Predictive Processing: A Circuit Approach to Psychosis.

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In recent years, substantial advances have been made in our understanding of the neuronal circuitry that underlies predictive processing in cortex. In this review, we summarize these findings and how they might relate to psychosis and to observed cell type-specific effects of antipsychotic drugs. We argue that quantifying the effects of antipsychotic drugs on specific neuronal circuit elements is a promising approach to understanding not only the mechanism of action of antipsychotic drugs but also psychosis. Finally, we outline some of the key experiments that should be done. The aims of this review are to provide an overview of the current circuit-based approaches to psychosis and to encourage further research in this direction. Expected final online publication date for the Annual Review of Neuroscience, Volume 47 is July 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Sensory processing in humans and mice fluctuates between external and internal modes.

Perception is known to cycle through periods of enhanced and reduced sensitivity to external information. Here, we asked whether such slow fluctuations arise as a noise-related epiphenomenon of limited processing capacity or, alternatively, represent a structured mechanism of perceptual inference. Using 2 large-scale datasets, we found that humans and mice alternate between externally and internally oriented modes of sensory analysis. During external mode, perception aligns more closely with the external sensory information, whereas internal mode is characterized by enhanced biases toward perceptual history. Computational modeling indicated that dynamic changes in mode are enabled by 2 interlinked factors: (i) the integration of subsequent inputs over time and (ii) slow antiphase oscillations in the impact of external sensory information versus internal predictions that are provided by perceptual history. We propose that between-mode fluctuations generate unambiguous error signals that enable optimal inference in volatile environments.

The value of confidence: Confidence prediction errors drive value-based learning in the absence of external feedback.

Reinforcement learning algorithms have a long-standing success story in explaining the dynamics of instrumental conditioning in humans and other species. While normative reinforcement learning models are critically dependent on external feedback, recent findings in the field of perceptual learning point to a crucial role of internally generated reinforcement signals based on subjective confidence, when external feedback is not available. Here, we investigated the existence of such confidence-based learning signals in a key domain of reinforcement-based learning: instrumental conditioning. We conducted a value-based decision making experiment which included phases with and without external feedback and in which participants reported their confidence in addition to choices. Behaviorally, we found signatures of self-reinforcement in phases without feedback, reflected in an increase of subjective confidence and choice consistency. To clarify the mechanistic role of confidence in value-based learning, we compared a family of confidence-based learning models with more standard models predicting either no change in value estimates or a devaluation over time when no external reward is provided. We found that confidence-based models indeed outperformed these reference models, whereby the learning signal of the winning model was based on the prediction error between current confidence and a stimulus-unspecific average of previous confidence levels. Interestingly, individuals with more volatile reward-based value updates in the presence of feedback also showed more volatile confidence-based value updates when feedback was not available. Together, our results provide evidence that confidence-based learning signals affect instrumentally learned subjective values in the absence of external feedback.

Non-stimulated regions in early visual cortex encode the contents of conscious visual perception.

Predictions shape our perception. The theory of predictive processing poses that our brains make sense of incoming sensory input by generating predictions, which are sent back from higher to lower levels of the processing hierarchy. These predictions are based on our internal model of the world and enable inferences about the hidden causes of the sensory input data. It has been proposed that conscious perception corresponds to the currently most probable internal model of the world. Accordingly, predictions influencing conscious perception should be fed back from higher to lower levels of the processing hierarchy. Here, we used functional magnetic resonance imaging and multivoxel pattern analysis to show that non-stimulated regions of early visual areas contain information about the conscious perception of an ambiguous visual stimulus. These results indicate that early sensory cortices in the human brain receive predictive feedback signals that reflect the current contents of conscious perception.

Autobiographical Script-Driven Imagery Has No Detectable Effect on Emotion Regulation in Healthy Individuals.

INTRODUCTION: Emotion regulation (ER), the ability to actively modulate one's own emotion reactions, likely depends on the individual's current emotional state. Here, we investigated whether negative emotions induced by an interpersonal autobiographic script affect the neuronal processes underlying ER. METHODS: Twenty healthy participants were recruited and underwent functional magnetic resonance imaging (fMRI) during performance of distancing, a specific ER strategy, while viewing emotionally arousing pictures. Participants were instructed to either naturally experience ("permit" condition) or to actively downregulate ("regulate" condition) their emotional responses to the presented stimuli. Before each of the 4 runs in total, a neutral or negative autobiographical audio script was presented. The negative script comprised an emotionally negative event from childhood or adolescence that represented either emotional abuse or emotional neglect. The second event comprised an everyday neutral situation. We aimed at identifying the neural correlates of ER and their modulation by script-driven imagery. RESULTS: fMRI analyses testing for greater responses in the "regulate" than the "permit" condition replicated previously reported neural correlates of ER in the right dorsolateral prefrontal cortex and the right inferior parietal lobule. A significant ER effect was also observed in the left orbitofrontal cortex. In the amygdala, we found greater responses in the "permit" compared to the "regulate" condition. We did not observe a significant modulation of the ER effects in any of these regions by the negative emotional state induced by autobiographical scripts. Bayesian statistics confirmed the absence of such modulations by providing marginal evidence for null effects. DISCUSSION: While we replicated previously reported neural correlates of ER, we found no evidence for an effect of mood induction with individualized autobiographical scripts on the neural processes underlying ER in healthy participants.

Believing is seeing: The link between paranormal beliefs and perceiving signal in noise.

Research suggests that at the core of paranormal belief formation is a tendency to attribute meaning to ambiguous stimuli. But it is unclear whether this tendency reflects a difference in perceptual sensitivity or a decision bias. Using a two-alternative forced choice task, we tested the relationship between paranormal belief and perceptual sensitivity. Participants were shown two stimuli presented in temporal succession. In one interval an ambiguous Mooney Face (i.e., signal) was presented, in the other interval a scrambled version of the image (i.e., noise) was presented. Participants chose in which of the two intervals the face appeared. Our results revealed that participants with stronger beliefs in paranormal phenomena were less sensitive to discriminating signal from noise. This finding builds on previous research using "yes/no" tasks, but importantly disentangles perceptual sensitivity from response bias and suggests paranormal believers perceive things differently.

When seeing is not believing: A mechanistic basis for predictive divergence.

Visual illusions provide a compelling case for the idea that perception and belief may remain incongruent. This can be explained by modular theories of mind, but it is not straightforwardly accommodated by the Predictive Processing framework, which takes perceptual and cognitive predictions to derive from the same underlying inferential hierarchy. Recent insights concerning the neural implementation of Predictive Processing may help elucidate this. Specifically, prior information is proposed to be approximated by mechanisms in both the top-down and bottom-up streams of information processing. While the former is context-dependent and flexible in updating, the latter is context-independent and difficult to revise. We propose that a stable divergence between perception and belief may emerge when flexible prior information at higher hierarchical levels contradicts inflexible prior information at lower ones. This allows Predictive Processing to account for conflicting percepts and beliefs while still maintaining a hierarchical and unitary conception of cognition.

Cognitive Behavioral Analysis System of Psychotherapy for inpatients with persistent depressive disorder: a naturalistic trial on a general acute psychiatric unit.

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) was originally developed for outpatients with persistent depressive disorder (PDD). We adapted CBASP as inpatient treatment on a general acute psychiatric ward and evaluated its outcome and feasibility. Sixty PDD patients received a 12-week multidisciplinary CBASP program. Hamilton Depression Rating Scale (HAMD24) and Beck Depression Inventory (BDI-II) served as primary and secondary outcome measures. Childhood maltreatment at baseline and change in interpersonal distress from pre to post were investigated as predictors of treatment outcome. A 6-month follow-up assessment was conducted. Feasibility was assessed through dropouts and satisfaction with the program. Fifty patients completed the program (16.7% dropouts). An ANOVA with three repeated measurements (pre, post, FU) in the ITT sample revealed a main effect of time. For the primary outcome, depressive symptoms decreased from pre (28.3) to post (11.5, response rate: 72.7%, d = 1.8), and from pre to FU (13.9, d = 1.2). Four patients relapsed. The secondary outcome confirmed the results; however, the response rate was lower (BDI-II: 31.7%, pre to post: d = 0.8, pre to FU: d = 0.3), and ten patients relapsed at FU. Reduction in interpersonal distress, but not childhood maltreatment, predicted BDI-II response. Key limitations of this naturalistic open trial are the lack of a comparison group and non-blinded HAMD24 ratings. Inpatient CBASP for PDD appears feasible on a general acute psychiatric ward with effect sizes comparable to specialized psychotherapy wards and to the outpatient setting.

Unreliable feedback deteriorates information processing in primary visual cortex.

It is well-established that increased sensory uncertainty impairs perceptual decision-making and leads to degraded neural stimulus representations. Recently, we also showed that providing unreliable feedback to choices leads to changes in perceptual decision-making similar to those of increased stimulus noise: A deterioration in objective task performance, a decrease in subjective confidence and a lower reliance on sensory information for perceptual inference. To investigate the neural basis of such feedback-based changes in perceptual decision-making, in the present study, two groups of healthy human participants (n = 15 each) performed a challenging visual orientation discrimination task while undergoing functional magnetic resonance imaging (fMRI). Critically, one group received reliable feedback regarding their task performance in an intervention phase, whereas the other group correspondingly received unreliable feedback - thereby keeping stimulus information constant. The effects of feedback reliability on performance and stimulus representation in the primary visual cortex (V1) were studied by comparing the pre- and post-intervention test phases between the groups. Compared to participants who received reliable feedback, those receiving unreliable feedback showed a decline in task performance that was paralleled by reduced distinctness of fMRI response patterns in V1. These results show that environmental uncertainty can affect perceptual inference at the earliest cortical processing stages.

No evidence for mnemonic modulation of interocularly suppressed visual input.

Visual working memory (VWM) allows for keeping visual information available for upcoming goal-directed behavior, while new visual input is processed concurrently. Interactions between the mnemonic and perceptual systems cause VWM to affect the processing of visual input in a content-specific manner: visual input that is initially suppressed from consciousness is detected faster when it matches rather than mismatches the content of VWM. It is currently under debate whether such mnemonic influences on perception occur prior to or after conscious access. To address this issue, we investigated whether VWM content modulates the neural response to visual input that remains suppressed from consciousness. We measured fMRI responses to interocularly suppressed stimuli in 20 human participants performing a delayed match-to-sample task: Participants were retro-cued to memorize one of two geometrical shapes for subsequent recognition. During retention, an interocularly suppressed peripheral stimulus (the probe) was briefly presented, which was either of the cued (memorized) or uncued (not memorized) shape category. We found no evidence that VWM content modulated the neural response to the probe. Substantial evidence for the absence of this modulation was found despite leveraging a highly liberal analysis approach: (1) selecting regions of interest that were particularly prone to detecting said modulation, and (2) using directional Bayesian tests favoring the presence of the hypothesized modulation. We did observe faster detection of memory-matching compared to memory-mismatching probes in a behavioral control experiment, thus validating the stimulus set. We conclude that VWM impacts the processing of visual input only once suppression is mostly alleviated.

Correction to: Migration and schizophrenia: meta-analysis and explanatory framework.

In the original article, the reference number #36 is listed with the wrong list of authors. The first author was unfortunately omitted. The correct reference #36 should read: Lasalvia A, Bonetto C, Tosato S, Cristofalo D, Salazzari D et al (2014) First-contact incidence of psychosis in north-eastern Italy: influence of age, gender, immigration and socioeconomic deprivation. Br J Psychiatry 205:127-134. https://doi.org/10.1192/bjp.bp.113.134445 .Additionally, this reference is cited in Table 1 and Fig. 2 as "Bonetto (2015)" and the correct citation is "Lasalvia (2014)".

Migration and schizophrenia: meta-analysis and explanatory framework.

Systematic reviews and meta-analyses suggest that there are increased rates of schizophrenia and related psychoses in first- and second-generation migrants and refugees. Here, we present a meta-analysis on the incidence of non-affective psychotic disorders among first- and second-generation migrants. We found substantial evidence for an increased relative risk of incidence among first- and second-generation migrants compared to the native population. As heterogeneity of included studies was high, effect estimates should be interpreted with caution and as guiding values rather than exact risk estimates. We interpret our findings in the context of social exclusion and isolation stress, and provide an explanatory framework that links cultural differences in verbal communication and experienced discrimination with the emergence of psychotic experiences and their neurobiological correlates. In this context, we discuss studies observing stress-dependent alterations of dopamine neurotransmission in studies among migrants versus non-migrants as well as in subjects with psychotic disorders. We suggest that social stress effects can impair contextualization of the meaning of verbal messages, which can be accounted for in Bayesian terms by a reduced precision of prior beliefs relative to sensory data, causing increased prediction errors and resulting in a shift towards the literal or "concrete" meaning of words. Compensatory alterations in higher-level beliefs, e.g., in the form of generalized interpretations of ambiguous interactions as hostile behavior, may contribute to psychotic experiences in migrants. We thus suggest that experienced discrimination and social exclusion is at the core of increased rates of psychotic experiences in subjects with a migration background.

The Neural Correlates of Hierarchical Predictions for Perceptual Decisions.

Sensory information is inherently noisy, sparse, and ambiguous. In contrast, visual experience is usually clear, detailed, and stable. Bayesian theories of perception resolve this discrepancy by assuming that prior knowledge about the causes underlying sensory stimulation actively shapes perceptual decisions. The CNS is believed to entertain a generative model aligned to dynamic changes in the hierarchical states of our volatile sensory environment. Here, we used model-based fMRI to study the neural correlates of the dynamic updating of hierarchically structured predictions in male and female human observers. We devised a crossmodal associative learning task with covertly interspersed ambiguous trials in which participants engaged in hierarchical learning based on changing contingencies between auditory cues and visual targets. By inverting a Bayesian model of perceptual inference, we estimated individual hierarchical predictions, which significantly biased perceptual decisions under ambiguity. Although "high-level" predictions about the cue-target contingency correlated with activity in supramodal regions such as orbitofrontal cortex and hippocampus, dynamic "low-level" predictions about the conditional target probabilities were associated with activity in retinotopic visual cortex. Our results suggest that our CNS updates distinct representations of hierarchical predictions that continuously affect perceptual decisions in a dynamically changing environment.SIGNIFICANCE STATEMENT Bayesian theories posit that our brain entertains a generative model to provide hierarchical predictions regarding the causes of sensory information. Here, we use behavioral modeling and fMRI to study the neural underpinnings of such hierarchical predictions. We show that "high-level" predictions about the strength of dynamic cue-target contingencies during crossmodal associative learning correlate with activity in orbitofrontal cortex and the hippocampus, whereas "low-level" conditional target probabilities were reflected in retinotopic visual cortex. Our findings empirically corroborate theorizations on the role of hierarchical predictions in visual perception and contribute substantially to a longstanding debate on the link between sensory predictions and orbitofrontal or hippocampal activity. Our work fundamentally advances the mechanistic understanding of perceptual inference in the human brain.

Decision-making in schizophrenia: A predictive-coding perspective.

Dysfunctional decision-making has been implicated in the positive and negative symptoms of schizophrenia. Decision-making can be conceptualized within the framework of hierarchical predictive coding as the result of a Bayesian inference process that uses prior beliefs to infer states of the world. According to this idea, prior beliefs encoded at higher levels in the brain are fed back as predictive signals to lower levels. Whenever these predictions are violated by the incoming sensory data, a prediction error is generated and fed forward to update beliefs encoded at higher levels. Well-documented impairments in cognitive decision-making support the view that these neural inference mechanisms are altered in schizophrenia. There is also extensive evidence relating the symptoms of schizophrenia to aberrant signaling of prediction errors, especially in the domain of reward and value-based decision-making. Moreover, the idea of altered predictive coding is supported by evidence for impaired low-level sensory mechanisms and motor processes. We review behavioral and neural findings from these research areas and provide an integrated view suggesting that schizophrenia may be related to a pervasive alteration in predictive coding at multiple hierarchical levels, including cognitive and value-based decision-making processes as well as sensory and motor systems. We relate these findings to decision-making processes and propose that varying degrees of impairment in the implicated brain areas contribute to the variety of psychotic experiences.

Access to awareness of direct gaze is related to autistic traits.

BACKGROUND: The atypical processing of eye contact is a characteristic hallmark of autism spectrum disorder (ASD). The severity of these symptoms, however, is thought to lie on a continuum that extends into the typical population. While behavioural evidence shows that differences in social cognitive tasks in typically developed (TD) adults are related to the levels of autistic-like traits, it remains unknown whether such a relation exists for the sensitivity to direct gaze. METHODS: In two experiments, we measured reaction times to detect the faces with direct and averted gaze, suppressed from awareness, i.e. the access to awareness. In experiment 1, we tested N = 19 clinically diagnosed adults with ASD and N = 22 TD matched controls, while in experiment 2, we tested an independent sample of N = 20 TD adults. RESULTS: In line with the literature, experiment 1 showed preferential processing of direct gaze in the TD group but not in the ASD group. Importantly, we found a linear relationship in both experiments between the levels of autistic traits within the groups of TD participants and their sensitivity to direct gaze: with increasing autistic characteristics, there was a decrease in sensitivity to direct gaze. CONCLUSION: These results provide the first evidence that differences in gaze processing and the sensitivity to direct gaze are already present in individuals with subclinical levels of autistic traits. Furthermore, they lend support to the continuum view of the disorder and could potentially help in an earlier diagnosis of individuals at high risk for autism.

Differences between chronic and nonchronic depression: Systematic review and implications for treatment.

BACKGROUND: There is still uncertainty if and to what extent chronic depression (CD) presents with specific features especially in contrast to the nonchronic course of major depressive disorder (non-CD). This systematic review aims to summarize the existing literature regarding sociodemographic factors, psychopathology, and course of disease in patients with CD in comparison to patients with non-CD. METHODS: A structured database search (MEDLINE, PsycINFO, Web of Science, CENTRAL) was performed. All studies comparing CD with non-CD patients were included. Twenty-eight studies, including cohort studies, cross-sectional studies, and observational studies, were identified in which both subgroups were diagnosed according to DSM-IV or DSM-5, respectively. Primary outcome were group comparisons focused on sociodemographic factors, childhood adversity, onset of the disorder, comorbidities, severity and course of the depressive symptoms, and specific psychopathology. RESULTS: Patients with CD had an earlier onset of depressive symptoms, higher rates of psychiatric comorbidities, and a complicated treatment course (e.g., higher rates of suicidality) compared to non-CD. We also found some evidence for specific features in the psychopathology of CD patients (submissive and hostile interpersonal styles) in contrast to non-CD patients. Results were inconsistent with regard to childhood maltreatment. No differences were found regarding the severity of depressive symptoms and most sociodemographic factors. CONCLUSION: Despite some inconsistencies, the results of this review verified important differences between CD and non-CD. However, future research is needed to characterize especially the specific psychopathology of CD in comparison to non-CD patients to develop more tailored treatment strategies.

Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk.

The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t(30) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.

Multistable Perception and the Role of the Frontoparietal Cortex in Perceptual Inference.

A given pattern of optical stimulation can arise from countless possible real-world sources, creating a dilemma for vision: What in the world actually gives rise to the current pattern? This dilemma was pointed out centuries ago by the astronomer and mathematician Ibn Al-Haytham and was forcefully restated 150 years ago when von Helmholtz characterized perception as unconscious inference. To buttress his contention, von Helmholtz cited multistable perception: recurring changes in perception despite unchanging sensory input. Recent neuroscientific studies have exploited multistable perception to identify brain areas uniquely activated in association with these perceptual changes, but the specific roles of those activations remain controversial. This article provides an overview of theoretical models of multistable perception, a review of recent neuroimaging and brain stimulation studies focused on mechanisms associated with these perceptual changes, and a synthesis of available evidence within the context of current notions about Bayesian inference that find their historical roots in von Helmholtz's work.

Visual Working Memory Enhances the Neural Response to Matching Visual Input.

Visual working memory (VWM) is used to maintain visual information available for subsequent goal-directed behavior. The content of VWM has been shown to affect the behavioral response to concurrent visual input, suggesting that visual representations originating from VWM and from sensory input draw upon a shared neural substrate (i.e., a sensory recruitment stance on VWM storage). Here, we hypothesized that visual information maintained in VWM would enhance the neural response to concurrent visual input that matches the content of VWM. To test this hypothesis, we measured fMRI BOLD responses to task-irrelevant stimuli acquired from 15 human participants (three males) performing a concurrent delayed match-to-sample task. In this task, observers were sequentially presented with two shape stimuli and a retro-cue indicating which of the two shapes should be memorized for subsequent recognition. During the retention interval, a task-irrelevant shape (the probe) was briefly presented in the peripheral visual field, which could either match or mismatch the shape category of the memorized stimulus. We show that this probe stimulus elicited a stronger BOLD response, and allowed for increased shape-classification performance, when it matched rather than mismatched the concurrently memorized content, despite identical visual stimulation. Our results demonstrate that VWM enhances the neural response to concurrent visual input in a content-specific way. This finding is consistent with the view that neural populations involved in sensory processing are recruited for VWM storage, and it provides a common explanation for a plethora of behavioral studies in which VWM-matching visual input elicits a stronger behavioral and perceptual response.SIGNIFICANCE STATEMENT Humans heavily rely on visual information to interact with their environment and frequently must memorize such information for later use. Visual working memory allows for maintaining such visual information in the mind's eye after termination of its retinal input. It is hypothesized that information maintained in visual working memory relies on the same neural populations that process visual input. Accordingly, the content of visual working memory is known to affect our conscious perception of concurrent visual input. Here, we demonstrate for the first time that visual input elicits an enhanced neural response when it matches the content of visual working memory, both in terms of signal strength and information content.

Multivariate pattern analysis for MEG: A comparison of dissimilarity measures.

Multivariate pattern analysis (MVPA) methods such as decoding and representational similarity analysis (RSA) are growing rapidly in popularity for the analysis of magnetoencephalography (MEG) data. However, little is known about the relative performance and characteristics of the specific dissimilarity measures used to describe differences between evoked activation patterns. Here we used a multisession MEG data set to qualitatively characterize a range of dissimilarity measures and to quantitatively compare them with respect to decoding accuracy (for decoding) and between-session reliability of representational dissimilarity matrices (for RSA). We tested dissimilarity measures from a range of classifiers (Linear Discriminant Analysis - LDA, Support Vector Machine - SVM, Weighted Robust Distance - WeiRD, Gaussian Naïve Bayes - GNB) and distances (Euclidean distance, Pearson correlation). In addition, we evaluated three key processing choices: 1) preprocessing (noise normalisation, removal of the pattern mean), 2) weighting decoding accuracies by decision values, and 3) computing distances in three different partitioning schemes (non-cross-validated, cross-validated, within-class-corrected). Four main conclusions emerged from our results. First, appropriate multivariate noise normalization substantially improved decoding accuracies and the reliability of dissimilarity measures. Second, LDA, SVM and WeiRD yielded high peak decoding accuracies and nearly identical time courses. Third, while using decoding accuracies for RSA was markedly less reliable than continuous distances, this disadvantage was ameliorated by decision-value-weighting of decoding accuracies. Fourth, the cross-validated Euclidean distance provided unbiased distance estimates and highly replicable representational dissimilarity matrices. Overall, we strongly advise the use of multivariate noise normalisation as a general preprocessing step, recommend LDA, SVM and WeiRD as classifiers for decoding and highlight the cross-validated Euclidean distance as a reliable and unbiased default choice for RSA.