Brain Research最新文献

{"title":"ZNF655-mediated neuroprotection in cerebral ischemia-reperfusion injury via Akt/Nrf2 pathway modulation","authors":"Wanyi Wei ,&nbsp;Zongkai Wu ,&nbsp;Yuehong Yue ,&nbsp;Yang Zhang ,&nbsp;Hebo Wang","doi":"10.1016/j.brainres.2025.150091","DOIUrl":"10.1016/j.brainres.2025.150091","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia–reperfusion injury (CIRI) involves complex pathological processes, including oxidative stress, inflammatory responses, and apoptosis. Zinc finger protein 655 (ZNF655) is implicated in the regulation of the Akt signaling pathway, which in turn activates nuclear factor erythroid 2–related factor 2 (Nrf2) via phosphorylation, enhancing its stability and transcriptional activity. This pathway plays a critical role in mediating antioxidant defenses, suppressing inflammation, and inhibiting apoptosis. This study aimed to explore the potential neuroprotective role of ZNF655 in CIRI through modulation of the Akt/Nrf2 signaling cascade.</div></div><div><h3>Methods</h3><div>An in vitro model of CIRI was established using SH-SY5Y cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). Cells were infected with adenoviral vector encoding ZNF655 to upregulate ZNF655 expression. The mRNA levels were measured by real-time quantitative PCR (RT-qPCR). Protein levels were determined by immunoblotting. Cell viability was assessed via cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Oxidative stress was monitored by dichlorofluorescein diacetate (DCFH-DA) probe. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay (ELISA).</div></div><div><h3>Results</h3><div>ZNF655 expression was significantly downregulated under OGD/R conditions compared with normoxic controls. Overexpression of ZNF655 markedly attenuated OGD/R-induced cell apoptosis, oxidative stress, and pro-inflammatory cytokine production. ZNF655 promoted Akt phosphorylation, facilitated Nrf2 nuclear translocation, and upregulated expression of downstream antioxidant genes.</div></div><div><h3>Conclusion</h3><div>Pharmacological inhibition of Akt or silencing of Nrf2 attenuated the neuroprotective effects of ZNF655. These findings indicate that ZNF655 exerts neuroprotective effects against OGD/R-induced injury by activating the Akt/Nrf2 signaling pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150091"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695848","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":"Examining functional connectivity in metabolic syndrome and small vessel disease: A novel approach to understanding olfactory dysfunction and Alzheimer’s disease","authors":"Hector Reyes ,&nbsp;Jaime Mondragon ,&nbsp;Conner Frank ,&nbsp;Claire Murphy","doi":"10.1016/j.brainres.2025.150084","DOIUrl":"10.1016/j.brainres.2025.150084","url":null,"abstract":"<div><h3>Introduction</h3><div>The prevalence of Alzheimer’s Disease (AD) is projected to triple by 2050, highlighting the need to identify early markers and underlying mechanisms associated with its progression. Olfactory dysfunction has emerged as an early indicator of AD, with its neural basis linked to changes in the medial temporal lobe and associated networks. Cardiovascular risk factors, including metabolic syndrome (MetS) and cerebral small vessel disease (SVD), have been implicated in neurodegenerative processes, yet their impact on olfactory network connectivity remains underexplored. This study aimed to investigate task-based functional connectivity in the olfactory network, medial temporal lobe, and default mode network among cognitively unimpaired individuals with MetS or SVD.</div></div><div><h3>Method</h3><div>Participants were grouped based on MetS and SVD status. Using fMRI, functional connectivity patterns during olfactory processing were analyzed for group differences.</div></div><div><h3>Results</h3><div>Functional connectivity revealed hypoconnectivity between the right angular gyrus and secondary olfactory cortex between MetS groups and altered connectivity between the hippocampus and frontoparietal control network between SVD groups. Both conditions demonstrated increased within-network cerebellar connectivity compared to controls.</div></div><div><h3>Discussion</h3><div>These findings highlight distinct neural alterations in olfactory and cognitive control networks associated with cardiovascular risk factors, providing novel insights into early brain changes linked to cardiovascular risk factors for dementia.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150084"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666425","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":"Serum phosphorylated IRS-1 at Ser307 as a potential biomarker of stress-induced depressive-like behavior in rats","authors":"Sayed Soran Ghafori ,&nbsp;Simin Mahakizadeh ,&nbsp;Maryam Farahmandfar ,&nbsp;Maryam Zahmatkesh ,&nbsp;Mohammad Nasehi ,&nbsp;Elham Bakhtiyari ,&nbsp;Mohammad Amini ,&nbsp;Gholamreza Hassanzadeh","doi":"10.1016/j.brainres.2025.150110","DOIUrl":"10.1016/j.brainres.2025.150110","url":null,"abstract":"<div><div>Accumulating evidence suggests that inflammation mediates stress-induced depression. Elevated pro-inflammatory cytokines may affect serum phosphorylated insulin receptor substrate-1 (phospho-IRS-1) levels. This study evaluated phospho-IRS-1 at Ser³⁰⁷ as a potential biomarker associated with stress-induced depressive-like behaviors. Male Wistar rats were assigned to four groups: (1) control (unstressed, ad libitum access); (2) sham (6 h/day food and water deprivation only); (3) RS14 (6 h/day restraint stress (RS) with concurrent food/water deprivation for 14 days, then stress-free until the end of the experiment); and (4) RS28 (6 h/day RS with food/water deprivation for 28 days). On day 15, serum corticosterone, IL-1β, TNF-α, and phospho-IRS-1 at Ser³⁰⁷ were measured, and depressive-like behaviors were assessed using FST and TST. Hippocampal histology was performed on days 15 and 30 using Nissl staining. On day 30, serum IL-1β, TNF-α, and phospho-IRS-1 at Ser³⁰⁷ were quantified, and behavioral assessments were conducted using FST and TST. On day 15, corticosterone, IL-1β, and TNF-α were significantly elevated in RS14 and RS28 vs. control/sham (P &lt; 0.05), while phospho-IRS-1 at Ser³⁰⁷ and FST/TST outcomes showed no differences. On both days 15 and 30, the percentage of pyknotic neurons in RS14 and RS28 was higher than in control/sham, and on day 30, RS28 showed a further significant increase compared with RS14. On day 30, RS14 exhibited elevated IL-1β and TNF-α vs. control/sham, but phospho-IRS-1 at Ser³⁰⁷ and depressive-like behaviors were not significantly changed. In contrast, RS28 showed further increases in IL-1β, TNF-α, and phospho-IRS-1 at Ser³⁰⁷, along with altered FST (swimming, climbing, immobility times) and TST (immobility latency/time) parameters compared with all other groups (P &lt; 0.05). These findings suggest that increased serum phospho-IRS-1 at Ser³⁰⁷ may serve as a biomarker for stress-induced depressive-like behaviors.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150110"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740315","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":"Strength of associations between regional brain volumes and dual decline in gait and memory","authors":"Sadhani Karunarathna ,&nbsp;Monique Breslin ,&nbsp;Jane Alty ,&nbsp;James Scott McDonald ,&nbsp;Richard Beare ,&nbsp;Velandai K. Srikanth ,&nbsp;Taya A. Collyer ,&nbsp;Michele L. Callisaya","doi":"10.1016/j.brainres.2025.150072","DOIUrl":"10.1016/j.brainres.2025.150072","url":null,"abstract":"<div><h3>Background</h3><div>Dual decline in gait and memory is associated with a higher risk of dementia. However, little is known about specific brain regions and their association with dual decline. Therefore, this study examined the strength of associations between baseline regional brain volumes and dual decline in gait speed and memory.</div></div><div><h3>Methods</h3><div>Participants aged over 60 years were randomly selected from the Southern Tasmanian electoral roll. Participants (n = 266) were classified into four groups depending on tertiles of annual decline in gait speed and delayed memory recall: non-decline, gait-only decline, cognitive-only decline, and dual decline. Multinomial logistic regression was used to examine the strength of associations between baseline regional brain volumes and the four groups.</div></div><div><h3>Results</h3><div>The mean age of participants was 70.9 ± SD 6.7 years. For the dual decline group, eight regions (in order of strength − orbitofrontal cortex, middle frontal gyrus, superior frontal gyrus, thalamus, anterior cingulate cortex, brainstem, inferior temporal gyrus and hippocampus) had relative risk ratios below 0.60 for a 1 SD increase in volume. For gait-only and cognitive-only decline, only the thalamus and cerebellum respectively, had relative risk ratios below 0.60.</div></div><div><h3>Conclusions</h3><div>In this study, we observed that smaller volumes in regions related to memory, executive function, motor, and sensory-motor integration had the strongest associations with dual decline.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150072"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647128","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":"Oxidative Stress-Induced mechanisms in neurodegeneration and Eryptosis: Implications for neurological and systemic disorders","authors":"Marijana Markovic Boras ,&nbsp;Vanja Krulj ,&nbsp;Alma Karahmet ,&nbsp;Kanita Omerbasic ,&nbsp;Asma Nawaz ,&nbsp;Doris Pavković ,&nbsp;Emina K. Sher","doi":"10.1016/j.brainres.2025.150111","DOIUrl":"10.1016/j.brainres.2025.150111","url":null,"abstract":"<div><div>The significant association between development of neurological diseases, like Alzheimer’s, Parkinson’s or depression and oxidative stress occurs from disturbance in the balance between oxidative and antioxidative processes due to chronic stress. Unlike previous reviews that focused only on neurological or systemic diseases, this review discusses the mechanisms that connect oxidative stress and neuroinflammation or eryptosis in both neurological, neurodegenerative, and various systemic diseases, clarifying two completely distinct mechanisms of response to oxidative stress that are common to multiple clinical conditions. This review explores the complex involvement of oxidative damage in neurodegeneration and explains its contribution to inflammation, protein aggregation, and disruption of cellular functions. Crucial components in this process are reactive oxygen and reactive nitrogen species, which can be generated both endogenously or exogenously. Primary sources of ROS in cells are NADPH oxidases, mitochondria, xanthine oxidase and growth factor receptors. Elevated ROS levels disrupt cellular homeostasis and cause oxidative damage and inflammatory responses in neurological disorders characterised by the activation of microglia, astrocytes, and infiltrating CD4 + T cells. Similarly, in systemic disease, this disruption happens through eryptosis. In addition, chronic stress damages antioxidant defence, which further worsens pathological processes. A deeper understanding of the underlying mechanisms provides novel insights into therapeutic strategies for reducing the effects of oxidative stress in both neurological and systemic diseases.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150111"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751741","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":"An organ-on-a-chip investigation into dose-dependent, temporal dynamic effects of radiosurgery on the blood–brain barrier and its immunological response","authors":"Adam D. Yock ,&nbsp;Jacquelyn A. Brown ,&nbsp;John Eley ,&nbsp;Cara Lwin ,&nbsp;Dandan Liu ,&nbsp;John P. Wikswo","doi":"10.1016/j.brainres.2025.150092","DOIUrl":"10.1016/j.brainres.2025.150092","url":null,"abstract":"<div><h3>Purpose</h3><div>This work used an organ-on-a-chip (OOC) model of the blood–brain barrier (BBB) to study effects of clinical radiation on barrier permeability and cytokine concentrations.</div></div><div><h3>Methods</h3><div>Gravity-perfused OOC devices developed in house for modeling the BBB were prepared with human endothelial cells, astrocytes, and pericytes. The devices were then irradiated to 0, 2, or 20 Gy with a 6 MV X-ray beam from a medical linear accelerator. At 0, 6, 24, and 48 h post irradiation, barrier permeability was assessed by measuring the diffusion across the barrier of Alexa Fluor-labeled dextran perfused into the vascular chamber. At these same time points, effluent was drawn from both the vascular and brain chambers and analyzed using a 10-cytokine panel.</div></div><div><h3>Results</h3><div>A statistically significant increase in barrier permeability was observed at 24 and 48 h and appeared similar between 2 and 20 Gy. For 20 Gy but not 2 Gy, a large initial increase was observed in the concentration of Granulocyte-Macrophage Colony-Stimulating Factor in the vascular chamber at 6 h, which subsequently decreased. An increase was also observed in the concentration of Interleukin-1α in the brain chamber starting at 24 h and continuing to 48 h. The concentration of Vascular Endothelial Growth Factor was observed to increase starting at 6 h and 24 h in the vascular chamber and brain chamber, respectively, and to subsequently decrease in both chambers.</div></div><div><h3>Conclusions</h3><div>Radiation effects on the BBB including barrier permeability and cytokine concentration can be observed in a dose- and time-dependent manner using an OOC.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150092"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693164","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":"Sex differences in interactions between the muscarinic-1 and orexin-1 receptors on cognitive flexibility in rats","authors":"Mutian Li ,&nbsp;Jim R. Fadel ,&nbsp;Joshua A. Burk","doi":"10.1016/j.brainres.2025.150081","DOIUrl":"10.1016/j.brainres.2025.150081","url":null,"abstract":"<div><div>Previous research has shown that cognitive flexibility, the ability to adjust to different rules, is affected by manipulations of orexin and acetylcholine (ACh). Because there are strong neural connections between orexin and ACh, these two neurotransmitter systems may interact to impact cognitive flexibility. In the present experiment, the effects of pharmacological manipulations of orexin-1 and muscarinic-1 receptors in rats were tested on cognitive flexibility. Rats received intraperitoneal injections of VU0453595, a positive allosteric modulator for the M1 subtype of ACh receptors, for seven days prior to a rule switch in a measure of cognitive flexibility. On the day of the rule switch, rats were given the orexin-1 receptor antagonist, SB-334867 or vehicle prior to task performance. As expected, SB-334867 increased the number of trials to criterion during the rule switch. Compared to vehicle, when VU0453595 was administered, orexin-1 receptor blockade increased regressive errors for males and perseverative errors for females. These findings support the hypothesis that there are interactions between the orexin and cholinergic systems affecting cognitive flexibility, but that these interactions affect cognitive flexibility differently for males and females.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150081"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629622","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":"MICU1 promotes Ca2+ homeostasis and curbs ferroptosis to attenuate brain tissue damage in rats with postoperative cognitive dysfunction","authors":"Na Zhou ,&nbsp;Yan Wang","doi":"10.1016/j.brainres.2025.150087","DOIUrl":"10.1016/j.brainres.2025.150087","url":null,"abstract":"<div><h3>Objective</h3><div>Postoperative cognitive dysfunction (POCD) is severe in patients after anesthesia and surgery. This study investigates the mechanism by which MICU1 regulates Ca²⁺ homeostasis and ferroptosis in POCD rats.</div></div><div><h3>Methods</h3><div>A POCD rat model was established, and hippocampal tissue was collected from the CA1 region to assess MICU1 expression. The lentivirus carrying Ad-MICU1 or the ferroptosis inducer Erastin was injected into the right lateral ventricle of POCD rats, followed by evaluation of motor function, learning ability, and memory capacity. Inflammatory cytokines were measured using ELISA. Nissl staining, NeuN staining, and HE staining were conducted to observe morphological changes in neurons, surviving neurons in the hippocampal CA1 subregion, and neuronal localization. ELISA was performed to assay the levels of ATP, Ca²⁺, Fe²⁺, MDA, SOD, LPO, and GSH in rat hippocampal tissue in the CA1 region. Flow cytometry was conducted to measure total ROS levels, mitochondrial ROS levels, and mitochondrial MPP. The Seahorse XFe 96 analyzer was employed to measure the mitochondrial oxygen consumption rate. Western blot was conducted to examine the levels of ferroptosis-related proteins.</div></div><div><h3>Results</h3><div>MICU1 was reduced in POCD rats. MICU1 overexpression partially improved motor function, learning ability, and memory capacity and alleviated central inflammation and hippocampal neuronal damage in POCD rats. MICU1 maintained Ca²⁺ homeostasis, reduced Ca²⁺, total ROS, and mitochondrial ROS levels, and inhibited ferroptosis. Erastin partially reversed the beneficial effects of MICU1 overexpression on POCD rats.</div></div><div><h3>Conclusion</h3><div>MICU1 promotes Ca²⁺ homeostasis, inhibits ferroptosis and ROS production, and alleviates brain tissue damage in POCD rats.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150087"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686937","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":"Hyperandrogenism associated deregulation of hippocampal adipokines may contribute to impaired memory function in mice","authors":"Ayushmita Dutta ,&nbsp;Rahul Kumar ,&nbsp;Guruswami Gurusubramanian ,&nbsp;Vikas Kumar Roy","doi":"10.1016/j.brainres.2025.150101","DOIUrl":"10.1016/j.brainres.2025.150101","url":null,"abstract":"<div><div>The elevation of androgen is called as hyperandrogenemia. Despite endocrinological imbalances, hyperandrogenism has also been linked to slight impairment in the cognitive functions along with depression and anxiety. Since the hippocampus regulates these function and also expresses adipokines such as leptin and adiponectin, and these adipokines have also shown deregulation in the hyperandrogenised conditions. Thus, this study aimed to explore the expression of leptin, leptin receptor, adiponectin, adipoR1 and adipoR2 along with androgen receptor and estrogen receptors in the hippocampus of letrozole-induced hyperandrogenised mice. Our results showed hyperandrogenism up-regulated the expression of leptin receptor and adipoR1, while down-regulated the expression of adipoR2. The immunostaining of leptin showed increased abundance and decreased abundance of adiponectin in the hippocampus. Furthermore, expression of androgen receptor was up-regulated and estrogen receptors expressions were down-regulated in the hippocampus of hyperandrogenised mice. The marker of apoptotic protein, active caspase3 was elevated and anti-apoptotic protein; BCL2 was suppressed in the letrozole-treated mice. Thus, it can be suggested that hyperandrogenism may be associated with deregulation of adipokines and steroid signaling along with neuronal degeneration in the hippocampus, and might also be linked to behavioral issues in the hyperandrogenised conditions with declined in spatial working memory when assessed in Y-Maze test. Since, our study was aimed to explore the expression of above proteins and linking with cognitive impairment in the hyperandrogenised conditions, yet, it is speculative and requires further investigation with auxiliary behavioral tests.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150101"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699554","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":"Yank-related changes in corticospinal recruitment gain in humans","authors":"Abdulkerim Darendeli ,&nbsp;Mathew Yarossi ,&nbsp;Spencer Lake Jakobs-Skolik ,&nbsp;Nathaniel Pinkes ,&nbsp;Vaishnavi Sharma ,&nbsp;Erica Kemmerling ,&nbsp;Eugene Tunik ,&nbsp;Oscar Soto","doi":"10.1016/j.brainres.2025.150090","DOIUrl":"10.1016/j.brainres.2025.150090","url":null,"abstract":"<div><div>The generation of muscle force is a key component of movement. Force is generated by increasing the number and firing rates of motor units (MU), but limited information is available on the corticospinal (CS) recruitment gain across the spectrum of magnitude and rate of force (yank). To assess the effects of force magnitude and yank on motor outputs, we recorded force (motor evoked twitches, METs) and EMG (motor evoked potentials, MEPs) in response to transcranial magnetic stimulation (TMS) during nearly isometric hand gripping tasks in 20 healthy subjects. Motor cortex TMS was applied during force ramps at different levels of voluntary force magnitude and yank. Yank robustly facilitated METs, maximally at lowest magnitudes of voluntary force, but this facilitation saturated at forces &gt; 50 % of the maximal voluntary contraction (MVC). At each level of force magnitude there was a linear relationship between the yank of voluntary force and MET amplitude. The slope of this relationship, representing the CS recruitment gain, decayed exponentially with increasing magnitude of force. Changes in CS recruitment gain associated with force magnitude and yank were better explained by METs than by MEPs. A positive yank resulted in larger estimated maximal MET at 0 % force compared to static contractions. These results suggest that METs capture a robust yank-related increase in CS recruitment gain, which is blunted by limited MU availability at high force magnitude. We showed that the estimation of maximal motor outputs is optimally achieved in tasks in which force production is achieved with high yank.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1872 ","pages":"Article 150090"},"PeriodicalIF":2.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686972","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}