Arjen Alink’s research while affiliated with University Medical Center Hamburg - Eppendorf and other places

Emotionally arousing events are typically vividly remembered, which is generally adaptive but may contribute to mental disorders such as post-traumatic stress disorder. Previous research on emotional memory focused primarily on events that were experienced only once, leaving the memory mechanisms underlying repeatedly encountered emotional events largely unexplored. Here, we aimed to elucidate the brain mechanisms associated with memory for recurring emotional events. Specifically, we sought to determine whether the memory enhancement for recurring emotional events is linked to more variable neural representations, as predicted by the encoding-variability hypothesis, or to more stable representations across repetitions, as suggested by a memory reinstatement account. To investigate this, we repeatedly presented healthy men and women with images of emotionally negative or neutral scenes during three consecutive runs in an MRI scanner. Subsequent free recall was, as expected, enhanced for emotional compared with neutral images. Neural data showed that this emotional enhancement of memory was linked to (1) activation of the amygdala and anterior hippocampus during the initial encounter of the emotional event and (2) increased neural pattern similarity in frontoparietal cortices across event repetitions. Most importantly, a multilevel-moderated mediation analysis revealed that the impact of neocortical pattern stability across repetitions on emotional memory enhancement was moderated by amygdala activity during the initial exposure to the emotional event. Together, our findings show that the amygdala response during the initial encounter of an emotional event boosts subsequent remembering through a more precise reinstatement of the event representation during subsequent encounters of the same event.

Memories undergo a time-dependent neural reorganization, which is assumed to be accompanied by a transformation from detailed to more gist-like memory. However, the nature of this transformation and its underlying neural mechanisms are largely unknown. Here, we report that the time-dependent transformation of memory is semantic in nature, while we find no credible evidence for a perceptual transformation. Model-based MRI analyses reveal time-dependent increases in semantically transformed representations of events in prefrontal and parietal cortices, while specific pattern representations in the anterior hippocampus decline over time. Posterior hippocampal memory reinstatement, in turn, increases over time and is linked to the semantic gist of the original memory, without a statistically significant link to perceptual details. These findings indicate that qualitative changes in memory over time, associated with distinct representational changes in the neocortex and within the hippocampus, reflect a semantic transformation, which may promote the integration of memories into abstract knowledge structures.

Gaining insight into the relationship between previously separate events allows us to combine these events into coherent episodes. This insight may occur via observation or imagination. Although much of our reasoning occurs in the absence of direct sensory stimuli, how mnemonic integration is accomplished via imagination has remained completely unknown. Here, we combined fMRI with representational similarity analysis and a real-life-like narrative-insight task (NIT) to elucidate the behavioral and neural effects of insight through imagination (vs. observation). Healthy participants performed the NIT in the MRI scanner and underwent memory testing one week later. Crucially, participants in the observation group gained insight through a video, while participants in the imagination group gained insight through an imagination instruction. Although we show that insight via imagination was weaker than insight via direct observation, the imagination group showed better detail memory. Moreover, the imagination group showed no representational change in the anterior hippocampus or increases in frontal and striatal activity for the linked events, as was the case in the observation group. However, the hippocampus and striatum were more activated during linking via imagination, which might indicate that their increased recruitment during imagination impedes concurrent mnemonic integration but may facilitate long-term memory.

Perception is an active inference in which prior expectations are combined with sensory input. It is still unclear how the strength of prior expectations is represented in the human brain. The strength, or precision, of a prior could be represented with its content, potentially in higher-level sensory areas. We used multivariate analyses of functional resonance imaging data to test whether expectation strength is represented together with the expected face in high-level face-sensitive regions. Participants were trained to associate images of scenes with subsequently presented images of different faces. Each scene predicted three faces, each with either low, intermediate, or high probability. We found that anticipation enhances the similarity of response patterns in the face-sensitive anterior temporal lobe to response patterns specifically associated with the image of the expected face. In contrast, during face presentation, activity increased for unexpected faces in a typical prediction error network, containing areas such as the caudate and the insula. Our findings show that strength-dependent face expectations are represented in higher-level face-identity areas, supporting hierarchical theories of predictive processing according to which higher-level sensory regions represent weighted priors.

Memories are not stored in isolation. Insight into the relationship of initially unrelated events may trigger a flexible reconfiguration of the mnemonic representation of these events. Such representational changes allow the integration of events into coherent episodes and help to build up-to-date-models of the world around us. This process is, however, frequently impaired in stress-related mental disorders resulting in symptoms such as fragmented memories in PTSD. Here, we combined a real life-like narrative-insight task, in which participants learned how initially separate events are linked, with fMRI-based representational similarity analysis to test if and how acute stress interferes with the insight-driven reconfiguration of memories. Our results showed that stress reduced the activity of medial temporal and prefrontal areas when participants gained insight into the link between events. Moreover, stress abolished the insight-related increase in representational dissimilarity for linked events in the anterior part of the hippocampus as well as its association with measures of subsequent memory that we observed in non-stressed controls. However, memory performance, as assessed in a forced-choice recognition test, was even enhanced in the stress group. Our findings suggest that acute stress impedes the neural integration of events into coherent episodes but promotes long-term memory for these integrated narratives and may thus have implications for understanding memory distortions in stress-related mental disorders.

Schemata enhance memory formation for related novel information. This is true even when this information is neutral with respect to schema-driven expectations. This assimilation of novel information into schemata has been attributed to more effective organizational processing that leads to more referential connections with the activated associative schema network. Animal data suggest that systems consolidation of novel assimilated information is also accelerated. In the current study, we used both multivariate and univariate fMRI analyses to provide further support for these proposals and to elucidate the neural underpinning of these processes. Twenty-eight participants (5 male) overlearned fictitious schemata for 7 weeks and then encoded novel related and control facts in the scanner. These facts were retrieved both immediately and 2 weeks later, also in the scanner. Our results conceptually replicate previous findings with respect to enhanced vmPFC-hippocampus coupling during encoding of novel related information and point to a prior knowledge effect that is distinct from situations where novel information is experienced as congruent or incongruent with a schema. Moreover, the combination of both multivariate and univariate results further specified the proposed contributions of the vmPFC, precuneus and angular gyrus network to the more efficient encoding of schema-related information. In addition, our data provide further evidence for more efficient systems consolidation of such novel schema-related and potentially assimilated information.SIGNIFICANCE STATEMENT Our prior knowledge in a certain domain, often termed schema, heavily influences whether and how we form memories for novel information that can be related to them. The results of the current study show how a ventromedial prefrontal-precuneal-angular network contributes to the more efficient encoding of novel related information. Furthermore, the observed increase in prefrontal-hippocampal coupling during this process points to a critical distinction from the previously described mechanisms supporting the encoding of information that is experienced as congruent with schema-driven expectations. In addition, we find further support for the proposal based on animal data that prior knowledge enhances also the consolidation of schema-related information.

Representational distinctions within categories are important in all perceptual modalities and also in cognitive and motor representations. Recent pattern-information studies of brain activity have used condition-rich designs to sample the stimulus space more densely. To test whether brain response patterns discriminate among a set of stimuli (e.g. exemplars within a category) with good sensitivity, we can pool statistical evidence over all pairwise comparisons. Here we describe a wide range of statistical tests of exemplar discriminability and assess the validity (specificity) and power (sensitivity) of each test. The tests include previously used and novel, parametric and nonparametric tests, which treat subject as a random or fixed effect, and are based on different dissimilarity measures, different test statistics, and different inference procedures. We use simulated and real data to determine which tests are valid and which are most sensitive. A popular test statistic reflecting exemplar information is the exemplar discriminability index (EDI), which is defined as the average of the pattern dissimilarity estimates between different exemplars minus the average of the pattern dissimilarity estimates between repetitions of identical exemplars. The popular across-subject t test of the EDI (typically using correlation distance as the pattern dissimilarity measure) requires the assumption that the EDI is 0-mean normal under H0. Although this assumption is not strictly true, our simulations suggest that the test controls the false-positives rate at the nominal level, and is thus valid, in practice. However, test statistics based on average Mahalanobis distances or average linear-discriminant t values (both accounting for the multivariate error covariance among responses) are substantially more powerful for both random- and fixed-effects inference.

It is commonly assumed that episodic memories undergo a time-dependent systems consolidation process, during which hippocampus-dependent memories eventually become reliant on neocortical areas. Here we show that systems consolidation dynamics can be experimentally manipulated and even reversed. We combined a single pharmacological elevation of post-encoding noradrenergic activity through the α2-adrenoceptor antagonist yohimbine with fMRI scanning both during encoding and recognition testing either 1 or 28 days later. We show that yohimbine administration, in contrast to placebo, leads to a time-dependent increase in hippocampal activity and multivariate encoding-retrieval pattern similarity, an indicator of episodic reinstatement, between 1 and 28 days. This is accompanied by a time-dependent decrease in neocortical activity. Behaviorally, these neural changes are linked to a reduced memory decline over time after yohimbine intake. These findings indicate that noradrenergic activity shortly after encoding may alter and even reverse systems consolidation in humans, thus maintaining vividness of memories over time. Memories are assumed to undergo a time-dependent systems consolidation, during which hippocampal contributions to memory decrease while neocortical contributions increase. Here, the authors show that noradrenergic arousal after encoding may reverse this course of systems consolidation in humans

The brain is capable of integrating signals from multiple sensory modalities. Such multisensory integration can occur in areas that are commonly considered unisensory, such as planum temporale (PT) representing the auditory association cortex. However, the roles of different afferents (feedforward vs. feedback) to PT in multisensory processing are not well understood. Our study aims to understand that by examining laminar activity patterns in different topographical subfields of human PT under unimodal and multisensory stimuli. To this end, we adopted an advanced mesoscopic (sub-millimeter) fMRI methodology at 7 T by acquiring BOLD (blood-oxygen-level-dependent contrast, which has higher sensitivity) and VAPER (integrated blood volume and perfusion contrast, which has superior laminar specificity) signal concurrently, and performed all analyses in native fMRI space benefiting from an identical acquisition between functional and anatomical images. We found a division of function between visual and auditory processing in PT and distinct feedback mechanisms in different subareas. Specifically, anterior PT was activated more by auditory inputs and received feedback modulation in superficial layers. This feedback depended on task performance and likely arose from top-down influences from higher-order multimodal areas. In contrast, posterior PT was preferentially activated by visual inputs and received visual feedback in both superficial and deep layers, which is likely projected directly from the early visual cortex. Together, these findings provide novel insights into the mechanism of multisensory interaction in human PT at the mesoscopic spatial scale.