Eur J Neurosci
· 2026 Jan · PMID 41578670
·
Full text
The continuity illusion occurs when a sound is perceived as continuous through noise-filled interruptions and has been indexed neurophysiologically as reduced auditory theta band (4-8 Hz) power and phase-locking at the i...The continuity illusion occurs when a sound is perceived as continuous through noise-filled interruptions and has been indexed neurophysiologically as reduced auditory theta band (4-8 Hz) power and phase-locking at the interruption boundaries. Here, we examined the behavioural and neurophysiological differences between musicians (n = 16) and nonmusicians (n = 16) as they listened to trisyllabic words and classical music with noise interruptions. Our aim was to assess two competing hypotheses: (H) because of their enhanced ability to detect acoustic gaps, musicians are less likely to perceive continuity and will therefore exhibit increased theta power/phase-locking at interruption boundaries compared to nonmusicians. Alternatively, (H) musicians are more likely to perceive continuity through an enhanced ability to utilize contextual cues to fill in missing information. This top-down influence should be demonstrated by reduced theta power/phase-locking in musicians. On each trial, participants reported whether a noise-interrupted music or speech stimulus sounded continuous or interrupted. Behaviorally, musicians and nonmusicians had similar rates of perceived continuity for music and speech, except musicians exhibited significantly greater continuity to speech at the shortest noise interruption. The oscillatory results demonstrated that relative to nonmusicians, musicians had weaker theta phase-locking to the interruption boundaries in both music and speech, supporting H. Musicians also exhibited enhanced alpha (8-13 Hz) and beta (14-30 Hz) power for both music and speech relative to nonmusicians, possibly reflecting inhibitory processes. We conclude that musicians exhibit enhanced auditory-motor inhibition to noise interruptions in both music and speech and infer this is due to their enhanced ability to utilize contextual cues.
Revuelta GJ, Lench D, Silva-Batista C
… +2 more, Dale ML, Mancini M
Eur J Neurosci
· 2026 Jan · PMID 41574817
·
Full text
Freezing of gait (FOG) is a disabling feature of Parkinson's Disease (PD) with unclear underlying pathophysiology. Evidence from multimodal neuroimaging studies suggests that complex interactions between cortical and sub...Freezing of gait (FOG) is a disabling feature of Parkinson's Disease (PD) with unclear underlying pathophysiology. Evidence from multimodal neuroimaging studies suggests that complex interactions between cortical and subcortical areas may occur in FOG. While noninvasive neuromodulation techniques, such as transcranial magnetic stimulation (TMS), can effectively modulate large-scale networks involved in FOG, the development of noninvasive neuromodulation interventions is limited by an incomplete understanding of the interactions between underlying network disruptions and FOG behavior. Recent studies have brought into question whether observed network changes in FOG are truly causal or secondary, and if secondary, are they adaptive, maladaptive, or not related? Although these questions go beyond correlative analyses, neuromodulation approaches provide an opportunity to systematically alter networks involved in FOG, providing evidence of a causal relationship. Here, we present evidence from noninvasive neuromodulation interventions of multiple cortical targets and their effects on behavior. In an attempt to leverage prior work to shed light onto the pathophysiology of FOG, we provide specific definitions of key aspects of gait behavior. We also aim to provide a framework under which adaptive and maladaptive network changes can be interpreted and targeted for the development of neuromodulation interventions. We encourage the design of future neuromodulation studies to consider including multimodal outcomes that will expand our understanding of the relationship between FOG behavior and treatment related network changes.
Mercier CL, Watanabe T, Okuno Y
… +11 more, Matsuyama K, Kushibe K, Denny H, Miyazaki T, Yamasaki M, Kawamura M, Abe M, Sakimura K, Watanabe M, Uesaka N, Kano M
Eur J Neurosci
· 2026 Jan · PMID 41574767
·
Full text
Synapse elimination during development is crucial for refining neural circuits by removing excess synapses formed around birth. In the neonatal cerebellum, Purkinje cells (PCs) are initially innervated by multiple climbi...Synapse elimination during development is crucial for refining neural circuits by removing excess synapses formed around birth. In the neonatal cerebellum, Purkinje cells (PCs) are initially innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During subsequent postnatal development, a single CF is strengthened and retained, while the other CFs are eliminated. Here, our PC-specific RNAi knockdown (KD) screening revealed that fibronectin type III domain containing 3B (FNDC3B), an endoplasmic reticulum protein, was involved in CF synapse elimination from around postnatal day 9 (P9) in mice. We showed that FNDC3B mRNA was expressed in PCs during CF synapse elimination. In PC-selective FNDC3B conditional knockout (FNDC3B-cKO) mice, CF synapse elimination from P10 was impaired, and the extension of CFs along PC dendrites was reduced at P21. However, these phenotypes were recovered by P40. In contrast, parallel fiber-mediated excitatory synaptic inputs and inhibitory synaptic inputs to PCs were not affected in FNDC3B-cKO mice. These results suggest that FNDC3B facilitates CF synapse elimination during postnatal development, highlighting a new role of FNDC3B in the developing brain.
Feld GB, Niethard N, Liu J
… +7 more, Gebhardt S, Kleist L, Brugger K, Fritsche A, Born J, Ngo HV, Hallschmid M
Eur J Neurosci
· 2026 Jan · PMID 41574685
·
Full text
Sleep supports memory formation by neurophysiological mechanisms that are yet to be fully uncovered. We investigated the contribution of the direct coupling of neurons via electrical synapses (gap junctions). The adminis...Sleep supports memory formation by neurophysiological mechanisms that are yet to be fully uncovered. We investigated the contribution of the direct coupling of neurons via electrical synapses (gap junctions). The administration of mefloquine (250 mg p.o. vs. placebo), an antimalarial, which blocks electrical synapses, to healthy young men before nocturnal sleep impaired the retention of word pairs learned before drug administration and disrupted the coupling of sleep spindles to EEG slow oscillations. In control experiments, in which participants received mefloquine before a consolidation interval of nocturnal wakefulness or after rather than before sleep, word-pair memory retention was not affected by the drug, suggesting that electrical synapses specifically support the sleep-dependent retention of verbal declarative memory. Irrespective of sleep, mefloquine enhanced the retention of sensorimotor memory assessed with a finger sequence tapping task. In supplemental experiments in rats, mefloquine administered i.p. at escalating doses of 20 and 40 mg/kg did not alter hippocampal sharp-wave/ripple activity, a prominent mechanism of hippocampal memory replay. While mefloquine effects beyond gap junctions in the present experiments cannot be fully excluded, we conclude that electrical coupling enhances the oscillatory coordination between sleep spindles and slow oscillations and, thereby, supports systems memory consolidation.
Monaghan AS, Monaghan PG, Takla TN
… +1 more, Fritz NE
Eur J Neurosci
· 2026 Jan · PMID 41565584
·
Full text
Gait impairment and falls are common in multiple sclerosis (MS), yet the neural substrates contributing to mobility decline remain poorly understood. While prior studies have linked regional gray matter atrophy to motor...Gait impairment and falls are common in multiple sclerosis (MS), yet the neural substrates contributing to mobility decline remain poorly understood. While prior studies have linked regional gray matter atrophy to motor outcomes, the role of diffuse cortical changes in complex gait tasks, such as backward walking, is less clear. This study examined whether diffuse cortical thinning is associated with forward and backward walking speed, and whether these relationships differ between fallers and nonfallers in MS. Forty-three individuals with MS (55 ± 10 years; 65% female) completed forward and backward Timed 25-Foot Walk assessments and high-resolution structural MRI. Cortical thickness and gray matter volume were estimated. Region-specific associations with gait speed were examined using regression with false discovery rate (FDR) correction. Principal component analysis revealed a global cortical thinning component that was associated with slower forward (β = -0.065, adjusted R = 0.14) and backward (β = -0.061, adjusted R = 0.19) walking speeds. In contrast, volumetric components did not significantly predict gait. Fallers and nonfallers did not differ in gait speed or cortical thinning, but exploratory moderation suggested stronger cortical thinning-gait associations in fallers, although effects did not remain significant after FDR correction. These preliminary findings suggest that diffuse cortical thinning is a consistent neural correlate of gait slowing in MS, with exploratory evidence suggesting that this relationship may be stronger among individuals with recent falls.
Eur J Neurosci
· 2026 Jan · PMID 41562398
·
Full text
Reduced vigilance can be captured as attentional lapses in sustained attention tasks, but just how these lapses relate to task-induced fatigue and motivation to maintain optimal performance across the age span is unclear...Reduced vigilance can be captured as attentional lapses in sustained attention tasks, but just how these lapses relate to task-induced fatigue and motivation to maintain optimal performance across the age span is unclear. We induced fatigue in 18 young (mean age = 22.6 years) and 16 older participants (mean age = 66.5) using the Sustained Attention to Response Task while simultaneously recording electroencephalography (EEG). In the final block, we manipulated motivation levels in half of the participants by offering a financial incentive for best overall performance. We found that the young and older adults differed markedly in their response strategies from the outset (adopting distinct speed-accuracy trade-off strategies) with faster/more erroneous responses in the young adults and slower/more accurate responses in the older participants that remained stable over the experiment, while subjective fatigue increased irrespective of group. Poststimulus EEG activity showed two distinguishable beta signatures: a fronto-central topography as a marker of the age-specific response strategy and a fronto-parietal signal modulated by motivation per se. We speculate that these two signatures contribute to offsetting performance declines over time. Finally, although subjective fatigue or mind-wandering scores and prestimulus alpha power increased with time-on-task, we did not identify a correlation between these measures. Hence, strategy and motivation more than fatigue were associated with performance differences across age in a sustained attention task, reflected in decoupled beta signatures.
Eur J Neurosci
· 2026 Jan · PMID 41562369
·
Full text
We live in an auditory world; we perceive and memorize sounds even before birth. Here, I have reviewed findings on the effects of implicit and explicit learning on auditory neurocognition. These findings, investigated in...We live in an auditory world; we perceive and memorize sounds even before birth. Here, I have reviewed findings on the effects of implicit and explicit learning on auditory neurocognition. These findings, investigated in the mismatch negativity (MMN) paradigm, indicate that both implicit and explicit auditory expertise can modulate the neural encoding of sounds at the preattentive level of human cognition. This modulation is reflected in the MMN parameters latency and amplitude and its generators. Thus, studies on MMN can illustrate various forms of human auditory learning during development and learning across the entire lifespan.
Albers C, Mirelman A, Avanzino L
… +11 more, Bloem BR, Botta A, van der Cruijsen J, de Lange E, Maidan I, Nieuwboer A, Pelosin E, Tosserams A, Weerdesteyn V, Gilat M, Nonnekes J
Eur J Neurosci
· 2026 Jan · PMID 41562323
·
Full text
Gait impairments impact independence and quality of life of persons with Parkinson's disease (PD). The application of external and internal cueing strategies can improve gait, but not every person benefits equally from t...Gait impairments impact independence and quality of life of persons with Parkinson's disease (PD). The application of external and internal cueing strategies can improve gait, but not every person benefits equally from the same strategy. It remains unclear (i) which patient characteristics mediate cueing efficacy, (ii) how cueing efficacy changes over time, (iii) which patient characteristics are associated with long-term compliance, and (iv) what the neural correlates of cueing are. The UNITE-PD study is a collaboration between the Radboud University Medical Center (NLD), KU Leuven (BEL), Tel Aviv Sourasky Medical Center (ISR), and IRCCS Policlinico San Martino (ITA). The study consists of a joint prospective cohort project and four site-specific projects. We here describe the joint project, with the site-specific projects included as supplementary materials. All participants undergo a baseline assessment, consisting of extensive clinical testing and an objective gait assessment with and without external and internal cueing. Responders and non-responders to the strategy will be followed for 6 months. Responders will be instructed to apply the effective cueing strategies, as much as possible in daily life using a mobile cueing application which tracks compliance. At 6 months post-baseline, responders and non-responders return to the lab, during which the baseline protocol will be repeated to quantify the change in efficacy of the cueing strategies over time. The UNITE-PD study will identify the relationship between patient characteristics, cueing efficacy, compliance, and the underlying mechanisms of cueing. This knowledge will help refine personalized rehabilitation and identify new avenues for neuroscientific inquiry in this domain.
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and a major genetic cause of autism spectrum disorders (ASDs). It results from the loss of fragile X mental retardation protein (FMRP)...Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and a major genetic cause of autism spectrum disorders (ASDs). It results from the loss of fragile X mental retardation protein (FMRP), an mRNA-binding protein critical for synaptic development and plasticity. Although sensory processing abnormalities are well recognized in FXS, the olfactory system remains relatively underexplored in both human and animal studies. Evidence from rodent and drosophila models reveals that FMRP loss profoundly alters olfactory circuitry and function. In Fmr1 knockout mice, aberrant mitral cell dendritic morphology and increased granule cell spine density disrupt excitation/inhibition (E/I) balance, leading to circuit hyperexcitability and impaired odor discrimination. Similarly, dfmr1-deficient flies show reduced GABAergic inhibition, broadened odor tuning, and altered odor-guided behaviors, reflecting conserved mechanisms of synaptic dysregulation. These findings parallel disruptions seen in other sensory systems, underscoring the olfactory bulb as a microcircuit model for studying FXS-related neural dysfunction. Human evidence remains limited, but studies in ASD suggest that structural alterations in the olfactory bulb and prefrontal cortex may contribute to sensory deficits in FXS. Integrating findings across species, this review highlights the olfactory system as a translational framework for linking molecular dysfunction to circuit-level and behavioral abnormalities. By focusing on this well-characterized sensory network, it emphasizes how early synaptic and structural disruptions in FXS give rise to E/I imbalance and sensory processing impairments, providing insights into broader neurodevelopmental mechanisms and potential therapeutic targets.
Eur J Neurosci
· 2026 Jan · PMID 41558461
·
Full text
Alongside models and methods, concepts are crucial tools to study and understand the brain. They help us pursue various goals, such as describing phenomena based on patterns in the data or explaining why these phenomena...Alongside models and methods, concepts are crucial tools to study and understand the brain. They help us pursue various goals, such as describing phenomena based on patterns in the data or explaining why these phenomena occur. Yet while terms such as "action potential" or "network" guide our efforts to reach these goals, other concepts have failed to advance our understanding of the brain. In this paper, we draw on recent work from philosophy of science to show that the success or failure of concepts in neuroscience depends on the epistemic goals the field aims to achieve. Looking at cases such as "default mode network," "cortical column," and "hierarchy," we formulate conditions under which introducing, refining, or replacing a concept succeeds or fails. These cases suggest that to better evaluate our concepts, we should make explicit which goals we aim to achieve when using them.
Neuropathic pain (NP), particularly postherpetic neuralgia (PHN), involves intricate mechanisms that extend far beyond neuronal dysfunction. In recent years, glial cell-mediated neuro-immune-inflammatory circuits mediate...Neuropathic pain (NP), particularly postherpetic neuralgia (PHN), involves intricate mechanisms that extend far beyond neuronal dysfunction. In recent years, glial cell-mediated neuro-immune-inflammatory circuits mediated by glial cells (including spinal microglia, astrocytes, and dorsal root ganglion satellite glia) have been regarded as one of the key pathological mechanisms for the occurrence and maintenance of NP. Glial cells exacerbate pain pathogenesis by driving neuroinflammation, amplifying nociceptive signaling, and modulating ion channels and pain-related signaling molecules. A systematic review of glial molecular and network alterations, correlated with the typical clinical phenotype of PHN, may provide practical clues for precise stratified therapy, drug repositioning, and novel targeted interventions (such as glial modulators, neuronutrition support, and neuro-immune pathway modulation). This review aims to summarize the latest progress in glial cells and neuropathic pain, with a focus on discussing its implications and suggestions for the treatment strategies of PHN.
Treatments for Parkinson's disease (PD) include medications like levodopa, surgical interventions such as deep brain stimulation (DBS), and rehabilitative approaches like exercise. While levodopa and DBS effects on the s...Treatments for Parkinson's disease (PD) include medications like levodopa, surgical interventions such as deep brain stimulation (DBS), and rehabilitative approaches like exercise. While levodopa and DBS effects on the subthalamic nucleus (STN) are well studied, how exercise modulates this circuitry is less clear. This study investigates the acute and long-term effects of a monthlong motorized cycling intervention on STN activity, using local field potential (LFP) recordings from 29 electrodes placed in 18 STNs across nine PD patients (8/1 M/F; age 66.4 ± 9.7 years, UPDRS 20.7 ± 2.56). While the acute changes were minimal, the long-term changes in LFP features were more pronounced in the dorsal STN compared with its ventral region. Repeated exercise sessions produced a progressive increase in total LFP power in the dorsal STN, driven by elevations in the aperiodic background; the ventral STN showed no significant change over the same interval. This aperiodic modulation parallels increases typically observed with levodopa or STN-DBS, suggesting engagement of overlapping-but not identical-neuromodulatory mechanisms. To probe intra-STN coupling, we quantified dorsal-ventral interactions using the imaginary part of coherency (iCOH) and the phase slope index (PSI). PSI values remained near zero (|PSI| < 0.05), indicating minimal directed coupling, whereas iCOH increased in the 24-29-Hz range. Given the absence of connection and nonzero iCOH, we posited a shared upstream driver acting on both subregions. Using a statistical SSTr framework mathematically able to confirm the presence of this upstream "hidden" source.
Eur J Neurosci
· 2026 Jan · PMID 41550043
·
Full text
A recent study by Hausdorf et al. reported that combining closed-loop acoustic stimulation with transcranial direct current stimulation during sleep does not improve memory consolidation. This contrasts with past studies...A recent study by Hausdorf et al. reported that combining closed-loop acoustic stimulation with transcranial direct current stimulation during sleep does not improve memory consolidation. This contrasts with past studies that reported a beneficial effect of each method individually. In this commentary, I discuss the relevance of the study in the current literature and offer potential explanations for this absence of effect.
The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. The aims of this study were to assess the anxiety-like responses and amygdala r...The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. The aims of this study were to assess the anxiety-like responses and amygdala redox state, in male and female offspring of dams submitted to caloric restriction (CR) or intermittent fasting (IF) diets during lactation. The litters (dam and 8 pups) received the diets: Control-received the lab chow ad libitum (n = 8 litters); CR-received 50% of the chow consumed by the control group (n = 8 litters); IF-received lab chow ad libitum for the first 24 h, followed by a 24-h period without access to food. Assessments of anxiety-like behaviour through the open field, elevated plus maze and light-dark box tests were performed in adolescence. Subsequently, the redox state of the amygdala of the animals was evaluated through FRAP, SOD and TBARS dosages. CR and IF diets during lactation promoted, in male and female offspring, persistent nutritional alterations related to undernutrition. The CR diet led to the development of anxiety-like behaviours in both males and females. Conversely, the IF diet induced a reduction in anxiety-like behaviours only in male offspring. The CR group also showed an increase in SOD enzyme activity in the amygdala, which may be related to the observed behavioural changes. The two models of dietary restriction led to undernutrition in the offspring (male and female), with differing effects on anxiety and redox status.
Anxiety is a future-oriented mood state that consists of a complex cognitive, affective, physiological and behavioural response system that prepares individuals for perceived or anticipated threats. Although the neural c...Anxiety is a future-oriented mood state that consists of a complex cognitive, affective, physiological and behavioural response system that prepares individuals for perceived or anticipated threats. Although the neural circuits underlying anxiety behaviours have been extensively studied, how inflammatory factors influence anxiety and the molecular links between them remains poorly understood. To gain novel insights into these mechanisms, we investigated the role of fam19a5a, a zebrafish ortholog of the human FAM19A5 gene, which encodes a secreted peptide, in anxiety-like responses. Gene expression analyses revealed widespread fam19a5a expression in anxiety-associated brain regions, including the septum, pallial amygdala and habenula. Using multiple behavioural assays and both loss-of-function and gain-of-function genetic models, we found that the loss of fam19a5a significantly reduced anxiety-like responses. Interestingly, neuronal overexpression of fam19a5a also reduced anxiety-like responses. Neuronal activity analysis showed altered activity in the septum, pallial amygdala and habenula in fam19a5a-knockout brain without changes in neurotransmitter levels. However, increased neuronal activity was observed in the preoptic area of neuronal fam19a5a-overexpressing zebrafish. Transcriptomic analyses revealed upregulation of anti-inflammatory chemokines and cytokines and downregulation of proinflammatory factors, in both fam19a5a-knockout and neuronal fam19a5a-overexpressing brains. All together, these findings suggest that fam19a5a regulates anxiety-like behaviours in zebrafish by modulating the anti-inflammatory chemokine/cytokine signalling pathways.
Despite age-related declines in the structure and function of auditory and language-related regions, many older adults retain a relatively preserved ability to understand speech in noisy environments. However, the neural...Despite age-related declines in the structure and function of auditory and language-related regions, many older adults retain a relatively preserved ability to understand speech in noisy environments. However, the neural mechanisms supporting this ability remain unclear. In this study, 30 older adults (59-71 years) with normal hearing listened to narratives spoken by a separate group of speakers at varying noise levels, with their neural activity recorded using functional near-infrared spectroscopy (fNIRS). Speaker-listener neural coupling analysis revealed that older listeners' neural activity across broad brain regions, including classical language regions and the prefrontal cortex, was coupled with the speaker's speech-production-related neural activity. Compared to younger listeners, older adults exhibited stronger prefrontal neural coupling, which was stably integrated with language-region coupling across noise levels. Crucially, as noise levels increased, prefrontal neural coupling became more strongly correlated with comprehension performance. These findings elucidate the neural mechanisms supporting natural speech-in-noise processing in the aging brain, highlighting the compensatory involvement of the prefrontal cortex in facilitating speech-in-noise comprehension in older adults and indicating it as a potential target for neuromodulatory and cognitive interventions to promote successful aging.
Prieto SG, Torres da Silva VRC, Almeida MC
… +1 more, Echeverry MB
Eur J Neurosci
· 2026 Jan · PMID 41527922
·
Full text
Extrapyramidal symptoms (EPS) are side effects observed after acute administration of D2 antagonists and nitric oxide synthase (NOS) inhibitors in rodents. To date, no study has examined NOS activity in parallel with c-F...Extrapyramidal symptoms (EPS) are side effects observed after acute administration of D2 antagonists and nitric oxide synthase (NOS) inhibitors in rodents. To date, no study has examined NOS activity in parallel with c-Fos immunoreactivity (c-Fos-IR) following multiple doses of these compounds. The aim of the present study was to evaluate whether catalepsy and motor balance deficits resulting from specific acute doses of haloperidol (Hal), metoclopramide (MCP), and L-NOARG could correlate with changes in the number of c-Fos-IR and nNOS-positive cells, as well as NADPH-diaphorase activity in the striatum. Male Swiss mice received Hal (0.1-1 mg/kg, ip), MCP (1-45 mg/kg, ip), L-NOARG (15-45 mg/kg, ip), or saline. An increased cataleptic effect was observed in all experimental groups. All doses of Hal and the higher doses of MCP resulted in deficits in the Rota-rod test, whereas L-NOARG did not affect Rota-rod performance. Histochemical analysis revealed increased c-Fos-IR in the dorsal striatum following Hal, as well as in the dorsolateral striatum after low and intermediate clinically relevant doses of MCP. Both types of D2R antagonists led to an increase in NADPH-diaphorase activity in the dorsal striatum. Similarly, the higher catalepsy-inducing doses of L-NOARG resulted in increased NADPH-diaphorase activity in the dorsal striatum; however, these same doses also reduced c-Fos-IR in the dorsolateral striatum and nucleus accumbens (NAc). In conclusion, all drugs acutely induced catalepsy, with motor balance preserved after L-NOARG treatment. Our findings suggest that EPS side effects may be attributed to NADPH-diaphorase activity in the dorsal striatum.
Chondroitin sulphate proteoglycans (CSPGs) are major contributors to the inhibitory microenvironment that hinders regeneration following spinal cord injury (SCI). Chondroitinase ABC (ChABC) mediated degradation of CSPGs...Chondroitin sulphate proteoglycans (CSPGs) are major contributors to the inhibitory microenvironment that hinders regeneration following spinal cord injury (SCI). Chondroitinase ABC (ChABC) mediated degradation of CSPGs is associated with enhanced regenerative potential following SCI. In this study, the molecular responses of Neurocan, NG2 and Phosphacan CSPGs, as well as cellular markers for pro-inflammatory and neuroprotective microglia, astrocytes, oligodendrocytes and neurons, were investigated following a single subpial injection of ChABC (0.2 U in 10 μL) 14 days after thoracic (Th9) spinal cord compression in adult Wistar rats. qRT-PCR of samples from the lesion epicentre and adjacent cranial and caudal segments, 1 and 7 days after treatment, show that ChABC significantly suppressed Neurocan, NG2 and Phosphacan gene expression and reduced astrocytic (GFAP, S100B) and microglial/macrophage (Iba1, Cx3Cr1) reactivity after 24 h. Although most markers recovered within a week of ChABC delivery, sustained increases were observed for GAP-43, particularly in cranial and caudal segments, suggesting the potential regenerative benefits of ChABC. Correlation analyses revealed region-specific interactions between CSPG expression and glial phenotypes. Phosphacan displayed the strongest positive correlation with pro-inflammatory microglial/macrophage markers (IL-1β, iNOS) and the weakest with neuroprotective markers, suggesting a significant pro-inflammatory role. NG2 was associated with both pro- and anti-inflammatory markers, indicating a more balanced modulatory role, while Neurocan exhibited stronger correlations with neuroprotective markers. These findings highlight the importance of spatial and temporal context for SCI regenerative therapies targeting glial scar responses and support the therapeutic potential of subpial ChABC delivery for modifying the anti-regenerative inhibitory microenvironment following SCI.