Spectro-temporal Unfolding of Temporal Orienting of Attention

AbstractAll behaviors unfold over time, therefore, our ability to perceive and adapt our behavior according to the temporal constraints of our environment is likely a fundamental requirement for successful behavior (Nobre et al., 2007). Temporal preparation has been defined as our ability to anticipate and prepare an optimal response to forthcoming events in our environment (Nobre et al., 2007). Temporal preparation requires integration of different types of temporal information. On the one hand, information can be provided by temporal predictions, i.e. temporal orienting of attention. On the other hand, information can be afforded by the duration of the previous temporal events, namely the sequential effects (e.g., Capizzi et al., 2012). In this project we are focusing in the time-frequency analysis during the delay period (i.e., foreperiod) from the cue onset until the target onset at the short interval. We followed the results of Capizzi et al.’s (2013) study which showed that the CNV component was increased in the delay period when the previous foreperiod was short as compared to long (Cappizi et al., 2013).Recent studies are concerned with the question of how oscillatory brain activity can provide a mechanism for regulating our temporal behavior (Cravo et al., 2011; Praamstra & Pope, 2007; Rohenkohl & Nobre, 2011). Oscillatory brain activity may be one of the mechanisms underlying the operation of different brain areas during cognitive functions (Buzsaki, 2006). When brain activity is recorded at the level of neural populations, the activity assumes a rhythmic temporal structure. Spectral analysis or time-frequency analysis is the study of brain rhythms. Using time-frequency analysis one can characterize the modulation of certain brain rhythms as those unfold in time. Additionally, different brain regions can engage in synchronized brain activity in certain frequency bands. Such synchronization may support inter-areal communication, which is likely fundamental to many of the cognitive functions producing behavior. Studying brain rhythms therefore has the potential of revealing mechanisms underlying cognitive function and behavior (Fries, 2009).Previous studies in the field of temporal preparation (Cravo et al., 2011; Rohenkohl & Nobre, 2011) have investigated oscillatory brain activity and how it is modulated over the time intervals in which target events are expected. Specifically, desynchronization of low frequency power (<30Hz) has been documented following the time course of predictable time intervals. In this project, we were interested in investigating the spectro-temporal profile of both temporal orienting and the sequential effects during the preparatory interval (foreperiod). Time/frequency analyses was focused on epochs locked to the cue onset and compared EEG activity related to early vs. late temporal expectations (temporal orienting) and EEG activity related to previous short vs. previous long foreperiods (sequential effects).With the aforementioned approach we aim to clarify whether or not sequential effects and temporal orienting effects are mediated by the same brain activity. The behavioral data from the previous study of Capizzi et al. (2012) indicated that temporal orienting and sequential effects are different aspects of temporal preparation and that sequential effects are related to automatic rather than to controlled processing unlike the temporal orienting effect. Time frequency analysis was performed in a total of fourteen subjects; cue locked analysis showed that when an early cue is followed by a short interval there is higher power in lower frequencies as compared to the power when a late cue is followed by a short interval. These results signify a difference in the power representation of the temporal preparation for explicit cuing compared when temporal preparation is guided by the presentation of a regular rhythm suggesting the involvement of dissociable mechanism

The Behavioral Mapping of Psychomotor Slowing in Psychosis Demonstrates Heterogeneity Among Patients Suggesting Distinct Pathobiology.

OBJECTIVES Psychomotor slowing (PS) occurs in up to half of schizophrenia patients and is linked to poorer outcomes. As standard treatment fails to improve PS, novel approaches are needed. Here, we applied the RDoC framework using 3 units of analysis, ie, behavior, self-report, and physiology to test, whether patients with PS are different from patients without PS and controls. METHODS Motor behavior was compared between 71 schizophrenia patients with PS, 25 without PS, and 42 healthy controls (HC) using 5 different measures: (1) for behavior, an expert rating scale: Motor score of the Salpêtrière Retardation Rating Scale, (2) for self-report, the International Physical Activity Questionnaire; and for physiology, (3) Actigraphy, which accounts for gross motor behavior, (4) Gait velocity, and (5) coin rotation task to assess manual dexterity. RESULTS The ANCOVAs comparing the 3 groups revealed differences between patients with PS and HC in expert ratings, self-report, and instrumental measures (all P ≤ .001). Patients with PS also scored higher in expert ratings and had lower instrumental activity levels compared to patients without PS (all P ≤ .045). Instrumental activity levels correlated with an expert rating of PS (rho = -0.51, P-fdr corrected <.001) and classified similarly at 72% accuracy. CONCLUSIONS PS is characterized by slower gait, lower activity levels, and slower finger movements compared to HC. However, only actigraphy and observer ratings enable to clearly disentangle PS from non-PS patients. Actigraphy may become the standard assessment of PS in neuroimaging studies and clinical trials

Psychomotor slowing alters gait velocity, cadence, and stride length and indicates negative symptom severity in psychosis.

Schizophrenia is a severe mental disorder, in which 50% of the patients present with motor abnormalities such as psychomotor slowing. Slow spontaneous gait has been reported in schizophrenia. However, comprehensive objective instrumental assessments of multiple gait conditions are missing. Finally, the specific gait patterns of subjects with psychomotor slowing are still unknown. Therefore, this study aimed to objectively assess multiple gait parameters at different walking conditions in patients with schizophrenia with and without psychomotor slowing. Also, we hypothesised gait impairments to correlate with expert ratings of hypokinetic movement disorders and negative symptoms. We collected gait data (GAITRite®) in 70 patients with psychomotor slowing (SRRS (Salpetriere retardation rating scale) ≥15), 22 non-psychomotor slowed patients (SRRS  16.18, all p < 0.001). Secondly, slower velocity was associated with more severe hypokinetic movement disorders and negative symptoms. In conclusion, gait impairments exist in a spectrum with healthy controls on one end and patients with psychomotor slowing on the other end. Patients with psychomotor slowing are specifically impaired when an adaptation of gait patterns is required, contributing to the deleterious effects of sedentary behaviours

Motor abnormalities are associated with poor social and functional outcomes in schizophrenia.

BACKGROUND Up to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by 10-20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia. METHODS We collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B). RESULTS Our analysis demonstrated that patients with catatonia (all F > 4.5; p  4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least -0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least -0.203, p-value<0.001) and between NES and SOFAS (tau = -0.137, p-value = 0.033). CONCLUSION Here, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning

Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression.

BACKGROUND: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. METHODS: 51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. RESULTS: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. CONCLUSION: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component

Neural Correlates of Formal Thought Disorder Dimensions in Psychosis.

BACKGROUND AND HYPOTHESIS Formal thought disorder (FTD) is a core symptom of psychosis, but its neural correlates remain poorly understood. This study tested whether four FTD dimensions differ in their association with brain perfusion and brain structure. STUDY DESIGN This cross-sectional study investigated 110 patients with schizophrenia spectrum disorders using 3T magnetic resonance imaging (MRI). The Thought and Language Disorder scale (TALD) was utilized, which comprises four subscales: Objective Positive (OP), Objective Negative (ON), Subjective Positive (SP), and Subjective Negative (SN). Resting-state cerebral blood flow (rsCBF), cortical thickness (CortTh), gray matter volume (GMV), and diffusion MRI tractography were tested for associations with TALD subscales controlling for age, medication, total intracranial volume, and for variance of the 3 other TALD subscales. STUDY RESULTS Following Bonferroni correction, the FTD dimensions presented distinct neural correlates. OP scores were associated with increased rsCBF and increased GMV in the right cerebellum lingual gyrus. Higher SP scores were linked to increased GMV in bilateral prefrontal cortex. In contrast, ON was associated with increased GMV in the right premotor cortex. At more liberal statistical thresholds, higher SP was associated with increased CortTh in the right inferior frontal gyrus, whereas SN scores were linked to decreased GMV in the right prefrontal lobe, the left inferior temporal gyrus, and the left supplementary motor area. Unadjusted analyses mostly corroborated these findings. CONCLUSION These findings stress the heterogeneity in FTD, suggesting distinct neural patterns for specific FTD experiences. In sum, FTD in psychosis may require distinct treatment strategies and further mechanistic investigations on single-item levels

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Mejora en el nivel de conocimiento, después de una intervención educativa, en resucitación cardiopulmonar básica en estudiantes de medicina en Piura

Introducción: La resucitación cardiopulmonar es un conjunto de maniobras que deben realizarse en forma sistemática y simultánea, para salvar vidas. El que las realice, debe tener un sólido conocimiento teórico-práctico de la técnica a usar. Objetivo: Determinar la diferencia en el conocimiento teórico-práctico de Reanimación Cardio Pulmonar según el tipo de intervención educativa en estudiantes de medicina del Perú. Métodos: Estudio de intervención de tipo educativo, realizado en estudiantes de dos universidades peruanas. La variable principal fue medir el cambio del nivel de conocimiento teórico-práctico según el tipo de instrucción (Teórico, teórico – practico o Practico), medida con un cuestionario previamente validado1. Se utilizó las pruebas estadísticas de chi cuadrado para las variables categóricas y ANOVA para el análisis de variables numéricas versus las categóricas, ajustado por la prueba de Barlett. Resultados: Según el tipo de intervención recibida, la diferencia entre los promedios finales teóricos no fue significativa (p>0,05), pero los promedios finales prácticos sí mostraron diferencias entre los grupos (p<0,001). En el análisis multivariado se encontró diferencias en el conocimiento práctico del grupo de instrucción práctica (p=0,020) y teórico-práctica (p=0,001) respecto al grupo de instrucción teórica exclusiva. Conclusión: La instrucción tipo práctica y teórico-práctica genera un cambio significativo en el nivel de conocimientos. Esto debe tomarse en cuenta para la generación de programas de instrucción, ya que, muchas veces los conocimientos solo teóricos resultan insuficientes para este tipo de aprendizaj

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia