Biology subjects

Hasegawa, H.

Publications and source records attributed to Hasegawa, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Dual Developmental Origins and Activity-dependent Specification of Mammalian Subplate Neurons

Subplate neurons (SpNs) are among the earliest-generated cortical neurons and are essential for neocortical circuit assembly. Despite this central role, they have long been considered a mammalian innovation, yet their evolutionary origin remains unresolved. Here, using comparative single-cell and spatial transcriptomics across amniotes (mice, chicks, and turtles), we identify two distinct developmental and evolutionary origins of SpNs: atypical SpNs (aSpNs), an Nr4a2-negative population conserved across amniotes and originating from the medial pallium, and mammalian-type SpNs (mSpNs), an Nr4a2-positive population preferentially expanded in mammals and arising from early-born cortical neurons. Cross-species analyses show that early-born pallial neurons in non-mammalian amniotes differentiate into thalamic input neurons, whereas this ancestral program is repurposed in mammals, with early-born neurons transiently adopting a subplate identity. We further show that this fate switch is controlled by Zbtb18 repression linked to thalamic input. Collectively, these findings establish a dual-origin model for SpNs and provide a unifying framework for understanding neocortical evolution. One-Sentence SummaryDevelopmental rewiring of an ancestral input-neuron program gave rise to the mammalian subplate.

evolutionary biology↗

bioRxiv2026

Demixing of bacterial CipA and CipB proteins in mammalian cell cytosol provides an orthogonal self-assembly platform for producing isolable multi-phase intracellular crystals

Crystalline inclusion proteins CipA and CipB from Photorhabdus luminescens serve as versatile scaffolds for clustering genetically fused heterologous enzymes into crystalline inclusion bodies. Although engineered Cip crystals are known to function as solid biocatalysts for improving metabolite production in bacterial cells, the phase separation behavior of Cip proteins in non-bacterial cellular environments, as well as their biochemical attributes in a soluble, non-crystalline state, remain poorly understood. This study demonstrates that CipA and CipB efficiently undergo crystallization in the cytosol of human embryonic kidney cells both at normal and hypothermic cell culture conditions. Within 72 hours post-transfection, CipA and CipB become the most abundant proteins in transfected cells and produce distinctive cytosolic crystals often exceeding 10 m at least in one of the dimensions. Co-expression of CipA and CipB drives spontaneous demixing into two distinct crystal populations, and the orthogonality is maintained even when an unrelated third protein crystallizes in the same cytosol, permitting three crystal types to coexist simultaneously. Intracellular crystals are readily isolable from cells, and once purified, these crystals are stable under physiological pH conditions. However, CipA and CipB show notable differences in their crystal dissolution kinetics and protein oligomerization states when solubilized under acidic or alkaline conditions. These findings suggest that CipA/CipB forms a robust orthogonal self-assembly pair and establish CipA/CipB crystals as an efficient platform for producing biochemically programmable intracellular crystals. These properties should extend the Cip-based scaffolding approach to mammalian cell systems for synthetic biology applications.

cell biology↗

bioRxiv2026

Near real-time data on the human neutralizing antibody landscape to influenza virus as of early 2026 to inform vaccine-strain selection

Twice each year, a decision is made on whether to update the strains included in the seasonal influenza vaccine to better match the most recent circulating viral strains. To characterize the antigenic properties of current seasonal influenza A strains to inform the upcoming decision about which strains to include in the 2026-2027 Northern Hemisphere vaccine, here we perform high-throughput sequencing-based neutralization assays using a library of 57 H3N2 and 34 H1N1 influenza hemagglutinins reflecting the circulating diversity of strains in late 2025 to early 2026. We assay this library against 302 human sera collected in late 2025. The resulting data set encompasses 27,409 titers, and provides a near real-time portrait of the human neutralizing antibody landscape against influenza virus. We find that many human sera have lower titers against the K subclade of H3N2 and the D.3.1.1 subclade of H1N1; these subclades have recently become dominant among their respective subtypes. Our measurements also reveal variability in titers to different subvariants within the K subclade of H3N2, with titers especially low to subclade K strains with additional mutations in antigenic regions D and E. We make all our data and accompanying visualizations publicly available to enable their use in vaccine-strain selection and analyses of influenza evolution and immunity.

microbiology↗

bioRxiv2026

Lhcf9 is a novel negative regulator of non-photochemical quenching in the diatom Chaetoceros gracilis

Photosynthetic organisms in aquatic environments experience rapid fluctuations in light intensity, light quality, and carbon availability, requiring tight regulation of photosynthetic energy conversion. In marine diatoms, non-photochemical quenching (NPQ), particularly energy-dependent quenching (qE), plays a central role in dissipating excess excitation energy as heat. However, excessive NPQ can reduce photosynthetic efficiency under light-limiting or carbon-rich conditions, and how this trade-off is regulated remains poorly understood. Here, we identify CgLhcf9, a previously uncharacterized light-harvesting complex (LHC) protein, as a negative regulator of qE-type NPQ in the centric diatom Chaetoceros gracilis. Expression of CgLhcf9 is induced under low red-light and high CO2 conditions and strongly suppressed by blue light, indicating regulation by both light quality and carbon availability. Functional analyses using CgLhcf9 knockout and overexpression lines reveal that CgLhcf9 suppresses qE: NPQ induction is enhanced in the absence of CgLhcf9, whereas its accumulation downregulates NPQ without affecting other established qE effectors, including Lhcx1 or xanthophyll cycle pigments. Notably, CgLhcf9 accumulation improves cellular growth under light-limiting conditions. These results identify CgLhcf9 as a novel LHC-type regulator that fine-tunes photosynthetic energy dissipation in response to environmental signals. Our findings establish a regulatory mechanism that balances photoprotection, electron transport, and carbon fixation, advancing our understanding of how marine diatoms optimize photosynthesis under fluctuating light and CO2 conditions. Significance statementPhotosynthetic microalgae must balance light-driven electron transport with carbon fixation to maximize growth under fluctuating light and CO2 conditions. While non-photochemical quenching (NPQ) protects photosystems from excess light, excessive NPQ can limit photosynthetic efficiency when light or carbon is limiting. Here, we identify the antenna protein CgLhcf9 as a negative regulator of energy-dependent NPQ in the marine diatom Chaetoceros gracilis. CgLhcf9 integrates light-quality and CO2 signals to suppress NPQ without altering canonical quenching effectors, thereby improving growth under light-limiting conditions. This study reveals a regulatory role for a light-harvesting complex protein in tuning the balance between photoprotection and photosynthetic efficiency, providing insight into how marine diatoms coordinate electron transport and carbon fixation in dynamic environments.

plant biology↗

bioRxiv2026

A lethal mouse model of Oz virus infection reveals hepatic involvement and enables evaluation of antiviral and vaccine efficacy

Oz virus (OZV), a member of the genus Thogotovirus in the family Orthomyxoviridae, is an emerging tick-borne virus reported in Japan. A fatal human case and seroepidemiological evidence of widespread exposure among wild animals and humans suggest its potential public health significance. However, no animal models suitable for pathogenic studies or evaluation of countermeasures are available for OZV. Here, we have established a lethal mouse model of OZV infection using cell-adapted virus and mice lacking type I interferon signaling (B6 Ifnar1 KO mice). OZV infection resulted in 100% mortality and was characterized by robust viral replication in the liver and spleen, severe hepatitis, and acute liver injury. Using this model, we also demonstrated that oral administration of T-705, an antiviral drug widely used against RNA viruses, as well as immunization with an inactivated whole virus particle vaccine, protected B6 Ifnar1 KO mice from lethal OZV infection by mitigating the acute hepatitis. The present study provides critical insights into OZV pathogenesis and establishes a practical in vivo platform for the development of countermeasures against OZV infection. Significance statementEmerging tick-borne viruses pose a growing public health concern, yet progress in understanding their pathogenesis and in developing countermeasures is often limited by the lack of relevant animal models. Oz virus (OZV), a recently identified thogotovirus associated with a fatal human case, exemplifies this challenge. Here, we establish a lethal mouse model of OZV infection that reveals pronounced hepatic involvement as a central pathological feature. Using this model, we demonstrate effective protection by both an antiviral drug and an inactivated vaccine against lethal OZV challenge. This study provides a practical in vivo platform for investigating OZV pathogenesis and for accelerating the development of medical countermeasures against this emerging tick-borne virus.

microbiology↗

bioRxiv2025

Combinational adjuvants delivered by ink-jet potentiate naked mRNA vaccines for robust protection against infectious diseases

The use of lipid nanoparticles (LNPs) to enhance delivery and immunogenicity of mRNA vaccines raises safety concerns due to strong reactogenicity. Developing naked mRNA vaccines, which can be delivered through liquid jet-injection to the skin, may offer a safer alternative, but their immunogenicity has been limited. To address this challenge, we screened clinically relevant adjuvants to enhance the potency of naked mRNA jet-injection vaccines in mouse models. Although many adjuvants showed little or inhibitory effects on inducing humoral or cellular immunity--despite their known ability to potentiate conventional non-mRNA vaccine platforms--we identified a combination of aluminum phosphate and CpG oligonucleotide that substantially enhanced both humoral and cellular immune responses with increased IgG2a/IgG1 ratio. This adjuvanted naked mRNA vaccine induced IgG2a and cellular immunity at levels comparable to those achieved with LNPs but with lower local and systemic reactogenicity. Mechanistic investigations revealed a key role for type I interferon signaling during immunization. Notably, this vaccine formulation in mice virtually eliminated infection by both SARS-CoV-2 and influenza A virus (A/California/7/2009 H1N1) in plaque-forming assays. Collectively, the adjuvanted naked mRNA jet-injection vaccine represents a novel, effective, and safe platform against infectious diseases, with potential for clinic-ready translational applications.

bioengineering↗

bioRxiv2025

Evolutionary origin and functional mechanism of Lhcx in the diatom photoprotection

Diatoms are red-lineage algae that utilize the light-harvesting complex (LHC) subfamily Lhcx for photoprotection via non-photochemical quenching (NPQ); however, its evolutionary origin and molecular mechanism remain poorly understood. Through molecular phylogenetic analysis, we show that diatom Lhcxs and green algal Lhcsrs evolved from a common ancestor, with green plants subsequently acquiring them via horizontal gene transfer. To investigate the functional role of Lhcx1, we generated knockout mutants of Chaetoceros gracilis, a diatom with low Lhcx redundancy. The lhcx1 mutants nearly abolished NPQ, and time-resolved fluorescence measurements revealed that Lhcx1-mediated quenching occurs in energetically detached antenna complexes. Clear-native PAGE with Amphipol further indicated that CgLhcx1 interacts with the FCP L-dimer, functioning as a peripheral antenna for the C2S2M2 PSII-FCPII supercomplex. Notably, under high-light acclimation, lhcx1 mutants exhibited higher PSII effective quantum yields than wild type, attributable to reduced antenna size and enhanced carbon fixation capacity. The absence of NPQ accelerated high-light acclimation and was accompanied by increased xanthophyll accumulation, indicating that compensatory mechanisms can enhance overall photosynthetic efficiency. Together, these findings reveal the evolutionary origin of Lhcx/Lhcsr proteins and define the molecular basis of Lhcx1-mediated photoprotection in diatoms, providing fundamental insights into LHC-based photoprotection across photosynthetic lineages.

plant biology↗

bioRxiv2025

Near real-time data on the human neutralizing antibody landscape to influenza virus to inform vaccine-strain selection in September 2025

The hemagglutinin of human influenza virus evolves rapidly to erode neutralizing antibody immunity. Twice per year, new vaccine strains are selected with the goal of providing maximum protection against the viruses that will be circulating when the vaccine is administered [~]8-12 months in the future. To help inform this selection, here we quantify how the antibodies in recently collected human sera neutralize viruses with hemagglutinins from contemporary influenza strains. Specifically, we use a high-throughput sequencing-based neutralization assay to measure how 188 human sera collected from Oct 2024 to April 2025 neutralize 140 viruses representative of the H3N2 and H1N1 strains circulating in humans as of the summer of 2025. This data set, which encompasses 26,148 neutralization titer measurements, provides a detailed portrait of the current human neutralizing antibody landscape to influenza A virus. The full data set and accompanying visualizations are available for use in vaccine development and viral forecasting.

microbiology↗

bioRxiv2025

Demixing of simultaneously co-expressed four phase-separating proteins in the endoplasmic reticulum lumen

Intracellular protein crystallization represents an intriguing form of biomolecular self-assembly. While the list of such crystallizing proteins is growing and their physiological roles are beginning to be elucidated, the underlying requirements and processes for intracellular protein crystallogenesis remain largely unknown. This study examines how simultaneously co-expressed phase-separating proteins influence each others phase-separation event in the endoplasmic reticulum (ER) lumen by using four cargoes selected based on their ability to produce distinctive crystals and droplet inclusion bodies. The co-expressed model proteins independently reached their respective threshold concentrations and spontaneously phase-separated into inclusions in the ER without losing their signature morphologic characteristics. The fact that protein crystals and droplets continued to grow in size over time suggests that nascent cargo proteins were continuously synthesized and folded in the ER to fuel the growth of corresponding inclusion bodies. Namely, despite the highly crowded molecular environment, overexpressed cargoes find their mates by self-association and propagate into microscale structures in the ER. This study demonstrates that cells can accommodate up to four distinct phase separation events simultaneously in the ER lumen, and the phase separation events proceed without interfering with each other and without morphological or content mixing.

cell biology↗

bioRxiv2025

The role of STN beta oscillations on lower extremity muscle activity in Parkinsonian stepping

Freezing of gait (FOG) is a devastating symptom of Parkinsons disease (PD) often resulting in disabling falls and loss of independence. It affects half of patients, yet current therapeutic strategies are insufficient, and the underlying neural mechanisms remain poorly understood. This study investigated beta oscillation dynamics in the STN during different locomotor states, while examining the effects of levodopa. In particular, it aimed to identify pathological activity by analysing the relationship between the STN and lower limb muscles during stepping. Local field potentials (LFP) in the STN and muscle activity (EMG) of the gastrocnemius and peroneus longus were recorded in 14 PD patients during standing and stepping, ON and OFF levodopa. Levodopa reduced stepping variability, implying improved stepping abilities. Distinct STN beta patterns were observed between stepping and standing, with lower high-beta and higher low-beta during stepping compared to standing, suggesting a distinct role of these frequency bands in motor control during postural and movement states. Levodopa reduced low-beta but increased high-beta activity, highlighting a potential physiological function of high-beta in the STN during standing and stepping. In addition, step-phase specific effects of levodopa included reduced broad-beta band activity in the STN and lower limb muscles during the late-stance and pushing-off phase of the contralateral leg when ON medication. Further analyses suggest that pathological STN activity amplifies muscle activation around movement initiation, potentially reducing the ability of the patient to move freely. These findings offer insight for developing phase-specific stimulation strategies targeting STN beta oscillations during gait.

neuroscience↗

bioRxiv2024

Neutralizing antibody evasion of SARS-CoV-2 JN.1 derivatives KP.3, KP.3.1.1, LB.1, and XEC

The emergence of SARS-CoV-2 variants poses ongoing challenges to vaccine efficacy. We evaluated neutralizing antibody responses against JN.1 and its derivatives (KP.3, KP.3.1.1, LB.1, and XEC) in healthcare workers who received seven doses of BNT162b2, including XBB.1.5 monovalent vaccine. In COVID-19-naive individuals, KP.3.1.1 and LB.1 showed substantial immune escape, while previously infected individuals maintained neutralization activity against all variants. We also demonstrated that JN.1-based immunization induces robust cross-neutralizing activity against emerging variants. A single amino acid deletion at position 31 in the spike protein significantly impacted immune evasion. These findings support the potential effectiveness of JN.1-based vaccines while highlighting the need for continued surveillance and vaccine optimization.

immunology↗

bioRxiv2024

Evoked resonant neural activity outperforms spectral markers in decoding sleep from the subthalamic nucleus

BackgroundDeep brain stimulation is a treatment for advanced Parkinsons disease and currently tuned to target motor symptoms during daytime. Parkinsons disease is associated with multiple nocturnal symptoms such as akinesia, insomnia and sleep fragmentation which may require adjustments of stimulation during sleep for best treatment outcome. ObjectivesThere is a need for a robust biomarker to guide stimulation titration across sleep stages. This study aimed to investigate whether evoked resonant neural activity (ERNA) is modulated during sleep. MethodsWe recorded local field potentials from the subthalamic nucleus of four Parkinsons patients with externalised electrodes while applying single stimulation pulses to investigate the effect of sleep on ERNA. ResultsWe found that ERNA features change with wakefulness and sleep stages, and are correlated with canonical frequency bands and heart rate. We further evaluated the performance of machine learning models in classifying non-REM sleep versus wakefulness and found that ERNA amplitude outperforms all spectral markers. ConclusionsGiven the heterogeneity of spectral features during sleep, their susceptibility to movement artefacts and superior classification accuracy of models using ERNA features, this study paves the way for ERNA as a marker for automatic stimulation titration during sleep and improved patient care.

neuroscience↗

bioRxiv2024

Rapid neutralizing assay for circulating H5N1 influenza virus in dairy cows

A rapid and safe neutralization assay is required for emerging highly pathogenic avian influenza viruses, including the H5N1 subtype, which was recently found in cows. Herein, we report a novel neutralization assay using HiBiT-tagged virus-like particles (hiVLPs). Our hiVLP-based neutralization test demonstrated a higher quantitative value and shorter assay time than conventional methods. We used this assay to evaluate whether the neutralizing antibodies induced by the candidate vaccine virus (NIID-002) were cross-reactive with cow-derived H5N1. Our results suggest that the circulating H5N1 virus in cows shares antigenic characteristics with NIID-002, providing significant implications for the development and preparation of vaccines.

microbiology↗

bioRxiv2024

Temperature-dependent intracellular crystallization of firefly luciferase in mammalian cells is suppressed by D-luciferin and stabilizing inhibitors.

Firefly luciferase (Fluc) from Photinus pyralis is one of the most widely used reporter proteins in biomedical research. Despite its widespread use, Flucs protein phase transition behaviors and phase separation characteristics have not received much attention. Current research uncovers Flucs intrinsic property to phase separate in mammalian cells upon a simple cell culture temperature change. Specifically, Fluc spontaneously produced needle-shaped crystal-like inclusion bodies upon temperature shift to the hypothermic temperatures ranging from 25{degrees}C to 31{degrees}C. The crystal-like inclusion bodies were not associated with or surrounded by membranous organelles and were likely built from the cytosolic pool of Fluc. Furthermore, the crystal-like inclusion formation was suppressed when cells were cultured in the presence of D-luciferin and its synthetic analog, as well as the benzothiazole family of so-called stabilizing inhibitors. These two classes of compounds inhibited intracellular Fluc crystallization by different modes of action as they had contrasting effects on steady-state luciferase protein accumulation levels. This study suggests that, under substrate insufficient conditions, the excess Fluc phase separates into a crystal-like state that can modulate intracellular soluble enzyme availability and protein turnover rate.

cell biology↗

bioRxiv2023

Understanding the biosynthesis of human IgMs through a combinatorial expression of mutant subunits that affect different assembly steps

Polymeric IgMs are secreted from plasma cells abundantly despite their structural complexity and intricate multimerization steps. To gain new insights into IgMs assembly mechanics that underwrite the high-level secretion, we characterized the biosynthetic process of a natural human IgM, SAM-6, using a recombinant HEK293 cell system. By creating a series of mutant subunits that differentially disrupt specific sets of inter-chain disulfide bonds, we assessed their effects on various aspects of IgM biosynthesis in 48 different mutant subunit combinations. The analysis included the visualization of intracellular biosynthetic events such as steady-state subcellular subunit distribution, secretory trafficking bottlenecks, and the ER-associated Russell body formation by fluorescent microscopy. We also characterized various extracellular events including secreted IgM product quality, secretion output, and the release of various assembly intermediates using biochemical and biophysical assays. In this combinatorial mutagenesis approach, we unexpectedly found that the loss of multiple inter-chain disulfide bonds, including the one between HC and {lambda}LC subunits, was tolerated in polymeric IgM formation and secretion. This finding revealed the vital role of underlying non-covalent protein-protein association not only during the orchestration of initial subunit interactions but also in maintaining the polymeric IgM product integrity during ER quality control steps, secretory pathway trafficking, and secretion. We suggest that the IgM assembly process is inherently robust and has a stopgap that permits the secretion of polymeric IgM even when not all the prescribed inter-chain disulfide bonds are formed. This study holistically presents the requirements and exemptions in polymeric IgM biosynthesis by encompassing the characterization of intracellular and extracellular events and the roles of covalent and non-covalent interactions. These findings can guide antibody engineering strategy when designing IgM-based multivalent modalities.

cell biology↗

bioRxiv2022

Use of the particle agglutination/particle agglutination-inhibition test for antigenic analysis of SARS-CoV-2

The antigenicity of SARS-CoV-2 is a critical issue for the effectiveness of the vaccine, and thus it should be phenotypically evaluated by serological assays as new field isolates emerge. The hemagglutination/hemagglutination-inhibition (HA/HI) tests are well-known as a representative method for antigenic analysis of influenza viruses, but SARS-CoV-2 is unlikely to agglutinate to human or guinea pig red blood cells. Therefore, the antigenic analysis requires complicated enzyme-linked immunosorbent assay (ELISA) or cell-based assays such as the microneutralization assay. In this study, we developed the particle agglutination/particle agglutination-inhibition (PA/PAI) test to easily and rapidly quantify the virus and antibody using human angiotensin-converting enzyme 2 (hACE2)-bound latex beads. The PA titer was positively correlated with the plaque-forming units. The PAI titer using post-infection Syrian hamster antisera clearly revealed the antigenic difference between the omicron and previous variants. The results show the PAI test is useful for easy and rapid antigenic analysis of SARS-CoV-2.

microbiology↗

bioRxiv2022

Impact of reinfection with SARS-CoV-2 Omicron variants in previously infected hamsters

The diversity of SARS-CoV-2 mutations raises the possibility of reinfection of individuals previously infected with earlier variants, and this risk is further increased by the emergence of the B.1.1.529 Omicron variant. In this study, we used an in vivo, hamster infection model to assess the potential for individuals previously infected with SARS-CoV-2 to be reinfected with Omicron variant and we also investigated the pathology associated with such infections. Initially, Syrian hamsters were inoculated with a lineage A, B.1.1.7, B.1.351, B.1.617.2 or a subvariant of Omicron, BA.1 strain and then reinfected with the BA.1 strain 5 weeks later. Subsequently, the impact of reinfection with Omicron subvariants (BA.1 and BA.2) in individuals previously infected with the BA.1 strain was examined. Although viral infection and replication were suppressed in both the upper and lower airways, following reinfection, virus-associated RNA was detected in the airways of most hamsters. Viral replication was more strongly suppressed in the lower respiratory tract than in the upper respiratory tract. Consistent amino acid substitutions were observed in the upper respiratory tract of infected hamsters after primary infection with variant BA.1, whereas diverse mutations appeared in hamsters reinfected with the same variant. Histopathology showed no acute pneumonia or disease enhancement in any of the reinfection groups and, in addition, the expression of inflammatory cytokines and chemokines in the airways of reinfected animals was only mildly elevated. These findings are important for understanding the risk of reinfection with new variants of SARS-CoV-2. IMPORTANCEThe emergence of SARS-CoV-2 variants and the widespread use of COVID-19 vaccines has resulted in individual differences in immune status against SARS-CoV-2. A decay in immunity over time and the emergence of variants that partially evade the immune response can also lead to reinfection. In this study, we demonstrated that, in hamsters, immunity acquired following primary infection with previous SARS-CoV-2 variants was effective in preventing the onset of pneumonia after reinfection with the Omicron variant. However, viral infection and multiplication in the upper respiratory tract were still observed after reinfection. We also showed that more diverse nonsynonymous mutations appeared in the upper respiratory tract of reinfected hamsters that had acquired immunity from primary infection. This hamster model reveals the within-host evolution of SARS-CoV-2 and its pathology after reinfection, and provides important information for countermeasures against diversifying SARS-CoV-2 variants.

microbiology↗

bioRxiv2022

The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism: a cross-species study in vivo

AO_SCPLOWBSTRACTC_SCPLOWPeriodic features of neural time series data, such as local field potentials (LFP), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically-relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in neuronal populations. Here, we used a cross-species in vivo electrophysiological approach to test the E/I hypothesis in the context of experimental and idiopathic Parkinsonism. We demonstrate in dopamine-depleted rats that aperiodic exponents and power at 30-100 Hz in subthalamic nucleus (STN) LFPs reflect defined changes in basal ganglia network activity; higher aperiodic exponents tally with lower levels of STN neuron firing and a balance tipped towards inhibition. Using STN-LFPs recorded from awake Parkinsons patients, we show that higher exponents accompany dopaminergic medication and deep brain stimulation (DBS) of STN, consistent with untreated Parkinsons manifesting as reduced inhibition and hyperactivity of STN. These results suggest that the aperiodic exponent of STN-LFPs in Parkinsonism reflects E/I balance, and might be a candidate biomarker for adaptive DBS.

neuroscience↗