Biology subjects

Rabe, F.

Publications and source records attributed to Rabe, F..

10 recordsLinked to original sources

bioRxiv2026

Centrally generated movement-related signals engage ipsilateral S1 finger representations after tetraplegia

Ipsilateral primary somatosensory cortex (S1) exhibits somatotopically organized activity during unilateral hand movements, but whether this activity depends on peripheral input remains debated. We addressed this question using functional magnetic resonance imaging (fMRI) in 14 individuals with tetraplegia and 18 able-bodied controls. Participants performed or attempted individual finger movements during 3T fMRI. We quantified movement-related univariate activity and multivariate representational structure within ipsilateral S1. Univariate activity within the anatomically defined ipsilateral S1 hand area did not differ significantly between groups, whereas a continuous spatial analysis identified greater movement-related activity in individuals with tetraplegia in S1 bands lateral to the hand representation. Multivariate analyses revealed reliable separation of finger-specific activity patterns in both groups, with no significant group difference in mean inter-finger distance. The typicality of the overall representational geometry also did not differ significantly between groups. Finally, a person with complete hand paralysis and no measurable feeling or movement still showed clear, finger-specific brain activity patterns and a typical representation of the affected hand. Together, these findings indicate that centrally generated movement-related signals can engage finger-specific representations in ipsilateral S1 without overt movement or measurable hand-related peripheral input. Ipsilateral somatotopic activity therefore cannot be explained solely by sensory reafference from the moving hand.

neuroscience↗

bioRxiv2026

Top-down processing alone activates the early somatosensory nuclei

The early somatosensory brainstem and thalamic nuclei are classically viewed as relays of peripheral input, yet research in animal models indicates they also receive top-down cortical signals. Whether such processing exists in humans remains unknown. Using cervical spinal cord injury (SCI), in which peripheral somatosensory input is reduced or absent while cortical processing is preserved, we tested whether top-down processing can elicit activation across the somatosensory nuclei. We combined 3 Tesla functional and quantitative MRI data to assess activity and structural properties along the somatosensory hand pathway in a cross-sectional study of 16 individuals with chronic cervical SCI (mean age {+/-} s.e.m.=52.4 {+/-} 3.5 years) and 20 age-, sex-, and handedness-matched able-bodied control subjects (mean age=50.8 {+/-} 3.5 years). Participants were visually cued to make overt or, in cases of hand paralysis, attempted right- and left-hand movements. Activation was quantified across the cuneate nucleus, ventroposterior lateral thalamus, and primary somatosensory hand cortex, while structural properties were assessed using quantitative MRI measures sensitive to myelin and tissue integrity, including magnetisation transfer saturation (MTsat) and effective transverse relaxation rate (R2*), alongside morphometric measures. Despite reduced or absent peripheral input, SCI participants exhibited robust and lateralised activation across all levels of the somatosensory pathway. This pattern persisted even in a participant with complete hand paralysis who lacked bottom-up afferent input during the fMRI task, indicating that top-down processing alone is sufficient to drive activity in early somatosensory relays. We simultaneously observed structural degeneration in the cuneate nucleus of SCI participants, marked by reduced volume and myelin-sensitive metrics (MTsat and R2*), consistent with secondary degeneration. The extent of atrophy was related to time since injury and reduced sensorimotor hand function, but showed no significant relationship with functional activation, suggesting that preserved corticocuneate signalling is not dependent on the degree of structural degeneration. This provides the first evidence that the cuneate nuclei in humans are subject to both bottom- up and top-down somatosensory processing. Although these nuclei are vulnerable to structural atrophy following dorsal column injury, our results suggest that top-down processing remains intact decades after SCI. This may have implications for the development of rehabilitation treatments targeting preserved somatosensory processing after injury.

neuroscience↗

bioRxiv2025

Disorganization impairs cognitive maps built from visual inputs

Background and HypothesisCognitive disorganization is a core disturbance across the psychosis spectrum, characterized by difficulties integrating perceptual information into coherent representations. How such disturbances affect the construction of internal cognitive maps remains unclear. A key question is whether these maps emerge from visual input as readily as from language structure. We hypothesized that cognitive disorganization would impair cognitive maps derived from visual input while sparing performance when structure was provided linguistically. Study DesignParticipants with varying schizotypy learned food items associated with two attributes: who consumed the food (age group) and when it was consumed (time of day). These attributes were presented as images or language descriptions and organized in a two-dimensional (2D) conceptual space. Participants then completed similarity judgment and reward-learning tasks requiring inference of the underlying relational structure. Study ResultsAmong individuals with higher cognitive disorganization, 2D distances were less predictive of similarity judgments, but only when relational structure had to be inferred from visual input. In the reward-learning task, computational modeling indicated that decisions were guided by spatial representations (Gaussian process). Higher cognitive disorganization was associated with weakened spatial generalization when structure had to be inferred from visual input, but not when it was provided through language. ConclusionsCognitive disorganization disrupts the ability to build and use cognitive maps from visual input, while performance appeared preserved when structure was conveyed through language. These findings support the shallow cognitive map hypothesis and suggest that cognitive disorganization selectively disrupts the transformation of perceptual input into stable relational representations.

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bioRxiv2025

Neural Traces of Forgotten Memories Persist in Humans and are Behaviorally Relevant

For a long time, forgetting has been taken as the dissipation of the neural memory traces (engrams). However, recent engram research in mice suggests that the engrams of forgotten memories do persist. This raises the question of whether engrams underlying human episodic memories also persist despite forgetting? And do forgotten memories influence human behavior implicitly? To address these questions, we used high-resolution functional magnetic resonance imaging at 7 Tesla to map the fate of 96 associative memories at the systems level from learning to a 30-minute and onward to a 24-hour memory test. Upon each retrieval attempt, participants indicated whether they remembered or forgot the memory. Univariate and multivariate analyses of the functional brain data revealed that the engrams of forgotten memories remain implemented in the episodic memory network and continue to influence the accuracy of guessing responses at the memory test. Overnight, the engrams of forgotten memories became implemented more deeply within bilateral hippocampus, while consciously accessible memories were neocorticalized overnight. The engrams of both consciously accessible and inaccessible (forgotten) memories shifted from the 30-minute to the 24-hour memory test within the right hippocampus and anterior cingulate gyrus as evidenced by the occurrence of pattern dissimilarities that supported correct retrieval responses at 24 hours. Hence, forgotten human episodic memories remain implemented in the episodic memory system and continue to influence decisions.

neuroscience↗

bioRxiv2025

Revisiting face-to-hand area remapping in the human primary somatosensory cortex after a cervical spinal cord injury

Spinal cord injury (SCI) leads to profound disruptions in sensorimotor processing. Seminal research in non-human primates suggests this sensory deprivation causes functional remapping in the primary somatosensory cortex (S1), where somatotopic representations of deprived body parts, such as the hand in cervical SCI, become responsive to touch on intact body parts, such as the face. However, evidence for such remapping in humans remains inconclusive. We investigated face-to-hand remapping in 16 chronic cervical SCI patients and 21 able-bodied controls using two fMRI experiments. Experiment 1 employed a lip movement task, while Experiment 2 investigated the full architecture of S1 face reorganisation through vibrotactile stimulation of the forehead, lips and chin. We assessed (1) the level of face activity in the anatomical S1 hand area, (2) cortical shifts in peak face activity, (3) face-part separability in the S1 hand area and (4) correlations with clinical characteristics that may drive face-to-hand area remapping. Our results revealed no significant evidence in favour of face-to-hand area remapping in tetraplegic patients across markers of face-to-hand remapping during either lip movement or vibrotactile stimulation of face parts. Furthermore, our markers of remapping did not correlate with clinical characteristics. These findings suggest that cortical face-to-hand remapping is not apparent in human cervical SCI patients. Beyond providing insight into the limitations of cortical reorganisation in humans, this highlights the need to reassess rehabilitation strategies based on the assumption of large-scale face-to-hand reorganisation after an SCI.

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bioRxiv2024

Distinguishing the activity of adjacent somatosensory nuclei within the brainstem using 3T fMRI

Experimental evidence in animal models indicates that the brainstem plays a major role in sensory modulation. However, mapping functional activity within the human brainstem presents many methodological challenges. These constraints have deterred essential research into human sensory brainstem processing. Here, using a 3T fMRI sequence optimised for the brainstem, combined with uni- and multivariate analysis approaches, we investigated the extent to which functional activity of neighbouring somatosensory nuclei can be delineated in the brainstem, thalamus and primary somatosensory cortex (S1). Whilst traditional univariate approaches offered limited differentiation between adjacent hand and face activation in the brainstem, multivariate classification enabled above-chance decoding of these activity patterns across S1, the thalamus, and the brainstem. Our findings establish a robust methodological approach to explore signal processing within the brainstem and across the entire somatosensory stream. This is a fundamental step towards broadening our understanding of somatosensory processing within humans and determining what changes in sensory integration may occur in clinical populations following sensory deprivation.

neuroscience↗

bioRxiv2024

Genetic analysis of retinal cell types reveals synaptic pathology in schizophrenia

ImportanceAs an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders. However, it remains largely unclear whether primary disease mechanisms within the retina contribute to the observed retinal alterations and which specific retinal cell types and biological mechanisms are involved. ObjectiveTo determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types. Design, Setting, and ParticipantsIn this study, we combined findings from genome-wide association studies in schizophrenia, bipolar disorder, major depressive disorder, multiple sclerosis, Parkinson disease, Alzheimer disease, and stroke with retinal single-cell transcriptomic data sets from humans, macaques, and mice. To identify susceptible cell types, we applied MAGMA cell type enrichment analyses and performed subsequent pathway analyses. Furthermore, we translated the cellular top hit to the structural level by using retinal optical coherence tomography and genotyping data in the large population-based UK Biobank cohort (n = 36,349). Main Outcomes and MeasuresCell type-specific enrichment of genetic risk loading for neuropsychiatric and neurological disorder traits in the gene expression profiles of retinal cells. ResultsAmacrine cells (interneurons within the retina) were robustly enriched in schizophrenia genetic risk across mammalian species and in different developmental stages. This enrichment was primarily driven by genes involved in synapse biology. On the structural level, higher polygenic risk for schizophrenia was associated with thinning of the ganglion cell-inner plexiform layer, which contains dendrites and synaptic connections of amacrine cells. Moreover, retinal immune cell populations were enriched in multiple sclerosis genetic risk. No consistent cell type associations were found for bipolar disorder, major depressive disorder, Parkinson and Alzheimer disease, or stroke. Conclusions and RelevanceThis study provides novel insights into the cellular underpinnings of retinal alterations in neuropsychiatric and neurological disorders and highlights the retina as a potential proxy to study synaptic pathology in schizophrenia.

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bioRxiv2023

Estimating multimodal brain variability in schizophreniaspectrum disorders: A worldwide ENIGMA study

ObjectiveSchizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia. MethodsThis meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy. ResultsWe found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region. ConclusionsHigher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.

neuroscience↗

bioRxiv2022

Prior information improves tactile representation in primary somatosensory cortex

Perception and adaptive decision making rely on the integration of incoming sensory input with prior knowledge or expectations. While tactile stimuli play a significant role in shaping our perception and decision making, if and how prior information modulates the representation of tactile stimuli in early somatosensory cortices is largely unknown. Here, we employed functional magnetic resonance imaging (fMRI) and a vibrotactile detection paradigm to study the effect of prior information on tactile perception and tactile stimulus representation in early somatosensory areas. The supra-voxel somatotopic organization of early somatosensory areas allowed us to assess the effect of prior information on finger-specific representations. We found that vibrotactile stimuli congruent with expectations are associated with improved vibrotactile detection performance and a decrease of the mean blood-oxygen-level-dependent (BOLD) signal in the contralateral primary somatosensory cortex (S1). Concurrently, finger-specific activity associated with anticipated vibrotactile stimulation revealed higher multivariate decoding accuracies and better alignment with S1s somatotopic organization. In addition, we observed that prior information induced somatotopically organized activity in contralateral S1 even before tactile stimulation onset. The accuracy of the multivariate decoding of stimulus-specific expectations was therefore strongly associated with upcoming behavioral detection performance. Thus, our results reveal a role for S1 in the integration of upcoming tactile stimuli with prior information based on its somatotopic organization as well as the presence of behaviorally relevant activity in S1 before stimulation onset.

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bioRxiv2021

Finger representations in primary somatosensory cortex are modulated during vibrotactile working memory

It is well-established that several cortical areas represent vibrotactile stimuli in somatotopic maps. However, whether such somatotopic representations remain active during the delay period of working memory (WM) tasks, i.e. in the absence of any tactile stimulation, is unknown. In our experiment, participants had to compare two tactile stimuli with different vibration frequencies that were separated by a delay period (memory condition) or they were exposed to identical stimuli but did not have to solve a WM task (no memory condition). Importantly, both vibrotactile stimuli were either applied to the right index or little finger. Analyzing the delay period, we identified a well-known fronto-parietal network of brain regions involved in WM but we did not find WM specific activity in S1. However, using multi-voxel pattern analysis (MVPA) and representational similarity analysis (RSA), we found that S1 finger representations were more dissimilar during the delay period of the WM condition than during the control condition. These results indicate that WM processes modulate the representational geometry of S1 suggesting that some aspects of the tactile WM content are represented in a somatotopic fashion. HIGHLIGHTSO_LIMultivariate approaches were used to identify finger specific representational changes during vibrotactile frequency discrimination. C_LIO_LIVibrotactile working memory modulates somatotopic finger representations in contralateral S1 during the delay period, i.e. in the absence of any tactile stimuli C_LI

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