bioRxiv Science⌕ Search

Biology subjects

Gerloff, C.

Publications and source records attributed to Gerloff, C..

At least 19 recordsLinked to original sources

A Pose-Informed De-Noising Diffusion Model for Adult Naturalistic EEG Signals

Artifact contamination in EEG (electroencephalogram) signals is a significant problem, especially in naturalistic settings where participants can move freely. This contamination stems from various sources like eye movements, muscle activity, sweat, and electrical interference, whose effects differ greatly from each other. Traditional denoising methods, such as Independent Component Analysis, are limited because they assume a linear relationship between the source of the artifacts and the EEG signals, and often require the dominance of one noise source over others. Moreover, these methods need expert knowledge in EEG analysis and lack an objective standard for evaluation. To overcome these challenges, we propose two innovations: Firstly, we introduce the use of "video-estimated" pose coordinates - the x and y positions of different body points (like wrists, eyes, and ankles) - to assist in the EEG denoising process. Secondly, we present a denoising diffusion model, EEG-DDM, that utilizes both the contaminated EEG signals and these pose coordinates to effectively denoise the EEG. Our findings show that incorporating keypoints (pose coordinates) improves denoising performance and helps maintain cross-spatial dependencies in the data. Additionally, we enhance human interpretability of the process by displaying saliency maps generated by our model, which explain the contributions of these keypoints in the denoising process.

neuroscience↗

Cortical high gamma power relates to movement speed and is disproportionately reduced after stroke

Motor cortical high-gamma oscillations (60 to 90 Hz) occur at the onset of movement and are spatially focused over the contralateral primary motor cortex. Although high-gamma oscillations are widely recognized for their significance in human motor control, their precise function on a cortical level remains elusive. Importantly, their relevance in human stroke pathophysiology is unknown. Understanding the neurophysiological processes of motor coding could be an important step in improving motor recovery after stroke. We recorded magnetoencephalography data during a thumb movement speed task in 14 chronic stroke survivors, 15 age-matched control participants and 29 healthy young participants. Motor cortical high-gamma oscillations showed a strong relation with movement speed as trials with higher movement speed were associated with greater high-gamma power. Stroke survivors showed reduced cortical high-gamma power, surpassing the effect attributable to decreased movement speed in these participants. Even though motor skill acquisition was evident in all groups, it was not linked to high-gamma power. Our study is, to our knowledge, the first to quantify high-gamma oscillations after stroke, revealing a reduction in movement-related high-gamma power. Moreover, we provide strong evidence for a pivotal role of motor cortical high-gamma oscillations in encoding movement speed.

neuroscience↗

Lesion aware automated processing pipeline for multimodal neuroimaging stroke data and The Virtual Brain (TVB)

BackgroundProcessing stroke magnetic resonance imaging (MRI) brain data can be susceptible to lesion-based abnormalities. In this study we developed and validated the Lesion Aware automated Processing Pipeline (LeAPP) that incorporates mitigation measures, improving volumetric and connectomics outputs compared to current standards in automated MRI processing pipelines. MethodsBuilding upon the Human Connectome Project (HCP) minimal processing pipeline, we introduced correction measures, such as cost-function masking and virtual brain transplant, and extended functional and diffusion processing to match acquisition protocols often found in a clinical context. A total of 51 participants (36 stroke patients (65.7{+/-}12.96 years, 18 female) and 15 healthy controls (69.2{+/-}7.4 years, 7 female)) were processed across four time points for patients (3-5, 30-40, 85-95, 340-380 days after stroke onset) and one time point for controls. Artificially lesioned brains (N=82), derived from healthy brains and informed by real stroke lesions were created, thus generating ground-truth data for validation. The processing pipeline and validation framework are available as containerized open-source software. Reconstruction quality has been quantified on whole brain level and for lesion affected and unaffected regions-of-interest (ROIs) using metrics like dice score, volume difference and center-of-gravity distance. Global and local level connectome reconstruction was assessed using node strength, node centrality and clustering coefficient. ResultsThe new pipeline LeAPP provides close reconstructions of the ground truth. Deviations in reconstructed averaged whole brain node strength and all ROI based volume and connectome metrics were significantly reduced compared to the HCP pipeline without stroke specific mitigation measures. ConclusionsLeAPP improves reconstruction quality of multimodal MRI processing for brain parcellation and structural connectome estimation significantly over the non-adapted HCP in the presence of lesions and provides a robust framework for diffusion and functional image processing of clinical stroke data. This novel open-source automated processing pipeline contributes to a development towards reproducible research. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/555078v1_ufig1.gif" ALT="Figure 1"> View larger version (85K): org.highwire.dtl.DTLVardef@ca58aborg.highwire.dtl.DTLVardef@8342f4org.highwire.dtl.DTLVardef@1a0d4b9org.highwire.dtl.DTLVardef@1edf1cf_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Early functional connectivity alterations in contralesional motor networks influence outcome after severe stroke

Connectivity studies have significantly extended the knowledge on motor network alterations after stroke. Compared to interhemispheric or ipsilesional networks, changes in the contralesional hemisphere are poorly understood. Data obtained in the acute stage after stroke and in severely impaired patients are remarkably limited. This study aimed to investigate early functional connectivity changes of the contralesional parieto-frontal motor network and their relevance for the functional outcome after severe motor stroke. Resting-state functional imaging data were acquired in 19 patients within the first two weeks after severe stroke. Nineteen healthy participants served as a control group. Functional connectivity was calculated from five key motor areas of the parieto-frontal network on the contralesional hemisphere as seed regions and compared between the groups. Connections exhibiting stroke-related alterations were correlated with clinical follow-up data obtained after 3 to 6 months. The main finding was an increase in coupling strength between the contralesional supplementary motor area and the sensorimotor cortex. This increase was linked to persistent clinical deficits at follow-up. Thus, an upregulation in contralesional motor network connectivity might be an early pattern in severely impaired stroke patients. It might carry relevant information regarding the outcome which adds to the current concepts of brain network alterations and recovery processes after severe stroke.

neuroscience↗

The effect of deep brain stimulation on cortico-subcortical networks in Parkinson's disease patients with freezing of gait: Exhaustive exploration of a basic model

Current treatments of Parkinsons disease (PD) have limited efficacy in alleviating freezing of gait (FoG). In this context, concomitant deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) has been suggested as a potential therapeutic approach. However, the mechanisms underlying this approach are unknown. While the current rationale relies on network-based hypotheses of intensified disinhibition of brainstem locomotor areas to facilitate the release of gait motor programs, it is still unclear how simultaneous high-frequency DBS in two interconnected basal ganglia nuclei affects large-scale cortico-subcortical network activity. Here, we use a basic model of neural excitation, the susceptible-excited-refractory (SER) model, to compare effects of different stimulation modes of the network underlying FoG. We develop a network-based computational framework to compare subcortical DBS targets through exhaustive analysis of the brain attractor dynamics in the healthy, PD and DBS states. We demonstrate the validity of the approach and the superior performance of combined STN+SNr DBS in the normalization of spike propagation flow in the FoG network. The framework aims to move towards a mechanistic understanding of the network effects of DBS and may be applicable to further perturbation-based therapies of brain disorders. AUTHOR SUMMARYParkinsons disease patients with Freezing of Gait (FoG) may be treated by deep brain stimulation, which produces effects mediated by brain networks. Currently, the approach of combined DBS of the subthalamic nucleus and the substantia nigra pars reticulata is investigated for being particularly beneficial for patients with axial symptoms, but the exact mechanisms of this effect are unknown. Here, we present a network-based computational framework using a basic excitable model that enables us to simulate the complete activity patterns of the brain network involved in FoG. These simulations reveal network mechanisms underlying STN+SNr DBS and its efficacy in alleviating FoG. The proposed framework can capture the influence of the DBS target sites on cortico-subcortical networks and help to identify suitable stimulation targets.

neuroscience↗

Ventral premotor cortex influences spinal cord activation during force generation

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is influenced by cerebral primary motor and premotor areas is poorly understood. Here we conducted combined cortico-spinal functional MRI during a simple visually guided isometric force generation task in a group of 20 healthy young subjects. Activation was localized in the ipsilateral cervical spinal cord and contralateral primary motor and premotor areas. The main finding is that spinal activation was influenced by ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding which extends our understanding about human motor function beyond the animal literature.

neuroscience↗

Revealing the Neurobiology Underlying Interpersonal Neural Synchronization with Multimodal Data Fusion

Humans synchronize with one another to foster successful interactions. Here, we use a multimodal data fusion approach with the aim of elucidating the neurobiological mechanisms by which interpersonal neural synchronization (INS) occurs. Our meta-analysis of 22 functional magnetic resonance imaging and 69 near-infrared spectroscopy hyperscanning experiments (740 and 3,721 subjects) revealed robust brain-regional correlates of INS in the right temporoparietal junction and left ventral prefrontal cortex. Integrating this meta-analytic information with public databases, biobehavioral and brain-functional association analyses suggested that INS involves sensory-integrative hubs with functional connections to mentalizing and attention networks. On the molecular and genetic levels, we found INS to be associated with GABAergic neurotransmission and layer IV/V neuronal circuits, protracted developmental gene expression patterns, and disorders of neurodevelopment. Although limited by the indirect nature of phenotypic-molecular association analyses, our findings generate new testable hypotheses on the neurobiological basis of INS.

neuroscience↗

Brain Network Architecture Constrains Age-related Cortical Thinning

Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including "hotspots" of strong age effects located in brain areas with high centrality (structural network hubs). Regional age-related differences were furthermore strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences as well as its change throughout the later lifespan was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks might act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.

neuroscience↗

Normalization of aperiodic ECoG components indicates fine motor recovery after sensory cortical stroke in mice

Electrophysiological signatures of ischemic stroke might help to develop a deeper understanding of the mechanisms of recovery. Here, analyses of multichannel electrocorticography (ECoG) in awake mice demonstrated that the shape of power spectral density (PSD) is modulated in the vicinity of sensory cortical stroke. PSD consists of both rhythmic oscillatory and non-rhythmic, aperiodic components. The alteration of spectrum shape was reflected in a transient increase of aperiodic exponents, while the relative power and frequency of slow oscillations remained unchanged in the peri-infarct cortex. Exponents derived from motor areas significantly correlated with recovery of fine motor deficits of the contralateral forepaw thus indicating functional modifications of neuronal activity. In conclusion, aperiodic spectral exponents exhibited a unique spatiotemporal profile in the mouse cortex after stroke and might complement future studies providing a dynamic link from pathophysiology to behavior.

neuroscience↗

A preclinical randomized multicenter trial of anti-IL-17A treatment for acute ischemic stroke

Multiple consensus statements have called for preclinical randomized controlled trials (pRCT) to improve translation in stroke research. Here, we investigated the efficacy of IL-17A neutralizing antibodies in a multicentric pRCT using a murine stroke model. C57/Bl.6 mice were subjected to transient middle cerebral artery occlusion (tMCAO). Mice were randomly allocated (1:1). Either anti-IL-17A (500 {micro}g) or isotype antibody (500 {micro}g) were administered 1 h after tMCAO. Primary analysis of infarct volumes was done by MRI after three days. Secondary analysis included mortality, neurological score, neutrophil infiltration and the impact of the gut microbiome on treatment effects. Out of 136 mice, 109 mice were included in the analysis. Mixed model analysis revealed that the IL-17A neutralization significantly reduced infarct sizes (anti IL-17A: 61.77 {+/-} 31.04 mm3; IgG control: 75.66 {+/-} 34.79 mm3; p=0.01). Secondary outcome measures showed a decrease in mortality (Hazard Ratio=3.43, 95% CI = 1.157 - 10.18; p=0.04) and neutrophil invasion into ischemic cortices. There was no difference in the neurological score. The analysis of the gut microbiome showed significant differences between centers. Taken together, this is the first positive pRCT in an ischemia reperfusion model. It suggests IL-17A neutralization as a potential target in stroke.

neuroscience↗

Caregiving quality modulates neuroendocrine and immunological markers in young children in foster care who have experienced early adversity

BackgroundEarly adversity is believed to alter the bodys stress response systems, putting children at increased risk for somatic and mental health problems. However, it remains unclear whether such alterations normalize under improved caregiving experiences. Thus, the goal of the present study was to investigate i) whether children in foster care show endocrine and immunological alterations relative to children living with their biological families, ii) whether these alterations change over time spent with the foster family and iii) whether the alterations are modulated by current caregiving experiences. MethodsA total of 94 children in foster care and 157 biological children, aged two to seven years, took part in a longitudinal study with three assessments conducted over a 12-month study period. At the initial assessment, children lived for an average of 18 months with their current foster families. Childrens cortisol, dehydroepiandrosterone (DHEA) and progesterone concentrations and cortisol/DHEA ratios were measured in scalp hair and childrens secretory immunoglobulin A (sIgA) levels in saliva. Caregiving quality was assessed based on caregiver-reports and observational measures of caregiver-child interactions. ResultsChildren in foster care had lower cortisol/DHEA ratios and higher progesterone concentrations than biological children, while no group differences were found for cortisol, DHEA or sIgA. Time spent with the current foster family did not significantly influence the childs endocrine or immunological markers. Importantly, caregiving quality modulated cortisol/DHEA ratios and sIgA concentrations: children in foster care of lower caregiving quality had lower cortisol/DHEA ratios than children in foster care of higher caregiving quality and showed decreasing, rather than increasing, sIgA concentrations across the study period. ConclusionsOur results indicate that caregiving quality in the foster family may have an important modulating effect on selected indicators of the childs stress response and could thereby mitigate the possible consequences of early childhood adversity.

physiology↗

Synchrony of mind and body are distinct in mother-child dyads

Hyperscanning studies have begun to unravel the brain mechanisms underlying social interaction, indicating a functional role for interpersonal neural synchronization (INS), yet the mechanisms that drive INS are poorly understood. While interpersonal synchrony is considered a multimodal phenomenon, it is not clear how different biological and behavioral synchrony markers are related to each other. The current study, thus, addresses whether INS is functionally-distinct from synchrony in other systems - specifically the autonomic nervous system (ANS) and motor behavior. To test this, we used a novel methodological approach, based on concurrent functional near-infrared spectroscopy-electrocardiography, recorded while N = 34 mother-child and stranger-child dyads (child mean age 14 years) engaged in cooperative and competitive tasks. Results showed a marked differentiation between neural, ANS and behavioral synchrony. Importantly, only in the neural domain was higher synchrony for mother-child compared to stranger-child dyads observed. Further, ANS and neural synchrony were positively related during competition but not during cooperation. These results suggest that synchrony in different behavioral and biological systems may reflect distinct processes. Mother-child INS may arise due to neural processes related to social affiliation, which go beyond shared arousal and similarities in behavior.

neuroscience↗

Interacting brains revisited: A cross-brain network neuroscience perspective

Elucidating the neural basis of social behavior is a long-standing challenge in neuroscience. Such endeavors are driven by attempts to extend the isolated perspective on the human brain by considering interacting persons brain activities, but a theoretical and computational framework for this purpose is still in its infancy. Here, we posit a comprehensive framework based on bipartite graphs for interbrain networks and address whether they provide meaningful insights into the neural underpinnings of social interactions. First, we show that the nodal density of such graphs exhibits nonrandom properties. While the current analyses mostly rely on global metrics, we encode the regions roles via matrix decomposition to obtain an interpretable network representation yielding both global and local insights. With Bayesian modeling, we reveal how synchrony patterns seeded in specific brain regions contribute to global effects. Beyond inferential inquiries, we demonstrate that graph representations can be used to predict individual social characteristics, outperforming functional connectivity estimators for this purpose. In the future, this may provide a means of characterizing individual variations in social behavior or identifying biomarkers for social interaction and disorders.

neuroscience↗

Sensory capability and information integration independently predict cognitive status in healthy older adults

Ageing is characterized by changes in sensory and cognitive abilities. While there is evidence that decline in sensory acuity and enhanced multisensory integration predict cognitive status in healthy older adults, potential mechanistic links between these age-related alterations remain unclear. In the current study, we assessed performance of younger and older healthy adults in a visuotactile delayed match-to-sample task and related indices of multisensory integration to unisensory perceptual thresholds and cognitive assessment data. Additionally, we applied transcranial alternating current stimulation (tACS) to modulate cortical networks found to underlie visuotactile interactions and working-memory matching in our previous work. Analysing response times and signal detection measures, we found older adults to show enhanced multisensory integration and benefit more from successful working memory matching. Both measures predicted cognitive status and correlated positively with each other, suggesting that they likely reflect a common underlying tendency to integrate information. Sensory capability, however, independently predicted cognitive status. tACS with beta frequency (20 Hz) accelerated task performance and this effect was more pronounced in the older group. We conclude that sensory capability and information integration represent independent predictors of cognitive status. Finally, we discuss a potential role of the parietal cortex in mediating augmented integration in older adults.

neuroscience↗

Crossmodal Pattern Discrimination in Humans and Robots: A Visuo-Tactile Case Study

The quality of crossmodal perception hinges on two factors: The accuracy of the independent unimodal perception and the ability to integrate information from different sensory systems. In humans, the ability for cognitively demanding crossmodal perception diminishes from young to old age.\n\nTo research to which degree impediments of these two abilities contribute to the age-related decline and to evaluate how this might apply to artificial systems, we replicate a medical study on visuo-tactile crossmodal pattern discrimination utilizing state-of-the-art tactile sensing technology and artificial neural networks. We explore the perception of each modality in isolation as well as the crossmodal integration.\n\nWe show that in an artificial system the integration of complex high-level unimodal features outperforms the comparison of independent unimodal classifications at low stimulus intensities where errors frequently occur. In comparison to humans, the artificial system outperforms older participants in the unimodal as well as the crossmodal condition. However, compared to younger participants, the artificial system performs worse at low stimulus intensities. Younger participants seem to employ more efficient crossmodal integration mechanisms than modelled in the proposed artificial neural networks.\n\nOur work creates a bridge between neurological research and embodied artificial neurocognitive systems and demonstrates how collaborative research might help to derive hypotheses from the allied field. Our results indicate that empirically-derived neurocognitive models can inform the design of future neurocomputational architectures. For crossmodal processing, sensory integration on lower hierarchical levels, as suggested for efficient processing in the human brain, seems to improve the performance of artificial neural networks.

neuroscience↗

Reduced frontal white matter microstructure in healthy older adults with low tactile recognition performance

Aging leads to a reduction of connectivity in large-scale structural brain networks. Sensory processing and other cognitive processes rely on information flow between distant brain areas. However, data linking age-related structural brain alterations to cognitive functioning, especially sensory processing, is sparse.\n\nAiming to determine group differences in sensory processing between older and younger participants, we implemented a complex tactile recognition task and investigated to what extent changes in microstructural white matter integrity of large-scale brain networks might reflect success in task performance. Structural brain integrity was accessed by means of diffusion-weighted imaging and fractional anisotrophy.\n\nThe data revealed that poor performance in complex tactile recognition in older, neurologically healthy individuals is related to decreased structural integrity pronounced in the anterior corpus callosum. This region was strongly connected to the prefrontal cortex. Our data suggests decreased fractional anisotrophy in the anterior corpus callosum as a surrogate marker for progressed brain aging, leading to disturbances in networks relevant for higher-order cognitive processing. Complex tactile recognition might be a sensitive marker for identifying these starting cognitive impairments in older adults.

neuroscience↗

Congruency effects can compensate for deficits of healthy older adults in crossmodal integration

One of the pivotal challenges of aging is to maintain independence in the activities of daily life. In order to adapt to changes in the environment, it is crucial to continuously process and accurately combine simultaneous input from different sensory systems, i.e., crossmodal integration.\n\nWith aging, performance decreases in multiple cognitive domains. The processing of sensory stimuli constitutes one of the key features of this deterioration. Age-related sensory impairments affect all modalities, substantiated by decreased acuity in visual, auditory or tactile detection tasks.\n\nHowever, whether this decline of sensory processing leads to impairments in crossmodal integration remains an unresolved question. While some researchers propose that crossmodal integration degrades with age, others suggest that it is conserved or even gains compensatory importance.\n\nTo address this question, we compared behavioral performance of older and young participants in a well-established crossmodal matching task, requiring the evaluation of congruency in simultaneously presented visual and tactile patterns. Older participants performed significantly worse than young controls in the crossmodal task when being stimulated at their individual unimodal visual and tactile perception thresholds. Performance increased with adjustment of stimulus intensities. This improvement was driven by better detection of congruent stimulus pairs (p<0.01), while detection of incongruent pairs was not significantly enhanced (p=0.12).\n\nThese results indicate that age-related impairments lead to poor performance in complex crossmodal scenarios and demanding cognitive tasks. Performance is enhanced when inputs to the visual and tactile systems are congruent. Congruency effects might therefore be used to develop strategies for cognitive training and neurological rehabilitation.

neuroscience↗

Effects of transcranial alternating-current stimulation to secondary motor areas on cortical oscillations in stroke patients

BackgroundThere is growing evidence that secondary motor areas are relevant for recovery after motor stroke. Communication among brain areas occurs via synchronization of oscillatory activity which can potentially be modulated via transcranial alternating-current stimulation (tACS).\n\nHypothesisWe hypothesized that tACS to secondary motor areas of the stroke-lesioned hemisphere leads to modulation of task-related connectivity among primary and secondary motor areas, reflected in metrics of EEG coupling in the frequency domain.\n\nMethodsWe applied focal tACS at 1mA peak-to-peak intensity to ipsilesional ventral premotor cortex (PMv) and supplementary motor area (SMA) in chronic stroke patients while they moved their impaired hand. To probe effects of stimulation on cortical oscillations, several task-related EEG-based connectivity metrics (coherence, imaginary coherence, phase-locking value, mutual information) were assessed before and after each stimulation.\n\nResultsOverall, we found significant but weak modulations of the motor network by tACS. Stimulation of PMv reduced task-related coupling between (i) both primary motor cortices (M1) (coherence, -0.0514{+/-}0.0665 (mean{+/-}SD, active stimulation) vs. 0.0085{+/-}0.0888 (sham), p=0.0029) and (ii) between ipsilesional M1 and contralesional PMv (coherence, - 0.0386{+/-}0.0703 vs. 0.0226{+/-}0.0694, p=0.0283; phase-locking value, -0.0363{+/-}0.0581 vs. 0.0036{+/-}0.0497, p=0.0097) compared with sham stimulation.\n\nConclusionsIn this exploratory analysis, tACS to the ipsilesional PMv induced a weak decrease of task-related connectivity between ipsilesional M1 and contralesional M1 and PMv. As an excess of interhemispheric coupling is under discussion as maladaptive phenomenon of motor reorganization after stroke (e.g., bimodal balance-recovery model), tACS-induced reduction of coupling might be an interesting approach to assist re-normalization of the post-stroke motor network.

neuroscience↗