Usefulness of aqueous and vitreous humor analysis in infectious uveitis.

OBJECTIVE: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis. METHODS: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii. RESULTS: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH. CONCLUSION: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Usefulness of aqueous and vitreous humor analysis in infectious uveitis

OBJECTIVE: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis. METHODS: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii. RESULTS: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH. CONCLUSION: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Neural Correlates of Preference: A Transmodal Validation Study.

Liking is one of the most important psychological processes associated with the reward system, being involved in affective processing and pleasure/displeasure encoding. Currently, there is no consensus regarding the combination of physiological indicators which best predict liking, especially when applied to dynamic stimuli such as videos. There is a lack of a standard methodology to assess likeability over time and therefore in assessing narrative and semantic aspects of the stimulus. We developed a time-dependent method to evaluate the physiological correlates of likeability for three different thematic categories, namely: adventure (AV), comedy (CM), and nature landscape (LS). Twenty-eight healthy adults with ages ranging from 18 to 35 years (average: 23.85 years) were enrolled in the study. The participants were asked to provide likeability ratings for videos as they watched them, using a response box. Three 60-s videos were presented, one for each category, in randomized order while the participant's physiological data [electroencephalogram (EEG), electrocardiogram (ECG) and eye tracking (ET)] was recorded. The comedy video (CM) presented the smallest minimum accumulated normalized rating (ANR; p = 0.013) and the LS video presented the highest maximum ANR (p = 0.039). The LS video presented the longest time for first response (p < 0.001) and the AV video presented the shortest time for maximum response (p = 0.016). The LS video had the highest mean likeability rating with 1.43 ± 2.31 points; and the CM video had the lowest with 0.57 ± 1.77. Multiple linear regression models were created to predict the likeability of each video using the following physiological indicators; AV: power in beta band at C4 and P4 (p = 0.004, adj. R 2 = 0.301); CM: alpha power in Fp2 (p = 0.001, adj. R 2 = 0.326) and LS: alpha power in P4, F8, and Fp2; beta power in C4 and P4 and pupil size, (p = 0.002, adj. R 2 = 0.489). Despite its limitations (e.g., using one 1-min video per category) our findings suggest that there is a considerable difference in the psychophysiological correlates of stimuli with different contextual properties and that the use of time-dependent methods to assess videos should be considered as best practices.

Clinical relevance of protruded retinal layers in minimum rim width measurement of the optic nerve head.

BACKGROUND/AIMS: Optical coherence tomography (OCT) imaging of the optic nerve head minimum rim width (MRW) has recently been shown to sometimes contain components besides extended retinal nerve fibre layer (RNFL). This study was conducted to determine whether excluding these components, termed protruded retinal layers (PRLs), from MRW increases diagnostic accuracy for detecting glaucoma. METHODS: In this cross-sectional study, we included 123 patients with glaucoma and 123 normal age-similar controls with OCT imaging of the optic nerve head (24 radial scans) and RNFL (circle scan). When present, PRLs were manually segmented, and adjusted MRW measurements were computed. We compared diagnostic accuracy of adjusted versus unadjusted MRW measurement. We also determined whether adjusted MRW correlates better with RNFL thickness compared with unadjusted MRW. RESULTS: The median (IQR) visual field mean deviation of patients and controls was -4.4 (-10.3 to -2.1) dB and 0.0 (-0.6 to 0.8) dB, respectively. In the 5904 individual B-scans, PRLs were identified less frequently in patients (448, 7.6%) compared with controls (728, 12.3%; p<0.01) and were present most frequently in the temporal sector of both groups. Areas under the receiver operating characteristic curves and sensitivity values at 95% specificity indicated that PRL adjustment did not improve diagnostic accuracy of MRW, globally or temporally. Furthermore, adjusting MRW for PRL did not improve its correlation with RNFL thickness in either group. CONCLUSION: While layers besides the RNFL are sometimes included in OCT measurements of MRW, subtracting these layers does not impact clinical utility.

Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders.

(Reprinted with permission from PLoS ONE, (8)5: e63773, 2013).

Risk of Irritability With Psychostimulant Treatment in Children With ADHD: A Meta-Analysis.

OBJECTIVE: Irritability is listed as a common side effect of psychostimulant medications. However, psychostimulants have been demonstrated as an effective treatment in reducing irritability and aggression in children with attention-deficit/hyperactivity disorder (ADHD). The goal of this study was to quantify the risk of irritability as a side effect of psychostimulant treatment for ADHD. DATA SOURCES AND STUDY SELECTION: A PubMed search was conducted on August 18, 2013, to identify all double-blind, randomized, placebo-controlled trials published in English examining the efficacy of psychostimulant medications in the treatment of children with ADHD. Trials were excluded if (1) they required additional psychiatric or medical comorbidity in addition to ADHD, (2) they involved fewer than 20 subjects (parallel group trials), or (3) children received psychostimulant medication for less than 1 week. DATA EXTRACTION: A fixed-effects meta-analysis was used to examine the risk ratio of irritability reported as a side effect in children treated with psychostimulants compared to placebo. Stratified subgroup analysis and meta-regression were used to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of irritability. RESULTS: From 92 potentially eligible trials, the meta-analysis identified 32 trials involving 3,664 children with ADHD that reported data on irritability as a side effect. The relative risk of irritability significantly differed between psychostimulant classes (test for subgroup differences χ²1 = 7.6, P = .006). Methylphenidate derivatives were associated with a significantly decreased risk of irritability compared to placebo (risk ratio [RR] = 0.89 [95% CI, 0.82 to 0.96], z = -2.87, P = .004, k = 32, I² = 50%), whereas amphetamine derivatives were associated with a significantly increased risk of irritability (RR = 2.90 [95% CI, 1.26 to 6.71], z = 2.5, P = .01, k = 5, I² = 0%). CONCLUSIONS: This meta-analysis suggests an increased risk of irritability may be confined to amphetamine-derived psychostimulants. Future meta-analyses examining the effects of amphetamine and methylphenidate derivatives on irritability as a continuous measure, as well as head-to-head trials between methylphenidate and amphetamine derivatives examining effects on irritability, will be important to replicate the findings of this meta-analysis.

Meta-Analysis: Reduced Risk of Anxiety with Psychostimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Anxiety is a commonly reported side-effect of psychostimulant treatment. Our goal was to quantify the risk of anxiety as a side effect of psychostimulant treatment for attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD. We used a fixed-effects meta-analysis to examine the risk ratio of anxiety reported as a side effect in children treated with psychostimulants compared with those treated with placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of anxiety. RESULTS: We identified 23 studies involving 2959 children with ADHD for inclusion in our meta-analysis. The risk of anxiety associated with psychostimulant treatment was significantly lower than that experienced with placebo (relative risk [RR] = 0.86 [95% CI: 0.77, 0.95], z = -2.90, p < 0.05). Higher doses of psychostimulants were associated with a reduced measured risk of anxiety of psychostimulants when compared with placebo (ß = -0.0039 [95% CI: -0.00718, -0.00064], z = -2.34, p = 0.019). CONCLUSIONS: Meta-analysis suggests that treatment with psychostimulants significantly reduced the risk of anxiety when compared with placebo. This finding does not rule out the possibility that some children experience increased anxiety when treated with psychostimulants, but suggests that those risks are outweighed by the number of children who experience improvement in anxiety symptoms (possibly as a secondary effect of improved control of ADHD symptoms). Clinicians should consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

OBJECTIVE: Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. METHOD: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. RESULTS: We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. CONCLUSION: Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Meta-analysis: melatonin for the treatment of primary sleep disorders.

STUDY OBJECTIVES: To investigate the efficacy of melatonin compared to placebo in improving sleep parameters in patients with primary sleep disorders. DESIGN: PubMed was searched for randomized, placebo-controlled trials examining the effects of melatonin for the treatment of primary sleep disorders. Primary outcomes examined were improvement in sleep latency, sleep quality and total sleep time. Meta-regression was performed to examine the influence of dose and duration of melatonin on reported efficacy. PARTICIPANTS: Adults and children diagnosed with primary sleep disorders. INTERVENTIONS: Melatonin compared to placebo. RESULTS: Nineteen studies involving 1683 subjects were included in this meta-analysis. Melatonin demonstrated significant efficacy in reducing sleep latency (weighted mean difference (WMD) = 7.06 minutes [95% CI 4.37 to 9.75], Z = 5.15, p<0.001) and increasing total sleep time (WMD = 8.25 minutes [95% CI 1.74 to 14.75], Z = 2.48, p = 0.013). Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time. Overall sleep quality was significantly improved in subjects taking melatonin (standardized mean difference = 0.22 [95% CI: 0.12 to 0.32], Z = 4.52, p<0.001) compared to placebo. No significant effects of trial duration and melatonin dose were observed on sleep quality. CONCLUSION: This meta-analysis demonstrates that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use. Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents.

Clinical efficacy of a new automated hemoencephalographic neurofeedback protocol.

Among the ongoing attempts to enhance cognitive performance, an emergent and yet underrepresented venue is brought by hemoencefalographic neurofeedback (HEG). This paper presents three related advances in HEG neurofeedback for cognitive enhancement: a) a new HEG protocol for cognitive enhancement, as well as b) the results of independent measures of biological efficacy (EEG brain maps) extracted in three phases, during a one year follow up case study; c) the results of the first controlled clinical trial of HEG, designed to assess the efficacy of the technique for cognitive enhancement of an adult and neurologically intact population. The new protocol was developed in the environment of a software that organizes digital signal algorithms in a flowchart format. Brain maps were produced through 10 brain recordings. The clinical trial used a working memory test as its independent measure of achievement. The main conclusion of this study is that the technique appears to be clinically promising. Approaches to cognitive performance from a metabolic viewpoint should be explored further. However, it is particularly important to note that, to our knowledge, this is the world's first controlled clinical study on the matter and it is still early for an ultimate evaluation of the technique.

Clinical Efficacy of a New Automated Hemoencefalographic Neurofeedback Protocol

Among the ongoing attempts to enhance cognitive performance, an emergent and yet underrepresented venue is brought by hemoencefalographic neurofeedback (HEG). This paper presents three related advances in HEG neurofeedback for cognitive enhancement: a) a new HEG protocol for cognitive enhancement, as well as b) the results of independent measures of biological efficacy (EEG brain maps) extracted in three phases, during a one year follow up case study; c) the results of the first controlled clinical trial of HEG, designed to assess the efficacy of the technique for cognitive enhancement of an adult and neurologically intact population. The new protocol was developed in the environment of a software that organizes digital signal algorithms in a flowchart format. Brain maps were produced through 10 brain recordings. The clinical trial used a working memory test as its independent measure of achievement. The main conclusion of this study is that the technique appears to be clinically promising. Approaches to cognitive performance from a metabolic viewpoint should be explored further. However, it is particularly important to note that, to our knowledge, this is the world's first controlled clinical study on the matter and it is still early for an ultimate evaluation of the technique (AU)

Entre los intentos en curso para mejorar el rendimiento cognitivo, uno emergente y todavía insuficientemente representado es el neurofeedback hemoencefalográphico (HEG). Este trabajo presenta tres avances relacionados con HEG neurofeedback para la mejora cognitiva: a) un nuevo protocolo HEG para la mejora cognitiva, así como b) los resultados de las medidas independientes de la eficacia biológica (mapas cerebrales EEG) extraídos en tres fases durante un año estudio de seguimiento de casos; c) los resultados del primer ensayo clínico controlado de HEG, diseñado para evaluar la eficacia de la técnica para la mejora cognitiva de población adulta y neurológicamente sana. El nuevo protocolo fue desarrollado en el marco de un software que organiza algoritmos de señales digitales en un formato de diagrama de flujo. Los mapas de cerebro fueron producidos a través de 10 registros cerebrales. El ensayo clínico utilizó un test de memoria de trabajo como medida independiente de sus logros. La principal conclusión de este estudio es que la técnica parece ser clínicamente prometedora. Los enfoques para el rendimiento cognitivo desde un punto de vista metabólico deben investigarse más a fondo. Sin embargo, es particularmente importante tener en cuenta que, a nuestro entender, este es el primer estudio clínico controlado sobre el tema en el mundo, y aún es pronto para una evaluación final de la técnica (AU)

Coping with Bargains in the Ultimatum Game: The Triple Circuit Hypothesis

This paper aims to present a new hypothesis on cognitive and neurobiological processes involved in the evaluation of offers, based on Ultimatum Game (UG). Recently, different studies have linked serotonin and serotonin-related compounds to rejection rates in this game, through the mediation of intolerance to unfairness, thus leading to the serotonin hypothesis of UG. Despite the great interest of these findings, the current paper shows that the behavior of a responder in the game is much more complex than originally thought, and that are needed at least three cognitive schemas and neurobiological processes to properly cope with that behavior. This paper is designed as a classic scientific hypothesis. First, it defines the epistemological basis of the hypothesis, which is introduced in relation to limitations of the field that are expected to be overcome by this endeavor. Next, it presents evidence for the hypothesis, and finally it makes predictions that can be used to test it. The new hypothesis is named triple-circuit hypothesis; it states that at the cognitive level, the minimum schemas to represent the responder’s behavior are: pre-consciousness discrepancy; attributional schema based upon valence activation; and the counterfactual tendency to repress impulsive behaviors. At the neurobiological level, it proposes that the essential circuit relies on: transient decreases in phasic activity of neurons located in the dorsolateral portion of midbrain (error processing); MPFC excitatory firings toward the limbic system (especially the amygdala), mainly through glutamatergic pathways; dopaminergic activity toward the MPFC, generating inhibitory activity, which disinhibits limbie activity. Several evidences in support our hypothesis are presented (AU)

Se presenta una nueva hipótesis sobre los procesos cognitivos y neurobiológicos implica- dos en la evaluación de ofertas en el Juego del Ultimatum (UG). Recientemente, diversos estudios han relacionado la serotonina y los compuestos relacionados con ella a las tasas de rechazo en el UG, a través de la mediación de la intolerancia a la injusticia, lo que ha conducido a formular la “hipótesis de la serotonina” del UG. A pesar del gran interés de estos hallazgos, este artículo pretende mostrar que la conducta de un jugador en este juego es mucho más compleja y son necesarios, al menos tres esquemas cognitivos y procesos neurobiológicos para explicarla. Este artículo ha sido diseñado como la presentación de hipótesis científica clásica, en la que primero se definen las bases epistemológicas presen- tadas teniendo en cuenta las limitaciones del campo a la espera de que esfuerzo ayude a clarificarlas. En segundo lugar, se presentan las evidencias de la hipótesis para, finalmente, elaborar las predicciones que pueden usarse para verificarla. La nueva hipótesis presentada se denomina hipótesis del triple circuito, y afirma que, a nivel cognitivo, los esquemas mínimos para representar la conducta del jugador son: la discrepancia preconsciente, el esquema atribucional basado en la activación, y la tendencia contrafactual para controlar las conductas impulsivas. A nivel neurobiológico, la hipótesis propone que el circuito esencial descansa sobre un descenso transitorio en la actividad fásica de las neuronas localizadas en la porción dorsolateral del cerebro medio (procesamiento de errores), disparos excita- torios de la MPFC hacia el sistema límbico (especialmente la amígdala), principalmente a través de las rutas glutamatérgicas, y actividad dopaminérgica hacia la MPFC que genera actividad inhibitoria que desinhibe la actividad limbia. Se presentan diversas evidencias en apoyo de nuestra hipótesis (AU)