{"title":"Decoding the brain's excitatory–inhibitory metabolite balance in relation to sensory responsivity and autistic traits","authors":"Chenyi Chen , Shang-Yueh Tsai , Valentino Marcel Tahamata , Yi-Hsin Chuang , Yawei Cheng , Yang-Teng Fan","doi":"10.1016/j.neuroimage.2025.121470","DOIUrl":"10.1016/j.neuroimage.2025.121470","url":null,"abstract":"<div><div>Brain excitatory–inhibitory (E–I) balance plays a fundamental role in sensory and social processing. Alterations in E–I neurotransmitter systems—commonly indexed by the glutamate and glutamine (Glx)/GABA ratio—have been implicated in various neurodevelopmental conditions, including autism spectrum disorder (ASD). However, how individual differences in E–I balance relate to sensory responsivity and autism-spectrum-related traits in neurotypical populations remains poorly understood. In this study, we evaluated E-I balance across sensory-related brain regions in 92 neurotypical participants to explore its association with sensory responsivity and autistic traits. Our findings revealed that individuals with higher levels of self-reported autistic traits also exhibited stronger associations with sensory responsivity and higher Glx/GABA ratios. In cross-correlation analyses, the Glx/GABA ratio was significantly associated with both autistic traits and sensory responsivity, whereas Glx alone showed fewer associations. Clustering analyses further grouped autistic traits with the Glx/GABA ratio, rather than with the individual metabolite concentrations, suggesting that the ratio may be more behaviorally relevant than either metabolite alone. Moreover, the prefrontal Glx/GABA ratio demonstrated stronger associations with both autistic traits and sensory responsivity compared to other brain regions, a finding further supported by hierarchical moderation and mediation analyses. Overall, these results suggest that individual variability in regional E–I balance may be meaningfully related to sensory and social-affective traits, even within non-clinical populations. These findings may offer insights into the broader neurobiological mechanisms underlying sensory-affective processing across the general population spectrum.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121470"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-15DOI: 10.1016/j.neuroimage.2025.121469
Yanlin Li , Geng Li , Yang Liu , Chengzhen Liu , Antao Chen
{"title":"Neural mechanisms of emotion-focused interventions: A meta-analytic review of fMRI studies","authors":"Yanlin Li , Geng Li , Yang Liu , Chengzhen Liu , Antao Chen","doi":"10.1016/j.neuroimage.2025.121469","DOIUrl":"10.1016/j.neuroimage.2025.121469","url":null,"abstract":"<div><div>Emotion-focused interventions are emerging as promising tools to improve emotional functioning across clinical and nonclinical populations, yet their underlying neural mechanisms remain unclear. We conducted a coordinate-based meta-analysis (CBMA) using Seed-based d Mapping (SDM) of 20 task-based fMRI studies (N = 620) to quantify bidirectional activation changes associated with emotion-focused interventions. Results showed small-to-moderate improvements in emotional task performance (Hedges’ g = 0.29) and self-reported affective outcomes (g = 0.54). Meta-analytic neuroimaging revealed increased activation in the right caudate and decreased activation in the right insula and left inferior frontal gyrus. Moderator analyses identified intervention type, emotional content, and delivery format as key modulators of these neural effects. Notably, reduced insula activity predicted better emotional outcomes, while right caudate activation increased with age. These findings are consistent with a dual-pathway model of neural plasticity—one marked by frontostriatal engagement (right caudate) and another by dampened salience and semantic-control responses (right insula, left inferior frontal gyrus). The results offer mechanistic insights into how emotion-focused training recalibrates regulatory networks and inform the development of targeted interventions.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121469"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-15DOI: 10.1016/j.neuroimage.2025.121464
Xianqing Zeng , Yan Huang , Keyu Wang , Jiujiu Wang , Ming Meng
{"title":"Divergent neural mechanisms of selective attention in dichotic listening and binocular rivalry perception: Evidence from functional brain network analysis","authors":"Xianqing Zeng , Yan Huang , Keyu Wang , Jiujiu Wang , Ming Meng","doi":"10.1016/j.neuroimage.2025.121464","DOIUrl":"10.1016/j.neuroimage.2025.121464","url":null,"abstract":"<div><div>Although selective attention similarly modulates bistable perception in auditory and visual domains, its neural mechanisms remain unclear. Using fMRI within a naturalistic paradigm—dichotic listening (DL) with narrative stimuli and binocular rivalry (BR) with movie clips—we combined multiscale ICA-based brain network analysis (inter-/intra-subject correlation and dynamic FC) to investigate attentional mechanisms in DL and BR. In DL, when participants attended to the same narrative, the inter-SC of both right executive control network (RECN) and sensorimotor network (SMN) increased compared to when they attended to different narratives, indicating that the RECN and SMN were involved in the attentional mechanism of DL. Regardless of attentional content consistency, the auditory network (AudN) showed significant synchrony in both inter-SC and intra-SC analyses, suggesting stimulus-driven processing in DL. For BR, significant inter- and intra-SC were only observed in networks related to stimulus-driven processing, namely the higher visual network (HVN) and language network (LN), while no selective attention-related cognitive networks were identified. Furthermore, no dFC effects in the DL task were found. However, in the BR condition, the FC between the HVN and LN was significantly enhanced when attending to characters versus architecture, and the difference was robustly positively correlated with the difference in perceptual dominance duration of character-related movies between the two conditions. In summary, our results demonstrate that the modulation mechanisms of selective attention differ substantially between DL and BR. The former involves executive control, whereas the latter relies on neural circuits supporting perceptual processing.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121464"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-14DOI: 10.1016/j.neuroimage.2025.121455
Yin Jiang , Hutao Xie , Yutong Bai , Quan Zhang , Yu Diao , Houyou Fan , Xin Zhang , Hua Zhang , Jian Li , Anchao Yang , Fangang Meng , Jianguo Zhang
{"title":"Subthalamic nucleus stimulation at high and low frequencies engages different brain networks to enhance gait performance in Parkinson's disease","authors":"Yin Jiang , Hutao Xie , Yutong Bai , Quan Zhang , Yu Diao , Houyou Fan , Xin Zhang , Hua Zhang , Jian Li , Anchao Yang , Fangang Meng , Jianguo Zhang","doi":"10.1016/j.neuroimage.2025.121455","DOIUrl":"10.1016/j.neuroimage.2025.121455","url":null,"abstract":"<div><h3>Background</h3><div>Subthalamic nucleus (STN) deep brain stimulation (DBS) is used to treat Parkinson’s disease (PD), yet neither high-frequency stimulation (HFS) nor low frequency stimulation (LFS) fully resolves gait issues. Previous studies indicate that STN-DBS modulates motor-related brain networks. Given that PD patients with gait disturbances exhibit cognitive deficits—and considering the extensive projections between the STN and cerebral cortex—we hypothesized that varying STN stimulation frequencies may improve gait by modulating distinct brain networks.</div></div><div><h3>Methods</h3><div>We collected gait data, cortical electrophysiological signals, and resting-state fMRI from 44 PD patients and 32 healthy controls. Multi-network cortical activity and functional connectivity were c ompared under three conditions: DBS OFF, HFS, and LFS. Additionally, the connectivity values were correlated to the gait behaviors and clinical assessment scores.</div></div><div><h3>Results</h3><div>We found that: (1) HFS improved both motor and gait performance, while LFS enhanced gait but may not be optimal for long-term use; (2) STN-DBS induced widespread modulation across sensorimotor, frontoparietal, salience, dorsal attention, and default mode networks. HFS improved motor and gait functions via network modulation related to motor control, whereas LFS may enhance gait by boosting executive-related cortical activities and connections; (3) Relative to healthy controls, PD exhibited widespread reductions in functional connectivity, with DBS modulation trending toward normalization.</div></div><div><h3>Conclusions</h3><div>These results reveal distinct brain network responses to different STN-DBS frequencies in PD, offering a theoretical basis for optimizing DBS treatment for gait impairments. These findings provide critical insights for tailoring DBS parameters to maximize both motor and cognitive benefits in PD patients.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121455"},"PeriodicalIF":4.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An ALE meta-analysis of activation patterns in phantom limb pain: Novel insights into multisensory integration across movement tasks, facial stimulation, and pain-reducing interventions","authors":"Daniël S.L. Loewenstein , Sezai Özkan , Kris Vissers , Dylan Henssen","doi":"10.1016/j.neuroimage.2025.121463","DOIUrl":"10.1016/j.neuroimage.2025.121463","url":null,"abstract":"<div><h3>Background</h3><div>Phantom limb pain (PLP) is a debilitating neuropathic pain syndrome characterized by the perception of pain in an amputated or deafferented limb. Maladaptive cortical reorganization is proposed as its primary mechanism, yet a comprehensive analysis of functional alterations is lacking due to methodological variability across studies.</div></div><div><h3>Methods</h3><div>We employed an activation likelihood estimation (ALE) meta-analysis of fMRI and [<sup>15</sup>O]H<sub>2</sub>O-PET studies to compare brain activity in post-amputation PLP patients with that of healthy controls. A systematic search of PubMed, Embase, Scopus, Cochrane Library, and Web of Science identified relevant studies. Following exclusion of unsuitable studies, an ALE meta-analysis was conducted with sub-analyses for movement tasks, facial stimulation, and pain-reducing interventions.</div></div><div><h3>Results</h3><div>A total of 972 articles was identified, of which eleven met the inclusion criteria. ALE results of the sub-analysis for facial stimulation (four studies; 43 PLP patients) showed increased activation in medial pain network regions (e.g., anterior cingulate cortex and anterior insula). The movement analysis sub-analysis (seven studies, 66 PLP patients) revealed heightened activity in the same medial pain network regions, though also in multisensory integration areas, particularly the posterior parietal cortex (PPC). Intervention-related analyses (four studies, 46 PLP patients) demonstrated reduced activation in the PPC but not in the medial pain network regions.</div></div><div><h3>Conclusion</h3><div>The observed hyperactivity in multisensory integration regions supports the hypothesis that PLP arises from attempts to reconcile conflicting sensory inputs, leading to a dysregulated PPC that modulates pain intensity. Further research should elucidate the role of the PPC in PLP, guiding novel therapeutic interventions.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121463"},"PeriodicalIF":4.5,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-12DOI: 10.1016/j.neuroimage.2025.121462
Tongtong Zhu , Jianru Bi , Linzi Wang , Zimeng Xin , Luyao Jin , Yi Zhou , Kelong Lu , Xinyue Wang , Ning Hao , Yanmei Wang
{"title":"Your smiles inspired my smiles: the interpersonal neural coupling of positive emotion contagion during social interactions","authors":"Tongtong Zhu , Jianru Bi , Linzi Wang , Zimeng Xin , Luyao Jin , Yi Zhou , Kelong Lu , Xinyue Wang , Ning Hao , Yanmei Wang","doi":"10.1016/j.neuroimage.2025.121462","DOIUrl":"10.1016/j.neuroimage.2025.121462","url":null,"abstract":"<div><div>Emotional contagion refers a process that by which the emotions of a perceiver become more similar to those of others as a result of exposure to these emotions. The present study investigated the behavioral and interpersonal neural coupling mechanisms underlying positive emotional contagion. We recruited forty-six stranger dyads and created an emotional contagion task using the fNIRS-based hyper-scanning technique to track brain activities of interactive partners (the sender, the perceiver), examining brain regions such as the prefrontal cortex and temporo-parietal junction, which are parts of the cognitive control and mirroring brain networks. In each dyad, the senders were demanded to watch positive/neutral clips or imitate the actor’s non-emotional facial actions, the perceivers were demanded to observe the senders’ positive/neutral facial expressions or non-emotional facial movements passively. Results revealed that interactive partners exhibited more synchronous facial expressions, higher interpersonal brain synchronizations (IBS) associated with the mirror neuron system (IFG, SMG) and the cognitive control system (DLPFC) and reported more positive emotions in the positive condition than neural condition or facial movements condition, indicating positive emotional contagion has occurred. Furthermore, the perceiver’s self-rated valence scores positively mediated the relationship between facial expression synchrony and IBS of mirror neuron system between dyads (IFG_TRI <sub>sender</sub> - left_SMG <sub>perceiver</sub>). Our findings revealed that automatic mimicry of other’s positive emotional expressions (indicating by facial expression synchronization) might be one of the mechanisms responsible for the contagion of positive emotions among strangers. We discussed the evolutional benefits of positive emotional contagion adhering to an automatic mimicry process.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121462"},"PeriodicalIF":4.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-12DOI: 10.1016/j.neuroimage.2025.121457
Yiwei Li , Sijin Li , Yuyao Tang , Shuai Hao , Dandan Zhang
{"title":"Causal evidence for the role of prefrontal theta oscillations in emotion regulation using neurofeedback training","authors":"Yiwei Li , Sijin Li , Yuyao Tang , Shuai Hao , Dandan Zhang","doi":"10.1016/j.neuroimage.2025.121457","DOIUrl":"10.1016/j.neuroimage.2025.121457","url":null,"abstract":"<div><h3>Background</h3><div>Prefrontal theta oscillations play a critical role in cognitive control processes that facilitate emotion regulation. However, causal evidence linking their modulation to improved emotion regulation outcomes remains limited.</div></div><div><h3>Results</h3><div>Using a double-blind, randomized controlled design, this study demonstrates that EEG neurofeedback (NF) targeting prefrontal theta oscillations significantly enhances emotion regulation abilities. Participants in the experimental group exhibited specific upregulation of prefrontal theta power during NF training, leading to reduced negative emotional ratings and diminished late positive potential (LPP) amplitudes. Mediation analysis further revealed that NF-induced enhancements in prefrontal theta power partially mediated the relationship between training efficiency and emotion regulation benefits.</div></div><div><h3>Conclusion</h3><div>These findings underscore the theoretical significance of prefrontal theta oscillations as a core mechanism of cognitive control in emotional contexts. This study advances our understanding of the neural underpinnings of emotion regulation and highlights theta-NF as a promising, non-invasive intervention for enhancing emotional resilience.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121457"},"PeriodicalIF":4.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-12DOI: 10.1016/j.neuroimage.2025.121461
Xianyang Wang , Hongliang Lu , Lingwei Zeng , Kewei Sun , Shuyi Liang , Ru Li , Congchong Li , Chaoxian Wang , Xufeng Liu , Shengjun Wu
{"title":"The sensory-motor overlap in motor imitation: evidence from motor imagery","authors":"Xianyang Wang , Hongliang Lu , Lingwei Zeng , Kewei Sun , Shuyi Liang , Ru Li , Congchong Li , Chaoxian Wang , Xufeng Liu , Shengjun Wu","doi":"10.1016/j.neuroimage.2025.121461","DOIUrl":"10.1016/j.neuroimage.2025.121461","url":null,"abstract":"<div><div>Motor imitation is crucial for acquiring motor skills and social cognition, yet the theoretical understanding of its underlying mechanism remains partial. The direct matching hypothesis suggests that the overlap between observed and executed motions is crucial for effective motor imitation. This study aimed to investigate the behavioral benefits of motor imitation, and to validate its theoretical basis by examining its brain activation pattern during motor imagery. We recruited 56 college students and compared their motor proficiency and imagery quality after different learning strategies. Participants were randomly assigned to observation, observation with disturbance, imitation, or control groups. The observation with disturbance group was designed as a sensory-motor conflict condition to contrast with imitation where the sensory and motor representations aligned. The results showed that both motor imitation and observation enhanced motor proficiency with only imitation outperforming control group, and only imitation improved imagery quality. The functional near-infrared spectroscopy (fNIRS) analysis revealed a significant increase in the primary somatosensory cortex activation following imitation, and a contrasting change pattern following observation with disturbance. The fNIRS results highlighted the necessity of sensory-motor overlap for effective motor imitation. These findings confirmed that motor imitation was an optimal strategy for motor learning, with the primary somatosensory cortex as the key neural substrate, and validated the direct matching hypothesis.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121461"},"PeriodicalIF":4.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-11DOI: 10.1016/j.neuroimage.2025.121456
Zijian Gao , Ziqin Zhou , Ziqiang Yu , Qianxue Shan , Jack Lee , Jill Abrigo , Edward Hui , Tiffany So , Weitian Chen
{"title":"Orientation-independent magnetization transfer imaging of brain white matter","authors":"Zijian Gao , Ziqin Zhou , Ziqiang Yu , Qianxue Shan , Jack Lee , Jill Abrigo , Edward Hui , Tiffany So , Weitian Chen","doi":"10.1016/j.neuroimage.2025.121456","DOIUrl":"10.1016/j.neuroimage.2025.121456","url":null,"abstract":"<div><div>White matter in the brain has a highly anisotropic structure, leading to orientation-dependent MRI contrasts, such as those observed in quantitative magnetization transfer (MT). These orientation-dependent contrasts can complicate the quantification of tissue parameters, posing significant challenges for correction methods. A common physical mechanism underlying this orientation dependence is residual dipolar coupling (RDC), which plays a critical role in the anisotropy observed in MRI spin relaxation.</div><div>A novel technique, macromolecular proton fraction mapping based on spin-lock (MPF-SL), was recently proposed to achieve orientation-independent MT measurements by minimizing RDC effects during data acquisition. This study aimed to validate the orientation independence of MPF-SL in vivo in brain white matter. Experiments were conducted on 20 healthy volunteers, with data collected at two different head orientations. MRI exams were repeated one week apart. MPF-SL measurements showed negligible differences (<2%) between head orientations, while conventional quantitative MT imaging exhibited statistically significant variation (<em>p</em> < 0.05). Both methods demonstrated good repeatability, with intraclass correlation coefficients (ICC) > 0.75, bias < 0.05%, and limits of agreement < 0.5%.</div><div>These findings confirm that MPF-SL effectively addresses orientation-dependent limitations in MT measurements of white matter, offering a reliable approach for future clinical and research applications.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121456"},"PeriodicalIF":4.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroImagePub Date : 2025-09-11DOI: 10.1016/j.neuroimage.2025.121451
Venkatagiri Krishnamurthy , Lisa C. Krishnamurthy
{"title":"CBF gradient and excitatory-inhibitory balance measured from pre-SMA – importance in aging and semantic fluency task difficulties","authors":"Venkatagiri Krishnamurthy , Lisa C. Krishnamurthy","doi":"10.1016/j.neuroimage.2025.121451","DOIUrl":"10.1016/j.neuroimage.2025.121451","url":null,"abstract":"<div><div>In this report, we aim to systematically investigate the neural changes related to healthy aging in the presupplementary motor area (pre-SMA) and how these changes are associated with the semantic fluency task difficulty. We quantified a spatial cerebral blood flow (CBF) gradient based on previously identified task-specific subregions of the pre-SMA using pseudo-Continuous Arterial Spin Labeling, and we assessed the excitatory-inhibitory balance (EIB) using the ratio of gamma-aminobutyric acid (GABA+) to glutamate and glutamine complex (Glx) using magnetic resonance spectroscopy. We identified an ascending gradient in CBF from anterior to posterior among younger participants, which was absent in older participants. We interpret this loss of the CBF gradient in the context of neural dedifferentiation. There was a notable difference in tissue-corrected EIB between younger and older participants. Older participants exhibited a stronger inhibitory tone in the pre-SMA, driven by reduced tissue-corrected Glx in the older cohort. We interpret the increased EIB as a potential marker of under- or over-compensated synaptic scaling. Additionally, we found no relationship between neural dedifferentiation, as indicated by the CBF gradient, and synaptic scaling (EIB), suggesting that these are two distinct processes related to age-related neural changes. The tissue-corrected EIB exhibited a positive relationship with the difficulty of the semantic fluency task. However, we found no correlation between behavior and the CBF gradient. Our findings indicate that the inhibitory tone and synaptic scaling in the pre-SMA, rather than the CBF gradient and neural dedifferentiation, are crucial for managing the challenges posed by the semantic fluency task.</div></div>","PeriodicalId":19299,"journal":{"name":"NeuroImage","volume":"320 ","pages":"Article 121451"},"PeriodicalIF":4.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}