Biology subjects

Simmons, A. M.

Publications and source records attributed to Simmons, A. M..

11 recordsLinked to original sources

bioRxiv2026

Biomimetic MRI Nanoprobe for Mapping Cerebrovascular Inflammation After Traumatic Brain Injury

Cerebrovascular inflammation is a critical driver of secondary injury following traumatic brain injury (TBI), yet no noninvasive tool currently exists to map its spatial heterogeneity across the injured brain. Here, we report MoNP-SPION, a monocyte-mimetic nanoprobe that selectively targets activated cerebrovascular endothelium after TBI and enables quantitative MRI of spatiotemporally heterogeneous cerebrovascular inflammation. MoNP-SPION binding to inflamed brain endothelium scaled with activation state, enabling rapid, spatially heterogeneous targeting of injured cerebral vasculature. MoNP-SPION-enhanced MRI revealed dynamic reductions in T2* throughout the brain that extended beyond the injury penumbra and captured both subacute vascular injury and therapy-induced recovery. Importantly, spatiotemporal reductions in T2* strongly correlated with VCAM1 upregulation, supporting MoNP-SPION as a molecularly specific readout of endothelial activation. Together, these findings establish MoNP-SPION as a promising platform for longitudinal, noninvasive monitoring of cerebrovascular inflammation in TBI and other neurological disorders involving vascular dysfunction. TEASERCell-mimicking MRI nanoprobe maps cerebrovascular injury and recovery dynamics following brain trauma.

bioengineering↗

bioRxiv2026

Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a preclinical traumatic brain injury model

Accumulating evidence supports sex differences in traumatic brain injury (TBI) outcomes, however the underlying processes that lead to sex differences are not well understood. TBI results in the initiation of molecular and cellular responses that facilitate the progression of neurodegeneration. Importantly, little is known about how the circulating hormone profile is altered in response to TBI, and whether sex differences in endocrine responses might shape secondary injury pathologies. Using intact male and female mice in a preclinical TBI model, we assessed changes in plasma hormone concentrations and cortical gene expression at 24 and 72 hours after TBI. We demonstrate that males and females exhibit sex-specific alterations in circulating levels of progesterone, testosterone, androstenedione, estradiol and dehydroepiandrosterone (DHEA) in response to TBI. We also identified sex differences in the expression of genes that are involved in immune responses and tissue remodeling after injury. Moreover, we report divergent circulating hormone and gene expression correlations between sexes.

neuroscience↗

bioRxiv2025

Echolocation calls of some bat species in western Uganda

With the rise of accessible recording technology, passive acoustic monitoring can be an affordable and rapid way to assess species richness, even when individual animals cannot be captured due to regulatory or practical obstacles. Motivated by the relative lack of data and in partnership with the local populace, we recorded echolocation calls of freely-flying bats across six locations in rural western Uganda using opportunistic passive acoustic recordings. Frequency-modulated echolocation calls were recorded at all six locations, while constant-frequency calls were recorded only at sites near entrances to caves. Preliminary species identifications were made using Kaleidoscope Pro, habitat distribution maps for Uganda, and by reference to published work. We make our acoustic recordings publicly available to serve as a resource for further explorations of the richness of bat species in Uganda.

zoology↗

bioRxiv2024

Enhanced Working Memory Representations for Rare Events

Rare events (oddballs) produce a variety of enhanced physiological responses relative to frequent events (standards), including the P3b component of the event-related potential (ERP) waveform. Previous research has suggested that the P3b is related to working memory, which implies that working memory representations will be enhanced for rare stimuli. To test this hypothesis, we devised a modified oddball paradigm where a target disk was presented at one of 16 different locations, which were divided into rare and frequent sets. Participants made a binary response on each trial to report whether the target appeared in the rare set or the frequent set. As expected, the P3b was much larger for stimuli appearing at a location within the rare set. We also included occasional probe trials in which the subject reported the exact location of the target. Accuracy was higher for rare than frequent locations. In addition, memory reports on rare trials were more accurate in participants with larger P3b amplitudes on rare trials (although reports were not more accurate for trials with larger P3b amplitudes within participants). We also applied multivariate pattern analysis to the ERP data to "decode" the remembered location of the target. Decoding accuracy was greater for locations within the rare set than for locations within the frequent set. We then replicated and extended our behavioral findings in a follow-up experiment. These behavioral and electrophysiological results demonstrate that although both frequent and rare events are stored in working memory, working memory performance is enhanced for rare oddball events. Impact StatementFor many decades, researchers have observed that rare events elicit a broad range of physiological responses, and there has been much speculation about the functional significance of these responses. One such response is the P3b component, which is a large voltage deflection in scalp EEG recordings. Over 40 years ago, the P3b was hypothesized to reflect "context updating" (now often called "working memory updating"). However, there has been no direct evidence that working memory is actually enhanced for rare, P3b-eliciting events. In the present study, we found that both behavioral and electrophysiological measures of working memory were enhanced for rare events. However, it is not clear that the increased P3b-related brain activity actually caused the enhancement of working memory.

neuroscience↗

bioRxiv2023

Using Multivariate Pattern Analysis to Increase Effect Sizes for Event-Related Potential Analyses

Multivariate pattern analysis approaches can be applied to the topographic distribution of event-related potential (ERP) signals to decode subtly different stimulus classes, such as different faces or different orientations. These approaches are extremely sensitive, and it seems possible that they could also be used to increase effect sizes and statistical power in traditional paradigms that ask whether an ERP component differs in amplitude across conditions. To assess this possibility, we leveraged the open-source ERP CORE dataset and compared the effect sizes resulting from conventional univariate analyses of mean amplitude with two multivariate pattern analysis approaches (support vector machine decoding and the cross-validated Mahalanobis distance, both of which are easy to compute using open-source software). We assessed these approaches across seven widely studied ERP components (N170, N400, N2pc, P3b, lateral readiness potential, error related negativity, and mismatch negativity). Across all components, we found that multivariate approaches yielded effect sizes that were as large or larger than the effect sizes produced by univariate approaches. These results indicate that researchers could obtain larger effect sizes, and therefore greater statistical power, by using multivariate analysis of topographic voltage patterns instead of traditional univariate analyses in many ERP studies.

neuroscience↗

bioRxiv2023

Evaluating the Effectiveness of a Common Approach to Artifact Correction and Rejection in Event-related Potential Research

Eyeblinks and other large artifacts can create two major problems in event-related potential (ERP) research, namely confounds and increased noise. Here, we developed a method for assessing the effectiveness of artifact correction and rejection methods at minimizing these two problems. We then used this method to assess a common artifact minimization approach, in which independent component analysis (ICA) is used to correct ocular artifacts, and artifact rejection is used to reject trials with extreme values resulting from other sources (e.g., movement artifacts). This approach was applied to data from five common ERP components (P3b, N400, N170, mismatch negativity, and error-related negativity). Four common scoring methods (mean amplitude, peak amplitude, peak latency, and 50% area latency) were examined for each component. We found that eyeblinks differed systematically across experimental conditions for several of the components. We also found that artifact correction was reasonably effective at minimizing these confounds, although it did not usually eliminate them completely. In addition, we found that the rejection of trials with extreme voltage values was effective at reducing noise, with the benefits of eliminating these trials outweighing the reduced number of trials available for averaging. For researchers who are analyzing similar ERP components and participant populations, this combination of artifact correction and rejection approaches should minimize artifact-related confounds and lead to improved data quality. Researchers who are analyzing other components or participant populations can use the method developed in this study to determine which artifact minimization approaches are effective in their data.

neuroscience↗

bioRxiv2023

Dmnt1 and Wnt in the production of oocytes

The function of methylation in insects and the DNA methyltransferase (Dnmt) genes that influence methylation remains uncertain. We used RNAi to reduce the gene expression of Dnmt1 within the whitefly Bemisia tabaci, a hemipteran species that relies on Dnmt1 for proper gametogenesis. We then used RNA-seq to test an a priori hypothesis that meiosis related genetic pathways would be perturbed. We generally did not find an overall effect on meiosis related pathways. However, we found that genes in the Wnt pathway, genes associated with the entry into meiosis in vertebrates, were differentially expressed. Our results are consistent with Dnmt1 knockdown influencing specific pathways and not causing general transcriptional response. This is a finding that is also seen with other insect species. We also characterized the methylome of B. tabaci and assessed the influence of Dnmt1 knockdown on cytosine methylation. This species has methylome characteristics comparable to other hemipterans regarding overall level, enrichment within gene bodies, and bimodal distribution of methylated/non-methylated genes. Very little differential methylation was observed, and difference of methylation were not associated with differences of gene expression. The effect on Wnt presents an interesting new candidate pathway for future studies.

genomics↗

bioRxiv2022

Non-invasive auditory brainstem responses to FM sweeps in awake big brown bats

We introduce two EEG techniques, one based on conventional monopolar electrodes and one based on a novel tripolar electrode, to record for the first time auditory brainstem responses (ABRs) from the scalp of unanesthetized, unrestrained big brown bats. Stimuli were frequency-modulated (FM) sweeps varying in sweep direction, sweep duration, and harmonic structure. As expected from previous invasive ABR recordings, upward-sweeping FM signals evoked larger amplitude responses (peak-to-trough amplitude in the latency range of 3-5 ms post-stimulus onset) than downward-sweeping FM signals. Scalp-recorded responses displayed amplitudelatency trading effects as expected from invasive recordings. These two findings validate the reliability of our noninvasive recording techniques. The feasibility of recording noninvasively in unanesthetized, unrestrained bats will energize future research uncovering electrophysological signatures of perceptual and cognitive processing of biosonar signals in these animals, and allows for better comparison with ABR data from echolocating cetaceans, where invasive experiments are heavily restricted. Because experiments can be repeated in the same animal over time without confounds of stress or anesthesia, our technique requires fewer captures of wild bats, thus helping to preserve natural populations and addressing the goal of reducing animal numbers used for research purposes.

neuroscience↗

bioRxiv2022

Connexin36 expression in the cochlear nucleus complex of the echolocating bat, Eptesicus fuscus

Gap junctions and electrical synapses in the central nervous system are associated with rapid temporal processing and coincidence detection. Using histology, immunohistochemistry, and in situ hybridization, we investigated the distribution of Connexin36 (Cx36), a protein that comprises neuronal gap junctions, throughout the cochlear nucleus complex of the echolocating big brown bat, Eptesicus fuscus, a species exhibiting extreme behavioral sensitivity to minute temporal changes in ultrasonic echoes. For comparison, we visualized Cx36 expression in the cochlear nucleus of transgenic Cx36 reporter mice, species that hear ultrasound but do not echolocate. We observed Cx36 expression in the anteroventral and dorsal cochlear nucleus, with more limited expression in the posteroventral cochlear nucleus, of both species. Several different morphological cell types were labeled, including globular and spherical bushy, octopus, stellate, and fusiform cells. Labeled Cx36 puncta were also observed. Cx36 expression in the bat was spread throughout a relatively smaller area of the cochlear nucleus than in the mouse, even though the bat cochlear nucleus is hypertrophied. In the bat, the anteroventral cochlear nucleus showed higher percent area label than the dorsal cochlear nucleus, with a trend towards the opposite result in the mouse. The presence of gap junctions appears to be a conserved feature of the mammalian cochlear nucleus and thus not uniquely tied to the temporal hyperacuity of echolocation.

neuroscience↗

bioRxiv2021

Amplitude discrimination is predictably affected by echo frequency filtering in wideband echolocating bats

Big brown bats emit wideband frequency modulated (FM) ultrasonic pulses for echolocation. They perceive target range from echo delay and target size from echo amplitude. Their sounds contain two prominent down-sweeping harmonic sweeps (FM1, [~]55-22 kHz; FM2, [~]100-55 kHz), which are affected differently by propagation out to the target and back to the bat. FM2 is attenuated more than FM1 during propagation. Bats anchor target ranging asymmetrically on the low frequencies in FM1, while FM2 only contributes if FM1 is present as well. These experiments tested whether the bats ability to discriminate target size from the amplitude of echoes is affected by selectively attenuating upper or lower frequencies. Bats were trained to perform an echo amplitude discrimination task with virtual echo targets 83 cm away. While echo delay was held constant and echo amplitude was varied to estimate threshold, either lower FM1 frequencies or higher FM2 frequencies were attenuated. The results parallel effects seen in echo delay experiments; bats performance was significantly poorer when the lower frequencies in echoes were attenuated, compared to higher frequencies. The bats ability to distinguish between virtual targets at the same simulated range from echoes arriving at the same delay indicates a high level of focused attention for perceptual isolation of one and suppression of the other.

animal behavior and cognition↗

bioRxiv2020

A comprehensive computational model of animal biosonar signal processing

Computational models of animal biosonar seek to identify critical aspects of echo processing responsible for the superior, real-time performance of echolocating bats and dolphins in target tracking and clutter rejection. The Spectrogram Correlation and Transformation (SCAT) model replicates aspects of biosonar imaging in both species by processing wideband biosonar sounds and echoes with auditory mechanisms identified from experiments with bats. The model acquires broadband biosonar broadcasts and echoes, represents them as time-frequency spectrograms using parallel bandpass filters, translates the filtered signals into ten parallel amplitude threshold levels, and then operates on the resulting time-of-occurrence values at each frequency to estimate overall echo range delay. It uses the structure of the echo spectrum by depicting it as a series of local frequency nulls arranged regularly along the frequency axis of the spectrograms after dechirping them relative to the broadcast. Computations take place entirely on the timing of threshold-crossing events for each echo relative to threshold-events for the broadcast. Threshold-crossing times take into account amplitude-latency trading, a physiological feature absent from conventional digital signal processing. Amplitude-latency trading transposes the profile of amplitudes across frequencies into a profile of time-registrations across frequencies. Target shape is extracted from the spacing of the objects individual acoustic reflecting points, or glints, using the mutual interference pattern of peaks and nulls in the echo spectrum. These are merged with the overall range-delay estimate to produce a delay-based reconstruction of the objects distance as well as its glints. Clutter echoes indiscriminately activate multiple parts in the null-detecting system, which then produces the equivalent glint-delay spacings in images, thus blurring the overall echo-delay estimates by adding spurious glint delays to the image. Blurring acts as an anticorrelation process that rejects clutter intrusion into perceptions. Author summaryBats and dolphins use their biological sonar as a versatile, high-resolution perceptual system that performs at levels desirable in man-made sonar or radar systems. To capture the superior real-time capabilities of biosonar so they can be imported into the design of new man-made systems, we developed a computer model of the sonar receiver used by echolocating bats and dolphins. Our intention was to discover the processing methods responsible for the animals ability to find and identify targets, guide locomotion, and prevent classic types of sonar or radar interference that hamper performance of man-made systems in complex, rapidly-changing surroundings. We have identified several features of the ears, hearing, time-frequency representation, and auditory processing that are critical for organizing echo-processing methods and display manifested in the animals perceptions.

neuroscience↗