170,717 research outputs found
Playing with free energy
No full textMark Solms's “New Project for a Scientific Psychology” represents an invaluable step in the direction of a generative model of the mental apparatus. In particular, the idea of drawing a connection between conscious processing and variations in the precision of predictions, is an idea worth pursuing. However, the imperative always to minimize free energy is far too limiting. There is no stronger sign of evolutionary fitness than not needing to minimize it and instead playing with it. We may therefore assume that the mental apparatus, and conscious processing especially, have evolved also in order to display their skill at allowing for and handling an abundance of free energy
A generative framework for the study of delusions
Full text linkDespite the ubiquity of delusional information processing in psychopathology and everyday life, formal characterizations of such inferences are lacking. In this article, we propose a generative framework that entails a computational mechanism which, when implemented in a virtual agent and given new information, generates belief updates (i.e., inferences about the hidden causes of the information) that resemble those seen in individuals with delusions. We introduce a particular form of Dirichlet process mixture model with a sampling-based Bayesian inference algorithm. This procedure, depending on the setting of a single parameter, preferentially generates highly precise (i.e. over-fitting) explanations, which are compartmentalized and thus can co-exist despite being inconsistent with each other. Especially in ambiguous situations, this can provide the seed for delusional ideation. Further, we show by simulation how the excessive generation of such over-precise explanations leads to new information being integrated in a way that does not lead to a revision of established beliefs. In all configurations, whether delusional or not, the inference generated by our algorithm corresponds to Bayesian inference. Furthermore, the algorithm is fully compatible with hierarchical predictive coding. By virtue of these properties, the proposed model provides a basis for the empirical study and a step toward the characterization of the aberrant inferential processes underlying delusions
How could we get nosology from computation?
No full textPsychiatry has found it difficult to develop a nosology that allows for the targeted treatment of disorders of the mind. The historic inability of the field to agree on a nosology based on clinical experience has led it to retreat to diagnoses based on symptom checklists as laid down in the Diagnostic and Statistical Manual of Mental Disorders (DSM). While this has increased the reliability of diagnoses, hopes that biological findings would lead to the emergence of mechanistically founded diagnostic entities have not been realized despite considerable advances in neurobiology. This article sets out a possible way forward: harnessing systems theory to provide the conceptual constraints needed to link clinical phenomena with neurobiology. This approach builds on the insight that the mind is a system which, to regulate its environment, needs to have a model of that environment and needs to update predictions about it using the rules of inductive logic (i.e., Bayesian inference). The application of the rules of inductive logic is called Bayesian inference because Bayes’s theorem is the most important consequence of these rules, prescribing how beliefs need to be updated in response to new information. Importantly, while Bayesian inference is by definition consistent with the rules of inductive logic, it can still be false (to the point of being pathological), in the
sense of leading to false predictions, because the model underlying the inference is inadequate. Further, it can be shown that Bayesian inference can be reduced to updating beliefs based on precision-weighted prediction errors, where a prediction error is the difference between actual and predicted input, and precision is the confidence associated with the input prediction. Precision weighting of prediction errors entails that a given discrepancy between outcome and prediction means more, and leads to greater belief updates, the more confidently the prediction was made. This provides a conceptual framework linking clinical experience with the pathophysiology underlying disorders of the mind. Limitations of this approach are discussed and ways to work around them illustrated with examples. Finally, initial steps and possible future directions toward a nosology based on failures of precision weighting are discussed. Copyright MIT & Frankfurt Institute of Advaced Studies
The role of GW182 proteins in microRNA-mediated gene silencing
Full text linkMicroRNAs are endogenous approximately 21-nucleotide-long non-coding RNAs that act as post-transcriptional regulators of gene expression by base pairing to target mRNAs. Mature miRNAs form part of ribonucleoprotein complexes, called miRNA-induced silencing complexes (miRISCs), that contain Argonaute (AGO) and GW182 as core proteins. Drosophila melanogaster contains only one GW182 protein (DmGW182) but there are three GW182 paralogs, TNRC6A, TNRC6B, and TNRC6C, encoded in mammalian genomes. Proteins of the GW182 family play an important role in the execution of miRNA-mediated repression. However, the molecular mechanism of GW182-mediated repression is not entirely understood.
In order to get a more comprehensive understanding of the mechanism of miRNA-mediated repression, we studied the function of GW182 proteins using human HEK293 cells and Drosophila S2 cells as model systems. As a result of these investigations, we identified the C-terminal fragment of the human GW182 protein TNRC6C (CED) as a key region mediating miRNA-induced repression by interacting with PABP via its PAM2 motif and by recruiting the PAN2-PAN3 and CCR4-CAF1-NOT deadenylase complexes via conserved tryptophan-containing motifs (W-motifs).
In addition, tethering assays in HEK293 cells and Drosophila S2 cells revealed that the C-terminal regions of GW182 proteins are able to repress not only polyadenylated but also poly(A)-free mRNAs. Interestingly, the W-motifs which are essential for interaction of the CED with the CCR4-CAF1-NOT complex, were also required for the repression of poly(A)-free mRNAs by the tethered CEDs of human TNRC6C and DmGW182. Indeed, direct tethering of CCR4-CAF1-NOT complex components in HEK293 or S2 cells repressed not only polyadenylated but also poly(A)-free mRNAs and the RNA levels of poly(A)-free mRNAs were either not affected or only slightly reduced, indicating that the major part of the repression was due to inhibition of translation. Finally, repression of poly(A)-free mRNAs in Drosophila S2 cells by tethered DmGW182 or its CED depended on NOT1 but repression by tethered CAF1 or CNOT1 was independent of GW182, indicating that NOT1 acts downstream of GW182 in the repression of poly(A)-free mRNAs.
Taken together, these data indicate that recruitment of the CCR4-CAF1-NOT complex mediated by W-motifs of GW182 proteins, in addition to inducing deadenylation, also contributes to translational repression
Hierarchical Gaussian Filtering of Sufficient Statistic Time Series for Active Inference
No full textActive inference relies on state-space models to describe the environments that agents sample with their actions. These actions lead to state changes intended to minimize future surprise. We show that surprise minimization relying on Bayesian inference can be achieved by filtering of the sufficient statistic time series of exponential family input distributions, and we propose the hierarchical Gaussian filter (HGF) as an appropriate, efficient, and scalable tool for active inference agents to achieve this
Computational approaches to psychiatry
No full textA major reason for disappointing progress of psychiatric diagnostics and nosology is the lack of tests which enable mechanistic inference on disease processes within individual patients. The resulting inability to pursue formal differential diagnosis has forced the field to stick to symptom-based diagnostic schemes with limited predictive validity concerning treatment response and clinical outcome. A promising new approach is the use of computational modeling for inferring mechanisms which generate observed behavior and brain activity in psychiatric patients. However, while this computational approach to psychiatry is rapidly gaining attention, much work remains to be done to finesse existing computational models, making them 'fit for practice' in a clinical setting and proving their validity in longitudinal studies. This review outlines recent methodological advances and strategies in this regard, focusing on generative models which infer mechanistically interpretable parameters (of computational or physiological processes) from measured behavior and brain activity. © 2013 Elsevier Ltd
Construction et validation d’une échelle dimensionnelle de l’humeur : multidimensional assessment of thymic states (MAThyS)
No full textDu fait de la grande hétérogénéité clinique des épisodes thymiques, et afin de compléter les définitions actuelles par une approche pouvant être plus en adéquation avec les stratégies thérapeutiques, nous avons créé un nouvel outil basé sur une approche dimensionnelle considérant a priori cinq sous-échelles (réactivité émotionnelle, vitesse des cognitions, motricité, motivation, perception sensorielle). L’objectif de cette étude est de valider cette échelle d’évaluation dimensionnelle des états thymiques, la multidimensional assessment of thymic states (MAThyS).
Méthode
Cent quatre-vingt-seize sujets (44 sujets témoins et 152 patients bipolaires soit en phase normothymique, maniaque ou dépressive) ont été inclus. La MAThyS est une échelle visuelle analogique ayant pour objectif de situer les différents types d’épisodes thymiques par rapport au fonctionnement de base du sujet et selon un continuum allant de l’inhibition à l’excitation.
Résultats
Considérant la structure de l’instrument, les analyses de type confirmatoire ont mis en évidence une bonne validité de face de l’outil, des validités convergente et divergente correctes (analyses multitraits multiméthodes (MTMM)), et une bonne cohérence interne de l’outil et de ses sous-échelles (coefficients alpha de Cronbach compris entre 0,70 et 0,93). La MAThyS est modérément corrélée avec la Montgomery and Åsberg depression rating scale (MADRS) qui évalue l’intensité de la symptomatologie dépressive (r = −0,5) et la mania rating scale (MAS) évaluant l’intensité de la symptomatologie maniaque (r = 0,56). Certaines dimensions sont liées entre elles (réactivité émotionnelle et vitesse des cognitions, r = 0,71 ; motivation et motricité, r = 0,70). L’analyse de la validité discriminante des items nous a incité à reformuler légèrement trois d’entre eux. Suite à cette étape de validation, des analyses complémentaires exploratoires ont permis de reconsidérer la structure de l’échelle selon une structure factorielle à quatre dimensions. Ces résultats sont discutés par rapport à la clinique.
Conclusions
Le modèle statistique final reste très proche de la représentation à cinq dimensions proposées initialement et permet de décrire les états thymiques en fonction de la réactivité émotionnelle, la motricité, le niveau de motivation et la perception sensorielle. Cependant, en tenant compte de la littérature, il semble pertinent de conserver dans l’approche clinique la dimension vitesse des cognitions.The heterogeneity of mood episodes in bipolar disorders makes it difficult in some cases to define appropriate therapeutic strategies. Therefore, we proposed a new tool based on a dimensional approach, with five a priori subscales (emotional reactivity, thought processes, psychomotricity, motivation and sense perception) expected to help define subgroups of mood episodes predictive of the response to treatment. This study was designed to validate this multidimensional assessment of thymic states (MAThyS) scale. One hundred and ninety six subjects were included: 44 controls and 152 bipolar patients in various states: euthymic, manic or depressed. The MAThyS is a visual analog scale consisting of 20 items, ranging from inhibition to excitation. These items corresponded to five dimensions, namely: emotional reactivity, thought processes, psychomotricity, motivation and sense perception. They were selected since they represent clinically relevant quantitative traits. Confirmatory analyses demonstrated a good validity for this scale, fair convergent and divergent validity (multitrait multimethod analyses (MTMM)), good internal consistency both at global and dimensional level (Alpha Cronbach ranging from 0.70 to 0.93). The MathyS scale is moderately correlated with both the Montgomery and Asberg depression rating scale (MADRS) (depression score; r=-0.45) and the mania rating scale (MAS) (manic score; r=0.56). Some dimensions were linked (emotional reactivity and thought processes, r=0.71; psychomotricity and motivation, r=0.70). Analysing the divergent validity of items led us to redefine three of them. Following this validation step, exploratory analyses suggest that a four-dimension factorial structure is more appropriate. However, the statistical model is very close to the clinically relevant five-dimensional model. Further studies are needed to explore the relevance of retaining this dimension as a useful descriptive element
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Hierarchical bayesian models of social inference for probing persecutory delusional ideation
No full textWhile persecutory delusions (PDs) have been linked to fallacies of reasoning and social inference, computational characterizations of delusional tendencies are rare. Here, we examined 151 individuals from the general population on opposite ends of the PD spectrum (Paranoia Checklist [PCL]). Participants made trial-wise predictions in a probabilistic lottery, guided by advice from a more informed human and a nonsocial cue. Additionally, 2 frames differentially emphasized causes of invalid advice: (a) the adviser’s possible intentions (dispositional frame) or (b) the rules of the game (situational frame). We applied computational modeling to examine possible reasons for group differences in behavior. Comparing different models, we found that a hierarchical Bayesian model (hierarchical Gaussian filter) explained participants’ responses better than other learning models. Model parameters determining participants’ belief updates about the adviser’s fidelity and the contribution of prior beliefs about fidelity to trial-wise decisions, respectively, showed significant Group × Frame interactions: High PCL scorers held more rigid beliefs about the adviser’s fidelity across both experimental frames and relied less on advice in situational frames than low scorers. These results suggest that PD tendencies are associated with rigid beliefs and prevent adaptive use of social information in “safe” contexts. This supports previous proposals of a link between PD and aberrant social inference. (PsycInfo Database Record (c) 2021 APA, all rights reserved
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
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