Biology subjects

Ross, J. M.

Publications and source records attributed to Ross, J. M..

At least 19 recordsLinked to original sources

bioRxiv2026

Cognitive load modulates cortical excitability in the human prefrontal cortex

The prefrontal cortex dynamically adjusts its excitability to meet changing cognitive demands, yet our understanding of how these rapid state changes unfold in real time remains limited. Existing evidence relies predominantly on correlational neuroimaging and invasive electrophysiology in clinical populations, neither of which affords causal measurement in healthy humans. Here, using concurrent single-pulse TMS-EEG during a parametric cognitive multi-source interference task (MSIT) in 27 healthy participants, we causally probed left prefrontal excitability across conditions spanning a range of cognitive interference levels. Prefrontal excitability scaled systematically with cognitive load, peaking at intermediate incongruency levels where trial-type uncertainty was greatest, and differentiating high-from low-conflict trials at the single-subject level. Critically, prefrontal excitability and midfrontal theta power showed parallel state dependency patterns, linking causal perturbation of prefrontal circuit responsiveness to an established oscillatory marker of cognitive control. The observed excitability modulation was selective to the left prefrontal cortex: stimulation of right dlPFC, pre-SMA, and vertex in a separate control cohort (N=5) produced no load-dependent effects. These results position prefrontal excitability as a real-time, regionally selective physiological readout of how the human prefrontal cortex adapts to cognitive demand. HighlightsO_LIWe evaluated the links between cognitive interference, prefrontal excitability, and intrinsic theta activity during a multi-source interference task C_LIO_LICognitive load, estimated based on behavioral performance, was greatest at at intermediate interference levels (33% congruent), where trial-type uncertainty was maximal C_LIO_LIPrefrontal excitability, measured via single-pulse TMS-evoked potentials, scaled with cognitive load C_LIO_LIEffects were observed at the single subject level and were specific to prefrontal stimulation C_LIO_LIPrefrontal excitability changes and midfrontal theta power showed parallel scaling with cognitive load, linking causal probing to established oscillatory markers C_LIO_LIThis noninvasive technique provides causal measurement of prefrontal engagement during cognitive processing C_LIO_LIThe methodology demonstrates potential for tracking brain state dynamics in both healthy cognition and neuropsychiatric disorders C_LI

neuroscience↗

bioRxiv2026

Systemic CYP3A inhibition by ritonavir enables selective targeting of hypoxic tumour cells by prodrugs of DNA-PK inhibitors

Hypoxic tumour cells are resistant to many forms of cancer therapy, particularly radiotherapy. Hypoxia-activated prodrugs (HAPs) can potentially address this problem through selective release of drugs ( effectors) in oxygen-deficient microenvironments, via metabolic reduction of a nitro(hetero)aromatic trigger moiety. While many such HAPs show marked selectivity for hypoxia in cell culture, none have yet been approved for clinical use. Here, we report HAPs that release a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK) which, like hypoxia, is a major contributor to radioresistance. These ether-linked HAPs provide hypoxia-dependent radiosensitisation in cell culture, but in mice systemic generation of the DNA-PK inhibitor is observed. Using in vitro hepatic metabolism models we demonstrate hypoxia-independent metabolic activation of HAP 4 via oxidation of its linker, which is mediated exclusively by CYP3A. We extend this finding to HAPs with other triggers, linkers and effectors. The clinically used CYP3A-specific inhibitor ritonavir suppressed hepatic metabolism of 4 under oxia without interfering with its hypoxia-dependent activation. In mice, ritonavir markedly enhanced oral bioavailability of the HAP, suppressed systemic formation of the DNA-PK inhibitor, and selectively radiosensitised HCT116 tumours but not the gastrointestinal tract in the radiation field. This combination offers the prospect of increasing the therapeutic ratio of DNA-PK inhibitor-mediated radiosensitisation in patients.

pharmacology and toxicology↗

bioRxiv2026

A Key Regulator of Dendritic Morphology in Supragranular Neocortex Impacts Mismatch Negativity

BackgroundCytoskeletal structure and neuronal function are heavily intertwined, and altered pyramidal neuron morphology (e.g., reduced dendritic arbors) has been consistently identified in the neocortex of individuals with psychiatric disorders. A missense mutation in Kalrn (Kalrn-PT) enhances activation of RhoA, a cytoskeletal regulator, and leads to adolescent-onset dendritic regression in supragranular auditory cortex. To investigate the relationship between this spatiotemporally altered cytoskeletal structure and psychiatric-relevant dysfunction, we examine the functional impacts of this genetic mutation, focusing on mismatch negativity - a common biomarker of altered sensory integration that matures across adolescence. MethodsIn Kalrn-PT and littermate wild-type mice, pyramidal dendritic morphology was assessed across primary visual cortex (V1) layers using Golgi staining (n=172 neurons/26 mice). Local field potentials (LFPs) and neuronal spiking were recorded during a visual oddball sequence (n=25 mice). Deviance detection - the rodent neural analogue of mismatch negativity - was analyzed across V1 layers. ResultsKalrn-PT mice exhibit reductions in V1 dendritic length specific to layer 2/3, mirroring observations in post-mortem samples from people with psychiatric disorders. Deviance detection was reduced in LFPs from Kalrn-PT mice and absent in layer 2/3 neurons, despite typical feature selectivity and firing rates. These deficits were accompanied by reduced functional connectivity between visual and frontal areas. ConclusionsThese results highlight alterations in higher-level sensory cortical integration in Kalrn-PT mice and demonstrate that adolescent-onset, disease-relevant structural and functional phenotypes can be linked by a common upstream effector. Further, these alterations appear restricted to supragranular layers, demonstrating an outsized role for Kalrn, particularly longer isoforms, in superficial neocortex.

neuroscience↗

bioRxiv2026

Scalable high-fidelity human vascularized cortical assembloids recapitulate neurovascular co-development and cell specialization

Human cortical development involves the coupling of neurogenesis and cerebrovascular growth. However, interactions between neural and vascular cells are largely missing in most brain organoids, which are crucial models for studying neurodevelopment and disease. Here, we establish vascularized cortical assembloids (vCAs) by fusing mesoderm-derived vascular organoids (VOs) with cortical organoids (COs). vCAs self-assemble lumenized networks of endothelial cells, pericytes, and perivascular fibroblasts that acquire blood-brain barrier (BBB) specialization and arteriovenous specification in vitro. Single-cell RNA-sequencing and immunofluorescence imaging revealed that vascularization improves neuroepithelial architecture, reduces hypoxia and apoptosis, expands cortical progenitor pools, and enhances neuronal maturation and connectivity compared with COs. Moreover, atlas-level integration with human neurodevelopmental tissue and cross-protocol benchmarking demonstrate superior transcriptional concordance, especially for vascular cell and glial populations, relative to existing approaches. This scalable and reproducible platform improves fidelity and throughput for modeling human neurovascular co-development and enables systematic studies across brain regions and diseases using engineered or patient-derived iPSCs.

developmental biology↗

bioRxiv2026

Global context rapidly shapes sensory responses in V1

Context modulates sensory processing in the cerebral cortex by suppressing responses to expected stimuli and enhancing responses to unexpected ones. Recent proposals argue that early sensory areas such as primary visual cortex (V1) are shaped only by local context, including recent stimulus history, whereas modulation by global context, such as learned temporal structure, is present exclusively in higher cortical areas. This view is incompatible with predictive coding theories. To directly dissociate local and global contextual influences, we used a global/local oddball paradigm in which mice viewed five-item sequences. Across conditions, sequence structure was held constant while stimulus identity and predictability were selectively manipulated, allowing the isolation of response modulations due to local deviance, global expectation, and stimulus repetition independently. In the canonical sequence (AAAA-B), B is locally deviant but globally predictable. Using two-photon calcium imaging and LFP recordings in mouse V1, we found that global predictability abolished context modulation: responses to B were equivalent to those evoked by a random sequence control (e.g., CDEAB). This effect emerged rapidly, after only <10 sequence repetitions, demonstrating fast learning of global structure. When the stimulus was globally deviant, either by replacing B with a novel stimulus (AAAA-C) or by presenting B unpredictably in a standard oddball paradigm, V1 exhibited robust response enhancement. These effects required feedback from anterior cingulate area (ACa), establishing a causal role for higher cortical circuits in conveying global predictions to V1. Strikingly, when an additional A replaced B (AAAA-A), responses were strongly suppressed despite global deviance, indicating that stimulus-specific adaptation may constrain the expression of global prediction error signals in early sensory cortex. HighlightsGlobal context rapidly modulates neural responses in V1 Global deviations, but not predictable local deviants, elicit enhanced responses Downstream brain region ACa is necessary for global context modulation in V1 Standard oddball paradigms involve higher-order contextual modulation

neuroscience↗

bioRxiv2025

The Effect of Musical Groove on Sensorimotor Network Cortical Dynamics during Active Tapping and Passive Listening

Musical groove, defined as the urge to move in response to rhythmic stimuli, drives spontaneous entrainment and engagement with music. Recent studies have investigated the activation of the sensorimotor network (SMN), focusing on the {micro} rhythm, an oscillatory activity in the alpha (8-12 Hz) and beta (16-24 Hz) ranges that reflects motor system engagement. While {micro} modulation differs between passive listening and active movement, it remains unclear whether these responses are shaped by the level of musical groove. Clarifying this relationship is crucial for understanding how neural oscillations transform rhythmic perception into embodied movement and how auditory and motor systems interact to generate the spontaneous urge to move. The present study investigates SMN dynamics by examining {micro} modulation across two factors: mode of engagement - active motor entrainment (finger tapping) versus passive listening, and groove level - low versus high. Electroencephalography (EEG) recordings were used to assess SMN activity, with a focus on {micro} rhythm modulation in the alpha and beta frequency bands. Channel and cluster-based EEG analyses revealed stronger {micro} suppression during active tapping compared to passive listening, as well as an effect of musical groove. Self-reported groove ratings were not affected by the tapping task. Together, these findings highlight the modulation of the {micro} rhythm in the SMN, describing distinctive patterns of neural engagement during the experience of musical groove.

neuroscience↗

bioRxiv2025

Associations Between Frailty and Cognitive Outcomes Across the Lifespan of Mice

Advancements in monitoring biological and brain aging with precise measures of health and longevity have the potential to accelerate research on pharmacological, genetic, and aging-related interventions. Over the past decade, frailty index has been used as an assessment tool for rodents, evaluating more than 30 non-invasive parameters that are strongly associated with chronological age, correlated with mortality, and sensitive to lifespan-altering interventions. However, whether aging phenotypes captured by the frailty index reflect brain aging remains unclear. In this study, we examined the relationship between frailty index and cognitive ability in young (3-4 months), middle-aged (12 months), and old (24 months) male and female C57BL/6J mice using a battery of behavioral and locomotor assays to determine whether frailty index scores can predict performance in tasks evaluating behavioral and cognitive function. Among the behavioral assays tested, frailty index scores had good correlation with the percentage of time spent in the center of the open-field apparatus, the duration spent in the open arms of the elevated plus maze, and the time spent in the target hole of the Barnes maze. These findings indicate that the frailty index not only reflects general physiological aging but may also serve as a reliable predictor of age-related cognitive decline in mice, providing a valuable tool for studies of interventions targeting brain aging.

neuroscience↗

bioRxiv2025

DNA Break Induced Epigenetic Alterations Promote Plaque Formation and Behavioral Deficits in an Alzheimer's Disease Mouse Model

The dramatic increase in human longevity over recent decades has contributed to a rising prevalence of age-related diseases, including neurodegenerative disorders such as Alzheimers disease (AD). While accumulating evidence implicates DNA damage and epigenetic alterations in the pathogenesis of AD, their precise mechanistic role remains unclear. To address this, we developed a novel mouse model, DICE (Dementia from Inducible Changes to the Epigenome), by crossing the APP/PSEN1 (APP/PS1) transgenic AD model with the ICE (Inducible Changes to the Epigenome) model, which allows for the controlled induction of double-strand DNA breaks (DSBs) to stimulate aging-related epigenetic drift. We hypothesized that DNA damage induced epigenetic alterations could influence the onset and progression of AD pathology. After experiencing DNA damage for four weeks, DICE mice, together with control, ICE, and APP/PS1 mice, were allowed to recover for six weeks before undergoing a battery of behavioral assessments including the open-field test, light/dark preference test, elevated plus maze, Y-maze, Barnes maze, social interaction, acoustic startle, and pre-pulse inhibition (PPI). Molecular and histological analyses were then performed to assess A{beta} pathology and neuroinflammatory markers. Our findings reveal that DNA damage-induced epigenetic changes significantly affect cognitive behavior and alters A{beta} plaque morphology and neuroinflammation as early as six months of age. These results provide the first direct evidence that DNA damage can modulate amyloid pathology in a genetically susceptible AD model. Future studies will be aimed at investigating DNA damage- induced epigenetic remodeling across additional models of AD and neurodegeneration to further elucidate its role in brain aging and disease progression.

neuroscience↗

bioRxiv2025

Mismatch negativity develops in adolescence and independently of microglia

Higher brain functions and cognition undergo a critical period of development during adolescence, when psychiatric disorders such as schizophrenia typically onset. Understanding how developmental processes during adolescence interact with schizophrenia pathophysiology and risk remains a central goal in psychiatry. Here we show that a well-established biomarker of schizophrenia, mismatch negativity, matures during adolescence in mouse primary visual cortex, along with a strengthening of fronto-visual functional connectivity. Because microglia are implicated in schizophrenia risk and disease states, we further investigated what role microglia may play in the development of mismatch responses under physiological conditions. We found that microglial depletion with PLX5622 in adolescence arrests the development of resting oscillations in frontal areas, but does not affect the development of deviance detection, other signatures of visual context processing, or prefrontal-visual functional connectivity. Our findings suggest (a) a key component of mismatch negativity develops in adolescence, a period of vulnerability to schizophrenia, and (b) the development underlying this component does not require robust microglia activity, clarifying the developmental role of microglia in higher order visual processing.

neuroscience↗

bioRxiv2025

Noninvasive profiling of input-output excitability curves in human prefrontal cortex

Abstract.O_ST_ABSBackgroundC_ST_ABSThe prefrontal cortex plays a critical role in cognitive control and behavior, and its dysfunction has been linked to numerous psychiatric and neurological disorders. However, noninvasive measurement of prefrontal activity remains challenging, limiting our understanding of how to optimize prefrontal treatments. Input-output relationships reveal how neural circuits respond to different inputs and are essential for determining optimal treatment parameters and understanding individual variability in treatment response, yet systematic investigation of prefrontal input-output relationships has been lacking. ObjectiveTo characterize human prefrontal excitability with input-output (I/O) curves. MethodsWe employed transcranial magnetic stimulation (TMS) with electroencephalography in a randomized mixed-block design with 28 healthy participants receiving single-pulse TMS to left dorsolateral prefrontal cortex (dlPFC) across 12 stimulation intensities (60-140% of resting motor threshold). We quantified prefrontal excitability using early local TMS-evoked potentials (EL-TEPs), cortical responses measured locally 20-60 ms post-stimulus. ResultsWe observed a strong effect of TMS intensity on prefrontal EL-TEP amplitudes. Sigmoidal EL-TEP I/O curves were observed in 57% of participants, with the sigmoidality partially explained by EL-TEP signal quality. Correlations were observed between EL-TEP and motor-evoked potential curve parameters, but intensity parameterization approaches did not significantly differ in explaining inter-individual EL-TEP response variability. Reliable EL-TEPs could be obtained using fewer TMS pulses at high intensities, and test- retest assessments revealed robust I/O curve profiles. ConclusionsThese findings provide a systematic noninvasive characterization of prefrontal input-output physiology, establishing a framework for estimating prefrontal excitability. The comparison of various intensity parameterizations motivates the need for enhanced models and individualized measurement of stimulation responses. HighlightsO_LIWe present noninvasive input-output curves for prefrontal TMS. C_LIO_LIEL-TEPs exhibit robust dose-dependent responses to TMS intensity. C_LIO_LISigmoidal I/O curves observed in 57% of participants, with a strong dependence on signal quality. C_LIO_LICorrelations observed between MEP and prefrontal EL-TEP curve parameters. C_LIO_LIHigh test-retest reliability and rapid protocols at [≥]110% rMT C_LI

neuroscience↗

bioRxiv2025

Sensory Entrained TMS (seTMS) enhances motor cortex plasticity

Neural excitability fluctuates with sensory events, creating windows of opportunity to enhance brain stimulation. Repetitive transcranial magnetic stimulation (TMS), including intermittent theta burst stimulation (iTBS), is a promising treatment for neurological and psychiatric disorders, but does not account for fluctuations in neural excitability, likely contributing to variable outcomes. Sensory Entrained TMS (seTMS) leverages sensorimotor oscillations to enhance corticospinal responses, but the sustained effects as a repetitive protocol are unknown. We extended seTMS to iTBS measuring motor-evoked potentials (MEPs) as a physiological readout in a randomized crossover study comparing standard iTBS with sensory entrained iTBS (se-iTBS, n=20). se-iTBS more than doubled the MEP effect (55% vs. 26% MEP enhancement) and persisted for at least 30 minutes. Notably, more than 80% of participants showed larger responses with se-iTBS at all time points. se-iTBS may provide a robust and practical framework for optimizing TMS that bridges electrophysiological mechanisms and clinical applications.

neuroscience↗

bioRxiv2025

Duet model of predictive coding unifies diverse neuroscienceexperimental protocols

The brain continuously generates predictions about the external world. When stimulus X is presented repeatedly, the brain predicts that the next one is also X. A deviant stimulus Y elicits a stronger sensory response than the baseline, reflecting the amplification of an unexpected stimulus. Here, we introduce the duet predictive coding model, a minimal and biologically plausible framework in which neurons encode both positive and negative prediction errors. This model reproduces neural responses observed in vision and audition across diverse predictive coding paradigms, particularly omission. Our proposed circuit mechanism predicts (1) neurons tuned to negative prediction errors in the oddball paradigm, supported by experimental evidence in mice; (2) the magnitude of unexpected responses quantitatively depends on the dissimilarity between standard and deviant stimuli and diminishes with increasing interstimulus interval. Our findings suggest that the brains deviance detection relies on dual-error computation, offering a unifying explanation across seemingly disparate experimental protocols.

neuroscience↗

bioRxiv2025

Short-Term Exposure to Polystyrene Microplastics Alters Cognition, Immune, and Metabolic Markers in an APOE Genotype and Sex-Dependent Manner

Alzheimers disease (AD) is one of the most prevalent neurodegenerative disorders and one of the leading causes of death in individuals over the age of 65. Most cases of AD develop sporadically, however, there are several risk factors that have been identified which significantly increases an individuals risk for developing AD. The most prominent of these is Apolipoprotein E4 (APOE4), which can potentially result in an up to 10-fold greater risk of developing AD. The presence of APOE4 alone, however, cannot be solely responsible for AD as the disease may occur even in the absence of APOE4. Therefore, there must be other contributing factors such as exposure to environmental toxins including heavy metals and pesticides, which have independently been shown to contribute to AD. Nano- and microplastics (NMPs) are plastic particles less than 1 m and 5 mm in size, respectively, and have only recently been identified as a major environmental pollutant with serious health concerns. Given the adverse health effects that are increasingly being associated with NMPs exposure, we sought to understand how the combination of APOE4 and NMPs exposure may work synergistically to promote cognitive dysfunction and alter key regulatory pathways to impact overall health. Following an acute (3 week) exposure to pristine spherical fluorescently-labeled 0.1 and 2 {micro}m polystyrene (PS) NMPs, we found significant sex-dependent alterations in locomotor and recognition memory in APOE4 mice, but not in APOE3 controls. We additionally found that exposure to PS-NMPs resulted in sex and genotype specific alterations in astrocytic and microglial markers in the brain, and in CYP1A1, a major metabolizer of environmental polycyclic aromatic hydrocarbons, in the liver. These results suggest PS-NMPs may interact with the APOE4 allele to promote cognitive dysfunction and alter immune and metabolic pathways which may contribute to disease-like states.

neuroscience↗

bioRxiv2025

Mitochondrial Dysfunction Induces Hepatic Lipid Accumulation and Inflammatory Responses in mtDNA Mutator Mice

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD), now referred to as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a widespread and complex health issue characterized by the accumulation of lipids in liver cells, not linked to alcohol consumption or other known liver problems. Despite its strong association with insulin resistance and obesity, a notable proportion of lean individuals develop NAFLD, suggesting the involvement of additional factors. Mitochondrial dysfunction has emerged as a potential contributor, given its role in lipid homeostasis and the generation of reactive oxidative species (ROS). MethodsIn this study, we took advantage of the mtDNA mutator mouse model, characterized by oxidative phosphorylation deficiency due to accelerated accumulation of mitochondrial DNA (mtDNA) mutations, to investigate how mitochondrial dysfunction affects liver homeostasis triggering fat accumulation. ResultsWe found that mitochondrial dysfunction induces liver steatosis and inflammation in this mouse model at a young age, independent of obesity. Using quantitative mass spectrometry, we reveal that mitochondrial dysfunction alters the levels of multiple proteins involved in lipid metabolism, cholesterol homeostasis, and inflammation. In vitro data show a shift in cellular metabolism toward the glycolytic pathway and confirm the upregulation of inflammatory genes. These changes are associated with oxidative stress and occur independently of mtDNA molecule release into the cytoplasm. ConclusionOur findings demonstrate that liver steatosis might develop as result of mitochondrial dysfunction without obesity and insulin resistance, underscoring the importance of mitochondrial dysfunction in NAFLD development in lean individuals and providing valuable insights into the molecular mechanisms underlying this complex metabolic disorder. This mouse model offers a unique platform for further investigations aimed at unraveling the intricacies of NAFLD pathogenesis and potential therapeutic targets beyond conventional risk factors.

cell biology↗

bioRxiv2025

A novel inducible mtDNA mutator mouse model to study mitochondrial dysfunction with temporal and spatial control

Mitochondrial dysfunction is a hallmark of aging and numerous age-related diseases. A wealth of studies supports the accumulation of mitochondrial DNA (mtDNA) mutations as a contributing factor to mitochondrial dysfunction in aging and disease. One of the best models to study the relationship between mtDNA mutations and mitochondrial dysfunction is the mtDNA mutator mouse, which expresses a proofreading-deficient version of mtDNA polymerase-{gamma} (PolgA). Despite its groundbreaking contributions to mitochondrial biology and aging research, this model is limited by the whole-body accumulation of mtDNA mutations, which prevents the investigation of tissue-specific differences in mitochondrial dysfunction. To overcome this limitation, we developed a novel inducible knock-in mtDNA mutator mouse model that allows spatial and temporal control of mtDNA mutations, enabling the precise study of mitochondrial dysfunction in a tissue- and time-specific manner. Here, we report the generation and validation of this novel model through whole-body induction via Cre recombinase. Our data demonstrate that, upon induction, this model recapitulates the phenotype of the original mtDNA mutator mouse manifesting the same behavioral and biochemical alterations. This work establishes the functionality of our model and highlights its value as a powerful tool for studying the impact of mtDNA mutations with enhanced specificity and control.

genetics↗

bioRxiv2024

Sensory Entrained TMS (seTMS) enhances motor cortex excitability

Transcranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant variability, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Variable responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity. We introduce Sensory Entrained TMS (seTMS), a novel approach that uses musical rhythms to synchronize brain oscillations and time TMS pulses to enhance cortical excitability. Focusing on the sensorimotor alpha rhythm, a neural oscillation associated with motor cortical inhibition, we examine whether rhythm-evoked sensorimotor alpha phase alignment affects primary motor cortical (M1) excitability in healthy young adults (n=33). We first confirmed using electroencephalography (EEG) that passive listening to musical rhythms desynchronizes inhibitory sensorimotor brain rhythms (mu oscillations) around 200 ms before auditory rhythmic events (27 participants). We then targeted this optimal time window by delivering single TMS pulses over M1 200 ms before rhythmic auditory events while recording motor-evoked potentials (MEPs; 19 participants), which resulted in significantly larger MEPs compared to standard single pulse TMS and an auditory control condition. Neither EEG measures during passive listening nor seTMS-induced MEP enhancement showed dependence on musical experience or training. These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for optimizing non-invasive brain stimulation outcomes.

neuroscience↗

bioRxiv2024

Real-time optimization to enhance noninvasive cortical excitability assessment in the human dorsolateral prefrontal cortex

ObjectiveWe currently lack a robust noninvasive method to measure prefrontal excitability in humans. Concurrent TMS and EEG in the prefrontal cortex is usually confounded by artifacts. Here we asked if real-time optimization could reduce artifacts and enhance a TMS-EEG measure of left prefrontal excitability. MethodsThis closed-loop optimization procedure adjusts left dlPFC TMS coil location, angle, and intensity in real-time based on the EEG response to TMS. Our outcome measure was the left prefrontal early (20-60 ms) and local TMS-evoked potential (EL-TEP). ResultsIn 18 healthy participants, this optimization of coil angle and brain target significantly reduced artifacts by 63% and, when combined with an increase in intensity, increased EL-TEP magnitude by 75% compared to a non-optimized approach. ConclusionsReal-time optimization of TMS parameters during dlPFC stimulation can enhance the EL-TEP. SignificanceEnhancing our ability to measure prefrontal excitability is important for monitoring pathological states and treatment response. HighlightsO_LIWe developed a real-time closed-loop optimization procedure to obtain high amplitude early local TEPs (EL-TEPs) from dlPFC TMS. C_LIO_LISequential optimization of coil angle and brain target reduced artifacts by 63%. C_LIO_LISequential optimization of coil angle, brain target, and intensity increased EL-TEP amplitude by 75%. C_LI

neuroscience↗

bioRxiv2023

Effects of auditory noise intensity and color on the dynamics of upright stance

Previous work assessing the effect of additive noise on the postural control system has found a positive effect of white noise on postural dynamics. This study covers two separate experiments that were run sequentially to better understand how the structure of the additive noise signal affects postural dynamics, while also furthering our knowledge of how the intensity of auditory stimulation of noise may elicit this phenomenon. Across the two experiments, we introduced three auditory noise stimulations of varying structure (white, pink, and brown noise). Experiment 1 presented the stimuli at 35 dB while Experiment 2 was presented at 75 dB. Our findings demonstrate a decrease in variability of the postural control system regardless of the structure of the noise signal presented, but only for high intensity auditory stimulation.

neuroscience↗