Biology subjects

Wagner, I. C.

Publications and source records attributed to Wagner, I. C..

12 recordsLinked to original sources

bioRxiv2026

No effects of APOE ε4 on spatial navigation and broader cognition in young adults genetically at risk for Alzheimer's disease

Alzheimers disease (AD) causes progressive memory loss and disorientation. It is preceded by a prolonged preclinical phase marked by pathological changes in medial temporal lobe regions involved in spatial navigation. Spatial navigation tasks have been proposed for early AD detection, and altered navigation performance was reported in older carriers of the apolipoprotein E (APOE) {varepsilon}4 allele, the major genetic risk factor for sporadic AD. However, whether spatial navigation or other cognitive abilities are affected in younger {varepsilon}4 carriers remains unclear. Here, we genotyped 1000 healthy young adults (18-35 years) who completed the app-based navigation game "Sea Hero Quest" and several tasks assessing working memory, processing speed, executive functioning, and face recognition. {varepsilon}4 carriers ({varepsilon}3{varepsilon}4, N = 88) showed no significant differences from non-carriers ({varepsilon}3{varepsilon}3, N = 327) in spatial navigation or other cognitive abilities, supported by equivalence testing and Bayesian analyses. Exploratory findings suggested altered spatial navigation in {varepsilon}2 carriers ({varepsilon}2{varepsilon}2/{varepsilon}2{varepsilon}3/{varepsilon}2{varepsilon}4, Ns = 7/51/7) versus {varepsilon}3{varepsilon}3 controls, who stayed closer to environmental borders and showed better memory updating, face recognition, and processing speed. Therefore, APOE-related behavioural differences in young adults appear small at best, highlighting the need for paradigms sensitive to very subtle changes decades before potential dementia onset.

neuroscience↗

bioRxiv2025

Gut microbial diversity and inferred capacity to produce butyrate modulate cortisol reactivity following acute stress in healthy adults

Acute stress triggers the release of stress hormones such as cortisol, increasing stress reactivity and aiding post-stress recovery. Rodent studies revealed that stress reactivity is modulated by the gut microbiota, and few interventional studies have provided evidence for an effect on human cortisol dynamics. However, it remains unclear whether stress reactivity is related to interindividual variations in gut microbial composition and to ones capacity to produce microbial metabolites such as short-chain fatty acids (SCFAs). To close this gap, we analyzed data from 74 healthy human adults who completed the study in the laboratory and were either exposed to a well-established, standardized intervention that induced acute stress or to a non-stressful control condition (n = 35/39 per stress/control group). Stool samples were obtained at baseline, and the gut microbiota were characterized through 16S rRNA gene amplicon sequencing. Cortisol changes were assessed from repeated saliva sampling, paralleled by measurements of subjectively experienced stress. We found that higher gut microbial alpha diversity was associated with higher cortisol and subjective stress reactivity across individuals of the stress group, but not in controls. Cortisol stress reactivity was also associated with the relative abundance of bacterial taxa inferred to encode metabolic pathways for the production of butyrate and propionate, two key SCFAs. The results are the first to highlight the link between gut microbial diversity, inferred SCFA production capacity, and the acute stress response in healthy adults, underscoring the microbiotas potential to flexibly modulate human psychophysiology in the aftermath of stress.

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bioRxiv2025

Method of loci training yields unique neural representations that support effective memory encoding

The method of loci is a technique to effectively boost memory, but its impact on the underlying neural representations is poorly understood. Here, we used functional magnetic resonance imaging and representational similarity analysis to compare the neural representations of memory athletes ranked among the worlds top 50 in memory sports to those of mnemonics-naive controls. In a second study, mnemonics-naive individuals underwent a 6-week-long memory training, working memory training, or no intervention. Results showed distinct neural representations in the prefrontal cortex, inferior temporal, and posterior parietal regions as memory athletes and the memory training group studied novel content. Neural representations were also distinct between these experienced individuals, which was related to better memory performance after 4 months. In parallel, the data revealed increased neural pattern similarity in the anterior hippocampus and precuneus, suggesting a more generalised role of these regions in episodic memory formation and retrieval. Our findings highlight how extensive memory training affects neocortical memory engrams. We suggest that the method of loci may bolster memory uniqueness within ones "memory palace", setting the stage for exceptional memory performance.

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bioRxiv2024

Entorhinal grid-like codes for visual space during memory formation

Eye movements, such as saccades, allow us to gather information about the environment and, in this way, can shape memory. In non-human primates, saccades are associated with the activity of grid cells in the entorhinal cortex. Grid cells are essential for spatial navigation, but whether saccade-based grid-like signals play a role in human memory formation is currently unclear. Here, human participants underwent functional magnetic resonance imaging (fMRI) and continuous eye gaze monitoring while studying scene images. Recognition memory was probed immediately thereafter. Results revealed saccade-based grid-like codes in the left entorhinal cortex while participants studied the scene images, a finding that was replicated with an independent data set reported here. The grid-related effects were time-locked to activation increases in the frontal eye fields. Most importantly, saccade-based grid-like codes were associated with recognition memory, such that grid-like codes were lower the better participants performed in subsequently recognizing the scene images. Collectively, our findings suggest an entorhinal map of visual space that is timed with neural activity in oculomotor regions, supporting memory formation.

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bioRxiv2023

Action observation reveals a network with divergent temporal and parietal lobe engagement in dogs compared to humans

Action observation is a fundamental pillar of social cognition. Neuroimaging research has revealed a human and primate action observation network (AON) encompassing fronto-temporo-parietal areas with links to a species imitation tendencies and relative lobe expansion. Dogs (Canis familiaris) have good action perception and imitation skills and a less expanded parietal than temporal lobe, but their AON remains unexplored. We conducted a functional MRI study with 28 dogs and 40 humans and found functionally analogous involvement of somatosensory and temporal brain areas of both species AONs and responses to transitive and intransitive action observation in line with their imitative skills. However, activation and task-based functional connectivity measures suggested significantly less parietal lobe involvement in dogs than in humans. These findings advance our understanding of the neural bases of action understanding and the convergent evolution of social cognition, with analogies and differences resulting from similar social environments and divergent brain expansion, respectively.

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bioRxiv2022

Entorhinal grid-like codes and time-locked network dynamics track others navigating through space

Navigating through crowded, dynamically changing social environments requires the ability to keep track of other individuals. Grid cells in the entorhinal cortex are a central component of self-related navigation but whether they also track others movement is unclear. Here, we propose that entorhinal grid-like codes make an essential contribution to socio-spatial navigation. Sixty human participants underwent functional magnetic resonance imaging (fMRI) while observing and re-tracing different paths of a demonstrator that navigated a virtual reality environment. Results revealed that grid-like codes in the entorhinal cortex tracked the other individual navigating through space. Further, the activity of grid-like codes was time-locked to increases in co-activation and entorhinal-cortical connectivity that included the striatum, the hippocampus, parahippocampal and right posterior parietal cortices, altogether modulated by accuracy when subsequently re-tracing the paths. This suggests that network dynamics time-locked to entorhinal grid-cell-related activity might serve to distribute information about the socio-spatial map throughout the brain.

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bioRxiv2022

Saccades are coordinated with directed circuit dynamics and stable but distinct hippocampal patterns that promote memory formation

During natural viewing, humans explore their environment by moving the eyes - a process that involves saccades to guide attention and shape memory. Saccades are controlled by visuo-oculomotor regions and are known to impact medial temporal lobe processing, but the circuit dynamics in humans are unclear. Here, we asked which of the functional routes between the visual cortex, frontal eye fields, and the hippocampus facilitates memory encoding during visual exploration and whether saccades affect neural representations. Forty-eight human participants underwent functional magnetic resonance imaging (fMRI) and continuous monitoring of eye gaze while studying scenes and performing a recognition memory test thereafter. We discovered saccade-related excitatory coupling from the visual cortex and frontal eye fields towards the hippocampus, independent of memory. This was complemented by hippocampal inhibition of the visual cortex that determined whether participants would later remember or forget. Moreover, saccades were associated with overall stable but distinct hippocampal voxel patterns during memory formation and the degree of pattern distinctiveness positively scaled with inhibition along the hippocampus-to-visual cortex route. This suggests that eye movements are timed to the orchestration of circuit connectivity and neural representations, setting the stage for memory formation.

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bioRxiv2021

Similarities and differences of face and body perception in the dog (Canis familiaris) and human brain

Comparing the neural correlates of socio-cognitive skills across species provides insights into the evolution of the social brain and has revealed face- and body-sensitive regions in the primate temporal lobe. Although from a different lineage, dogs share convergent visuo-cognitive skills with humans and a temporal lobe which evolved independently in carnivores. We investigated the neural correlates of face and body perception in dogs (N = 15) and humans (N = 40) using functional MRI. Combining univariate and multivariate analysis approaches, we found functionally analogous occipito-temporal regions involved in the perception of animate entities and bodies in both species, while only humans had regions specialized for face perception. Though unpredicted, we also observed neural representations of faces compared to inanimate objects, and dog compared to human bodies in dog olfactory regions. These findings shed light on the evolutionary foundations of human and dog social cognition and the predominant role of the temporal lobe.

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bioRxiv2020

Durable memories and efficient neural coding through mnemonic training using the method of loci

Mnemonic techniques, such as the method of loci, can powerfully boost memory. Here, we compared memory athletes ranked among the worlds top 50 in memory sports to mnemonics-naive controls. In a second study, participants completed a six-weeks memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. fMRI during encoding and recognition revealed task-based activation decreases in lateral prefrontal, as well as in parahippocampal and retrosplenial cortices in both memory athletes and participants after memory training, partly associated with better performance after four months. This was complemented by hippocampal-neocortical coupling during consolidation, which was stronger the more durable memories participants formed. Our findings are the first to demonstrate that mnemonic training boosts durable memory formation via decreased task-based activation and increased consolidation thereafter. This is in line with conceptual accounts of neural efficiency and highlights a complex interplay of neural processes critical for extraordinary memory.

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bioRxiv2020

Tailored haemodynamic response function increases detection power of fMRI in awake dogs (Canis familiaris)

Functional magnetic resonance imaging (fMRI) of awake and unrestrained dogs (Canis familiaris) has been established as a novel opportunity for comparative neuroimaging, promising important insights into the evolutionary roots of human brain function and cognition. However, data processing and analysis pipelines are often derivatives of methodological standards developed for human neuroimaging, which may be problematic due to profound neurophysiological and anatomical differences between humans and dogs. Here, we explore whether dog fMRI studies would benefit from a tailored dog haemodynamic response function (HRF). In two independent experiments, dogs were presented with different visual stimuli. BOLD signal changes in the visual cortex during these experiments were used for (a) the identification and estimation of a tailored dog HRF, and (b) the independent validation of the resulting dog HRF estimate. Time course analyses revealed that the BOLD signal in the primary visual cortex peaks significantly earlier in dogs compared to humans, while being comparable in shape. Deriving a tailored dog HRF significantly improved the model fit in both experiments, compared to the canonical HRF used in human fMRI. Using the dog HRF yielded significantly increased activation during visual stimulation, extending from the occipital lobe, to the caudal parietal cortex, the bilateral temporal cortex, and into bilateral hippocampal and thalamic regions. In sum, our findings provide robust evidence for an earlier onset of the dog HRF in a visual stimulation paradigm, and suggest that using such an HRF will be important to increase fMRI detection power in canine neuroimaging. By providing the parameters of the tailored dog HRF and related code, we encourage and enable other researchers to validate whether our findings generalize to other sensory modalities and experimental paradigms. HighlightsO_LIDog fMRI typically uses human HRF, but underlying neurophysiology might differ C_LIO_LIV1 BOLD signal peaked earlier in dogs than predicted by the human HRF C_LIO_LITailored dog HRF improved model fit when tested with independent data C_LIO_LIWhole-brain comparisons confirmed increased detection power for tailored dog HRF C_LIO_LIDog fMRI will benefit from increased detection power of tailored HRF C_LI

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bioRxiv2019

Pattern similarity and connectivity of hippocampal-neocortical regions support empathy for pain

Empathy is thought to engage mental simulation, which in turn is known to rely on hippocampal-neocortical processing. Here, we tested how hippocampal-neocortical pattern similarity and connectivity contributed to pain empathy. Using this approach, we analyzed a data set of 102 human participants who underwent functional MRI while painful and non-painful electrical stimulation was delivered to themselves or to a confederate. As hypothesized, results revealed increased pattern similarity between fist-hand pain and pain empathy (compared to non-painful control conditions) within the hippocampus, retrosplenial cortex, the temporo-parietal junction and anterior insula. While representations in these regions were unaffected by confederate similarity, pattern similarity in the dorsal MPFC was increased the more dissimilar the other individual was perceived. Moreover, hippocampal connectivity with regions engaged in first-hand pain was also increased during pain empathy, during which hippocampal coupling with the fusiform gyrus positively scaled with self-report measures of individual perspective taking skills. These findings highlight that shared representations and interactions within a hippocampal-neocortical network support pain empathy. This potentially reflects memory-based mental simulation processes, which seem partially modulated by personality traits and the perceived similarity of the other individual in pain.

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bioRxiv2019

Placebo-induced pain reduction is associated with inverse network coupling at rest

Placebos can reduce pain by inducing beliefs in the effectiveness of an actually inert treatment. Such top-down effects on pain typically engage lateral and medial prefrontal regions, the insula, somatosensory cortex, as well as the thalamus and brainstem during pain anticipation or perception. Considering the level of large-scale brain networks, these regions spatially align with fronto-parietal/executive control, salience, and sensory-motor networks, but it is unclear if and how placebos alter interactions between them during rest. Here, we investigated how placebo analgesia affected intrinsic network coupling. Ninety-nine human participants were randomly assigned to a placebo or control group and underwent resting-state fMRI after pain processing. Results revealed inverse coupling between sensory-motor and salience-like networks in placebo but not control participants. Specifically, networks were centered on the bilateral somatosensory cortex, as well as on the brainstem, thalamus, striatal regions, dorsal and rostral anterior cingulate cortex, and the insula, respectively. Across participants, more negative between-network coupling was associated with lower individual pain intensity as assessed during a preceding pain task, but was unrelated to expectations of medication effectiveness in the placebo group. Altogether, these findings provide initial evidence that placebo analgesia affects the intrinsic communication between large-scale brain networks, even in the absence of pain. We suggest a model where placebo analgesia increases activation within a descending pain-modulatory network, segregating it from somatosensory regions that might code for painful experiences.\n\nHighlightsO_LIPlacebo analgesia affects resting-state connectivity between networks.\nC_LIO_LISalience-related and somatosensory regions are negatively coupled at rest.\nC_LIO_LIThis coupling is negative following placebo, but not in control participants.\nC_LIO_LIMore negative between-network coupling is related to lower pain intensity.\nC_LI

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