Increased functional activity, bottom-up and intrinsic effective connectivity in autism.

Sensory perceptual alterations such as sensory sensitivities in autism have been proposed to be caused by differences in sensory observation (Likelihood) or in forming models of the environment (Prior), which result in an increase in bottom-up information flow relative to top-down control. To investigate this conjecture, we had autistic individuals (AS) and neurotypicals (NT) perform a decision-under-uncertainty paradigm while undergoing functional magnetic resonance imaging (fMRI). There were no group differences in task performance and in Prior and Likelihood representations in brain activity. However, there were significant group differences in overall task activity, with the AS group showing significantly greater activation in the bilateral precuneus, mid-occipital gyrus, cuneus, superior frontal gyrus (SFG) and left putamen relative to the NT group. Further, when pooling the data across both groups, we found that those with higher AQ scores showed greater activity in the left cuneus and precuneus. Effective connectivity analysis using dynamic causal modelling (DCM) revealed that group differences in BOLD signals were underpinned by increased activity within sensory regions and a net increase in bottom-up connectivity from the occipital region to the precuneus and the left SFG. These findings support the hypothesis of increased bottom-up information flow in autism during sensory learning tasks.

Reduced Context Updating but Intact Visual Priors in Autism.

A general consensus persists that sensory-perceptual differences in autism, such as hypersensitivities to light or sound, result from an overreliance on new (rather than prior) sensory observations. However, conflicting Bayesian accounts of autism remain unresolved as to whether such alterations are caused by more precise sensory observations (precise likelihood model) or by forming a less precise model of the sensory context (hypo-priors model). We used a decision-under-uncertainty paradigm that manipulated uncertainty in both likelihoods and priors. Contrary to model predictions we found no differences in reliance on likelihood in autistic group (AS) compared to neurotypicals (NT) and found no differences in subjective prior variance between groups. However, we found reduced context adjustment in the AS group compared to NT. Further, the AS group showed heightened variability in their relative weighting of sensory information (vs. prior) on a trial-by-trial basis. When participants were aligned on a continuum of autistic traits, we found no associations with likelihood reliance or prior variance but found an increase in likelihood precision with autistic traits. These findings together provide empirical evidence for intact priors, precise likelihood, reduced context updating and heightened variability during sensory learning in autism.

Cognitive Capacity Limits Are Remediated by Practice-Induced Plasticity between the Putamen and Pre-Supplementary Motor Area.

Humans show striking limitations in information processing when multitasking yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 human individuals and the plasticity caused by practice. We observed that multitasking costs, and their practice-induced remediation, are best explained by modulations in information transfer between the striatum and the cortical areas that represent stimulus-response mappings. Specifically, our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). Moreover, we propose that modulations to information transfer between these two regions leads to practice-induced improvements in multitasking.

Auditory prediction errors and auditory white matter microstructure associated with psychotic-like experiences in healthy individuals.

Our sensory systems actively predict sensory information based on previously learnt patterns, which are continuously updated with information from the actual sensory input via prediction errors. Individuals with schizophrenia consistently show reduced auditory prediction errors as well as altered fractional anisotropy (indicative of white matter changes) in the arcuate fasciculus and the auditory interhemispheric pathway, both of which are auditory white matter pathways associated with prediction errors. However, it is not clear if healthy individuals with psychotic-like experiences exhibit similar deficits. Participants underwent electroencephalography (EEG) recordings while listening to a classical two-tone duration deviant oddball paradigm (n = 103) and a stochastic oddball paradigm (n = 89). A subset of participants (n = 89) also underwent diffusion-weighted magnetic resonance imaging (MRI). Fractional anisotropy (FA), was extracted from the arcuate fasciculi and the auditory interhemispheric pathway. While prediction errors evoked by the classical oddball paradigm failed to reveal significant effects, the stochastic oddball paradigm elicited significant clusters at the typical mismatch negativity time window. Furthermore, we observed that FA of the arcuate fasciculi and auditory interhemispheric pathway significantly improved predictive models of psychotic-like experiences in healthy individuals over and above predictions made by auditory prediction error responses alone. Specifically, we observed that decreasing FA in the auditory interhemispheric pathway and reducing ability to learn stochastic irregularities are associated with increasing CAPE + scores. To the extent that these associations have previously been reported in patients with schizophrenia, the findings from this study suggest that both, auditory prediction errors and white matter changes in the auditory interhemispheric pathway, may have the potential to be translated into early screening markers for psychosis.

Sensory prediction errors in the continuum of psychosis.

Sensory prediction errors are fundamental brain responses that signal a violation of expectation in either the internal or external sensory environment, and are therefore crucial for survival and adaptive behaviour. Patients with schizophrenia show deficits in these internal and external sensory prediction errors, which can be measured using electroencephalography (EEG) components such as N1 and mismatch negativity (MMN), respectively. New evidence suggests that these deficits in sensory prediction errors are more widely distributed on a continuum of psychosis, whereas psychotic experiences exist to varying degrees throughout the general population. In this paper, we review recent findings in sensory prediction errors in the auditory domain across the continuum of psychosis, and discuss these in light of the predictive coding hypothesis.

Auditory prediction errors as individual biomarkers of schizophrenia.

Schizophrenia is a complex psychiatric disorder, typically diagnosed through symptomatic evidence collected through patient interview. We aim to develop an objective biologically-based computational tool which aids diagnosis and relies on accessible imaging technologies such as electroencephalography (EEG). To achieve this, we used machine learning techniques and a combination of paradigms designed to elicit prediction errors or Mismatch Negativity (MMN) responses. MMN, an EEG component elicited by unpredictable changes in sequences of auditory stimuli, has previously been shown to be reduced in people with schizophrenia and this is arguably one of the most reproducible neurophysiological markers of schizophrenia. EEG data were acquired from 21 patients with schizophrenia and 22 healthy controls whilst they listened to three auditory oddball paradigms comprising sequences of tones which deviated in 10% of trials from regularly occurring standard tones. Deviant tones shared the same properties as standard tones, except for one physical aspect: 1) duration - the deviant stimulus was twice the duration of the standard; 2) monaural gap - deviants had a silent interval omitted from the standard, or 3) inter-aural timing difference, which caused the deviant location to be perceived as 90° away from the standards. We used multivariate pattern analysis, a machine learning technique implemented in the Pattern Recognition for Neuroimaging Toolbox (PRoNTo) to classify images generated through statistical parametric mapping (SPM) of spatiotemporal EEG data, i.e. event-related potentials measured on the two-dimensional surface of the scalp over time. Using support vector machine (SVM) and Gaussian processes classifiers (GPC), we were able classify individual patients and controls with balanced accuracies of up to 80.48% (p-values = 0.0326, FDR corrected) and an ROC analysis yielding an AUC of 0.87. Crucially, a GP regression revealed that MMN predicted global assessment of functioning (GAF) scores (correlation = 0.73, R2 = 0.53, p = 0.0006).

The maturation of mismatch negativity networks in normal adolescence.

OBJECTIVE: We investigated the neurophysiological mechanisms underpinning the generation of the mismatch negativity (MMN) and its development from adolescence to early adulthood. METHODS: We used dynamic causal modelling (DCM) to study connectivity models for healthy adults and adolescents. MMN was elicited with an auditory oddball paradigm in two groups of healthy subjects with mean age 14 (n=52) and 26 (n=26). We tested models with different hierarchical complexities including up to five cortical nodes. RESULTS: We showed that the network generating MMN consisted of 5 nodes that could modulate all intra- and internodal connections. The inversion of this model showed that adolescents had reduced backward connection from rIFG to rSTG (p<0.04) together with increased excitatory activity in rSTG (p<0.02). There was a reduced modulation of excitability in rSTG (p<0.02) and of forward connectivity from lA1 to lSTG (p<0.03). CONCLUSION: The cortical network generating MMN continues to develop in adolescence up to adulthood. Cortical regions in the temporal and frontal lobes, involved in auditory processing, mature with increasing fronto-temporal connectivity together with increased sensitivity in the temporal regions for changes in sound stimuli. SIGNIFICANCE: This study may offer an explanation for the neurobiological maturation of the MMN in adolescence.

Andalusian Registry for familial adenomatous polyposis. Analysis of patients included.

OBJECTIVE: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. MATERIAL AND METHODS: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. RESULTS: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p < 0.05). CONCLUSIONS: The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic-genotypic correlation with statistical significance.

Síncope: manejo desde el Servicio de Urgencias de Atención Primaria / No disponible

El síncope es un problema médico importante por su alta frecuencia y la gran variedad de causas responsables del mismo. El pronóstico se relaciona con su etiología, aunque no se puede llegar a un diagnóstico de presunción al menos en el 30% de los casos, por ello desde Atención Primaria es importante estratificar el riesgo de estos pacientes mediante la realización de una historia clínica completa, la exploración física y las exploraciones complementarias, cuyos resultados nos indicarán las directrices en cuanto a criterios de derivación o medidas terapéuticas a tomar (AU)

The syncope is an important medical problem because of its high frequency and the great variety of reasons responsible for it. The prognosis is related with its etiology, though a diagnosis of presumption cannot be reached in at least 30%of the cases. Thus, it is important to stratify the risk of these patients in Primary Care with the physical and complementary examinations, whose results will provide us with the guidelines in regards to referral criteria or therapeutic measures to be used (AU)