Biology subjects

Johnson, E. L.

Publications and source records attributed to Johnson, E. L..

18 recordsLinked to original sources

bioRxiv2026

The development of slow and fast theta oscillations in the human brain

Theta oscillations are pivotal for attention and memory, with developmental shifts in theta activity and connectivity tracking memory ability across the lifespan. Building on initial evidence that the theta band separates into slow and fast sub-bands across development within the medial temporal lobe (MTL) and the prefrontal cortex (PFC), this preregistered study (https://osf.io/gsru7) characterized the frequencies of slow (~1.5-4.5 Hz) and fast (~4.5-9.0 Hz) theta oscillations across the brain in a large developmental cohort. We analyzed intracranial EEG (iEEG) recordings from widespread brain regions in 101 children and adults (5.93-54.00 years, 63 males; n electrodes = 5691) using task-based (attention to to-be-remembered visual stimuli) and task-free (resting-state) data. We reveal distinct slow and fast theta oscillations in all regions and identify a spatial gradient in both frequency ranges, with slow theta oscillations speeding up and fast theta oscillations slowing down from posterior to anterior regions. The dissociation between slow and fast theta frequencies peaks during young adulthood, mirroring the developmental trajectory of attention and memory. In the hippocampus and PFC, attentional state (task-based, task-free) modulated age effects, and individual differences in task-based slow theta frequencies predicted individual differences in memory performance, linking the development of slow theta oscillations to the development of memory. Gray matter volume was not associated with age- or task-related differences in theta frequencies, suggesting that the development of theta oscillations is independent of regional brain structure. This study establishes developmental trajectories of slow and fast theta oscillations in localized brain regions and links the maturation of hippocampal and PFC slow theta oscillations to the development of attention and memory.

neuroscience↗

bioRxiv2026

Differential roles of frontoparietal regions in working memory and decision-making

Working memory (WM) and decision-making (DM) are closely linked cognitive processes that rely on frontoparietal regions, yet their distinct and shared neural dynamics remain unclear. Using intracranial EEG recordings from 24 human subjects performing a delayed match-to-sample task, we examined high-frequency broadband (HFB) activity to dissociate WM- and DM-related processes with high spatiotemporal resolution. Principal component analysis of frontoparietal HFB activity revealed multiple temporally distinct patterns spanning stimulus presentation and delay phases. The most dominant component reflected sustained WM-related activity across task phases, consistent with persistent maintenance of internal representations. Additional components captured transient WM encoding across trial phases, as well as both stimulus-linked and ramping DM-related activity suggesting dual early and late stages of evaluative processing. These processes were distributed across frontoparietal regions but showed systematic differences in anatomical focus, with WM-related activity concentrated in dorsolateral prefrontal cortex (PFC) and DM-related activity concentrated in ventrolateral PFC, while inferior parietal cortex preferentially tracked the behavioral significance of incoming stimuli and superior parietal cortex tracked the appearance of new information that may require updating ongoing processing. Together, these findings demonstrate that WM and DM processes are separable yet interleaved over time within distributed cortical networks, revealing coordinated but functionally distinct contributions to goal-directed behavior.

neuroscience↗

bioRxiv2026

Opposing effects of slow and fast theta synchrony on working memory in the human hippocampal-orbitofrontal network

Working memory (WM) enables us to maintain and manipulate information over time, but how the brain organizes sequential information locally and across networks remains unclear. Recent work suggests that slow and fast theta oscillations serve different roles in memory, yet their distinct contributions to sequential WM are unknown. Based on evidence that the hippocampus (HC) and orbitofrontal cortex (OFC) support sequential WM and that slower theta cycles provide optimal temporal windows for organizing items in WM, we predicted that these regions would coordinate via slow theta dynamics. We analyzed intracranial EEG from the HC, OFC, and amygdala (AMY) in 21 neurosurgical patients (7 female, 13-54 years of age; M {+/-} SD, 30 {+/-} 11.2 years) performing a delayed match-to-sample WM task. We assessed phase locking between regions, phase-amplitude coupling within regions, and neuronal phase coding for slow (~1-4.5 Hz) and fast (~4.5-8 Hz) theta oscillations. We found significant slow and fast theta synchrony between all regions, but identical anatomical pathways produced opposing behavioral effects depending on oscillatory frequency, particularly during higher cognitive demand. Slow theta synchrony was associated with faster response times (RTs), while fast theta synchrony between HC and OFC hindered both accuracy and RTs. Unexpectedly, AMY modulated RT through demand-dependent slow theta synchrony, where AMY-OFC synchrony predicted faster RTs during maintenance and HC-AMY synchrony predicted faster RTs during higher cognitive demand. Sustained coupling between slow theta oscillations and high-frequency broadband activity within each region suggests that local organization coincides with beneficial network behavioral effects. These results establish a frequency-opponent mechanism in which theta oscillation frequencies determine whether HC-OFC circuits facilitate or impair sequential WM.

neuroscience↗

bioRxiv2025

Distinct neurophysiological features and memory representations along the long axis of the developing medial temporal lobe

The medial temporal lobe (MTL) is crucial for episodic memory, whereby posterior MTL preferentially represents visuospatial information, and anterior MTL is involved in the representation of semantic or conceptual information. The neurophysiological underpinnings of content-preferential organization in the developing MTL are largely unknown. Here we utilized rare electrocorticography (ECoG) recordings from 23 pediatric epilepsy patients who completed a visual scene recognition memory task to systematically examine the neurophysiological underpinnings of memory formation along the MTL long axis. The timing of high-frequency activity (HFA, [~]70-150 Hz) differed between the posterior and anterior MTL, peaking after scene onset in the posterior MTL and around scene category response (indoor/outdoor scene categorization) in the anterior MTL. Further, in the posterior MTL, HFA was predictive of successful memory formation and positively linked to memory performance, highlighting the importance of posterior MTL HFA to memory formation. In contrast, theta frequency in the anterior MTL was linked to memory performance, and theta-HFA phase-amplitude coupling before scene category responses was predictive of successful memory formation, highlighting the importance of anterior MTL theta oscillations to memory formation. Our findings establish distinct neurophysiological features along the posterior-to-anterior axis of the developing MTL that differentially support the representation of perceptual and conceptual information during memory formation.

neuroscience↗

bioRxiv2025

Distributed theta networks support the control of working memory: Evidence from scalp and intracranial EEG

We combined scalp EEG and intracranial EEG (iEEG) to identify spectral and network-level signatures of executive control during a delayed match-to-sample task working memory task. To isolate executive processes, we contrasted test and sample phases, matched in perceptual input but differing in cognitive demand. Scalp EEG revealed increased frontal midline theta event-related spectral perturbations (ERSPs), dynamic increases and decreases in posterior theta-alpha ERSPs, and decreased central alpha-beta ERSPs during the test phase. These local spectral changes were accompanied by enhanced frontoposterior theta phase synchrony and network hub strength, predicting higher behavioral accuracy. Using a novel cross-modal scalp EEG-iEEG ERSP similarity approach, we localized the sources of scalp-derived frontal midline, posterior, and central control effects to medial frontal, parietal, temporal, and occipital regions. Our results integrate power and connectivity measures across scalp and iEEG, linking local spectral fluctuations to broader network organization. Together, they support a model in which executive control emerges from flexible, temporally precise coordination between medial frontal control hubs and posterior representational systems.

neuroscience↗

bioRxiv2025

High frequency broadband activity detected noninvasively in infants distinguishes wake from sleep states

High frequency broadband activity (HFB; 70-150 Hz) indexes local brain activity. It is predominantly studied using invasive measures due to signal drop off from skull attenuation. We hypothesized that HFB is detectable in infants noninvasively through fontanelles and thin skull that have not fully developed. We analyzed scalp electroencephalography (EEG) data during wake and sleep states in 19 channels from 18 infants (1-4 months, both sexes). At the group level, linear mixed-effects models revealed greater HFB power in wake versus sleep states in midline and central channels near fontanelles, as well as in occipital channels over thin skull. These differences were detected with 90% reliability using as few as 25 seconds of data per state in as few as 10 subjects. On the individual level, linear mixed-effects models revealed the same wake > sleep effect with a mean reliability of 60% when using at least 50 seconds of data per state. These findings establish that noninvasive HFB detection in infants is not only possible at sites where the skull has not fully developed, but sufficiently robust to enable systematic investigation of early cognitive development.

neuroscience↗

bioRxiv2025

Targeting intracranial electrical stimulation to network regions defined within individuals causes network-level effects

Intracranial electrical stimulation (ES) is routinely used therapeutically, diagnostically, and to provide causal evidence in neuroscience studies. However, our understanding of the brain network-level effects of ES remains limited. We applied precision functional mapping (PFM), based on functional magnetic resonance imaging (fMRI), to define large-scale networks within individual epilepsy patients. We show that single-pulse electrical stimulation (SPES) and high-frequency electrical stimulation (HFES) are more likely to evoke within-network responses and elicit network-related behavioral effects, respectively, when applied near to a PFM-defined network region. Network-level effects were more likely when stimulating sites in white matter, in close proximity to the targeted network, and within a region predominantly occupied by the targeted network. Further, network-specific modulation may be achievable by applying lower current intensities at these sites. Our findings support that modulation of specific networks is achievable by targeting ES to a functional anatomic "sweet spot" that can be identified using PFM.

neuroscience↗

bioRxiv2025

One of these things is not like the others: Theta, beta, & ERP dynamics of mismatch detection

Working memory (WM) enables the detection of mistakes by permitting one to notice when sensory input is mismatched to their internal prediction. Prior studies support the role of frontal midline theta activity, with an overlapping N200 event-related potential (ERP), as a mechanism for comparing incoming sensory stimuli to the internal model. Additionally, posterior low-beta activity has been proposed as a mechanism for processing incoming sensory stimuli in WM. However, it is unknown whether frontal midline theta activity and the N200 support mismatch detection, or whether posterior low-beta activity extends from sensory processing to detecting a mismatch between sensory input and the internal model. Here, we reveal that frontal midline theta supports mismatch detection and explains individual WM performance. Unexpectedly, instead of the N200, results show a positive slow wave ERP overlapping with the frontal midline theta mismatch response. Results additionally indicate a late posterior low-beta response persisting from stimulus presentation into the post-stimulus delay. Our findings establish frontal midline theta as a marker of successful mismatch detection, challenge the domain-general role of the N200 in error detection, and support theories linking posterior low-beta to processing incoming sensory stimuli.

neuroscience↗

bioRxiv2025

On variability in local field potentials

Neuronal coding and decoding would be compromised if neuronal responses were highly variable. Intriguingly, neuronal spike counts (SCs) show a reduction in across-trial variance (ATV) in response to sensory stimulation, when SC variance is normalized by SC mean, that is, when using the Fano factor 1. Inspired by this seminal finding, ATV has also been studied in electroencephalography (EEG) signals, revealing effects of various stimulus and cognitive factors as well as disease states. Here, we empirically show that outside of evoked potentials, the ATV of the EEG or local field potential (LFP) is very highly correlated to the intra-trial variance (ITV), which corresponds to the well-known power metric. We propose that the LFP power, rather than the raw LFP signal, should be considered with regard to putative changes of its variability. We quantify LFP power variability as the standard deviation of the logarithm of the power ratio between an active and a baseline condition, normalized by the mean of that log(power ratio), that is the coefficient of variation (CV) of the log(power ratio). This CV(log(power ratio)) is reduced for gamma and alpha power when they are enhanced by stimulation, and it is enhanced for alpha power when it is reduced by stimulation. This suggests a potential inverse relation between changes in band-limited power and the corresponding CV. We propose that the CV(log(power ratio)) is a useful metric that can be computed for numerous existing and future LFP, EEG or MEG datasets, which will provide insights into those signals frequency-specific variability and how they might be used for neuronal coding and decoding.

neuroscience↗

bioRxiv2025

Declarative Memory Through the Lens of Single-Trial Peaks in High-Frequency Power

Declarative memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global network organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated throughout the network. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across the medial temporal lobe (MTL) and prefrontal cortex (PFC). HFB peak activity was earlier in the MTL than PFC. Anchoring analyses of theta phase clustering and connectivity to HFB peaks revealed strong phase clustering locked to HFB peaks in the PFC, as well as connectivity between the PFC and MTL that predicted individual memory performance. Graph analysis revealed specific connections amidst sparse network connectivity during memory success. This study demonstrates that transient brain states linked to internal physiological events support memory and refines our understanding of local and network-level process interactions. HighlightsO_LIMemory-linked theta activity is time-locked to internal brain events C_LIO_LINetwork connectivity changes dynamically during memory processing C_LIO_LISparse network connectivity supports successful memory C_LIO_LISpecific sequences of transient states may be critical for declarative memory C_LI

neuroscience↗

bioRxiv2024

Distinct immune responses to HIV and CMV in Hofbauer cells across gestation highlight evolving placental immune dynamics

Placental immune responses to Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (CMV) vary across gestational stages and may influence postnatal outcomes. This study investigates the innate immunity of Hofbauer cells from placentae obtained at early/mid-gestation (18-21.6 weeks) and term (>37 weeks). RNA sequencing and cytokine profiling reveal that early/mid-gestation HCs exhibit heightened differential gene expression responses compared to term HCs, indicating a distinct transcriptional activity in early pregnancy. Significant overlap in gene expression profiles of early/mid-gestation cells in response to CMV and HIV suggest similar innate immune responses, while term cells exhibit distinct patterns, reflecting the temporal evolution of placental immunity. Integration with Human Protein Atlas database reveals more placental-specific differentially expressed genes in early/mid-gestation HCs exposed to HIV and CMV compared to term cells. Functional analysis reveals downregulation of pathways related to oxygen stress, estrogen response, and KRAS signaling pathway in early/mid-gestation HCs, with HIV uniquely upregulating reactive oxygen species and CMV uniquely disrupting WNT {beta}-Catenin signaling. In term HCs, CMV exposure upregulates antiviral interferon (IFN) signaling and inflammatory pathways. Co-expression analysis highlights distinct molecular pathway enrichments across gestation, particularly with upregulation of IFN signaling and disruption of lipid metabolism in term CMV-exposed HCs. Cytokine profiling shows enhanced expression of GM-CSF, IFN-{gamma}, and Th2-associated cytokines in early/mid-gestation HCs, indicating heightened immune responsiveness. These findings reveal the dynamic nature of placental immunity and underscore the need for targeted interventions to address unique immune and metabolic disruptions caused by viral infections at distinct stages of pregnancy to improve fetal and infant health outcomes.

pathology↗

bioRxiv2024

The development of aperiodic neural activity in the human brain

The neurophysiological mechanisms supporting brain maturation are fundamental to attention and memory capacity across the lifespan. Human brain regions develop at different rates, with many regions developing into the third and fourth decades of life. Here, in this preregistered study (https://osf.io/gsru7), we analyzed intracranial EEG (iEEG) recordings from widespread brain regions in a large developmental cohort. Using task-based (i.e., attention to-be-remembered visual stimuli) and task-free (resting-state) data from 101 children and adults (5.93 - 54.00 years, 63 males; n electrodes = 5691), we mapped aperiodic (1/[f]-like) activity, a proxy of neural noise, with steeper slopes indexing less noise and flatter slopes indexing more noise. We reveal that aperiodic slopes flatten with age into young adulthood in both association and sensorimotor cortices, challenging models of early sensorimotor development based on brain structure. In prefrontal cortex (PFC), attentional state modulated age effects, revealing steeper task-based than task-free slopes in adults and the opposite in children, consistent with the development of cognitive control. Age-related differences in task-based slopes also explained age-related gains in memory performance, linking the development of PFC cognitive control to the development of memory. Last, with additional structural imaging measures, we reveal that age-related differences in gray matter volume are similarly associated with aperiodic slopes in association and sensorimotor cortices. Our findings establish developmental trajectories of aperiodic activity in localized brain regions and illuminate the development of PFC control during adolescence in the development of attention and memory.

neuroscience↗

bioRxiv2021

Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism

Zinc (Zn) plays a critical role in maintaining intestinal homeostasis by regulating intestinal epithelial cells, host immune cells, and gut microbiome community composition. Deletion of metal transporter Slc39a14/Zip14 causes spontaneous intestinal permeability with low-grade chronic inflammation, mild hyperinsulinemia, and greater body fat with insulin resistance in adipose, suggesting a role for ZIP14-mediated intestinal metal transport in regulating both intestinal homeostasis and systemic metabolism. Here, we showed the function of ZIP14-mediated Zn transport in the gut microbiome composition and how ZIP14-linked changes to gut microbiome community composition are correlated with changes in host metabolism. Deletion of Zip14 generated Zn-deficient epithelial cells and luminal content in the entire intestinal tract; reduced bacterial diversity and Saccharomyces cerevisiae (S. cerevisiae) overgrowth; altered host metabolome; and shifted host energy metabolism toward glucose utilization. This work provides evidence for the regulation of gut microbiome composition, host metabolome, and energy metabolism by metal transporter ZIP14. SignificanceIntestinal permeability, gut dysbiosis, and Zn dyshomeostasis are emerging signatures of inflammatory bowel diseases and metabolic disorders such as type-2-diabetes and obesity. Zn deficiency is a common clinical finding among these diseases. Zn is essential for the regulation of the intestinal epithelial cells, host immune cells, and the gut microbiome. Transporter-mediated mobilization of Zn plays a critical role in maintaining intestinal homeostasis by facilitating the targeted tissue/cell-specific function. However, studies are lacking in linking transporter-mediated Zn mobilization, gut microbiome, hosts intestinal health, and metabolism. Using the systems-level approach, this study revealed novel findings that deletion of Slc39a14/Zip14 resulted in altered intestinal Zn homeostasis, gut microbiome composition, host metabolome and energy metabolism.

physiology↗

bioRxiv2021

Highly task-specific and distributed neural connectivity in working memory revealed by single-trial decoding in mice and humans

Working memory (WM), the capacity to briefly and intentionally maintain mental items, is key to successful goal-directed behaviour and impaired in a range of psychiatric disorders. To date, several brain regions, connections, and types of neural activity have been correlatively associated with WM performance. However, no unifying framework to integrate these findings exits, as the degree of their species- and task-specificity remains unclear. Here, we investigate WM correlates in three task paradigms each in mice and humans, with simultaneous multi-site electrophysiological recordings. We developed a machine learning-based approach to decode WM-mediated choices in individual trials across subjects from hundreds of electrophysiological measures of neural connectivity with up to 90% prediction accuracy. Relying on predictive power as indicator of correlates of psychological functions, we unveiled a large number of task phase-specific WM-related connectivity from analysis of predictor weights in an unbiased manner. Only a few common connectivity patterns emerged across tasks. In rodents, these were thalamus-prefrontal cortex delta- and beta-frequency connectivity during memory encoding and maintenance, respectively, and hippocampal-prefrontal delta- and theta-range coupling during retrieval, in rodents. In humans, task-independent WM correlates were exclusively in the gamma-band. Mostly, however, the predictive activity patterns were unexpectedly specific to each task and always widely distributed across brain regions. Our results suggest that individual tasks cannot be used to uncover generic physiological correlates of the psychological construct termed WM and call for a new conceptualization of this cognitive domain in translational psychiatry.

neuroscience↗

bioRxiv2021

Synergistic positive feedback underlying seizure initiation

Seizure onset is a critically important brain state transition that has proved very difficult to predict accurately from recordings of brain activity. Here we show that an intermittent, optogenetic, stimulation paradigm reveals a latent change in dendritic excitability that is tightly correlated to the onset of seizure activity. Our data show how the precipitous nature of the transition can be understood in terms of multiple, synergistic positive feedback mechanisms: raised intracellular Cl- and extracellular K+, coupled to a reduced threshold for dendritic plateau potentials, and which in turn leads to a switch to pyramidal burst firing. Notably, the stimulation paradigm also delays the evolving epileptic activity, meaning that not only can one monitor seizure risk safely, it may even have an additional anti-epileptic benefit. One Sentence SummaryRapid transitions into seizures arise from mutually accelerating feedback loops, involving changes in dendritic excitability

neuroscience↗

bioRxiv2020

Dietary sphinganine is selectively assimilated by members of the gut microbiome

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remain largely unknown. A class of lipids known as sphingolipids are bioactive components of most foods and are produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet-microbiome interactions. Here, we use a click-chemistry based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne - SAA) into the gut microbial community (Click). Identification of microbe and SAA-specific metabolic products was achieved by fluorescence-based sorting of SAA containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together this approach, Click-Sort-Seq-Spec (ClickSSS), revealed that SAA-assimilation was nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice showed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activity via Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. Therefore, ClickSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet-microbiome interactions.

microbiology↗

bioRxiv2019

Sphingolipid production by gut Bacteroidetes regulates glucose homeostasis

Levels of Bacteroidetes in the gut microbiome are positively associated with insulin resistance (IR) in humans. Considering that IR is promoted by elevations in hepatic sphingolipids (SL), particularly ceramides, and that Bacteroidetes are the only microbiome phylum possessing genes encoding serine palmitoyltransferase (SPT), which mediates SL synthesis, we investigated a potential link between bacterial SL production, host SL metabolism, and IR. In vitro, bacterial SLs entered colonocytes and were metabolized into complex SL, including ceramides. In mice, administration of WT Bacteroides thetaiotaomicron, but not a SPT-deficient mutant, resulted in elevated levels of liver ceramides and reduced responsiveness to exogenously administered insulin. This work establishes bacterial SLs as a new class of microbiome-derived molecule capable of impacting host metabolism.\n\nOne Sentence SummarySL production by gut Bacteroidetes regulates liver ceramide levels and insulin sensitivity.

microbiology↗

bioRxiv2019

Expanding the watch list for potential Ebola virus antibody escape mutations

The 2014 outbreak of Ebola virus (EBOV) in Western Africa is the largest recorded filovirus disease outbreak and lead to the death of over 11,000 people. This deadly virus still poses a grave epidemic threat as evidenced by the current (since May 2018) EBOV outbreak in the Democratic Republic of the Congo which has already claimed the lives of over 250 people. One important strategy for combating EBOV epidemics is to anticipate how the evolution of EBOV might undermine treatment since the development of vaccines and antibody therapies are typically based on a single strain (often the 1976 Mayinga) of the EBOV envelope glycoprotein (GP). In a previous study we initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between EBOV GP and the monoclonal antibody KZ52. This watch list was generated using molecular modeling to estimate the effect of every possible mutation of GP. The final watch list containing 34 mutations were predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. In this study, we expand our watch list by including three more monoclonal antibodies with distinct epitopes on GP, namely Antibody 100 (Ab100), Antibody 114 (Ab114) and 13F6-1-2. Our updated watch list contains 127 mutations, three of which have been seen in humans or are experimentally associated with reduced efficacy of antibody treatment. We believe mutations on this broad watch list require attention since they may be a signal of an evolutionary response from EBOV to treatment that could diminish the effectiveness of interventions.

biophysics↗