Brain Research最新文献

{"title":"Therapeutic potential of iPSC-exosomes and miR-7 in Targeting Glioblastoma","authors":"Beyza Yilmaz ,&nbsp;Altay Savalan ,&nbsp;Ayyub Ebrahimi","doi":"10.1016/j.brainres.2026.150185","DOIUrl":"10.1016/j.brainres.2026.150185","url":null,"abstract":"<div><div>Exosomes play a vital role in intercellular communication, significantly influencing cell behavior and fate. Their influence is particularly evident in diseases like glioblastoma, one of the most challenging cancers to treat. Due to glioblastoma’s high resistance to conventional therapies, novel treatment strategies are urgently needed. Exosomes, being nano-sized vesicles capable of crossing the blood–brain barrier, can deliver bioactive molecules, including nucleic acids, proteins, and metabolites, to suppress tumor-promoting activities in cancer cells. Induced pluripotent stem cells (iPSCs), known for their unlimited proliferation potential and lack of ethical concerns compared to embryonic sources, present a valuable source of exosomes for therapeutic purposes. Although embryonic stem cell-derived exosomes have shown anti-tumor effects against glioblastoma, the therapeutic potential of iPSC-derived exosomes remains largely unexplored. In this study, we demonstrate that exosomes derived from iPSCs exert anti-tumorigenic effects on glioblastoma cells. We also focused on microRNAs (miRNAs), key regulators of cellular proliferation and apoptosis, which are considered promising therapeutic targets in glioblastoma. Specifically, we observed that microRNA-7 (miR-7) significantly inhibits glioblastoma cell proliferation, migration, and invasion. Our findings show that treatment with a miR-7-5p mimic reduces glioblastoma cell proliferation, and its combination with iPSC-derived exosomes leads to either additive or synergistic anti-cancer effects. These results highlight iPSC-derived exosomes and miR-7 as promising therapeutic candidates for glioblastoma and potentially other malignancies.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1875 ","pages":"Article 150185"},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The oral-gut-brain axis in periodontitis: microbial signaling in systemic and neuroinflammatory disease","authors":"V. Pravin,&nbsp;Chitra Vellapandian,&nbsp;V. Naveen Kumar","doi":"10.1016/j.brainres.2026.150168","DOIUrl":"10.1016/j.brainres.2026.150168","url":null,"abstract":"<div><div>Periodontitis, a chronic inflammatory disease of the oral cavity, has been identified as a modifiable risk factor of the development of systemic and neurological disorders via a complicated interplay of microbiological, immunological, and neural interactions. Periodontal pathogens breach local immune homeostasis, are translocated to the gut and brain, and trigger a cascade of immune deregulation, leaky gut, and blood–brain barrier, thereby forming a tri-directional communication network that links local oral inflammation to systemic and neurovascular conditions. This review synthesizes existing evidence on how oral dysbiosis, can spread to the gut and trigger systemic inflammation, leading to neuroinflammation and neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Mechanistically, the OGB axis acts through various processes, such as hematogenous spread, retrograde axonal transport, immune cell trafficking (Trojan horse mechanism), and extracellular vesicle-based signaling corresponding to the causes of neuroinflammation, microglial activation, and the pathology of tau and amyloid. The diagnostic and therapeutic implications of the OGB axis provide new pathways toward early intervention with precision medicine, microbiome remodeling, immune-based therapy, and neuroprotective approaches. Emerging technologies, including AI-based diagnostics and biosensing technologies, offers noninvasive tools to track host-microbial interactions and inflammatory biomarkers. This integrative view underscores the central importance of oral health in systemic homeostasis and the development of neurodegenerative conditions, necessitating collaborative approaches between dentistry, neurology, and immunology to cooperate to deliver efficacy in disease elimination and mitigation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1875 ","pages":"Article 150168"},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic structural and metabolic changes during the epileptogenesis in the pilocarpine model of temporal lobe epilepsy: A longitudinal MRI study","authors":"Luciana Ramalho Pimentel-Silva ,&nbsp;Renata Barbosa ,&nbsp;Alexandre Hilario Berenguer de Matos ,&nbsp;Raphael Fernandes Casseb ,&nbsp;Brunno Machado de Campos ,&nbsp;Mônica Mingone Cordeiro ,&nbsp;Juliana Francischinelli Casseb ,&nbsp;Elayne Vieira Dias ,&nbsp;Andre Schwambach Vieira ,&nbsp;Luis Concha ,&nbsp;Iscia Lopes-Cendes ,&nbsp;Fernando Cendes","doi":"10.1016/j.brainres.2026.150180","DOIUrl":"10.1016/j.brainres.2026.150180","url":null,"abstract":"<div><h3>Purpose</h3><div>We aimed to evaluate longitudinal structural and metabolic changes after induced <em>status epilepticus</em> (SE) in the pilocarpine model of TLE, over the three phases of epileptogenesis.</div></div><div><h3>Methods</h3><div>We analyzed 48 male eight-week-old Wistar rats assigned to sham-control and SE-induced groups. T2-weighted images and 1H-MR spectra were acquired using a 3 T MRI clinical scanner (Philips Achieva) equipped with an animal coil. We measured hippocampal volumes (dorsal-HVol) and total N-acetylaspartate ratios to total creatine (tNAA/tCr) in four points in time (MRI-scan): baseline (before pilocarpine or sham treatments), 48 h (acute phase), 15 days (silent period), and 30 days (beginning of the chronic phase) after experimental treatment. To test differences in dorsal-HVol and hippocampal tNAA/tCr we built generalized linear mixed effects models including groups (pilo-SE and control) and MRI-scan as main effects and a group*MRI-scan interaction.</div></div><div><h3>Results</h3><div>Pilo-SE and control animals showed similar baseline dorsal-HVol and hippocampal tNAA/tCr (both p &gt; 0.1). Pilo-SE showed reduced dorsal-HVol and tNAA/tCr at all MRI-scans (all p &lt; 0.001) when compared to controls. Intragroup analysis revealed that dorsal-HVol and tNAA/tCr significantly increased at 15- and 30-days (all p &lt; 0.001) when compared to 48 h, although remaining lower than the baseline scan. There were no changes over time in sham-controls (all p &gt; 0.4).</div></div><div><h3>Conclusions</h3><div>The novelty of our study was to analyze non-invasively structural and metabolic markers of hippocampal dysfunction across the three main phases of pilocarpine-induced epileptogenesis in comparison to the typical brain development over the same period. Acute dorsal hippocampal volume loss and hippocampal neuronal dysfunction are present as early as 48 h post-pilocarpine-induced SE, dynamically changing over time. This acute damage is followed by a pattern of gradual recovery throughout the silent and chronic phases of epileptogenesis, though with an offset for the pilo-SE group. A better understanding of the course of noninvasive markers of epileptogenesis and HS may contribute to stablish surrogate endpoints in interventions to treat or prevent focal epilepsy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1875 ","pages":"Article 150180"},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EAE models of neuropathic pain in multiple sclerosis do not require pertussis toxin","authors":"Sydney R. Lamerand ,&nbsp;Paramita Basu ,&nbsp;Nina E. Gakii ,&nbsp;Skyy S. Steber ,&nbsp;Bradley K. Taylor","doi":"10.1016/j.brainres.2026.150162","DOIUrl":"10.1016/j.brainres.2026.150162","url":null,"abstract":"<div><h3>Background</h3><div>Experimental autoimmune encephalomyelitis (EAE) is a preclinical model of multiple sclerosis (MS), typically induced with two inoculations of myelin oligodendrocyte glycoprotein (MOG_35-55) emulsified in complete Freund’s adjuvant (CFA), and supplemented with pertussis toxin (PTX). Although PTX has been considered essential, recent studies suggest that EAE pathology can develop without it.</div></div><div><h3>Objectives</h3><div>Indices of clinical disease and neuropathic pain were evaluated in a conventional model of EAE that included PTX (EAE-PTX) and one that lacked PTX (EAE-nPTX), as well as in multiple control groups that lacked MOG_35-55 (CFA-PTX and CFA-nPTX).</div></div><div><h3>Methods</h3><div>A battery of behavioral tests were used to evaluate motor dysfunction and hypersensitivity to mechanical, cold, and heat stimuli with a repeated-measures design in male and female C57BL/6 mice. One month after the first EAE inoculation, fluoromyelin staining was used to evaluate demyelination in spinal cord, cortex, and peripheral nerve, while ATF3 was used as a marker of injury in sensory neurons of lumbar L4-L5 dorsal root ganglia (DRG).</div></div><div><h3>Results</h3><div>Compared to CFA-PTX and CFA-nPTX controls, both EAE-PTX and EAE-nPTX groups developed motor dysfunction, behavioral hypersensitivity, and demyelination in ventral spinal cord but not cortex. Spinal demyelination was greater in EAE-nPTX than in EAE-PTX. ATF3 was detected in lumbar DRG of all EAE and CFA control groups, suggesting that systemic inflammation, rather than MOG_35-55-driven neuropathology, contributes to neuron damage.</div></div><div><h3>Conclusions</h3><div>PTX is not required for the manifestation of motor dysfunction and neuropathic pain in MOG_35-55-based EAE models. Newer EAE-nPTX models have the distinct advantage of mimicking MS disease while avoiding confounding effects of pertussis toxin.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1875 ","pages":"Article 150162"},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mouse model of a patient derived P544L mutation in the Slc6a8 gene shows hypoactivity and cognitive deficits","authors":"Marla K. Perna ,&nbsp;Lara N. Gechijian ,&nbsp;Heather S. Blanchette ,&nbsp;Rosalyn Liou ,&nbsp;Michael T. Williams ,&nbsp;Charles V. Vorhees ,&nbsp;Matthew R. Skelton","doi":"10.1016/j.brainres.2026.150151","DOIUrl":"10.1016/j.brainres.2026.150151","url":null,"abstract":"<div><div>Creatine (CR) is essential for normal brain function. A lack of brain CR results in intellectual disability, epilepsy, and language delay in humans. The most common cause of CR deficiency in humans results from mutations in the CR transporter (SLC6A8). Several large deletion models of Slc6a8 have been characterized and are excellent models for global creatine loss. However, other SLC6A8 variants are reported in humans with creatine transporter deficiency (CTD), including missense mutations, deletions, and point mutations resulting in phenotypes ranging from mild to severe in humans. The purpose of these experiments was to determine if mice carrying a point mutation of the <em>Slc6a8</em> gene showed cognitive deficits, further validating a new model of CTD. These <em>Slc6a8</em> knock-in (<em>Slc6a8^P544L)</em> mice carry the P544L proline to leucine substitution seen in some humans with CTD. The <em>Slc6a8^P544L</em> mice have lower overall body weight and lower brain creatine content. Behavioral assessment revealed deficits in spatial memory but not associative or object recognition memory in <em>Slc6a8^P544L</em> mice. These findings are in line with clinical findings and other CTD models. In addition, we show that <em>Slc6a8^P544L</em> mice are hypoactive in a home-cage environment. These experiments support the use of <em>Slc6a8^P544L</em> mice as a valid representative of behavioral changes in human patients and to develop targeted therapies to rescue specific behavioral deficits in CTD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150151"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated FKBP5 expression associates with epilepsy-related molecular changes and promotes neuronal hyperexcitability","authors":"Meng Cai ,&nbsp;Shuyang Wang ,&nbsp;Mingsu Liu ,&nbsp;Bin Lai ,&nbsp;Chen Chen ,&nbsp;Jing Ding ,&nbsp;Xin Wang","doi":"10.1016/j.brainres.2026.150157","DOIUrl":"10.1016/j.brainres.2026.150157","url":null,"abstract":"<div><h3>Objective</h3><div>Epilepsy is one of the neurological disorders, characterized by recurrent, spontaneous seizures arising from neuronal hyperexcitability and hypersynchrony in the brain. The mechanisms of epilepsy are intricate and remain elusive. FKBP5 has emerged as a significant protein implicated in neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This study aims to investigate the role of FKBP5 in a kainic acid (KA)-induced intrahippocampal epilepsy model and assessed how FKBP5 gain-of-function and FKBP51 inhibition influence neurotransmitter dynamics and neuronal excitability.</div></div><div><h3>Methods</h3><div>We examined the expression of FKBP5 in the hippocampus of the kainic acid (KA)-induced epilepsy model. To explore the impact of FKBP5 on neuronal activity, we overexpressed FKBP5 in primary cortical neurons and astrocytes, assessing extracellular glutamate levels in neuron–astrocytes co-cultures with or without the FKBP51-selective inhibitor SAFit2 (250 nM). Intrinsic excitability, voltage-gated Na⁺ currents, and network activity were evaluated using whole-cell patch-clamp recordings and high-density microelectrode arrays (HD-MEAs).</div></div><div><h3>Results</h3><div>We observed an elevated level of FKBP5 in the hippocampus of a kainic acid (KA)-induced chronic epilepsy mouse model, whereas cortical FKBP5 did not show clear changes across the examined post-insult time points.. Moreover, FKBP5 overexpression induced a remarkable increase in the extracellular glutamate level in co-cultured primary cortical neurons and astrocytes. Intriguingly, FKBP5 overexpression modifies the electrophysiological properties of primary neurons, resulting in increased intrinsic excitability and enhanced Na⁺ currents. Additionally, the network activity exhibits hyperexcitability with FKBP5 overexpression. Notably, SAFit2 treatment was also associated with elevated extracellular glutamate in the co-culture system, while intracellular FKBP5 and EAAT2 protein levels showed no significant group differences in the current dataset.</div></div><div><h3>Conclusion</h3><div>These findings suggested that FKBP5 played a significant role in regulating neuronal excitability and extracellular glutamate homeostasis. However, due to discrete sampling and the lack of continuous seizure monitoring, the present <em>in vivo</em> data do not establish a definitive causal contribution of FKBP5 to epileptogenesis, warranting future studies integrating longitudinal EEG and cell-type-specific manipulations.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150157"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysergic acid diethylamide modulates hippocampal and cortical local field potential oscillatory rhythms in male mice","authors":"B.S. Rabinovitch ,&nbsp;N. Silverman ,&nbsp;D. Ji ,&nbsp;D. Shizgal ,&nbsp;E.C. Lewis ,&nbsp;P.L. Carlen","doi":"10.1016/j.brainres.2025.150142","DOIUrl":"10.1016/j.brainres.2025.150142","url":null,"abstract":"<div><h3>Background and rationale</h3><div>Lysergic acid diethylamide (LSD) is a promising therapeutic for psychiatric disorders, but its physiological profile on the nervous system remains elusive. Rodent electrophysiological data has utilized <em>in vivo</em> single-unit electrophysiology recordings, while clinical neurophysiology studies have focused on spectral signatures using electroencephalography (EEG) and magnetoencephalography (MEG). No study to date has examined these spectral signatures in freely-behaving mice. Studying neural activity when an animal is physically restricted (i.e. head-fixed recordings) is stressful to animals, which informed our decision to avoid this confound of additional physical stress on observed effects. Moreover, how LSD acutely modulates intracranial oscillatory rhythms is not known.</div></div><div><h3>Experimental approach</h3><div>Here we present the first <em>in vivo</em> electrophysiological investigation of LSD’s cortico-hippocampal effects in freely-behaving male C57BL/6J mice using intracranial EEG (iEEG) recordings. We did not posit a hypothesis concerning the specific effects of LSD on power spectral density (PSD) due to the lack of preclinical literature as well as LSD’s promiscuous pharmacological profile. This study was purely exploratory.</div></div><div><h3>Key results</h3><div>Following intraperitoneal (IP) administration of 30 µg/kg LSD, there was a global decrease in PSD signal power in both broadband and discrete narrow band oscillatory rhythms of the ventral hippocampus CA1 and CA3 regions. Similar but less robust effects were observed in the somatosensory and medial prefrontal cortices. These data confer with the existing clinical neurophysiology data. Lastly, LSD increased between-subject PSD signal power variance, suggesting individual-specific effects.</div></div><div><h3>Conclusion and implications</h3><div>Our data lends further credibility to the entropic brain theory of psychedelic drug actions. We conclude that the preclinical intracranial acute spectral signatures of LSD coincide with their clinical counterparts. Further work is needed to study cross-regional connectivity, such as frequency coupling.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150142"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma protein signatures associated with functional outcome heterogeneity in rtPA-treated acute ischemic stroke","authors":"Lanjing Wang ,&nbsp;Tong Shen ,&nbsp;Shuangfeng Huang ,&nbsp;Yue Hu ,&nbsp;Yumin Luo ,&nbsp;Sijie Li","doi":"10.1016/j.brainres.2025.150121","DOIUrl":"10.1016/j.brainres.2025.150121","url":null,"abstract":"<div><h3>Objectives</h3><div>The mechanisms underlying heterogeneous neurological functional outcomes following recombinant tissue plasminogen activator (rtPA) therapy in acute ischemic stroke (AIS) remain elusive. This exploratory study aimed to explore proteomic signatures associated with rtPA response using data-independent acquisition (DIA) mass spectrometry.</div></div><div><h3>Methods</h3><div>We performed plasma proteomic profiling on 10 AIS patients (6 with favorable outcomes [90-day mRS ≤ 2], 4 with unfavorable outcomes [90-day mRS &gt; 2]) and 6 healthy controls. Differential protein expression analysis, functional enrichment (GO, KEGG), and weighted gene co-expression network analysis (WGCNA) were applied to identify outcome-related proteins and pathways.</div></div><div><h3>Results</h3><div>AIS induced significant perturbations in energy metabolism, inflammatory responses, and oxidative stress responses, with more pronounced proteomic dysregulation observed in unfavorable-outcome patients. The differentially expressed proteins (DEPs) associated with rtPA therapy (such as CP, CA1, CA2, ABCC2, COL1A2) were functionally linked to oxidative stress, metabolic transport, and transforming growth factor (TGF)-β receptor signaling. Pathway analysis revealed enrichment in porphyrin metabolism, nitrogen metabolism, and ABC transporter pathways. Additionally, DEPs between patients with distinct outcomes demonstrated significant enrichment in NF-κB signaling pathway and ABC transporters.</div></div><div><h3>Conclusions</h3><div>This exploratory study suggests that rtPA may influence acid-base balance, redox homeostasis, and TGF-β signaling. The association of NF-κB signaling and ABC transporters with outcome heterogeneity highlights their potential for further investigation as therapeutic targets. These findings provide preliminary mechanistic insights that warrant validation in larger cohorts.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150121"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aperiodic slope reflects glutamatergic tone in the human brain","authors":"Aislin A. Sheldon ,&nbsp;Hannah R. Moser ,&nbsp;Kamar S. Abdullahi ,&nbsp;Karly D. Allison ,&nbsp;Carter B. Mulder ,&nbsp;Samantha A. Montoya ,&nbsp;Scott R. Sponheim ,&nbsp;Małgorzata Marjańska ,&nbsp;Michael-Paul Schallmo","doi":"10.1016/j.brainres.2026.150161","DOIUrl":"10.1016/j.brainres.2026.150161","url":null,"abstract":"<div><div>Excitatory and inhibitory neural processes are essential for every aspect of brain function, but current non-invasive neuroimaging methods to study these in the human brain are limited. Recent studies which separate oscillatory and aperiodic components of electrophysiological power spectra have highlighted a relationship between aperiodic activity and functional brain states. Studies in both animal models and humans suggest that the aperiodic slope of electrophysiological power spectra reflects the local balance of excitatory:inhibitory (E:I) synaptic transmission. Aperiodic slope varies across individuals, brain states, and clinical populations, which may reflect important differences in E:I balance. However, there is currently a lack of evidence linking aperiodic slope to other measures of excitation and inhibition in the human brain. Here, we show that flatter (less steep) aperiodic slopes from human electroencephalography (EEG) are associated with higher concentrations of the excitatory neural metabolite glutamate measured with 7 T magnetic resonance spectroscopy (MRS) in the occipital lobe at rest. This suggests that individual differences in aperiodic neural activity reflect cortical glutamate concentrations, providing important insight for understanding changes in neural excitation across brain states and neuropsychiatric populations (e.g., schizophrenia) where glutamatergic function may differ. Our results support the use of aperiodic slope as a non-invasive marker for excitatory tone in the human brain.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150161"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient effects in corticospinal and reticulospinal tract excitability induced by motor skill and isometric resistance training","authors":"Rachel Hawthorn ,&nbsp;Natalie Phelps ,&nbsp;Carolyn Atkinson ,&nbsp;Rodolfo Keesey ,&nbsp;Zachary Seitz ,&nbsp;Haolin Nie ,&nbsp;Ismael Seáñez","doi":"10.1016/j.brainres.2025.150132","DOIUrl":"10.1016/j.brainres.2025.150132","url":null,"abstract":"<div><div>Coordinated movement relies on the proper integration of multiple neural circuits. Motor training can alter the excitability of neural circuits controlling movement, but the pathway-specific effects to the lower limb of motor skill versus isometric resistance training remain unclear. Here, we tested how single 30-minute sessions of cue-paced motor skill and isometric resistance training modulate corticospinal, reticulospinal, and spinal excitability in unimpaired adults (N = 23). Using motor-evoked potentials via transcranial magnetic stimulation, we found motor skill training increased corticospinal excitability, while isometric resistance training did not. In contrast, by assessing reticulospinal tract excitability by StartReact responses and measuring spinal excitability with H/M ratios, F-wave response amplitude, and persistence, we found that each tract’s excitability remained largely unchanged. These results suggest that short-term motor skill training selectively enhances corticospinal tract excitability without a measurable impact on spinal or reticulospinal circuits. These results highlight the influence of task complexity on distal lower limb excitability and provide a framework for evaluating neural adaptations across corticospinal, reticulospinal, and spinal circuits.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1874 ","pages":"Article 150132"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}