Daily Memantine (28 mg): A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients with Moderate-to-Severe Alzheimer’s Disease Taking Cholinesterase Inhibitors. CNS spectrums 2013 10.1371/journal.pone.0098769

Abstract INTRODUCTION: Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer’s disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors. METHODS: In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations. RESULTS: A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %). CONCLUSION: Extended-release memantine was efficacious, safe, and well tolerated in this population.

Martinez Martin P, Chaudhuri RK, Rojo-Abuin JM, Rodriguez-Blazquez C, Alvarez-Sanchez M, Arakaki T, Bergareche-Yarza A, Chade AR, Garretto N, Gershanik O, Kurtis MM, Martinez-Castrillo JC, et al..  Assessing the non-motor symptoms of Parkinson’s disease: MDS-UPDRS and NMS Scale. European Journal of Neurology 2013

BACKGROUND AND PURPOSE: Although Parkinson’s disease (PD) is characterized by typical motor manifestations, non-motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Part I – Non-Motor Aspects of Experiences of Daily Living (nM-EDL) compared with the Non-Motor Symptoms Scale (NMSS). METHODS: To this purpose, 434 consecutive patients with PD were included in an international, observational, cross-sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin’s Concordance Correlation Coefficient (LCCC) and Bland-Altman plot. RESULTS: As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (0.60). The total score correlation of the MDS-UPDRS Part I with UPDRS Section 1 was high (0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60-64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland-Altman plot; LCCC 0.60 for severe patients). CONCLUSIONS: (i) MDS-UPDRS Part I (nM-EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant

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.

Hornberger M, Yew B, Gilardoni S, Mioshi E, Gleichgerrcht E, Manes F, Hodges J R.  Ventromedial-frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer’s disease. Human Brain Mapping 2012 10.1186/s12993-015-0058-8.

Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer’s disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non-fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel-based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight.

Martinez Martin P, Rodriguez-Blazquez C, Alvarez-Sanchez M, Arakaki T, Bergareche-Yarza A, Chade AR, Garretto N,Gershanik O, Kurtis MM, Martinez-Castrillo JC, Mendoza-Rodriguez A, Moore HP, Rodriguez-Violante M, Singer C, Tilley B,Huang J, Stebbins G, Goetz CG.  Expanded and independent validation of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Journal of Neurology 2012

The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing satisfactory clinimetric results and has been proposed as the official benchmark scale for Parkinson’s disease. The present study, based on the official MDS-UPDRS Spanish version, performed the first independent testing of the scale and adds information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS Spanish version showed a comparative fit index ≥0.90 for each part (I-IV) relative to the English-language version and was accepted as the Official MDS-UPDRS Spanish version. Data from this scale, applied with other assessments to Spanish-speaking Parkinson’s disease patients in five countries, were analyzed for an independent and complementary clinimetric evaluation. In total, 435 patients were included. Missing data were negligible and moderate floor effect (30 %) was found for Part IV. Cronbach’s α index ranged between 0.79 and 0.93 and only five items did not reach the 0.30 threshold value of item-total correlation. Test-retest reliability was adequate with only two sub-scores of the item 3.17, Rest tremor amplitude, reaching κ values lower than 0.60. The intraclass correlation coefficient was higher than 0.85 for the total score of each part. Correlation of the MDS-UPDRS parts with other measures for related constructs was high (≥0.60) and the standard error of measurement lower than one-third baseline standard deviation for all subscales. Results confirm those of the original study and add information on scale reliability, construct validity, and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric characteristics.

Torralva T, Gleichgerrcht E, Lischinsky A, Roca M, Manes F.  «Ecological» and Highly Demanding Executive Tasks Detect Real-Life Deficits in High-Functioning Adult ADHD Patients. Journal of Attention Disorders 2012

Many adult ADHD patients with a convincing history of real-life executive deficits perform entirely within normal limits or with minimally impaired performance in classical executive tests. The authors assessed a group of high cognitive functioning adult ADHD participants on «ecological»and «highly demanding» executive tasks. METHOD: A total of 117 adult ADHD participants were classified as showing either a high-functioning (Hi-ADHD) or a low-functioning (Lo-ADHD) neuropsychological profile based on standard assessment. Their performance was compared with healthy controls (n = 21) on an ecological task of executive function (the hotel task) and computerized tasks of high cognitive demand. RESULTS: ADHD significantly differed from controls on multiple standard neuropsychological variables as well as on the experimental tasks. Hi-ADHD and healthy controls did not differ significantly on any of the standard neuropsychological variables, but a significant difference was found between the groups on measures of the experimental tasks. CONCLUSION: Real-life executive dysfunction of patients with ADHD who perform within normal range on standard assessment can be detected with the use of more ecological and highly demanding tasks.