Can neutral episodic memories become emotional? Evidence from facial expressions and subjective feelings.

Maladaptive emotional memories are a transdiagnostic feature of mental health problems. Therefore, understanding whether and how emotional memories can change might help to prevent and treat mental disorders. We tested whether neutral memories of naturalistic events can retroactively acquire positive or negative affect, in a preregistered three-day Modification of Valence in Episodes (MOVIE) paradigm. On Day 1, participants (N = 41) encoded memories of neutral movie scenes, representing lifelike naturalistic experiences. On Day 2, they retrieved each episode before viewing a happy, sad, or neutral scene from the same movie (yielding a within-subjects design with a neutral-negative, neutral-positive, and neutral-neutral condition). On Day 3, participants again retrieved each memory from Day 1. We assessed the affective tone of episodes through facial expressions of positive and negative affect (using facial electromyography, fEMG) and through self-reported feelings. Positive updating of neutral episodes led to increased expressions of positive affect, whereas negative updating led to increased self-reported negative feelings. These results suggest that complex neutral episodic memories can retroactively acquire an affective tone, but the effects were modest and inconsistent across affect readouts. Future research should investigate alternative approaches to updating emotional memories that produce more profound changes in the valence of memories.

A faulty compass: Why do some people choose situations that are not good for them?

Why do some people seem to be drawn to situations that are not good for them? While we all regularly end up in situations that we would have preferred to avoid, we tend to not choose situations or other people that are not good for us, and with time most of us get better at recognizing and avoiding these situations. However, it is a well-known clinical phenomenon that some people have a faulty compass when it comes to these situations, increasing the likelihood of repeated exposure to negative experiences and even trauma. In this paper, we reflect on the relationship between adverse experiences early in development and dysfunctional choices in adulthood, with the aim to reinvigorate interest in this clinically important phenomenon, which is in need of rigorous empirical study. Based on the literature and clinical observations, we distill four categories of hypotheses: people make dysfunctional choices 1) to process or master previous trauma, 2) out of habit and because of preferences for what is familiar, 3) to maintain a coherent view of themselves and the world, and 4) to avoid difficult emotions. We end with concrete questions that can help narrow down the heterogenous set of observations and explanations, providing a first step towards a better conceptualisation and systematic documentation of (factors contributing to) maladaptive situation selection. We dedicate this essay to Jack Rachman, who was a great inspirator for the field of experimental psychopathology with his essays highlighting phenomena that were overlooked and drawing attention to fresh ideas.

Emotional memory in the lab: Using the Trier Social Stress Test to induce a sensory-rich and personally meaningful episodic experience.

A myriad of clinical theories places emotional memory or mental representations at the root of mental disorders. Various cognitive-behavioural interventions are based on the assumption that targeting the underlying emotional memory is the working mechanism of treatment efficacy. To test the assumptions about the role of emotional memory in the development, maintenance, and treatment of mental disorders, we first need to establish ecologically valid paradigms that can induce emotional memory in the lab. For this, we used the Trier Social Stress Test (TSST), a standardized protocol to elicit social distress, paired with a neutral unfamiliar ambient odour, to create a sensory-rich and personally meaningful episodic experience. Seven days later, participants (N = 132) reactivated the memory of the TSST with the aid of auditory, olfactory, and visual retrieval cues, during which their heart rate and self-reported affective responses were collected. Although increases in heart rate were only observed during encoding, and not at retrieval, self-report ratings showed that cues which directly referred to the aversive experience evoked more negative valence, arousal, and feelings of lack of control during memory reactivation compared to control cues across sensory modalities. These findings are indicative of successful memory induction and corroborate the utility of ambient odours as retrieval aids. Moreover, the self-reported response to the reactivated emotional memory correlated with individual differences in indices of (social) anxiety and depression. Thereby, we provide preliminary evidence of the translational significance of this paradigm that offers potential for being a model to induce ecologically valid emotional memory in the lab.

More than just fear: Development and psychometric evaluation of the Spider Distress Scale to assess spider fear and spider-related disgust.

Spider fear is an excellent model to experimentally study processes in the maintenance and treatment of long-lasting fears. A valid, reliable, and practical tool to assess spider-related distress dimensionally, and to differentiate between spider-related fear and disgust in a time-sensitive manner, may help to better understand individual differences in these two emotions and to tailor treatments accordingly. We developed a concise self-report questionnaire, the Spider Distress Scale (SDS), that combines the strengths of established spider fear questionnaires and addresses their shortcomings. We explored (study 1 and 2) and confirmed (study 3) a two-factor structure of the SDS in samples from the general population (n = 370; n = 360; n = 423), recruited online via Prolific Academic from the United Kingdom, the Netherlands, and the United States. The fear and disgust factors of the SDS are highly internally consistent and the SDS has excellent test-retest reliability. We found good convergent and discriminant validity, based on self-report measures and spider behavioural approach tasks, and the SDS successfully differentiated between individuals with and without spider fear (study 4, n = 75). Our series of studies suggests that fear and disgust are functionally related, but that disgust towards spiders can be differentially assessed when focussing on unique elements of disgust-related information.

Jumping back onto the giants' shoulders: Why emotional memory should be considered in a network perspective of psychopathology.

Clinical psychology finds itself with a paradox: On the one hand, there is abundant empirical evidence showing that aversive experiences increase the risk for psychopathology. In fact, a learning and memory framework forms the foundation of numerous psychological theories and treatments. For example, various CBT approaches aim to target maladaptive emotional memories (e.g., schemas or cognitions) that are deemed to lie at the core of mental health conditions. On the other hand, a new approach - the network theory - is gaining ground, which ignores underlying causes for mental disorders and instead dictates a focus on symptoms and their causal interactions. While radical shifts are sometimes necessary in science, we argue why completely neglecting common causes, such as emotional memory, is not justified. We critically discuss the strengths and limitations of the network approach: While its transdiagnostic nature and recognition of symptom interactions have the potential to invigorate the field, the framework is merely descriptive, its concepts not well defined, and its clinical utility still to be established. To move forward, we propose an incorporation of latent constructs into the network model, starting with clearer definitions and operationalisations of concepts in both network and latent variable models.

Over the Edge: Extending the duration of a reconsolidation intervention for spider fear.

Pharmacologically disrupting fear memory reconsolidation dramatically reduces fear behaviour. For example, 2-3 min of tarantula exposure followed by 40 mg of propranolol HCl (i.e., a reconsolidation intervention) abruptly decreased spider avoidance, an effect that persisted one year later. However, the success of reconsolidation interventions is not guaranteed: Pavlovian fear-conditioning research shows that the window to target memory reconsolidation is small and easy to miss. If exposure is too long to trigger reconsolidation, but too short for extinction learning, an inactive transitional limbo state occurs, rendering the fear memory unchanged and insensitive to amnesic agents. In this pre-registered study, we aimed to find this behaviourally-controlled boundary condition. Spider-fearful participants underwent a ~3 min (n = 23) or ~14 min (n = 20) exposure to a tarantula, intended to trigger reconsolidation or the limbo state respectively, followed by 40 mg of propranolol. We expected greater spider fear reduction after 3 than 14 min of exposure. Unexpectedly, there were no group differences on any outcome measures. In both groups, Bayesian analysis revealed a marked reduction in fear behaviour towards a generalisation stimulus (a house spider) accompanied by lower self-reported distress, with a sharp decline in spider fear scores two days after treatment that persisted one year later. Possible explanations include that the boundary conditions of reconsolidation are wider in older and stronger memories than experimentally-induced fears, or that alternative processes caused the treatment effects. Although the mechanism is unclear, these results carry a tentative promising message for the potential of brief reconsolidation-targeting interventions to mitigate irrational fears.

A Naturalistic Paradigm to Investigate Postencoding Neural Activation Patterns in Relation to Subsequent Voluntary and Intrusive Recall of Distressing Events.

BACKGROUND: While neuroimaging has provided insights into the formation of episodic memories in relation to voluntary memory recall, less is known about neural mechanisms that cause memories to occur involuntarily, for example, as intrusive memories of trauma. Here, we investigated brain activity shortly after viewing distressing events as a function of whether memories for those events later intruded involuntarily. The postencoding period is particularly important because it is a period when clinical interventions could be applied. METHODS: A total of 32 healthy volunteers underwent functional magnetic resonance imaging while viewing distressing film clips, interspersed with 5 minutes of awake (postencoding) rest. Voluntary memories of the films were assessed using free recall and verbal and visual recognition tests after a week, while intrusive (involuntary) memories were recorded in a diary throughout that week. RESULTS: When analyzing functional magnetic resonance imaging responses related to watching the films, we replicated findings that those "hotspots" (salient moments within the films) that would later become intrusive memories elicited higher activation in parts of the brain's salience network. Surprisingly, while the postencoding persistence of multivoxel correlation structures associated with entire film clips predicted subsequent voluntary recall, there was no evidence that they predicted subsequent intrusions. CONCLUSIONS: Results replicate findings regarding the formation of intrusive memories during encoding and extend findings regarding the consolidation of information in postencoding rest in relation to voluntary memory. While we provided a first step using a naturalistic paradigm, further research is needed to elucidate the role of postencoding neural processes in the development of intrusive memories.

Model-based representational similarity analysis of blood-oxygen-level-dependent fMRI captures threat learning in social interactions.

Past research has shown that attributions of intentions to other's actions determine how we experience these actions and their consequences. Yet, it is unknown how such attributions affect our learning and memory. Addressing this question, we combined neuroimaging with an interactive threat learning paradigm in which two interaction partners (confederates) made choices that had either threatening (shock) or safe (no shock) consequences for the participants. Importantly, participants were led to believe that one partner intentionally caused the delivery of shock, whereas the other did not (i.e. unintentional partner). Following intentional versus unintentional shocks, participants reported an inflated number of shocks and a greater increase in anger and vengeance. We applied a model-based representational similarity analysis to blood-oxygen-level-dependent (BOLD)-MRI patterns during learning. Surprisingly, we did not find any effects of intentionality. The threat value of actions, however, was represented as a trial-by-trial increase in representational similarity in the insula and the inferior frontal gyrus. Our findings illustrate how neural pattern formation can be used to study a complex interaction.

Robust BOLD Responses to Faces But Not to Conditioned Threat: Challenging the Amygdala's Reputation in Human Fear and Extinction Learning.

Most of our knowledge about human emotional memory comes from animal research. Based on this work, the amygdala is often labeled the brain's "fear center", but it is unclear to what degree neural circuitries underlying fear and extinction learning are conserved across species. Neuroimaging studies in humans yield conflicting findings, with many studies failing to show amygdala activation in response to learned threat. Such null findings are often treated as resulting from MRI-specific problems related to measuring deep brain structures. Here we test this assumption in a mega-analysis of three studies on fear acquisition (n = 98; 68 female) and extinction learning (n = 79; 53 female). The conditioning procedure involved the presentation of two pictures of faces and two pictures of houses: one of each pair was followed by an electric shock [a conditioned stimulus (CS+)], the other one was never followed by a shock (CS-), and participants were instructed to learn these contingencies. Results revealed widespread responses to the CS+ compared with the CS- in the fear network, including anterior insula, midcingulate cortex, thalamus, and bed nucleus of the stria terminalis, but not the amygdala, which actually responded stronger to the CS- Results were independent of spatial smoothing, and of individual differences in trait anxiety and conditioned pupil responses. In contrast, robust amygdala activation distinguished faces from houses, refuting the idea that a poor signal could account for the absence of effects. Moving forward, we suggest that, apart from imaging larger samples at higher resolution, alternative statistical approaches may be used to identify cross-species similarities in fear and extinction learning.SIGNIFICANCE STATEMENT The science of emotional memory provides the foundation of numerous theories on psychopathology, including stress and anxiety disorders. This field relies heavily on animal research, which suggests a central role of the amygdala in fear learning and memory. However, this finding is not strongly corroborated by neuroimaging evidence in humans, and null findings are too easily explained away by methodological limitations inherent to imaging deep brain structures. In a large nonclinical sample, we find widespread BOLD activation in response to learned fear, but not in the amygdala. A poor signal could not account for the absence of effects. While these findings do not disprove the involvement of the amygdala in human fear learning, they challenge its typical portrayals and illustrate the complexities of translational science.

Neural Pattern Similarity Unveils the Integration of Social Information and Aversive Learning.

Attributing intentions to others' actions is important for learning to avoid their potentially harmful consequences. Here, we used functional magnetic resonance imaging multivariate pattern analysis to investigate how the brain integrates information about others' intentions with the aversive outcome of their actions. In an interactive aversive learning task, participants (n = 33) were scanned while watching two alleged coparticipants (confederates)-one making choices intentionally and the other unintentionally-leading to aversive (a mild shock) or safe (no shock) outcomes to the participant. We assessed the trial-by-trial changes in participants' neural activation patterns related to observing the coparticipants and experiencing the outcome of their choices. Participants reported a higher number of shocks, more discomfort, and more anger to shocks given by the intentional player. Intentionality enhanced responses to aversive actions in the insula, anterior cingulate cortex, inferior frontal gyrus, dorsal medial prefrontal cortex, and the anterior superior temporal sulcus. Our findings indicate that neural pattern similarities index the integration of social and threat information across the cortex.

Intrusive memories of trauma: A target for research bridging cognitive science and its clinical application.

Intrusive memories of a traumatic event can be distressing and disruptive, and comprise a core clinical feature of post-traumatic stress disorder (PTSD). Intrusive memories involve mental imagery-based impressions that intrude into mind involuntarily, and are emotional. Here we consider how recent advances in cognitive science have fueled our understanding of the development and possible treatment of intrusive memories of trauma. We conducted a systematic literature search in PubMed, selecting articles published from 2008 to 2018 that used the terms "trauma" AND ("intrusive memories" OR "involuntary memories") in their abstract or title. First, we discuss studies that investigated internal (neural, hormonal, psychophysiological, and cognitive) processes that contribute to intrusive memory development. Second, we discuss studies that targeted these processes using behavioural/pharmacological interventions to reduce intrusive memories. Third, we consider possible clinical implications of this work and highlight some emerging research avenues for treatment and prevention, supplemented by new data to examine some unanswered questions. In conclusion, we raise the possibility that intrusive memories comprise an alternative, possibly more focused, target in translational research endeavours, rather than only targeting overall symptoms of disorders such as PTSD. If so, relatively simple approaches could help to address the need for easy-to-deliver, widely-scalable trauma interventions.

The influence of acoustic startle probes on fear learning in humans.

Even though human fear-conditioning involves affective learning as well as expectancy learning, most studies assess only one of the two distinct processes. Commonly used read-outs of associative fear learning are the fear-potentiated startle reflex (FPS), pupil dilation and US-expectancy ratings. FPS is thought to reflect the affective aspect of fear learning, while pupil dilation reflects a general arousal response. However, in order to measure FPS, aversively loud acoustic probes are presented during conditioning, which might in itself exert an effect on fear learning. Here we tested the effect of startle probes on fear learning by comparing brain activation (fMRI), pupil dilation and US-expectancy ratings with and without acoustic startle probes within subjects. Regardless of startle probes, fear conditioning resulted in enhanced dACC, insula and ventral striatum activation. Interaction analyses showed that startle probes diminished differential pupil dilation between CS+ and CS- due to increased pupil responses to CS-. A trend significant interaction effect was observed for US-expectancy and amygdala activation. Startle probes affect differential fear learning by impeding safety learning, as measured with pupil dilation, a read-out of the cognitive component of fear learning. However, we observed no significant effect of acoustic startle probes on other measures of fear learning.

A translational perspective on neural circuits of fear extinction: Current promises and challenges.

Fear extinction is the well-known process of fear reduction through repeated re-exposure to a feared stimulus without the aversive outcome. The last two decades have witnessed a surge of interest in extinction learning. First, extinction learning is observed across species, and especially research on rodents has made great strides in characterising the physical substrate underlying extinction learning. Second, extinction learning is considered of great clinical significance since it constitutes a crucial component of exposure treatment. While effective in reducing fear responding in the short term, extinction learning can lose its grip, resulting in a return of fear (i.e., laboratory model for relapse of anxiety symptoms in patients). Optimization of extinction learning is, therefore, the subject of intense investigation. It is thought that the success of extinction learning is, at least partly, determined by the mismatch between what is expected and what actually happens (prediction error). However, while much of our knowledge about the neural circuitry of extinction learning and factors that contribute to successful extinction learning comes from animal models, translating these findings to humans has been challenging for a number of reasons. Here, we present an overview of what is known about the animal circuitry underlying extinction of fear, and the role of prediction error. In addition, we conducted a systematic literature search to evaluate the degree to which state-of-the-art neuroimaging methods have contributed to translating these findings to humans. Results show substantial overlap between networks in animals and humans at a macroscale, but current imaging techniques preclude comparisons at a smaller scale, especially in sub-cortical areas that are functionally heterogeneous. Moreover, human neuroimaging shows the involvement of numerous areas that are not typically studied in animals. Results obtained in research aimed to map the extinction circuit are largely dependent on the methods employed, not only across species, but also across human neuroimaging studies. Directions for future research are discussed.

Multiple memory systems, multiple time points: how science can inform treatment to control the expression of unwanted emotional memories.

Memories that have strong emotions associated with them are particularly resilient to forgetting. This is not necessarily problematic, however some aspects of memory can be. In particular, the involuntary expression of those memories, e.g. intrusive memories after trauma, are core to certain psychological disorders. Since the beginning of this century, research using animal models shows that it is possible to change the underlying memory, for example by interfering with its consolidation or reconsolidation. While the idea of targeting maladaptive memories is promising for the treatment of stress and anxiety disorders, a direct application of the procedures used in non-human animals to humans in clinical settings is not straightforward. In translational research, more attention needs to be paid to specifying what aspect of memory (i) can be modified and (ii) should be modified. This requires a clear conceptualization of what aspect of memory is being targeted, and how different memory expressions may map onto clinical symptoms. Furthermore, memory processes are dynamic, so procedural details concerning timing are crucial when implementing a treatment and when assessing its effectiveness. To target emotional memory in its full complexity, including its malleability, science cannot rely on a single method, species or paradigm. Rather, a constructive dialogue is needed between multiple levels of research, all the way 'from mice to mental health'.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

From neuroscience to evidence based psychological treatments - The promise and the challenge, ECNP March 2016, Nice, France.

This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches are not fully satisfactory, there is an imperative to understand why not. And when psychological therapies do work we need to understand why this is the case, and how we can improve them. We may be able to improve accessibility to treatment without understanding mechanisms. But for treatment innovation and improvement, mechanistic insights may actually help. Applying neuroscience in this way will become an additional mission for ECNP.

'I Can't Concentrate': A Feasibility Study with Young Refugees in Sweden on Developing Science-Driven Interventions for Intrusive Memories Related to Trauma.

BACKGROUND: The number of refugees is the highest ever worldwide. Many have experienced trauma in home countries or on their escape which has mental health sequelae. Intrusive memories comprise distressing scenes of trauma which spring to mind unbidden. Development of novel scalable psychological interventions is needed urgently. AIMS: We propose that brief cognitive science-driven interventions should be developed which pinpoint a focal symptom alongside a means to monitor it using behavioural techniques. The aim of the current study was to assess the feasibility and acceptability of the methodology required to develop such an intervention. METHOD: In this study we recruited 22 refugees (16-25 years), predominantly from Syria and residing in Sweden. Participants were asked to monitor the frequency of intrusive memories of trauma using a daily diary; rate intrusions and concentration; and complete a 1-session behavioural intervention involving Tetris game-play via smartphone. RESULTS: Frequency of intrusive memories was high, and associated with high levels of distress and impaired concentration. Levels of engagement with study procedures were highly promising. CONCLUSIONS: The current work opens the way for developing novel cognitive behavioural approaches for traumatized refugees that are mechanistically derived, freely available and internationally scalable.

First Steps in Using Multi-Voxel Pattern Analysis to Disentangle Neural Processes Underlying Generalization of Spider Fear.

A core symptom of anxiety disorders is the tendency to interpret ambiguous information as threatening. Using electroencephalography and blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI), several studies have begun to elucidate brain processes involved in fear-related perceptual biases, but thus far mainly found evidence for general hypervigilance in high fearful individuals. Recently, multi-voxel pattern analysis (MVPA) has become popular for decoding cognitive states from distributed patterns of neural activation. Here, we used this technique to assess whether biased fear generalization, characteristic of clinical fear, is already present during the initial perception and categorization of a stimulus, or emerges during the subsequent interpretation of a stimulus. Individuals with low spider fear (n = 20) and high spider fear (n = 18) underwent functional MRI scanning while viewing series of schematic flowers morphing to spiders. In line with previous studies, individuals with high fear of spiders were behaviorally more likely to classify ambiguous morphs as spiders than individuals with low fear of spiders. Univariate analyses of BOLD-MRI data revealed stronger activation toward spider pictures in high fearful individuals compared to low fearful individuals in numerous areas. Yet, neither average activation, nor support vector machine classification (i.e., a form of MVPA) matched the behavioral results - i.e., a biased response toward ambiguous stimuli - in any of the regions of interest. This may point to limitations of the current design, and to challenges associated with classifying emotional and neutral stimuli in groups that differ in their judgment of emotionality. Improvements for future research are suggested.

The trauma film paradigm as an experimental psychopathology model of psychological trauma: intrusive memories and beyond.

A better understanding of psychological trauma is fundamental to clinical psychology. Following traumatic event(s), a clinically significant number of people develop symptoms, including those of Acute Stress Disorder and/or Post Traumatic Stress Disorder. The trauma film paradigm offers an experimental psychopathology model to study both exposure and reactions to psychological trauma, including the hallmark symptom of intrusive memories. We reviewed 74 articles that have used this paradigm since the earliest review (Holmes & Bourne, 2008) until July 2014. Highlighting the different stages of trauma processing, i.e. pre-, peri- and post-trauma, the studies are divided according to manipulations before, during and after film viewing, for experimental as well as correlational designs. While the majority of studies focussed on the frequency of intrusive memories, other reactions to trauma were also modelled. We discuss the strengths and weaknesses of the trauma film paradigm as an experimental psychopathology model of trauma, consider ethical issues, and suggest future directions. By understanding the basic mechanisms underlying trauma symptom development, we can begin to translate findings from the laboratory to the clinic, test innovative science-driven interventions, and in the future reduce the debilitating effects of psychopathology following stressful and/or traumatic events.

Quantifying learning-dependent changes in the brain: Single-trial multivoxel pattern analysis requires slow event-related fMRI.

Single-trial analysis is particularly useful for assessing cognitive processes that are intrinsically dynamic, such as learning. Studying these processes with fMRI is problematic, as the low signal-to-noise ratio of fMRI requires the averaging over multiple trials, obscuring trial-by-trial changes in neural activation. The superior sensitivity of multivoxel pattern analysis over univariate analyses has opened up new possibilities for single-trial analysis, but this may require different fMRI designs. Here, we measured fMRI and pupil dilation responses during discriminant aversive conditioning, to assess associative learning in a trial-by-trial manner. The impact of design choices was examined by varying trial spacing and trial order in a series of five experiments (total n = 66), while keeping stimulus duration constant (4.5 s). Our outcome measure was the change in similarity between neural response patterns related to two consecutive presentations of the same stimulus (within-stimulus) and between patterns related to pairs of different stimuli (between-stimulus) that shared a specific outcome (electric stimulation vs. no consequence). This trial-by-trial similarity analysis revealed clear single-trial learning curves in conditions with intermediate (8.1-12.6 s) and long (16.5-18.4 s) intervals, with effects being strongest in designs with long intervals and counterbalanced stimulus presentation. No learning curves were observed in designs with shorter intervals (1.6-6.1 s), indicating that rapid event-related designs-at present, the most common designs in fMRI research-are not suited for single-trial pattern analysis. These findings emphasize the importance of deciding on the type of analysis prior to data collection.