Variability in the analysis of a single neuroimaging dataset by many teams.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Learning environment-specific learning rates.

People often have to switch back and forth between different environments that come with different problems and volatilities. While volatile environments require fast learning (i.e., high learning rates), stable environments call for lower learning rates. Previous studies have shown that people adapt their learning rates, but it remains unclear whether they can also learn about environment-specific learning rates, and instantaneously retrieve them when revisiting environments. Here, using optimality simulations and hierarchical Bayesian analyses across three experiments, we show that people can learn to use different learning rates when switching back and forth between two different environments. We even observe a signature of these environment-specific learning rates when the volatility of both environments is suddenly the same. We conclude that humans can flexibly adapt and learn to associate different learning rates to different environments, offering important insights for developing theories of meta-learning and context-specific control.

Effects of Experiencing CS-US Pairings on Instructed Fear Reversal.

Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms where an initially neutral conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (US), eventually leading to the CS also being perceived as aversive and threatening. Importantly, however, humans also show verbal fear learning. Namely, they have the ability to change their responses to stimuli rapidly through verbal instructions about CS-US pairings. Past research on the link between experience-based and verbal fear learning indicated that verbal instructions about a reversal of CS-US pairings can fully override the effects of previously experienced CS-US pairings, as measured through fear ratings, skin conductance, and fear-potentiated startle. However, it remains an open question whether such instructions can also annul learned CS representations in the brain. Here, we used a fear reversal paradigm (female and male participants) in conjunction with representational similarity analysis of fMRI data to test whether verbal instructions fully override the effects of experienced CS-US pairings in fear-related brain regions or not. Previous research suggests that only the right amygdala should show lingering representations of previously experienced threat ("pavlovian trace"). Unexpectedly, we found evidence for the residual effect of prior CS-US experience to be much more widespread than anticipated, in the amygdala but also cortical regions like the dorsal anterior cingulate or dorsolateral prefrontal cortex. This finding shines a new light on the interaction of different fear learning mechanisms, at times with unexpected consequences.SIGNIFICANCE STATEMENT Humans are able to learn about aversive stimuli both from experience (i.e., repeated pairings of conditioned stimulus (CS) and unconditioned stimulus (US; pavlovian conditioning), and from verbal instructions about stimulus pairings. Understanding how experience-based and verbal learning processes interact is key for understanding the cognitive and neural underpinnings of fear learning. We tested whether prior aversive experiences (CS-US pairings) affected subsequent verbal learning, searching for lingering threat signals after verbal instructions reversed a CS from being threatening to being safe. While past research suggested such threat signals can only be found in the amygdala, we found evidence to be much more widespread, including the medial and lateral PFC. This highlights how experience-based and verbal learning processes interact to support adaptive behavior.

Associative Visuomotor Learning Using Transcranial Magnetic Stimulation Induces Stimulus-Response Interference.

Classical conditioning states that the systematic co-occurrence of a neutral stimulus with an unconditioned stimulus can cause the neutral stimulus to, over time, evoke the same response as the unconditioned stimulus. On a neural level, Hebbian learning suggests that this type of learning occurs through changes in synaptic plasticity when two neurons are simultaneously active, resulting in increased connectivity between them. Inspired by associative learning theories, we here investigated whether the mere co-activation of visual stimuli and stimulation of the primary motor cortex using TMS would result in stimulus-response associations that can impact future behavior. During a learning phase, we repeatedly paired the presentation of a specific color (but not other colors) with a TMS pulse over the motor cortex. Next, participants performed a two-alternative forced-choice task where they had to categorize simple shapes and we studied whether the shapes' task-irrelevant color (and its potentially associated involuntary motor activity) affected the required motor response. Participants showed more errors on incongruent trials for stimuli that were previously paired with high intensity TMS pulses, but only when tested on the same day. Using a drift diffusion model for conflict tasks, we further demonstrate that this interference occurred early, and gradually increased as a function of associated TMS intensity. Taken together, our findings show that the human brain can learn stimulus-response associations using externally induced motor cortex stimulation. Although we were inspired by the Hebbian learning literature, future studies should investigate whether Hebbian or other learning processes were also what brought about this effect.

Reduced Primacy Bias in Autism during Early Sensory Processing.

Recent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context sensitivity is caused by faster updating of one's model of the world (i.e., higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing. An autism and matched control group of human adults (both n = 27, 8 female) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e., the standard and deviant sound in the first block) influences MMN amplitudes in later blocks. If autism is characterized by faster model updating, and thus a smaller primacy bias, we hypothesized (and demonstrate using a simple reinforcement learning model) that their MMN amplitudes should be less influenced by the initial context. In line with this hypothesis, we found that MMN responses in the autism group did not differ between the initial deviant and initial standard sounds as they did in the control group. These findings are consistent with the idea that autism is characterized by faster model updating during early sensory processing, as proposed by predictive coding accounts of autism.SIGNIFICANCE STATEMENT Recent theories of autism propose that a core deficit in autism is that they are faster to update their models of the world based on new sensory information. Here, we tested this hypothesis by investigating how first impressions shape brain responses during early sensory processing, and hypothesized that individuals with autism would be less influenced by these first impressions. In line with earlier studies, our results show that early sensory processing was influenced by first impressions in a control group. However, this was not the case in an autism group. This suggests that individuals with autism are faster to abandon their initial model, and is consistent with the proposal that they are faster to update their models of the world.

The impact of free will beliefs on implicit learning.

A growing number of studies demonstrate that belief in free will (FWB) is dynamic, and can be reduced experimentally. Most of these studies assume that doing so has beneficial effects on behavior, as FWBs are thought to subdue unwanted automatic processes (e.g. racial stereotypes). However, relying on automatic processes can sometimes be advantageous, for instance during implicit learning (e.g. detecting and exploiting statistical regularities in the environment). In this registered report, we tested whether experimentally reducing FWBs positively affected implicit motor learning. We hypothesized that reducing FWBs would lead to both faster and stronger implicit learning, as measured using the alternating serial reaction time (ASRT) task. While we did show a manipulation effect on free will beliefs, there was no detectable effect on implicit learning processes. This finding adds to the growing body of evidence that free will belief manipulations do not meaningfully affect downstream behavior.

Learning how to reason and deciding when to decide.

Research on human reasoning has both popularized and struggled with the idea that intuitive and deliberate thoughts stem from two different systems, raising the question how people switch between them. Inspired by research on cognitive control and conflict monitoring, we argue that detecting the need for further thought relies on an intuitive, context-sensitive process that is learned in itself.

The selective use of punishments on congruent versus incongruent trials in the Stroop task.

Conflict adaptation refers to the dynamic modulation of conflict processing across successive trials and reflects improved cognitive control. Interestingly, aversive motivation can increase conflict adaptation, although it remains unclear through which process this modulation occurs because previous studies presented punishment feedback following suboptimal performance on both congruent and incongruent trials. According to integrative accounts of conflict monitoring and aversive motivation in the dorsal anterior cingulate cortex, punishment feedback following slow or erroneous performance on incongruent trials in particular should lead to improved conflict adaptation. Second, selectively increasing motivation on incongruent trials should reduce the overall congruency effect. The current study sought to test both hypotheses. Specifically, we administered the confound-minimized Stroop task to a large group of participants and manipulated the position of feedback (following either congruent or incongruent trials) and aversive motivation (tied to a monetary loss or not) across different blocks. As expected, the congruency effect was found to be smaller when punishment was coupled with incongruent versus congruent trials. However, results showed that conflict adaptation was increased when punishment feedback was selectively coupled with congruent rather than incongruent trials. Together, these results suggest that aversive motivation does not uniformly improve cognitive control but this gain appears to be context dependent.

Shared Neural Representations of Cognitive Conflict and Negative Affect in the Medial Frontal Cortex.

Influential theories of Medial Frontal Cortex (MFC) function suggest that the MFC registers cognitive conflict as an aversive signal, but no study directly tested this idea. Instead, recent studies suggested that nonoverlapping regions in the MFC process conflict and affect. In this preregistered human fMRI study (male and female), we used MVPAs to identify which regions respond similarly to conflict and aversive signals. The results reveal that, of all conflict- and value-related regions, only the ventral pre-supplementary motor area (or dorsal anterior cingulate cortex) showed a shared neural pattern response to different conflict and affect tasks. These findings challenge recent conclusions that conflict and affect are processed independently, and provide support for integrative views of MFC function.SIGNIFICANCE STATEMENT Multiple theories propose that the MFC, and the dorsal ACC in particular, integrates information related to suboptimal outcomes from different psychological domains (e.g., cognitive control and negative affect) with the aim of adaptively steering behavior. In contrast to recent studies in the field, we provide evidence for the idea that cognitive control and negative affect are integrated in the MFC by showing that a classification algorithm trained on discerning cognitive control (conflict vs no conflict) can predict affect (negative vs positive) in the voxel pattern response of the dorsal ACC/pre-SMA.

The impact of implicit and explicit suggestions that 'there is nothing to learn' on implicit sequence learning.

We can sometimes efficiently pick up statistical regularities in our environment in the absence of clear intentions or awareness, a process typically referred to as implicit sequence learning. In the current study, we tried to address the question whether suggesting participants that there is nothing to learn can impact this form of learning. If a priori predictions or intentions to learn are important in guiding implicit learning, we reasoned that suggesting participants that there is nothing to learn in a given context should hamper implicit learning. We introduced participants to random contexts that indicated that there was nothing to learn, either implicitly (i.e., by presenting blocks of random trials in "Experiment 1"), or explicitly (i.e., by explicitly instructing them in "Experiment 2"). Next, in a subsequent learning phase, participants performed an implicit sequence learning task. We found that these implicit or explicit suggestions that 'there was nothing to learn' did not influence the emergence of implicit knowledge in the subsequent learning phase. Although these findings seem consistent with simple associative or Hebbian learning accounts of implicit sequence learning (i.e., not steered by predictions), we discuss potential limitations that should inform future studies on the role of a priori predictions in implicit learning.

Does incidental sequence learning allow us to better manage upcoming conflicting events?

Recent proposals emphasize the role of learning in empirical markers of conflict adaptation. Some of these proposals are rooted in the assumption that contingency learning works not only on stimulus-response events but also on covert processes such as selective attention. In the present study, we explored how these learning processes may apply to trial-to-trial modulations of selective attention, mirroring the sequential nature of congruency sequence effects. Two groups of participants performed a four-choice Stroop task in which the color to which they responded on each trial acted as a probabilistic predictor either of the external response to be emitted on the next trial, or the congruency level (and therefore control demands) on the next trial. The results showed clear effects of sequence learning for external responses, but no evidence of learning about sequential stimulus-conflict associations. The implications of these results are discussed in relation to other learning-based phenomena of conflict adaptation and suggest that learning of stimulus-control associations is strongly constrained by event boundaries.

Neural correlates of reward-related response tendencies in an equiprobable Go/NoGo task.

Previous research has shown that motivational signals bias action over inaction, which may be due to putative inherent valence-action mappings, similar to those observed in the emotional domain. In the present functional magnetic resonance imaging (fMRI) study we sought to investigate the neural underpinnings of such reward-related response tendencies, and in particular, how valence-action compatibility effects arising from predominant response tendencies are reflected at the neural level, and whether overlapping emotional valence amplifies these effects. To this end, we employed an equiprobable (50:50) Go/NoGo task in which reward (reward/no-reward) and response mode (Go/NoGo) were signaled by orthogonal features of number targets that were overlaid on emotional images (positive, neutral, negative). Reward-related targets led to response facilitation (faster Go responses) and impairment in withholding responses (more NoGo commission errors), consistent with a reward-induced action bias. This pattern was paralleled by modulations in the left dorsolateral prefrontal cortex (dlPFC), with increased activity in no-reward as compared to reward-related Go trials, and the reversed pattern in NoGo trials. Albeit being processed in ventral visual areas, emotional background did not modulate performance in the present task, suggesting that irrelevant emotional information is globally outweighed by reward. In the current paradigm, which neither favors Go responses generally nor allows for differential preparation in Go versus NoGo trials, reward-related targets promote action over inaction. In turn, additional effort is needed to inhibit responses to these targets as well as to initiate responses to (less salient) no-reward targets, which may be considered as a downside of direct stimulus-reward associations.

Humans show a higher preference for stimuli that are predictive relative to those that are predictable.

Recent studies suggest that humans prefer information that is linked to the process of prediction. Yet it remains to be specified whether preference judgments are biased to information that can be predicted, or information that enables to predict. We here use a serial reaction time task to disentangle these two options. In a first learning phase, participants were exposed to a continuous stream of arbitrary shapes while performing a go/no-go task. Embedded in this stream were hidden pairs of go-stimuli (e.g., shape A was always followed by shape B). Data show faster reaction times to predictable shapes (i.e., shape B) as compared to random and predictive shapes (i.e., shape A), indicating that participants learned the regularities and anticipated upcoming information. Importantly, in a subsequent, unannounced forced-choice preference task, the shapes that were predictive of others were significantly more preferred over random shapes than shapes that could be predicted. Because both the reaction time benefit in the learning phase and the effect in the preference phase could be considered rather small, we studied the relation between both. Interestingly, the preference correlated with the reaction time benefit from the learning phase. A closer look at this correlation further suggested that the difference in preference was only observed when participants picked up the contingencies between predictive and predictable shapes. This study adds evidence to the idea that prediction processes are not only fundamental for cognition, but contribute to the way we evaluate our external world.

The instruction-based congruency effect predicts task execution efficiency: Evidence from inter- and intra-individual differences.

In contrast to traditional conflict paradigms, which measure interference from (over)trained associations, recent paradigms have been introduced that investigate automatic interference from newly instructed, but never executed, associations. In these prospective-instruction paradigms, participants receive new task instructions (e.g., if cat press left, if dog press right), but before they have to apply the instructions, they are first presented with another task that measures the automatic interference from the instructed task information. The resulting instruction-based congruency (IBC) effect is assumed to reflect the strength with which instructions are encoded and maintained in view of their future application. If this assumption holds true, the IBC effect should be inversely related to the speed with which the task instructions are eventually executed. To test this hypothesis, we administered a prospective-instruction paradigm to a large sample of 184 participants and observed a negative correlation between the IBC effect and mean reaction time on the instructed task. Similarly, an analysis looking at within-subject variations in the IBC effect and instructed task reaction times showed the same negative relation. Finally, we also present additional analyses suggesting this effect is independent from standard (experience-based) interference effects, and report explorative analyses that tested possible correlations with personality trait questionaires. Together, these findings confirm a key assumption of the IBC effect in prospective-instruction paradigms, and further support the use of this paradigm in instruction research.

Executive functions are cognitive gadgets.

Many psychologists and neuroscientists still see executive functions as independent, domain-general, supervisory functions that are often dissociated from more "low-level" associative learning. Here, we suggest that executive functions very much build on associative learning, and argue that executive functions might be better understood as culture-sensitive cognitive gadgets, rather than as ready-made cognitive instincts.

Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies.SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research.

Encoding of Novel Verbal Instructions for Prospective Action in the Lateral Prefrontal Cortex: Evidence from Univariate and Multivariate Functional Magnetic Resonance Imaging Analysis.

Verbal instructions are central to humans' capacity to learn new behaviors with minimal training, but the neurocognitive mechanisms involved in verbally instructed behaviors remain puzzling. Recent functional magnetic resonance imaging (fMRI) evidence suggests that the right middle frontal gyrus and dorsal premotor cortex (rMFG-dPMC) supports the translation of symbolic stimulus-response mappings into sensorimotor representations. Here, we set out to (1) replicate this finding, (2) investigate whether this region's involvement is specific to novel (vs. trained) instructions, and (3) study whether rMFG-dPMC also shows differences in its (voxel) pattern response indicative of general cognitive processes of instruction implementation. Participants were shown instructions, which they either had to perform later or merely memorize. Orthogonal to this manipulation, the instructions were either entirely novel or had been trained before the fMRI session. Results replicate higher rMFG-dPMC activation levels during instruction implementation versus memorization and show how this difference is restricted to novel, but not trained, instruction presentations. Pattern similarity analyses at the voxel level further reveal more consistent neural pattern responses in rMFG-dPMC during the implementation of novel versus trained instructions. In fact, this more consistent neural pattern response seemed to be specific to the first instruction presentation and disappeared after the instruction had been applied once. These results further support a role of rMFG-dPMC in the implementation of novel task instructions and highlight potentially important differences in studying this region's gross activation levels versus (the consistency of) its response patterns.

The Role of Anterior Cingulate Cortex in the Affective Evaluation of Conflict.

An influential theory of ACC function argues that this brain region plays a crucial role in the affective evaluation of performance monitoring and control demands. Specifically, control-demanding processes such as response conflict are thought to be registered as aversive signals by ACC, which in turn triggers processing adjustments to support avoidance learning. In support of conflict being treated as an aversive event, recent behavioral studies demonstrated that incongruent (i.e., conflict inducing), relative to congruent, stimuli can speed up subsequent negative, relative to positive, affective picture processing. Here, we used fMRI to investigate directly whether ACC activity in response to negative versus positive pictures is modulated by preceding control demands, consisting of conflict and task-switching conditions. The results show that negative, relative to positive, pictures elicited higher ACC activation after congruent, relative to incongruent, trials, suggesting that ACC's response to negative (positive) pictures was indeed affectively primed by incongruent (congruent) trials. Interestingly, this pattern of results was observed on task repetitions but disappeared on task alternations. This study supports the proposal that conflict induces negative affect and is the first to show that this affective signal is reflected in ACC activation.

Reward anticipation modulates primary motor cortex excitability during task preparation.

Task preparation has been associated with a transient suppression of corticospinal excitability (CSE) before target onset, but it is an open question to what extent CSE suppression during task preparation is susceptible to motivational factors. Here, we examined whether CSE suppression is modulated by reward anticipation, and, if so, how this modulation develops over time. We administered a cue-target delay paradigm in which 1000ms before target onset a cue was presented indicating whether or not reward could be obtained for fast and accurate responses in a Simon task. Single-pulse transcranial magnetic stimulation was applied over left primary motor cortex (M1) during the delay period (400, 600, or 800ms after cue onset) or 200ms after target onset, and electromyography was obtained from the right first dorsal interosseous muscle. Behaviorally, the anticipation of reward improved performance (i.e. faster reaction times). Most importantly, during reward anticipation we observed a linear decrease of motor evoked potential amplitudes that was absent when no reward was anticipated. This suggests that reward anticipation modulates CSE during task preparation.

Fake feedback on pain tolerance impacts proactive versus reactive control strategies.

It is well-known that beliefs about one's own ability to execute a task influence task performance. Here, we tested the hypothesis that beliefs about a specific self-control capacity, namely pain tolerance, modulate basic cognitive control processes. Participants received fake comparative social feedback that their ability to tolerate painful stimulations was either very poor or outstanding after which they performed an unrelated go/no-go task. Participants receiving low-tolerance feedback, relative to high-tolerance feedback, were less successful at inhibiting their responses and more influenced by previous trial conditions, as indicated by an increased slowdown following errors and more failed inhibitions following go-trials. These observations demonstrate a shift from a more proactive to a more reactive control mode. This study shows that providing feedback about one's own capacity to control impulsive reactions to painful stimulations directly influences low-level cognitive control dynamics.