Search

Abstract Background Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies on a range of taxa have employed an orienting paradigm to investigate lateralized acoustic processing. In this paradigm, sounds are played directly from behind and the direction of turn is recorded. This assay rests on the assumption that a hemispheric asymmetry in processing is coupled to an orienting bias towards the contralateral side. To examine this largely untested assumption, speech stimuli as well as artificial sounds were presented to 224 right-handed human subjects shopping in supermarkets in Germany and in the UK. To verify the lateralized processing of the speech stimuli, we additionally assessed the brain activation in response to presentation of the different stimuli using functional magnetic resonance imaging (fMRI). Results In the naturalistic behavioural experiments, there was no difference in orienting behaviour in relation to the stimulus material (speech, artificial sounds). Contrary to our predictions, subjects revealed a significant left bias, irrespective of the sound category. This left bias was slightly but not significantly stronger in German subjects. The fMRI experiments confirmed that the speech stimuli evoked a significant left lateralized activation in BA44 compared to the artificial sounds. Conclusion These findings suggest that in adult humans, orienting biases are not necessarily coupled with lateralized processing of acoustic stimuli. Our results – as well as the inconsistent orienting biases found in different animal species – suggest that the orienting assay should be used with caution. Apparently, attention biases, experience, and experimental conditions may all affect head turning responses. Because of the complexity of the interaction of factors, the use of the orienting assay to determine lateralized processing of sound stimuli is discouraged.

Background: Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies on a range of taxa have employed an orienting paradigm to investigate lateralized acoustic processing. In this paradigm, sounds are played directly from behind and the direction of turn is recorded. This assay rests on the assumption that a hemispheric asymmetry in processing is coupled to an orienting bias towards the contralateral side. To examine this largely untested assumption, speech stimuli as well as artificial sounds were presented to 224 right-handed human subjects shopping in supermarkets in Germany and in the UK. To verify the lateralized processing of the speech stimuli, we additionally assessed the brain activation in response to presentation of the different stimuli using functional magnetic resonance imaging (fMRI).Results: In the naturalistic behavioural experiments, there was no difference in orienting behaviour in relation to the stimulus material (speech, artificial sounds). Contrary to our predictions, subjects revealed a significant left bias, irrespective of the sound category. This left bias was slightly but not significantly stronger in German subjects. The fMRI experiments confirmed that the speech stimuli evoked a significant left lateralized activation in BA44 compared to the artificial sounds.Conclusion: These findings suggest that in adult humans, orienting biases are not necessarily coupled with lateralized processing of acoustic stimuli. Our results -- as well as the inconsistent orienting biases found in different animal species -- suggest that the orienting assay should be used with caution. Apparently, attention biases, experience, and experimental conditions may all affect head turning responses. Because of the complexity of the interaction of factors, the use of the orienting assay to determine lateralized processing of sound stimuli is discouraged. [ABSTRACT FROM AUTHOR]

The brain's diverse intrinsic timescales enable us to perceive stimuli with varying temporal persistency. This study aimed to uncover the cortical organizational schemes underlying these variations, revealing the neural architecture for processing a wide range of sensory experiences. We collected resting-state fMRI, task-fMRI, and diffusion-weighted imaging data from 47 individuals. Based on this data, we extracted six organizational schemes: (1) the structural Rich Club (RC) architecture, shown to synchronize the connectome; (2) the structural Diverse Club architecture, as an alternative to the RC based on the network's module structure; (3) the functional uni-to-multimodal gradient, reflected in a wide range of structural and functional features; and (4) the spatial posterior/lateral-to-anterior/medial gradient, established for hierarchical levels of cognitive control. Also, we explored the effects of (5) structural graph theoretical measures of centrality and (6) cytoarchitectural differences. Using Bayesian model comparison, we contrasted the impact of these organizational schemes on (1) intrinsic resting-state timescales and (2) inter-subject correlation (ISC) from a task involving hierarchically nested digit sequences. As expected, resting-state timescales were slower in structural network hubs, hierarchically higher areas defined by the functional and spatial gradients, and thicker cortical regions. ISC analysis demonstrated hints for the engagement of higher cortical areas with more temporally persistent stimuli. Finally, the model comparison identified the uni-to-multimodal gradient as the best organizational scheme for explaining the chronotopy in both task and rest. Future research should explore the microarchitectural features that shape this gradient, elucidating how our brain adapts and evolves across different modes of processing., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024. Published by Elsevier Inc.)

Previous research has established that the brain uses episodic memories to make continuous predictions about the world and that prediction errors, so the mismatch between generated predictions and reality, can lead to memory updating. However, it remains unclear whether prediction errors can stimulate updating in memories for naturalistic conversations. Participants encoded naturalistic dialogues, which were later presented in a modified form. We found that larger modifications were associated with increased learning of the modified statement. Moreover, memory for the original version of the statement was weakened after medium-strong prediction errors, which resulted from the interplay of modification extent and strength of previous memory. After strong prediction errors, both original and modification were well-remembered. Prediction errors thus play a role in keeping representations of statements and therefore socially relevant knowledge about others up to date.

Motion information has been argued to be central to the subjective segmentation of observed actions. Concerning object-directed actions, object-associated action information might as well inform efficient action segmentation and prediction. The present study compared the segmentation and neural processing of object manipulations and equivalent dough ball manipulations to elucidate the effect of object-action associations. Behavioral data corroborated that objective relational changes in the form of (un-)touchings of objects, hand, and ground represent meaningful anchor points in subjective action segmentation rendering them objective marks of meaningful event boundaries. As expected, segmentation behavior became even more systematic for the weakly informative dough. fMRI data were modeled by critical subjective, and computer-vision-derived objective event boundaries. Whole-brain as well as planned ROI analyses showed that object information had significant effects on how the brain processes these boundaries. This was especially pronounced at untouchings, that is, events that announced the beginning of the upcoming action and might be the point where competing predictions are aligned with perceptual input to update the current action model. As expected, weak object-action associations at untouching events were accompanied by increased biological motion processing, whereas strong object-action associations came with an increased contextual associative information processing, as indicated by increased parahippocampal activity. Interestingly, anterior inferior parietal lobule activity increased for weak object-action associations at untouching events, presumably because of an unrestricted number of candidate actions for dough manipulation. Our findings offer new insights into the significance of objects for the segmentation of action., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Prediction errors (PEs) function as learning signals. It is yet unclear how varying compared to repetitive PEs affect episodic memory in brain and behavior. The current study investigated cerebral and behavioral effects of experiencing either multiple alternative versions ("varying") or one single alternative version ("repetitive") of a previously encoded episode. Participants encoded a set of episodes ("originals") by watching videos showing toy stories. During scanning, participants either experienced originals, one single, or multiple alternative versions of the previously encoded episodes. Participants' memory performance was tested through recall of original objects. Varying and repetitive PEs revealed typical brain responses to the detection of mismatching information including inferior frontal and posterior parietal regions, as well as hippocampus, which is further linked to memory reactivation, and the amygdala, known for modulating memory consolidation. Furthermore, experiencing varying and repetitive PEs triggered distinct brain areas as revealed by direct contrast. Among others, experiencing varying versions triggered activity in the caudate, a region that has been associated with PEs. In contrast, repetitive PEs activated brain areas that resembled more those for retrieval of originally encoded episodes. Thus, ACC and posterior cingulate cortex activation seemed to serve both reactivating old and integrating new but similar information in episodic memory. Consistent with neural findings, participants recalled original objects less accurately when only presented with the same, but not varying, PE during fMRI. The current findings suggest that repeated PEs interact more strongly with a recalled original episodic memory than varying PEs., (© 2024 Massachusetts Institute of Technology.)

Cognitive dysfunction constitutes a core characteristic of schizophrenia spectrum disorders (SZ). Specifically, deficits in updating generative models (i.e., cognitive flexibility) and shielding against distractions (i.e., cognitive stability) are considered critical contributors to cognitive impairment in these patients. Here, we examined the structural integrity of frontostriatal networks and their associations with reduced cognitive stability and flexibility in SZ patients. In a sample of 21 patients diagnosed with SZ and 22 healthy controls, we measured gray matter volume (GMV) using structural MRI. Further, cognitive stability and flexibility were assessed using a switch-drift paradigm, quantifying the successful ignoring of distracters and detection of rule switches. Compared to controls, patients showed significantly smaller GMV in the whole brain and three predefined regions of interest: the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), and caudate nucleus (CN). Notably, GMV in these areas positively correlated with correct rule-switch detection but not with ignoring rule-compatible drifts. Further, the volumetric differences between SZ patients and controls were statistically explainable by considering the behavioral performance in the switch-drift task. Our results indicate that morphological abnormalities in frontostriatal networks are associated with deficient flexibility in SZ patients and highlight the necessity of minimizing neurodevelopmental and progressive brain atrophy in this population., (© 2024 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Even though actions we observe in everyday life seem to unfold in a continuous manner, they are automatically divided into meaningful chunks, that are single actions or segments, which provide information for the formation and updating of internal predictive models. Specifically, boundaries between actions constitute a hub for predictive processing since the prediction of the current action comes to an end and calls for updating of predictions for the next action. In the current study, we investigated neural processes which characterize such boundaries using a repertoire of complex action sequences with a predefined probabilistic structure. Action sequences consisted of actions that started with the hand touching an object (T) and ended with the hand releasing the object (U). These action boundaries were determined using an automatic computer vision algorithm. Participants trained all action sequences by imitating demo videos. Subsequently, they returned for an fMRI session during which the original action sequences were presented in addition to slightly modified versions thereof. Participants completed a post-fMRI memory test to assess the retention of original action sequences. The exchange of individual actions, and thus a violation of action prediction, resulted in increased activation of the action observation network and the anterior insula. At U events, marking the end of an action, increased brain activation in supplementary motor area, striatum, and lingual gyrus was indicative of the retrieval of the previously encoded action repertoire. As expected, brain activation at U events also reflected the predefined probabilistic branching structure of the action repertoire. At T events, marking the beginning of the next action, midline and hippocampal regions were recruited, reflecting the selected prediction of the unfolding action segment. In conclusion, our findings contribute to a better understanding of the various cerebral processes characterizing prediction during the observation of complex action repertoires., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The brain's structural network follows a hierarchy that is described as rich club (RC) organization, with RC hubs forming the well-interconnected top of this hierarchy. In this study, we tested whether RC hubs are involved in the processing of hierarchically higher structures in stimulus sequences. Moreover, we explored the role of previously suggested cortical gradients along anterior-posterior and medial-lateral axes throughout the frontal cortex. To this end, we conducted a functional magnetic resonance imaging (fMRI) experiment and presented participants with blocks of digit sequences that were structured on different hierarchically nested levels. We additionally collected diffusion weighted imaging data of the same subjects to identify RC hubs. This classification then served as the basis for a region of interest analysis of the fMRI data. Moreover, we determined structural network centrality measures in areas that were found as activation clusters in the whole-brain fMRI analysis. Our findings support the previously found anterior and medial shift for processing hierarchically higher structures of stimuli. Additionally, we found that the processing of hierarchically higher structures of the stimulus structure engages RC hubs more than for lower levels. Areas involved in the functional processing of hierarchically higher structures were also more likely to be part of the structural RC and were furthermore more central to the structural network. In summary, our results highlight the potential role of the structural RC organization in shaping the cortical processing hierarchy., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Episodic memories can be modified, a process that is potentially driven by mnemonic prediction errors. In the present study, we used modified cues to induce prediction errors of different episodic relevance. Participants encoded episodes in the form of short toy stories and then returned for an fMRI session on the subsequent day. Here, participants were presented either original episodes or slightly modified versions thereof. Modifications consisted of replacing a single object within the episode and either challenged the gist of an episode (gist modifications) or left it intact (surface modifications). On the next day, participants completed a post-fMRI memory test that probed memories for originally encoded episodes. Both types of modifications triggered brain activation in regions we previously found to be involved in the processing of content-based mnemonic prediction errors (i.e., the exchange of an object). Specifically, these were ventrolateral pFC, intraparietal cortex, and lateral occipitotemporal cortex. In addition, gist modifications triggered pronounced brain responses, whereas those for surface modification were only significant in the right inferior frontal sulcus. Processing of gist modifications also involved the posterior temporal cortex and the precuneus. Interestingly, our findings confirmed the posterior hippocampal role of detail processing in episodic memory, as evidenced by increased posterior hippocampal activity for surface modifications compared with gist modifications. In the post-fMRI memory test, previous experience with surface modified, but not gist-modified episodes, increased erroneous acceptance of the same modified versions as originally encoded. Whereas surface-level prediction errors might increase uncertainty and facilitate confusion of alternative episode representations, gist-level prediction errors seem to trigger the clear distinction of independent episodes., (© 2023 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Cued sensory input occasionally fails to immediately ensue its respective trigger. Given that our environments are rich in sensory cues, we often end up processing other contextually relevant information in the meantime. The experimental design of the present study allowed us to investigate how such temporal delays and visual interferences may impact anticipatory processes. Thirty-four participants were trained to remember an individualised set of eight paired-up faces. These paired-up faces were presented pseudorandomly in sequences of unpaired face images. To keep participants engaged throughout the electroencephalography study, they were instructed to classify each face image, according to its sex, as fast as possible without compromising accuracy. We observed dissimilar modulations in alpha and beta power between the 6-s timeframe encompassing the onsets of predictive and expected images (temporal delay block) and the 6-s timeframe encompassing the predictive, interference and expected images (visual interference block). Furthermore, an expectation-facilitated reduction of the face-sensitive N170 component was only observed if an anticipated face image directly followed its corresponding predictive counterpart. This effect was no longer evident when the expected face was preceded by a distracting face image. Regardless of the block type, behavioural measures confirmed that anticipated faces were classified significantly faster and with fewer erroneous responses than faces not foretold by a predictive face. Collectively, these results demonstrate that whilst the brain continuously adjusts internal hierarchical generative models to account for temporal delays in stimulus onset and visual interferences, the higher levels, and subsequent predictions, fundamental for expectation-facilitated behaviours remain intact., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Retrieved memories of past events are often inaccurate. The scenario construction model (SCM) postulates that during encoding, only the gist of an episode is stored in the episodic memory trace and during retrieval, information missing from that trace is constructed from semantic information. The current study aimed to find behavioural evidence for semantic construction in a realistic, yet controlled setting by introducing a completely new paradigm and adjusted memory tests that measure semantic construction. Using a desktop virtual reality (VR), participants navigated through a flat in which some household objects appeared in unexpected rooms, creating conflicts between the experienced episode and semantic expectations. The manipulation of congruence enabled us to identify influences from semantic information in cases of episodic memory failure during recall. Besides, we controlled for objects to be task-relevant or task-irrelevant to the sequence of action. In addition to an established old/new recognition task we introduced spatial and temporal recall measures as possible superior memory measures quantifying semantic construction. The recognition task and the spatial recall revealed that both congruence and task-relevance predicted correct episodic memory retrieval. In cases of episodic memory failure, semantic construction was more likely than guessing and occurred more frequently for task-irrelevant objects. In the temporal recall object-pairs belonging to the same semantic room-category were temporally clustered together compared with object-pairs from different semantic categories (at the second retrieval delay). Taken together, our findings support the predictions of the SCM. The new VR paradigm, including the new memory measures appears to be a promising tool for investigating semantic construction.

Tools have coined human life, living conditions, and culture. Recognizing the cognitive architecture underlying tool use would allow us to comprehend its evolution, development, and physiological basis. However, the cognitive underpinnings of tool mastering remain little understood in spite of long-time research in neuroscientific, psychological, behavioral and technological fields. Moreover, the recent transition of tool use to the digital domain poses new challenges for explaining the underlying processes. In this interdisciplinary review, we propose three building blocks of tool mastering: (A) perceptual and motor abilities integrate to tool manipulation knowledge, (B) perceptual and cognitive abilities to functional tool knowledge, and (C) motor and cognitive abilities to means-end knowledge about tool use. This framework allows for integrating and structuring research findings and theoretical assumptions regarding the functional architecture of tool mastering via behavior in humans and non-human primates, brain networks, as well as computational and robotic models. An interdisciplinary perspective also helps to identify open questions and to inspire innovative research approaches. The framework can be applied to studies on the transition from classical to modern, non-mechanical tools and from analogue to digital user-tool interactions in virtual reality, which come with increased functional opacity and sensorimotor decoupling between tool user, tool, and target. By working towards an integrative theory on the cognitive architecture of the use of tools and technological assistants, this review aims at stimulating future interdisciplinary research avenues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schubotz, Ebel, Elsner, Weiss and Wörgötter.)

Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Neuropsychological symptoms such as inattention and distractibility constitute a core characteristic of attention deficit hyperactivity disorder (ADHD). Here, we tested the hypothesis that attentional dysfunctions result from a deficit in neural gain modulation, which translates into difficulty in predictively weighting relevant sensory input while ignoring distraction. We compared thirty-seven hitherto untreated adults diagnosed with ADHD and thirty-eight healthy participants with a serial switch-drift task that requires internal models of predictable digit sequences to be either updated or stabilized. Switches between sequences that had to be indicated by key presses and digit omissions within a sequence (drifts) that should be ignored varied by stimulus-bound surprise quantified as Shannon information. To investigate whether catecholaminergic modulation by increasing extracellular norepinephrine and dopamine levels leads to an amelioration in prediction gain, participants were tested twice, with patients receiving a single dose of methylphenidate, a norepinephrine/dopamine reuptake inhibitor, in the second session. Patients and controls differed in both updating and stabilizing, depending on the respective event surprise. Specifically, patients showed difficulty in detecting expectable switches, while having greater difficulty to ignore surprising distractions. Thus, underconfident prior beliefs in ADHD may fail to appropriately weight expected relevant input, whereas the gain of neural responses to unexpected irrelevant distractors is increased. Methylphenidate improved both flexibility and stability of prediction and had a positive effect on selective responding over time. Our results suggest that ADHD is associated with an impairment in the use of prior expectations to optimally weight sensory inputs, which is improved by increasing catecholaminergic neurotransmission., Competing Interests: Declarations of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

How susceptible a memory is to later modification might depend on how stable the episode has been encoded. This stability was proposed to increase when retrieving information more (vs. less) often and in a spaced (vs. massed) practice. Using fMRI, we examined the effects of these different pre-fMRI retrieval protocols on the subsequent propensity to learn from episodic prediction errors. After encoding a set of different action stories, participants came back for two pre-fMRI retrieval sessions in which they encountered original episodes either 2 or 8 times in either a spaced or a massed retrieval protocol. One week later, we cued episodic retrieval during the fMRI session by using original or modified videos of encoded action stories. Recurrent experience of modified episodes was associated with increasing activity in the episodic memory network including hippocampal and cortical areas, when leading to false memories in a post-fMRI memory test. While this observation clearly demonstrated learning from episodic prediction errors, we found no evidence for a modulatory effect of the different retrieval protocols. As expected, the benefit of retrieving an episode more often was reflected in better memory for originally encoded episodes. In addition, frontal activity increased for episodic prediction errors when episodes had been less frequently retrieved pre-fMRI. A history of spaced versus massed retrieval was associated with increased activation throughout the episodic memory network, with no significant effect on behavioral performance. Our findings show that episodic prediction errors led to false memories. The history of different retrieval protocols was reflected in memory performance and brain responses to episodic prediction errors, but did not interact with the brain's episodic learning response., (© 2022 Massachusetts Institute of Technology.)

Emotional experiences are proposed to arise from contextualized perception of bodily responses, also referred to as interoceptive inferences. The recognition of emotions benefits from adequate access to one's own interoceptive information. However, direct empirical evidence of interoceptive inferences and their neural basis is still lacking. In the present fMRI study healthy volunteers performed a probabilistic emotion classification task with videotaped dynamically unfolding facial expressions. In a first step, we aimed to determine functional areas involved in the processing of dynamically unfolding emotional expressions. We then tested whether individuals with higher interoceptive accuracy (IAcc), as assessed by the Heartbeat detection task (HDT), or higher interoceptive sensitivity (IS), as assessed by the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), benefit more from the contextually given likelihood of emotional valence and whether brain regions reflecting individual IAcc and/or IS play a role in this. Individuals with higher IS benefitted more from the biased probability of emotional valence. Brain responses to more predictable emotions elicited a bilateral activity pattern comprising the inferior frontal gyrus and the posterior insula. Importantly, individual IAcc scores positively covaried with brain responses to more surprising and less predictable emotional expressions in the insula and caudate nucleus. We show for the first time that IAcc score is associated with enhanced processing of interoceptive prediction errors, particularly in the anterior insula. A higher IS score seems more likely to be associated with a stronger weighting of attention to interoceptive changes processed by the posterior insula and ventral prefrontal cortex., (Copyright © 2022. Published by Elsevier Inc.)

Episodic memories are not static but can change on the basis of new experiences, potentially allowing us to make valid predictions in the face of an ever-changing environment. Recent research has identified prediction errors during memory retrieval as a possible trigger for such changes. In this study, we used modified episodic cues to investigate whether different types of mnemonic prediction errors modulate brain activity and subsequent memory performance. Participants encoded episodes that consisted of short toy stories. During a subsequent fMRI session, participants were presented videos showing the original episodes, or slightly modified versions thereof. In modified videos, either the order of two subsequent action steps was changed or an object was exchanged for another. Content modifications recruited parietal, temporo-occipital, and parahippocampal areas reflecting the processing of the new object information. In contrast, structure modifications elicited activation in right dorsal premotor, posterior temporal, and parietal areas, reflecting the processing of new sequence information. In a post-fMRI memory test, the participants' tendency to accept modified episodes as originally encoded increased significantly when they had been presented modified versions already during the fMRI session. After experiencing modifications, especially those of the episodes' structure, the recognition of originally encoded episodes was impaired as well. Our study sheds light onto the neural processing of different types of episodic prediction errors and their influence on subsequent memory recall., (© 2022 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Background: Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness., Methods: A total of 531 patients suffering from acute ( N = 250) or remitted ( N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v . remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects., Results: Disease state ( p FWE < 0.042) and number of hospitalizations ( p FWE < 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score ( p FWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant ( p FWE < 0.040) mapping to the right SLF., Conclusions: Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

Cognitive deficits are central attendant symptoms of major depressive disorder (MDD) with a crucial impact in patients' everyday life. Thus, it is of particular clinical importance to understand their pathophysiology. The aim of this study was to investigate a possible relationship between brain structure and cognitive performance in MDD patients in a well-characterized sample. N = 1007 participants (N MDD  = 482, healthy controls (HC): N HC  = 525) were selected from the FOR2107 cohort for this diffusion-tensor imaging study employing tract-based spatial statistics. We conducted a principal component analysis (PCA) to reduce neuropsychological test results, and to discover underlying factors of cognitive performance in MDD patients. We tested the association between fractional anisotropy (FA) and diagnosis (MDD vs. HC) and cognitive performance factors. The PCA yielded a single general cognitive performance factor that differed significantly between MDD patients and HC (P < 0.001). We found a significant main effect of the general cognitive performance factor in FA (P tfce-FWE  = 0.002) in a large bilateral cluster consisting of widespread frontotemporal-association fibers. In MDD patients this effect was independent of medication intake, the presence of comorbid diagnoses, the number of previous hospitalizations, and depressive symptomatology. This study provides robust evidence that white matter disturbances and cognitive performance seem to be associated. This association was independent of diagnosis, though MDD patients show more pronounced deficits and lower FA values in the global white matter fiber structure. This suggests a more general, rather than the depression-specific neurological basis for cognitive deficits., (© 2021. The Author(s).)

Intuitively, we assume that we remember episodes better when we actively participated in them and were not mere observers. Independently of this, we can recall episodes from either the first-person perspective (1pp) or the third-person perspective (3pp). In this functional magnetic resonance imaging (fMRI) study, we tested whether agency and perspective modulate neural activity during memory retrieval and subsequently enhance memory performance. Subjects encoded a set of different episodes by either imitating or only observing videos that showed short toy stories. A week later, we conducted fMRI and cued episodic retrieval by presenting the original videos, or slightly modified versions thereof, from 1pp or from 3pp. The hippocampal formation was sensitive to self-performed vs. only observed actions only when there was an episodic mismatch. In a post-fMRI memory test a history of self-performance did not improve behavioral memory performance. However, modified videos were often (falsely) accepted as showing truly experienced episodes when: (i) they were already presented in this modified version during fMRI or (ii) they were presented in their original form during fMRI but from 3pp. While the overall effect of modification was strong, the effects of perspective and agency were more subtle. Together, our findings demonstrate that self-performance and self-perspective modulate the strength of a memory trace in different ways. Even when memory performance remains the same for different agentive states, the brain is capable of detecting mismatching information. Re-experiencing the latter impairs memory performance as well as retrieving encoded episodes from 3pp., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jainta, Siestrup, El-Sourani, Trempler, Wurm, Werning, Cheng and Schubotz.)

Recognizing the actions of others depends on segmentation into meaningful events. After decades of research in this area, it remains still unclear how humans do this and which brain areas support underlying processes. Here we show that a computer vision-based model of touching and untouching events can predict human behavior in segmenting object manipulation actions with high accuracy. Using this computational model and functional Magnetic Resonance Imaging (fMRI), we pinpoint the neural networks underlying this segmentation behavior during an implicit action observation task. Segmentation was announced by a strong increase of visual activity at touching events followed by the engagement of frontal, hippocampal and insula regions, signaling updating expectation at subsequent untouching events. Brain activity and behavior show that touching-untouching motifs are critical features for identifying the key elements of actions including object manipulations., (Copyright © 2021. Published by Elsevier Inc.)

Emotional sensations and inferring another's emotional states have been suggested to depend on predictive models of the causes of bodily sensations, so-called interoceptive inferences. In this framework, higher sensibility for interoceptive changes (IS) reflects higher precision of interoceptive signals. The present study examined the link between IS and emotion recognition, testing whether individuals with higher IS recognize others' emotions more easily and are more sensitive to learn from biased probabilities of emotional expressions. We recorded skin conductance responses (SCRs) from forty-six healthy volunteers performing a speeded-response task, which required them to indicate whether a neutral facial expression dynamically turned into a happy or fearful expression. Moreover, varying probabilities of emotional expressions by their block-wise base rate aimed to generate a bias for the more frequently encountered emotion. As a result, we found that individuals with higher IS showed lower thresholds for emotion recognition, reflected in decreased reaction times for emotional expressions especially of high intensity. Moreover, individuals with increased IS benefited more from a biased probability of an emotion, reflected in decreased reaction times for expected emotions. Lastly, weak evidence supporting a differential modulation of SCR by IS as a function of varying probabilities was found. Our results indicate that higher interoceptive sensibility facilitates the recognition of emotional changes and is accompanied by a more precise adaptation to emotion probabilities., Competing Interests: The authors have declared that no competing interests exist.

Surprising scenarios can have different behavioural and neuronal consequences depending on the violation of the expectation. On the one hand, previous research has shown that the omission of a visual stimulus results in a robust cortical response representing that missing stimulus, a so-called negative prediction error. On the other hand, a large amount of studies revealed positive prediction error signals, entailing an increased neural response that can be attributed to the experience of a surprising, unexpected stimulus. However, there has been no evidence, so far, regarding how and when these prediction error signals co-occur. Here, we argue that the omission of an expected stimulus can and often does coincide with the appearance of an unexpected one. Therefore, we investigated whether positive and negative prediction error signals evoked by unpredicted cross-category stimulus transitions would temporally coincide during a speeded forced-choice fMRI paradigm. Foremost, our findings provide evidence of a behavioural effect regarding the facilitation of responses linked to expected stimuli. In addition, we obtained evidence for negative prediction error signals as seen in differential activation of FFA and PPA during unexpected place and face trials, respectively. Lastly, a psychophysiological interaction analysis revealed evidence for positive prediction error signals represented by context-dependent functional coupling between the right IFG and FFA or PPA, respectively, implicating a network that updates the internal representation after the appearance of an unexpected stimulus through involvement of this frontal area. The current results are consistent with a predictive coding account of cognition and underline the importance of considering the potential dual nature of expectation violations. Furthermore, our results put forward that positive and negative prediction error signalling can be directly linked to regions associated with the processing of different stimulus categories., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although statistical regularities in the environment often go explicitly unnoticed, traces of implicit learning are evident in our neural activity. Recent perspectives have offered evidence that both pre-stimulus oscillations and peri-stimulus event-related potentials are reliable biomarkers of implicit expectations arising from statistical learning. What remains ambiguous, however, is the origination and development of these implicit expectations. To address this lack of knowledge and determine the temporal constraints of expectation formation, pre-stimulus increases in alpha/beta power were investigated alongside a reduction in the N170 and a suppression in peri-/post-stimulus gamma power. Electroencephalography was acquired from naive participants who engaged in a gender classification task. Participants were uninformed, that eight face images were sorted into four reoccurring pairs which were pseudorandomly hidden amongst randomly occurring face images. We found a reduced N170 for statistically expected images at left parietal and temporo-parietal electrodes. Furthermore, enhanced gamma power following the presentation of random images emphasized the bottom-up processing of these arbitrary occurrences. In contrast, enhanced alpha/beta power was evident pre-stimulus for expected relative to random faces. A particularly interesting finding was the early onset of alpha/beta power enhancement which peaked immediately after the depiction of the predictive face. Hence, our findings propose an approximate timeframe throughout which consistent traces of enhanced alpha/beta power illustrate the early prioritisation of top-down processes to facilitate the development of implicitly cued face-related expectations., Competing Interests: The authors have declared that no competing interests exist.

Auditory and visual percepts are integrated even when they are not perfectly temporally aligned with each other, especially when the visual signal precedes the auditory signal. This window of temporal integration for asynchronous audiovisual stimuli is relatively well examined in the case of speech, while other natural action-induced sounds have been widely neglected. Here, we studied the detection of audiovisual asynchrony in three different whole-body actions with natural action-induced sounds-hurdling, tap dancing and drumming. In Study 1, we examined whether audiovisual asynchrony detection, assessed by a simultaneity judgment task, differs as a function of sound production intentionality. Based on previous findings, we expected that auditory and visual signals should be integrated over a wider temporal window for actions creating sounds intentionally (tap dancing), compared to actions creating sounds incidentally (hurdling). While percentages of perceived synchrony differed in the expected way, we identified two further factors, namely high event density and low rhythmicity, to induce higher synchrony ratings as well. Therefore, we systematically varied event density and rhythmicity in Study 2, this time using drumming stimuli to exert full control over these variables, and the same simultaneity judgment tasks. Results suggest that high event density leads to a bias to integrate rather than segregate auditory and visual signals, even at relatively large asynchronies. Rhythmicity had a similar, albeit weaker effect, when event density was low. Our findings demonstrate that shorter asynchronies and visual-first asynchronies lead to higher synchrony ratings of whole-body action, pointing to clear parallels with audiovisual integration in speech perception. Overconfidence in the naturally expected, that is, synchrony of sound and sight, was stronger for intentional (vs. incidental) sound production and for movements with high (vs. low) rhythmicity, presumably because both encourage predictive processes. In contrast, high event density appears to increase synchronicity judgments simply because it makes the detection of audiovisual asynchrony more difficult. More studies using real-life audiovisual stimuli with varying event densities and rhythmicities are needed to fully uncover the general mechanisms of audiovisual integration., Competing Interests: The authors have declared that no competing interests exist.

Background: Manifold cognitive deficits have been reported in schizophrenia spectrum disorders, including disturbances in flexible updating to altered circumstances as well as stabilization deficits in the face of distractors. In this functional magnetic resonance imaging study, we examined the neural correlates of these deficits as two complementary components of predictive processing., Methods: In 22 patients with schizophrenia spectrum disorders and 22 healthy matched control participants, we applied a serial predictive switch-drift task to assess flexibility as successful detection of prediction-rule switches, and stability as successfully ignoring distractors ("drifts")., Results: Patients compared with controls less reliably detected rule switches and also less efficiently inhibited drifts. A reduced striatal response to switches or drifts correlated with weaker switch-drift-discrimination in patients, suggesting impaired gating of prediction errors. The increase in activity in anterior cingulate cortex and hippocampus for detected vs. undetected switches was reduced in patients compared to controls, which may reflect impaired behavioral adaptation following prediction errors. The comparison between shielding against distractions and undetected switches showed increased activity in the inferior frontal cortex and posterior insula in controls but not in patients., Conclusion: Our results suggest new insights into the specific disruption of predictive flexibility and stability in schizophrenia spectrum disorders, which is characterized by impaired striatal gating and inadequate cortical encoding of predictive errors., (Copyright © 2021. Published by Elsevier Inc.)

Predicting other people's upcoming action is key to successful social interactions. Previous studies have started to disentangle the various sources of information that action observers exploit, including objects, movements, contextual cues and features regarding the acting person's identity. We here focus on the role of static and dynamic inter-object spatial relations that change during an action. We designed a virtual reality setup and tested recognition speed for ten different manipulation actions. Importantly, all objects had been abstracted by emulating them with cubes such that participants could not infer an action using object information. Instead, participants had to rely only on the limited information that comes from the changes in the spatial relations between the cubes. In spite of these constraints, participants were able to predict actions in, on average, less than 64% of the action's duration. Furthermore, we employed a computational model, the so-called enriched Semantic Event Chain (eSEC), which incorporates the information of different types of spatial relations: (a) objects' touching/untouching, (b) static spatial relations between objects and (c) dynamic spatial relations between objects during an action. Assuming the eSEC as an underlying model, we show, using information theoretical analysis, that humans mostly rely on a mixed-cue strategy when predicting actions. Machine-based action prediction is able to produce faster decisions based on individual cues. We argue that human strategy, though slower, may be particularly beneficial for prediction of natural and more complex actions with more variable or partial sources of information. Our findings contribute to the understanding of how individuals afford inferring observed actions' goals even before full goal accomplishment, and may open new avenues for building robots for conflict-free human-robot cooperation., Competing Interests: The authors have declared that no competing interests exist.

The influence of delayed auditory feedback on action evaluation and execution of real-life action-induced sounds apart from language and music is still poorly understood. Here, we examined how a temporal delay impacted the behavioral evaluation and neural representation of hurdling and tap-dancing actions in a functional magnetic resonance imaging (fMRI) experiment, postulating that effects of delay diverge between the two, as we create action-induced sounds intentionally in tap dancing, but incidentally in hurdling. Based on previous findings, we expected that conditions differ regarding the engagement of the supplementary motor area (SMA), posterior superior temporal gyrus (pSTG), and primary auditory cortex (A1). Participants were videotaped during a 9-week training of hurdling and tap dancing; in the fMRI scanner, they were presented with point-light videos of their own training videos, including the original or the slightly delayed sound, and had to evaluate how well they performed on each single trial. For the undelayed conditions, we replicated A1 attenuation and enhanced pSTG and SMA engagement for tap dancing (intentionally generated sounds) vs. hurdling (incidentally generated sounds). Delayed auditory feedback did not negatively influence behavioral rating scores in general. Blood-oxygen-level-dependent (BOLD) response transiently increased and then adapted to repeated presentation of point-light videos with delayed sound in pSTG. This region also showed a significantly stronger correlation with the SMA under delayed feedback. Notably, SMA activation increased more for delayed feedback in the tap-dancing condition, covarying with higher rating scores. Findings suggest that action evaluation is more strongly based on top-down predictions from SMA when sounds of intentional action are distorted., (Copyright © 2020 Heins, Trempler, Zentgraf, Raab and Schubotz.)

The brain's sensitivity to and accentuation of unpredicted over predicted sensory signals plays a fundamental role in learning. According to recent theoretical models of the predictive coding framework, dopamine is responsible for balancing the interplay between bottom-up input and top-down predictions by controlling the precision of surprise signals that guide learning. Using functional MRI, we investigated whether patients with Parkinson's disease (PD) show impaired learning from prediction errors requiring either adaptation or stabilisation of current predictions. Moreover, we were interested in whether deficits in learning over a specific time scale would be accompanied by altered surprise responses in dopamine-related brain structures. To this end, twenty-one PD patients tested on and off dopaminergic medication and twenty-one healthy controls performed a digit prediction paradigm. During the task, violations of sequence-based predictions either signalled the need to update or to stabilise the current prediction and, thus, to react to them or ignore them, respectively. To investigate contextual adaptation to prediction errors, the probability (or its inverse, surprise) of the violations fluctuated across the experiment. When the probability of prediction errors over a specific time scale increased, healthy controls but not PD patients off medication became more flexible, i.e., error rates at violations requiring a motor response decreased in controls but increased in patients. On the neural level, this learning deficit in patients was accompanied by reduced signalling in the substantia nigra and the caudate nucleus. In contrast, differences between the groups regarding the probabilistic modulation of behaviour and neural responses were much less pronounced at prediction errors requiring only stabilisation but no adaptation. Interestingly, dopaminergic medication could neither improve learning from prediction errors nor restore the physiological, neurotypical pattern. Our findings point to a pivotal role of dysfunctions of the substantia nigra and caudate nucleus in deficits in learning from flexibility-demanding prediction errors in PD. Moreover, the data witness poor effects of dopaminergic medication on learning in PD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Most human actions produce concomitant sounds. Action sounds can be either part of the action goal (GAS, goal-related action sounds), as for instance in tap dancing, or a mere by-product of the action (BAS, by-product action sounds), as for instance in hurdling. It is currently unclear whether these two types of action sounds-incidental or intentional-differ in their neural representation and whether the impact on the performance evaluation of an action diverges between the two. We here examined whether during the observation of tap dancing compared to hurdling, auditory information is a more important factor for positive action quality ratings. Moreover, we tested whether observation of tap dancing vs. hurdling led to stronger attenuation in primary auditory cortex, and a stronger mismatch signal when sounds do not match our expectations. We recorded individual point-light videos of newly trained participants performing tap dancing and hurdling. In the subsequent functional magnetic resonance imaging (fMRI) session, participants were presented with the videos that displayed their own actions, including corresponding action sounds, and were asked to rate the quality of their performance. Videos were either in their original form or scrambled regarding the visual modality, the auditory modality, or both. As hypothesized, behavioral results showed significantly lower rating scores in the GAS condition compared to the BAS condition when the auditory modality was scrambled. Functional MRI contrasts between BAS and GAS actions revealed higher activation of primary auditory cortex in the BAS condition, speaking in favor of stronger attenuation in GAS, as well as stronger activation of posterior superior temporal gyri and the supplementary motor area in GAS. Results suggest that the processing of self-generated action sounds depends on whether we have the intention to produce a sound with our action or not, and action sounds may be more prone to be used as sensory feedback when they are part of the explicit action goal. Our findings contribute to a better understanding of the function of action sounds for learning and controlling sound-producing actions., (Copyright © 2020 Heins, Pomp, Kluger, Trempler, Zentgraf, Raab and Schubotz.)

While prediction errors have been established to instigate learning through model adaptation, recent studies have stressed the role of model-compliant events in predictive processing. Specifically, probabilistic information at critical points in time (so-called checkpoints) has been suggested to be sampled in order to evaluate the internal model, particularly in uncertain contexts. This way, initial model-based expectations are iteratively reaffirmed under uncertainty, even in the absence of prediction errors. Using electroencephalography (EEG), the present study aimed to investigate the interplay of such global uncertainty information and local adjustment cues prompting on-line adjustments of expectations. Within a stream of single digits, participants were to detect ordered sequences (i.e., 3-4-5-6-7) that had a regular length of five digits and were occasionally extended to seven digits. Over time, these extensions were either rare (low irreducible uncertainty) or frequent (high uncertainty) and could be unexpected or indicated by incidental colour cues. Accounting for cue information, an N400 component was revealed as the correlate of locally unexpected (vs expected) outcomes, reflecting effortful integration of incongruous information. As for model-compliant information, multivariate pattern decoding within the P3b time frame demonstrated effective exploitation of local (adjustment cues vs non-informative analogues) and global information (high vs low uncertainty regular endings) sampled from probabilistic events. Finally, superior fit of a global model (disregarding local adjustments) compared to a local model (including local adjustments) in a representational similarity analysis underscored the precedence of global reference frames in hierarchical predictive processing. Overall, results suggest that just like error-induced model adaptation, model evaluation is not limited to either local or global information. Following the hierarchical organisation of predictive processing, model evaluation too can occur at several levels of the processing hierarchy., Competing Interests: The authors have declared that no competing interests exist.

The processing of congruent stimuli, such as an object or action in its typical location, is usually associated with reduced neural activity, probably due to facilitated recognition. However, in some situations, congruency increases neural activity-for example, when objects next to observed actions are likely versus unlikely to be involved in forthcoming action steps. Here, we investigated using fMRI whether the processing of contextual cues during action perception is driven by their (in)congruency and, thus, informative value to make sense of an observed scene. Specifically, we tested whether both highly congruent contextual objects (COs), which strongly indicate a future action step, and highly incongruent COs, which require updating predictions about possible forthcoming action steps, provide more anticipatory information about the action course than moderately congruent COs. In line with our hypothesis that especially the inferior frontal gyrus (IFG) subserves the integration of the additional information into the predictive model of the action, we found highly congruent and incongruent COs to increase bilateral activity in action observation nodes, that is, the IFG, the occipitotemporal cortex, and the intraparietal sulcus. Intriguingly, BA 47 was significantly stronger engaged for incongruent COs reflecting the updating of prediction in response to conflicting information. Our findings imply that the IFG reflects the informative impact of COs on observed actions by using contextual information to supply and update the currently operating predictive model. In the case of an incongruent CO, this model has to be reconsidered and extended toward a new overarching action goal.

Reduced fractional anisotropy (FA) associated with Major Depressive Disorder (MDD) overlaps anatomically with effects of childhood maltreatment experiences. The aim of this study was, therefore, to replicate the negative effect of childhood maltreatment on white matter fiber structure and to demonstrate, that alterations in MDD might be partially attributed to the higher occurrence of childhood maltreatment in MDD. Two independent cohorts (total N = 1 256) were investigated in a diffusion tensor imaging study: The Münster Neuroimaging Cohort (MNC, N = 186 MDD, N = 210 healthy controls, HC) as discovery sample and the Marburg-Münster Affective Disorders Cohort Study (MACS, N = 397 MDD, N = 462 HC) as replication sample. The effects of diagnosis (HC vs. MDD) and Childhood Trauma Questionnaire (CTQ) scores on FA were analyzed. A main effect of diagnosis with higher FA in MDD patients compared with HC was found in the MNC (p FWE  = 0.021), but not in the MACS (p FWE  = 0.52) before correcting for CTQ. A significant negative correlation of FA with CTQ emerged in both cohorts (MNC: p FWE  = 0.006, MACS: p FWE  = 0.012) in several tracts previously described in the literature. No CTQ × diagnosis interaction could be detected. Any main effect of diagnosis was abolished after correcting for CTQ (MNC: p FWE  = 0.562, MACS: p FWE  = 0.115). No differences in FA between MDD and HC could be found after correcting for childhood maltreatment, suggesting that previously reported group differences might be attributed partially to higher levels of maltreatment experiences in MDD rather than diagnosis itself. Furthermore, a well-established finding of reduced FA following childhood maltreatment experiences was replicated.

Background: There is increasing evidence that people with attention-deficit/hyperactivity disorder (ADHD) are impaired in emotion regulation, but psychophysiological and functional MRI data on emotion processing in adult patients with ADHD are scarce. We investigated the neural correlates of reappraisal as one of the most efficient emotion-regulation strategies., Methods: We included 30 adult patients with ADHD and 35 healthy controls in our study. We applied a well-established reappraisal paradigm in functional MRI and assessed behavioural emotion-regulation strategies with standardized questionnaires. We hypothesized that patients with ADHD would demonstrate impaired reappraisal related to reduced activations in the frontoparietal cognitive control network., Results: Despite our hypothesis, we found no significant activation differences in the neural reappraisal network between patients with ADHD and controls. As well, both groups revealed similar reappraisal success on the immediate behavioural ratings in the scanner. Interestingly, patients with ADHD revealed significantly increased activations in the dorsal and ventral anterior cingulate cortex (ACC) compared to controls when viewing negative > neutral pictures. These ACC activations were significantly correlated with the prevalence of habitual use of reappraisal in patients with ADHD only., Limitations: Patients withdrew medication only 24 hours before the experiment; we investigated negative, but not positive, emotion processing and regulation., Conclusion: Although emotion dysregulation is regarded as a core symptom of ADHD, explicit reappraisal does not seem to be impaired in adult patients. However, increased activation of the ACC implies stronger implicit emotion regulation induced by negative stimuli. This might be explained by emotional hyperresponsivity in patients with ADHD compared with controls., Competing Interests: None declared., (© 2019 Joule Inc. or its licensors)

While prediction errors (PE) have been established to drive learning through adaptation of internal models, the role of model-compliant events in predictive processing is less clear. Checkpoints (CP) were recently introduced as points in time where expected sensory input resolved ambiguity regarding the validity of the internal model. Conceivably, these events serve as on-line reference points for model evaluation, particularly in uncertain contexts. Evidence from fMRI has shown functional similarities of CP and PE to be independent of event-related surprise, raising the important question of how these event classes relate to one another. Consequently, the aim of the present study was to characterise the functional relationship of checkpoints and prediction errors in a serial pattern detection task using electroencephalography (EEG). Specifically, we first hypothesised a joint P3b component of both event classes to index recourse to the internal model (compared to non-informative standards, STD). Second, we assumed the mismatch signal of PE to be reflected in an N400 component when compared to CP. Event-related findings supported these hypotheses. We suggest that while model adaptation is instigated by prediction errors, checkpoints are similarly used for model evaluation. Intriguingly, behavioural subgroup analyses showed that the exploitation of potentially informative reference points may depend on initial cue learning: Strict reliance on cue-based predictions may result in less attentive processing of these reference points, thus impeding upregulation of response gain that would prompt flexible model adaptation. Overall, present results highlight the role of checkpoints as model-compliant, informative reference points and stimulate important research questions about their processing as function of learning und uncertainty., Competing Interests: The authors have declared that no competing interests exist.

This study investigated how attending to auditory and visual information systematically changes graph theoretical measures of integration and functional connectivity between three network modules: auditory, visual, and a joint task core. Functional MRI BOLD activity was recorded while healthy volunteers attended to colour and/or pitch information presented within an audiovisual stimulus sequence. Network nodes and modules were based on peak voxels of BOLD contrasts, including colour and pitch sensitive brain regions as well as the dorsal attention network. Network edges represented correlations between nodes' activity and were computed separately for each condition. Connection strength was increased between the task and the visual module when participants attended to colour, and between the task and the auditory module when they attended to pitch. Moreover, several nodal graph measures showed consistent changes to attentional modulation in form of stronger integration of sensory regions in response to attention. Together, these findings corroborate dynamical adjustments of both modality-specific and modality-independent functional brain networks in response to task demands and their representation in graph theoretical measures., Competing Interests: The authors have declared that no competing interests exist.

Recent fMRI findings revealed that impairment in a serial prediction task in patients suffering from Parkinson's disease (PD) results from hypoactivity of the SMA. Furthermore, hyperactivity of the lateral premotor cortex sustained performance after withdrawal of medication. To further explore these findings, we here examined the impact of deep brain stimulation of the subthalamic nucleus on the activity of the putamen and premotor areas while performing the serial prediction task. To this end, we measured eight male PD patients ON and OFF deep brain stimulation and eight healthy age-matched male controls using [ 15 O] water positron emission tomography to measure regional cerebral blood flow. As expected, PD patients showed poorer performance than healthy controls while performance did not differ between OFF and ON stimulation. Hypoactivity of the putamen and hyperactivity of the left lateral premotor cortex was found in patients compared to controls. Lateral premotor hyperactivity further increased OFF compared to ON stimulation and was positively related to task performance. These results confirm that the motor loop's dysfunction has impact on cognitive processes (here: prediction of serial stimuli) in PD. Extending prior data regarding the role of the lateral premotor cortex in cognitive compensation, our results indicate that lateral premotor cortex hyperactivity, while beneficial in moderate levels of impairment, might fail to preserve performance in more severe stages of the motor loop's degeneration., (Copyright © 2018. Published by Elsevier Ltd.)

Parkinson's disease (PD), which is caused by degeneration of dopaminergic neurons in the midbrain, results in a heterogeneous clinical picture including cognitive decline. Since the phasic signal of dopamine neurons is proposed to guide learning by signifying mismatches between subjects' expectations and external events, we here investigated whether akinetic-rigid PD patients without mild cognitive impairment exhibit difficulties in dealing with either relevant (requiring flexibility) or irrelevant (requiring stability) prediction errors. Following our previous study on flexibility and stability in prediction (Trempler et al. J Cogn Neurosci 29(2):298-309, 2017), we then assessed whether deficits would correspond with specific structural alterations in dopaminergic regions as well as in inferior frontal cortex, medial prefrontal cortex, and the hippocampus. Twenty-one healthy controls and twenty-one akinetic-rigid PD patients on and off medication performed a task which required to serially predict upcoming items. Switches between predictable sequences had to be indicated via button press, whereas sequence omissions had to be ignored. Independent of the disease, midbrain volume was related to a general response bias to unexpected events, whereas right putamen volume correlated with the ability to discriminate between relevant and irrelevant prediction errors. However, patients compared with healthy participants showed deficits in stabilisation against irrelevant prediction errors, associated with thickness of right inferior frontal gyrus and left medial prefrontal cortex. Flexible updating due to relevant prediction errors was also affected in patients compared with controls and associated with right hippocampus volume. Dopaminergic medication influenced behavioural performance across, but not within the patients. Our exploratory study warrants further research on deficient prediction error processing and its structural correlates as a core of cognitive symptoms occurring already in early stages of the disease.