Alexander Münchau’s research while affiliated with University of Lübeck and other places

Stimulus-response (S-R) bindings, which integrate sensory stimuli and motor responses into event files, are transient yet essential for adaptive behavior. This study investigated the EEG oscillatory dynamics underlying S-R binding processes, focusing on the roles of event-related desynchronization (ERD) and event-related synchronization (ERS) in the alpha/beta and theta frequency ranges during the integration and maintenance phases of S-R bindings. Using the S1R1-S2R2 task with response-stimulus intervals (RSIs) of 1000 ms and 3000 ms between the prime response and the onset of the probe display, we examined behavioral partial repetition costs and their neural correlates. Behavioral results confirmed the transient nature of S-R bindings, with greater partial repetition costs observed in the shorter RSI condition. EEG time-frequency analyses revealed a significant negative correlation between alpha/beta power changes (ERD) during the initial integration time window around the prime response and behavioral S-R binding. Beamformer analysis localized this correlation effect to the secondary visual cortex. Additionally, a significant positive correlation was observed between alpha power increase (ERS) during the maintenance time window before the probe display onset and behavioral S-R binding. No significant correlation between theta power and behavioral S-R binding was observed. Together, these findings highlight the distinct contributions of alpha/beta ERD and alpha ERS to the temporal dynamics of S-R bindings and advance our understanding of the neural oscillatory mechanisms underpinning perception-action integration and event-file maintenance.

How do we make sense of our surroundings? A widely recognized field in cognitive psychology suggests that many important functions like memory of incidents, reasoning, and attention depend on the way we segment the ongoing stream of perception (Zacks & Swallow, 2007). An open question still is, how the structure generated from a perceptual stream translates into behavior. To address this question, we combined the findings in event segmentation literature with another influential body of literature that analyzes mechanisms behind the control of individual actions (Frings et al., 2020). Specifically, we analyzed how two very basic mechanisms in action control (binding and retrieval) are affected by boundaries between events. Two comic scenarios with different characters were used to implement events and boundaries between events. In two experiments, we measured binding and retrieval between individually executed responses that could be part of the same or separate events. In Experiment 1, we found larger binding effects for responses that were integrated within an event than for responses that had to be integrated across an event boundary. In Experiment 2, we found that the effect of retrieval of a past response on further actions was hampered by an event boundary. Together, the experiments indicate that the structure we pick up from our environment can translate into ongoing action via modulation of the two basic mechanisms binding and retrieval.

Purpose: Short-read genome sequencing (GS) is a comprehensive genetic testing method capable of detecting multiple variant types. Despite its technical advantages, systemic comparisons of singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) in real-world diagnostics remain limited. Methods: We systematically compared sGS, tGS, and SoC genetic testing in 448 patients with rare diseases in a blinded, prospective study. Three independent teams evaluated the diagnostic yield, variant detection capabilities, and clinical feasibility of GS as a first-tier test. Diagnostic yield was assessed through both prospective and retrospective analyses. Results: In prospective analyses, tGS achieved the highest diagnostic yield for likely pathogenic/pathogenic variants (36.8%) in a newly trained team, outperforming the experienced SoC team (36.0%) and the sGS team (30.4%). Retrospective analyses, accounting for technical variant detection and team experience differences, reported diagnostic yields of 38.6% for SoC, 41.3% for sGS, and 42.2% for tGS. GS excelled in identifying deep intronic, non-coding, and small copy-number variants missed by SoC. Notably, tGS additionally identified three de novo variants classified as likely pathogenic based on recent GeneMatcher collaborations and newly published gene-disease association studies. Conclusion: GS, particularly tGS, demonstrated superior diagnostic performance, supporting its use as a first-tier genetic test. sGS offers a cost-effective alternative, enabling faster, more efficient diagnoses for rare disease patients.

We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs.

A major concept in cognitive neuroscience is that brains are “prediction machines”. Yet, conceptual frameworks on how perception and action become integrated still lack the concept of predictability and it is unclear how neural processes may implement predictive coding during dynamic perception-action integration. We show that distinct neurophysiological mechanisms of nonlinearly directed connectivities in the theta and alpha band between cortical structures underlie these processes. During the integration of perception and motor codes, especially theta band activity in the insular cortex and temporo-hippocampal structures is modulated by the predictability of upcoming information. Here, the insular cortex seems to guide processes. Conversely, the retrieval of such integrated perception-action codes during actions heavily relies on alpha band activity. Here, directed top-down influence of alpha band activity from inferior frontal structures on insular and temporo-hippocampal structures is key. This suggests that these top-down effects reflect attentional shielding of retrieval processes operating in the same neuroanatomical structures previously involved in the integration of perceptual and motor codes. Through neurophysiology, the present study connects predictive coding mechanisms with frameworks specifying the dynamic integration of perception and action.

Functional movement disorders (FMD) are amongst the most common and disabling neurological conditions, placing a significant burden on the healthcare system. Despite the frequency and importance of FMD, our understanding of the underlying pathophysiology is limited, hindering the development of causal treatment options. Traditionally, FMD was considered as a psychiatric condition, associated with involuntary movements triggered by psychological stressors. Recent neurophysiological studies have unveiled cognitive alterations in affected individuals, suggesting that FMD might be better characterized by overarching neural principles governing cognitive functions. For instance, recent research has shown that the retrieval of stimulus-response bindings is altered in FMD patients. Building upon these recent findings, our study delves into whether the initial integration of stimulus and response information is also disrupted in FMD patients. To accomplish this, we reanalysed previously collected EEG data using refined analysis methods that provide insights into oscillatory activity and functional neuroanatomy associated with the integration of stimulus-response bindings. Our results demonstrate that post-movement beta synchronization (i) predicts behavioural stimulus-response binding and (ii) is significantly increased in FMD patients compared to healthy controls. Utilizing beamformer analysis, we localized the difference effect to a cluster centred around the left supplementary motor area (SMA) and the correlation effect to the right SMA. Extending beyond recent research that focused on the retrieval of stimulus-response bindings, our present findings reveal that the integration of stimulus and response information is already impaired in FMD patients. These results uncover a phenomenon of hyperbinding between perception and action, which may represent a fundamental mechanism contributing to the movement impairments in patients with FMD.

Adaptive behavior is based on flexibly managing and integrating perceptual and motor processes, and the reconfiguration thereof. Such adaptive behavior is also relevant during inhibitory control. Although research has demonstrated local activity modulations in theta and alpha frequency bands during behavioral adaptation, the communication of brain regions is insufficiently studied. Examining directed connectivity between brain regions using a machine learning approach, a generally increased activity, but decreased connectivity within a temporo-occipital theta band network was revealed during the reconfiguration of perception-action associations during inhibitory control. Additionally, a fronto-occipital alpha-theta interplay yielded a decrease in directed connectivity during reconfiguration processes, which was associated with lower error rates in behavior. Thus, adaptive behavior relies on both local increases and decreases of activity depending on the frequency band, and concomitant decreases in communication between frontal and sensory cortices. The findings reframe common conceptualizations about how adaptive behavior is supported by neural processes.