Biology subjects

Brunner, P.

Publications and source records attributed to Brunner, P..

32 records · Page 2Linked to original sources

bioRxiv2024

Does Vibrotactile Stimulation of the Auricular Vagus Nerve Enhance Working Memory? A Behavioral and Physiological Investigation

BackgroundWorking memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular VNS (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact. ObjectiveWe aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter. MethodThis study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the participants performed N-back tasks under three conditions: vibrotactile taVNS delivered to the cymba concha, earlobe (sham control), and no stimulation (baseline control). ResultsIn 4-back tasks, which demand maximal working memory capacity, active vibrotactile taVNS significantly improved the performance metric d compared to the baseline but not to the sham. Moreover, we found that the reduction rate of d with increasing task difficulty was significantly smaller during vibrotactile taVNS sessions than in both baseline and sham conditions. Arousal, measured as skin conductance and pupil diameter, declined over the course of the tasks. Vibrotactile taVNS rescued this arousal decline, leading to arousal levels corresponding to optimal working memory levels. Moreover, pupil diameter and skin conductance level were higher during high-cognitive-load tasks when vibrotactile taVNS was delivered to the concha compared to baseline and sham. ConclusionOur findings suggest that vibrotactile taVNS modulates the arousal pathway and could be a potential intervention for enhancing working memory. HighlightsO_LIVibrotactile stimulation of the auricular vagus nerve increases general arousal. C_LIO_LIVibrotactile stimulation of the auricular vagus nerve mitigates arousal decreases as subjects continuously perform working memory tasks. C_LIO_LI6 Hz Vibrotactile auricular vagus nerve stimulation is a potential intervention for enhancing working memory performance. C_LI

bioengineering↗

bioRxiv2024

Diffusion-limited cytokine signaling in T cell populations

Effective immune-cell responses depend on collective decision-making mediated by diffusible intercellular signaling proteins called cytokines. Here, we designed a spatio-temporal modeling framework and a precise finite-element simulation setup, to systematically investigate the origin and consequences of spatially inhomogeneous cytokine distributions in lymphoid tissues. We found that such inhomogeneities are critical for effective paracrine signaling, and they do not arise by diffusion and uptake alone, but rather depend on properties of the cell population such as an all-or-none behavior of cytokine secreting cells. Furthermore, we assessed the regulatory properties of negative and positive feedback in combination with diffusion-limited signaling dynamics, and we derived statistical quantities to characterize the spatio-temporal signaling landscape in the context of specific tissue architectures. Overall, our simulations highlight the complex spatiotemporal dynamics imposed by cell-cell signaling with diffusible ligands, which entails a large potential for fine-tuned biological control especially if combined with feedback mechanisms.

biophysics↗

bioRxiv2023

Novel Cyclic Homogeneous Oscillation Detection Method for High Accuracy and Specific Characterization of Neural Dynamics

Detecting temporal and spectral features of neural oscillations is essential to understanding dynamic brain function. Traditionally, the presence and frequency of neural oscillations are determined by identifying peaks over 1/f noise within the power spectrum. However, this approach solely operates within the frequency domain and thus cannot adequately distinguish between the fundamental frequency of a non-sinusoidal oscillation and its harmonics. Non-sinusoidal signals generate harmonics, significantly increasing the false-positive detection rate -- a confounding factor in the analysis of neural oscillations. To overcome these limitations, we define the fundamental criteria that characterize a neural oscillation and introduce the Cyclic Homogeneous Oscillation (CHO) detection method that implements these criteria based on an auto-correlation approach that determines the oscillations periodicity and fundamental frequency. We evaluated CHO by verifying its performance on simulated sinusoidal and non-sinusoidal oscillatory bursts convolved with 1/f noise. Our results demonstrate that CHO outperforms conventional techniques in accurately detecting oscillations. Specifically, we determined the sensitivity and specificity of CHO as a function of signal-to-noise ratio (SNR). We further assessed CHO by testing it on electrocorticographic (ECoG, 8 subjects) and electroencephalographic (EEG, 7 subjects) signals recorded during the pre-stimulus period of an auditory reaction time task and on electrocorticographic signals (6 SEEG subjects and 6 ECoG subjects) collected during resting state. In the reaction time task, the CHO method detected auditory alpha and pre-motor beta oscillations in ECoG signals and occipital alpha and pre-motor beta oscillations in EEG signals. Moreover, CHO determined the fundamental frequency of hippocampal oscillations in the human hippocampus during the resting state (6 SEEG subjects). In summary, CHO demonstrates high precision and specificity in detecting neural oscillations in time and frequency domains. The methods specificity enables the detailed study of non-sinusoidal characteristics of oscillations, such as the degree of asymmetry and waveform of an oscillation. Furthermore, CHO can be applied to identify how neural oscillations govern interactions throughout the brain and to determine oscillatory biomarkers that index abnormal brain function.

neuroscience↗

bioRxiv2023

Anatomical registration of intracranial electrodes. Robust model-based localization and deformable smooth brain-shift compensation methods

Precise electrode localization is important for maximizing the utility of intracranial EEG data. Electrodes are typically localized from post-implantation CT artifacts, but algorithms can fail due to low signal-to-noise ratio, unrelated artifacts, or high-density electrode arrays. Minimizing these errors usually requires time-consuming visual localization and can still result in inaccurate localizations. In addition, surgical implantation of grids and strips typically introduces non-linear brain deformations, which result in anatomical registration errors when post-implantation CT images are fused with the pre-implantation MRI images. Several projection methods are currently available, but they either fail to produce smooth solutions or do not account for brain deformations. To address these shortcomings, we propose two novel algorithms for the anatomical registration of intracranial electrodes that are almost fully automatic and provide highly accurate results. We first present GridFit, an algorithm that simultaneously localizes all contacts in grids, strips, or depth arrays by fitting flexible models to the electrodes CT artifacts. We observed localization errors of less than one millimeter (below 8% relative to the inter-electrode distance) and robust performance under the presence of noise, unrelated artifacts, and high-density implants when we ran [~]6000 simulated scenarios. Furthermore, we validated the method with real data from 20 intracranial patients. As a second registration step, we introduce CEPA, a brain-shift compensation algorithm that combines orthogonal-based projections, spring-mesh models, and spatial regularization constraints. When tested with real data from 15 patients, anatomical registration errors were smaller than those obtained for well-established alternatives. Additionally, CEPA accounted simultaneously for simple mechanical deformation principles, which is not possible with other available methods. Inter-electrode distances of projected coordinates smoothly changed across neighbor electrodes, while changes in inter-electrode distances linearly increased with projection distance. Moreover, in an additional validation procedure, we found that modeling resting-state high-frequency activity (75-145 Hz) in five patients further supported our new algorithm. Together, GridFit and CEPA constitute a versatile set of tools for the registration of subdural grid, strip, and depth electrode coordinates that provide highly accurate results even in the most challenging implantation scenarios. The methods presented here are implemented in the iElectrodes open-source toolbox, making their use simple, accessible, and straightforward to integrate with other popular toolboxes used for analyzing electrophysiological data.

bioinformatics↗

bioRxiv2022

Intracranial recordings reveal three distinct neural response patterns in the language network

Despite long knowing what brain areas support language comprehension, our knowledge of the neural computations that these frontal and temporal regions implement remains limited. One important unresolved question concerns functional differences among the neural populations that comprise the language network. Leveraging the high spatiotemporal resolution of intracranial recordings, we examined responses to sentences and linguistically degraded conditions and discovered three response profiles that differ in their temporal dynamics. These profiles appear to reflect different temporal receptive windows (TRWs), with average TRWs of about 1, 4, and 6 words, as estimated with a simple one-parameter model. Neural populations exhibiting these profiles are interleaved across the language network, which suggests that all language regions have direct access to distinct, multi-scale representations of linguistic input--a property that may be critical for the efficiency and robustness of language processing.

neuroscience↗

bioRxiv2022

Homunculus Interruptus: A motor association area in the depth of the central sulcus

Cells in the precentral gyrus of the human brain directly send signals to the periphery to generate movement and are topologically organized as a map of the body. We find that movement induced electrophysiological changes from implanted depth electrodes extend this map 3-dimensionally throughout the volume of the gyrus. Unexpectedly, this organization is interrupted by a motor association area in the depths of the central sulcus at its mid-lateral aspect that is active during many different types of movements from both sides of the body.

neuroscience↗

bioRxiv2022

A mind-body interface alternates with effector-specific regions in motor cortex

Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down precentral gyrus from foot to face representations1,2. The motor homunculus has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric functional zones3 and maps of complex actions4. Using our highest precision functional magnetic resonance imaging (fMRI) data and methods, we discovered that the classic homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function, alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, and to prefrontal, insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive action5 and physiological control6, arousal7, and processing of errors8 and pain9. This interdigitation of action control-linked and motor effector regions was independently verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI revealed potential cross-species analogues and developmental precursors of the inter-effector system. An extensive battery of motor and action fMRI tasks documented concentric somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-effector regions lacked movement specificity and co-activated during action planning (coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These results, together with prior work demonstrating stimulation-evoked complex actions4 and connectivity to internal organs (e.g., adrenal medulla)10, suggest that M1 is punctuated by an integrative system for implementing whole-body action plans. Thus, two parallel systems intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot, hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative whole-organism coordination of goals, physiology, and body movement.

neuroscience↗

bioRxiv2022

Spatio-temporal modeling reveals a layer of tunable control circuits for the distribution of cytokines in tissues

Cytokines are diffusible mediators of cell-cell communication among immune cells with critical regulatory functions for cell differentiation and proliferation. Previous studies have revealed considerable spatial inhomogeneities in the distribution of cytokine molecules in tissues, potentially shaping the efficacy and range of paracrine cytokine signals. How such cytokine gradients emerge and are controlled within cell populations is incompletely understood. In this work, we employed a spatial reaction-diffusion model to systematically investigate the formation and influence of spatial cytokine gradients. We found the fraction of cytokine secreting cells to be the main source of spatial inhomogeneity and subsequent activation. Positive feedback from local cytokine levels upon cytokine receptor expression leads to further increased spatial cytokine inhomogeneities. By exploring the effect of co-clustering cytokine secreting cells and cells with large amounts of receptor expression, as in the presence of regulatory T cells in the vicinity of antigen-presenting cells, we found that such constrained tissue architecture can have profound effects on the range of paracrine cytokine signals.

systems biology↗

bioRxiv2022

Encoding and decoding analysis of music perception using intracranial EEG

Music perception engages multiple brain regions, however the neural dynamics of this core human experience remains elusive. We applied predictive models to intracranial EEG data from 29 patients listening to a Pink Floyd song. We investigated the relationship between the song spectrogram and the elicited high-frequency activity (70-150Hz), a marker of local neural activity. Encoding models characterized the spectrotemporal receptive fields (STRFs) of each electrode and decoding models estimated the population-level song representation. Both methods confirmed a crucial role of the right superior temporal gyri (STG) in music perception. A component analysis on STRF coefficients highlighted overlapping neural populations tuned to specific musical elements (vocals, lead guitar, rhythm). An ablation analysis on decoding models revealed the presence of unique musical information concentrated in the right STG and more spatially distributed in the left hemisphere. Lastly, we provided the first song reconstruction decoded from human neural activity.

neuroscience↗

bioRxiv2021

Revealing the Physiological Origin of Event-Related Potentials using Electrocorticography in Humans

The scientific and clinical value of event-related potentials (ERPs) depends on understanding the contributions to them of three possible mechanisms: (1) additivity of time-locked voltage changes; (2) phase resetting of ongoing oscillations; (3) asymmetrical oscillatory activity. Their relative contributions are currently uncertain. This study uses analysis of human electrocorticographic activity to quantify the origins of movement-related potentials (MRPs) and auditory evoked potentials (AEPs). The results show that MRPs are generated primarily by endogenous additivity (88%). In contrast, P1 and N1 components of AEPs are generated almost entirely by exogenous phase reset (93%). Oscillatory asymmetry contributes very little. By clarifying ERP mechanisms, these results enable creation of ERP models; and they enhance the value of ERPs for understanding the genesis of normal and abnormal auditory or sensorimotor behaviors.

neuroscience↗

bioRxiv2020

SnToxA, SnTox1 and SnTox3 originated in Parastagonospora nodorum in the Fertile Crescent

The center of origin of the globally distributed wheat pathogen Parastagnospora nodorum has remained uncertain because only a small number of isolates from the Fertile Crescent, a region in the Middle East where wheat was domesticated from wild grasses, were included in earlier population genetic and phylogeographic studies. We isolated and genetically analyzed 193 P. nodorum strains from three naturally infected wheat fields distributed across Iran, a country located within the Fertile Crescent, using eleven neutral microsatellite loci. Compared to previous studies that included populations from North America, Europe, Africa, Australia and China, the populations from Iran had the highest genetic diversity globally and also exhibited greater population structure over smaller spatial scales, patterns typically associated with a species center of origin. Genes encoding the necrotrophic effectors SnToxA, SnTox1 and SnTox3 were found at a high frequency in the Iranian population. By sequencing 96 randomly chosen Iranian strains, we detected new alleles for all three effector genes. Analyses of allele diversity showed that all three effector genes had higher diversity in Iran than in any population included in previous studies, with Iran acting as a hub for the effector diversity that was found in other global populations. Taken together, these findings support the hypothesis that P. nodorum originated either within or nearby the Fertile Crescent with a genome that already encoded all three necrotrophic effectors during its emergence as a pathogen on wheat. Our findings also suggest that P. nodorum was the original source of the ToxA genes discovered in the wheat pathogens Phaeosphaeria avenaria f. sp. tritici 1, Pyrenophora tritici-repentis and Bipolaris sorokiniana.

plant biology↗

bioRxiv2019

Natural selection drives population divergence for local adaptation in a wheat pathogen

Evolution favors the emergence of locally-adapted optimum phenotypes that are likely to differ across a wide array of environmental conditions. The emergence of favorable adaptive characteristics is accelerated in agricultural pathogens due to the unique properties of agro-ecosystems. We performed a QST - FST comparison using 164 strains of Parastagonospora nodorum sampled from eight global field populations to disentangle the predominant evolutionary forces driving population divergence in a wheat pathogen. We used digital image analysis to obtain quantitative measurements of growth rate and melanization at different temperatures and under different fungicide concentrations in a common garden experiment. FST measures were based on complete genome sequences obtained for all 164 isolates. Our analyses indicated that all measured traits were under selection. Growth rates at 18{degrees}C and 24{degrees}C were under stabilizing selection (QST < FST), while diversifying selection (QST > FST) was the predominant evolutionary force affecting growth under fungicide and high temperature stress. Stabilizing selection (QST < FST) was the predominant force affecting melanization across the different environments. Melanin production increased at 30{degrees}C but was negatively correlated with higher growth rates, consistent with a trade-off under heat stress. Our results demonstrate that global populations of P. nodorum possess significant evolutionary potential to adapt to changing local conditions, including warmer temperatures and applications of fungicides.

evolutionary biology↗

bioRxiv2019

Unexpected sound omissions are signaled in human posterior superior temporal gyrus: an intracranial study

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent any auditory evoked activity by assessing the response to omitted expected sounds. Electrophysiological signals were recorded directly from the superior temporal gyrus (STG) and superior temporal sulcus (STS) in patients with medically refractory epilepsy. Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found a high frequency band (HFB, 70-150Hz) response to omissions, which overlap with a posterior subset of auditory active electrodes. This response is distinct from omission activations observed in non-auditory selective sites in STG. Heard syllables could be classified reliably from STG, but not the identity of the omitted stimulus. Both omission- and target detection activations were also observed in prefrontal cortex.\n\nWe propose that the posterior STG and STS are central for implementing predictions in the auditory environment. HFB omission activations in this region appear to index mismatch-signaling or salience detection processes.

neuroscience↗

bioRxiv2019

Intracranial recordings from human auditory cortex reveal a neural population selective for musical song

How are neural representations of music organized in the human brain? While neuroimaging has suggested some segregation between responses to music and other sounds, it remains unclear whether finer-grained organization exists within the domain of music. To address this question, we measured cortical responses to natural sounds using intracranial recordings from human patients and inferred canonical response components using a data-driven decomposition algorithm. The inferred components replicated many prior findings including distinct neural selectivity for speech and music. Our key novel finding is that one component responded nearly exclusively to music with singing. Song selectivity was not explainable by standard acoustic features and was co-located with speech- and music-selective responses in the middle and anterior superior temporal gyrus. These results suggest that neural representations of music are fractionated into subpopulations selective for different types of music, at least one of which is specialized for the analysis of song.

neuroscience↗