The European Journal Of Neuroscience[JOURNAL]
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200 papers
Instability of Oculomotor Control in Parkinson's Disease Without Freezing of Gait: Evidence From Reflexive and Voluntary Saccade Variability.
Daeinejad FS, Foumani MS, Behzadipour S … +1 more , Alibiglou L
Eur J Neurosci · 2026 Mar · PMID 41866244 · Full text
Parkinson's disease (PD) is associated with alterations in both voluntary and reflexive eye movements; however, the characteristics of oculomotor variability across task contexts remain incompletely understood. This stud...
Parkinson's disease (PD) is associated with alterations in both voluntary and reflexive eye movements; however, the characteristics of oculomotor variability across task contexts remain incompletely understood. This study investigated prosaccade, antisaccade and fixation parameters in 15 individuals with early- to midstage PD, assessed in the on-medication state and 15 age- and sex-matched neurologically healthy controls. Eye movements were recorded during structured saccadic tasks and during free-viewing of dynamic video stimuli using high-resolution binocular eye tracking. Compared with controls, participants with PD exhibited significantly higher prosaccade error rates and an increased peak velocity-to-amplitude ratio. Trial-to-trial variability, quantified using coefficients of variation, was consistently elevated in the PD group across multiple saccade parameters. During the video-viewing condition, changes in saccade metrics following video exposure were observed in the control group but not in the PD group, whereas fixation-based measures did not reliably differentiate groups. Together, these findings indicate that increased variability and reduced consistency of saccadic execution are prominent features of oculomotor control in PD without freezing of gait, particularly during reflexive saccade tasks. The results underscore the value of variability-based analyses for probing sensorimotor control in PD and motivate future work to examine their task dependence, longitudinal stability and relevance across disease stages.
Computational Modelling of Novelty Detection in the Mismatch Negativity Protocols and Its Impairments in Schizophrenia.
Eissa A, Fredrik Kismul J, Pentz AB … +9 more , Elvsåshagen T, Metzner C, Akkouh I, Djurovic S, Shadrin A, Linne ML, Einevoll GT, Andreassen OA, Mäki-Marttunen T
Eur J Neurosci · 2026 Mar · PMID 41862424 · Full text
The human auditory system rapidly distinguishes between novel and familiar sounds, a process reflected in mismatch negativity (MMN), an electroencephalogram (EEG)-based biomarker of auditory novelty detection. MMN is imp...
The human auditory system rapidly distinguishes between novel and familiar sounds, a process reflected in mismatch negativity (MMN), an electroencephalogram (EEG)-based biomarker of auditory novelty detection. MMN is impaired in psychiatric conditions, most notably schizophrenia (SCZ), yet the neuronal mechanisms underlying this deficit remain unclear. Here, we combined computational modelling and genetic analyses to investigate how SCZ-associated cellular abnormalities affect auditory novelty detection. We developed an integrate-and-fire spiking network model capable of detecting four types of auditory novelty, including stimulus omission. Based on assumptions of short-term depressing synapses between the subpopulations of the network and the existence of neuronal inputs that are phase-locked to the rhythm of the recently experienced stimulus sequence, we showed that the model reliably reproduced MMN-like novelty detection and allowed systematic testing of SCZ-related cellular alterations. We also demonstrated that the required phase locking can theoretically be achieved in a synfire chain network exhibiting spike-timing dependent plasticity (STDP) in its feedback synapses that becomes entrained to the rhythmic stimulus. Simulations of our novelty-detecting network revealed that both reduced pyramidal cell excitability, linked to ion channel dysfunction, and decreased spine density impaired novelty detection, with the latter producing stronger deficits. Our work provides a flexible spiking network model of auditory novelty detection that can link cellular-level abnormalities to measurable MMN deficits, improving their mechanistic interpretation and helping to explain the heterogeneity of SCZ.
Parietal Alpha-Band Connectivity Tracks Listening Effort in Hearing-Aid Users Under Competing Speech and Noise.
Shahsavari Baboukani P, Alickovic E, Østergaard J … +1 more , Eskelund K
Eur J Neurosci · 2026 Mar · PMID 41860413 · Full text
This study examines how the signal-to-noise-interference ratio (SNIR) influences auditory performance and neural responses associated with listening effort (LE). A new dataset was collected from individuals with moderate...
This study examines how the signal-to-noise-interference ratio (SNIR) influences auditory performance and neural responses associated with listening effort (LE). A new dataset was collected from individuals with moderate hearing loss, all fitted with hearing aids (HAs). Participants listened to two competing audiobooks presented via front-facing loudspeakers, while 16-talker babble noise was delivered from background speakers. Six SNIR levels (5.47, 3.55, 2.13, 1.19, 0.64, and 0.27 dB) were tested. Participants were instructed to attend to one audiobook while ignoring the competing speech and background noise and were subsequently assessed on content of the attended speech and perceived LE. The performance results revealed a significant linear effect of SNIR on subjective ratings of LE and a primarily quadratic effect on comprehension questionnaire accuracy, suggesting that perceived effort decreases steadily with improving SNIR, while comprehension questionnaire performance exhibits a plateau at higher SNIR levels. The EEG analyses demonstrated a significant relationship between SNIR and local connectivity, specifically in the parietal electrodes and in the alpha frequency band. Further analysis confirmed that parietal local connectivity correlates linearly with subjective LE ratings. Moreover, spectral power analysis showed that parietal alpha power is not significantly related to SNIR, indicating that local connectivity may serve as a more sensitive neural marker. While local connectivity and alpha power may share some neural underpinnings, they offer complementary, yet non-identical insights. These findings highlight the potential of local EEG connectivity as a reliable estimate of LE in acoustically challenging environments.
Mobile Powerhouses: Mitochondria Transfer via Tunnelling Nanotubes in Brain Health and Neurodegenerative Diseases.
Henrich A, Scheiblich H
Eur J Neurosci · 2026 Mar · PMID 41858106 · Full text
Mitochondria are central regulators of cellular metabolism, calcium homeostasis and survival. Owing to the brain's exceptional energy demand, mitochondrial dysfunction is tightly linked to neurodegenerative and neuroinfl...
Mitochondria are central regulators of cellular metabolism, calcium homeostasis and survival. Owing to the brain's exceptional energy demand, mitochondrial dysfunction is tightly linked to neurodegenerative and neuroinflammatory disorders. Recent evidence challenges the traditional view of mitochondria as strictly cell-autonomous organelles, revealing that they can be exchanged between cells via intercellular transfer by extracellular vesicles, gap junctions or tunnelling nanotubes (TNTs) as part of an adaptive mechanism of metabolic support and signalling. Among the pathways mediating this intercellular exchange, TNTs-thin, actin-rich cytoplasmic bridges-have emerged as key conduits for mitochondrial transfer in the nervous system. TNTs enable bidirectional exchange of mitochondria between neurons, glia and vascular cells, thereby promoting bioenergetic recovery after injury and modulating immune and inflammatory responses. This review summarizes current evidence for TNT-mediated mitochondrial transfer in the brain and highlights the underlying molecular mechanisms that coordinate mitochondrial movement, including cytoskeletal dynamics, mitochondrial trafficking machinery and stress-induced signalling cascades. While mitochondrial donation can restore metabolic balance and promote neuroprotection, it may also facilitate the spread of pathological proteins, contributing to disease progression. Understanding the underlying molecular mechanism of TNT-mediated mitochondrial transfer provides a new framework for exploring metabolic communication and cellular resilience in the brain. By emphasizing emerging conceptual and mechanistic insights, we outline how advancing this field could pave the way for the development of innovative therapeutic strategies for neurodegenerative and neuroinflammatory disorders.
Postinjury Carnosine Treatment Prevents Neurotrophic Factor Decline in Denervated Muscle and Spinal Cord After Traumatic Injury.
Kucharova K, Kuruc T, Magurova M … +5 more , Ihnatova L, Ileninova M, Kisucka A, Galik J, Lukacova N
Eur J Neurosci · 2026 Mar · PMID 41853954 · Publisher ↗
Local intraspinal or intramuscular administration of brain-derived or glial cell line-derived neurotrophic factors (BDNF, GDNF) is known to protect neural tissue after traumatic spinal cord injury (SCI). In this study, w...
Local intraspinal or intramuscular administration of brain-derived or glial cell line-derived neurotrophic factors (BDNF, GDNF) is known to protect neural tissue after traumatic spinal cord injury (SCI). In this study, we investigated whether oral supplementation with antioxidant carnosine, a natural dipeptide, could stimulate endogenous production of these neuroprotective molecules within the neural and muscle microenvironment 6 weeks after SCI. We assessed the effects of 6-week carnosine treatment in female Zucker rats, administered either before (CB-I) or after injury (CA-I). The impact of thoracic SCI and carnosine treatment was evaluated in in/active microenvironments of fore limb and hind limb muscles, along with their corresponding innervation regions. To better understand how carnosine treatment affects the neural microenvironment, we analysed mRNA expression levels of neurotrophic factors and their receptors. We also examined molecules that may indicate which cell types are involved in producing or responding to BDNF or GDNF in the spinal cord. Six weeks after thoracic SCI, we observed better locomotor recovery in CA-I compared to CB-I treated rats. In the hind limb, posttraumatic carnosine treatment prevented SCI-induced reductions in BDNF and GDNF protein levels. Additionally, this treatment blocked the SCI-induced reduction of GDNF protein levels and the oligodendrocyte-specific gene Olig2 in the lumbar and cervical spinal cord segments. Interestingly, the postinjury treatment elevated the gene expression in BDNF receptor- and astrocyte-specific genes in the cervical segments. The finding that carnosine may prevent BDNF and GDNF declines in denervated hind limb muscles positions this dipeptide as a promising candidate for inclusion in future combination therapies.
A Relative Authorship Index: A New Metric for Evaluating Individual Contribution in Scientific Research.
Siano F, Segreti M, Pani P … +2 more , Brunamonti E, Genovesio A
Eur J Neurosci · 2026 Mar · PMID 41848394 · Full text
This study presents the relative authorship index (RAI), a novel metric designed to address the limitations of traditional bibliometric indicators, such as publication counts, citation numbers, and the h-index, by correc...
This study presents the relative authorship index (RAI), a novel metric designed to address the limitations of traditional bibliometric indicators, such as publication counts, citation numbers, and the h-index, by correcting for authorship inflation. Conventional metrics can overestimate productivity by failing to account for the number of co-authors or the possibility of inflated authorship. To detect such inflation, this index evaluates the number of co-authors on a paper relative to the number of authors in the references cited within the same paper, which are assumed to reflect the researcher's specific field of study. By using this field-specific baseline, the index identifies whether a publication involves an unusually high number of co-authors compared to field standards, thus flagging potential authorship inflation. Applied to neuroscience articles authored by researchers affiliated with Italian universities, the index revealed significant regional and university differences, with higher values in southern regions and private universities. A case study of a single department also revealed high variability among individual researchers, indicating that the index can capture consistent patterns in authorship practices. In addition, we propose an authorship correction formula to adjust bibliometric indicators. The formula introduces parameters that penalize authorship inflation based on the RAI and also penalize large co-author counts, with the latter scaled according to whether the researcher occupies key authorship positions (first, last, and/or corresponding author).
Corticocerebellar Effective Connectivity During Adapting to vs. Ignoring Delayed Visual Movement Feedback.
Wang Z, Limanowski J
Eur J Neurosci · 2026 Mar · PMID 41841583 · Full text
Internal models in the brain may enable flexible action control by calculating estimates of the body's state and predictions of the sensory consequences that its actions will produce. These processes are thought to be im...
Internal models in the brain may enable flexible action control by calculating estimates of the body's state and predictions of the sensory consequences that its actions will produce. These processes are thought to be implemented by interactions among cortical and subcortical brain regions including the cerebellum. During a virtual reality based hand-target matching task, in which delayed visual movement feedback was behaviorally relevant (i.e., requiring visuomotor adaptation) or irrelevant (i.e., needed to be ignored), we had observed increased hemodynamic responses in the cerebellum (left Crus I/right Lobule VI), V5, and intraparietal sulcus during the adaptation condition. These activity changes suggested processes specific to delay-dependent adaptation. Here, we used dynamic causal modeling (DCM) to test if these regional activity changes could be explained in terms of task (i.e., adaptation)-dependent between-region connectivity changes. During visuomotor adaptation, DCM revealed an increased excitatory influence of the right cerebellum (Lobule VI) on bilateral V5 (and on the IPS), and an increased mutual excitation among the right cerebellum and the left IPS. Our results support the idea that the communication of cerebellar predictions to the cortical visuomotor network underlies visuomotor adaptation.
Cortical Network Disruption and Transcriptional Profiles in Poststroke Aphasia: A Functional Connectivity Gradient Approach.
Wang L, Yang J, Yan R … +7 more , Wang X, Sang L, Zhang J, Zhang Y, Qiao L, Qiu M, Liu C
Eur J Neurosci · 2026 Mar · PMID 41823306 · Publisher ↗
Poststroke aphasia significantly impacts the quality of life in older adults, yet the underlying neural mechanisms linking macro-scale network hierarchy and micro-scale molecular architecture remain unclear. This study i...
Poststroke aphasia significantly impacts the quality of life in older adults, yet the underlying neural mechanisms linking macro-scale network hierarchy and micro-scale molecular architecture remain unclear. This study investigated alterations of the principal functional connectivity gradient and their transcriptomic underpinnings in older adults with poststroke aphasia. We recruited 27 patients with aphasia and 29 age-matched healthy controls. Resting-state fMRI data were analyzed using diffusion map embedding to characterize the principal functional connectivity gradient. Patients exhibited a compressed gradient range, characterized by diminished differentiation in unimodal networks (visual and somatomotor) and disordered integration in multimodal networks, including the ventral attention network and the default mode network. These gradient alterations were significantly correlated with language deficits. Furthermore, partial least squares regression revealed that the spatial pattern of gradient changes was associated with normative gene expression profiles related to synaptic transmission, trans-synaptic signaling, and calcium ion binding. Machine learning models incorporating gradient features and lesion volume successfully predicted individual differences in language performance. These findings suggest that poststroke aphasia involves a disruption of the cortical functional hierarchy that is constrained by specific molecular architectures, providing novel insights into the neurobiological mechanisms of language recovery and potential targets for precision rehabilitation in aging populations.
Postsynaptic Induction and Presynaptic Expression of Long-Term Potentiation at Excitatory Synapses on Layer 2/3 VIP Interneurons in the Somatosensory Cortex.
Bogaj K, Urban-Ciecko J
Eur J Neurosci · 2026 Mar · PMID 41817386 · Publisher ↗
Synaptic transmission between specific connection motifs undergoes plastic changes during the learning process; however, the exact mechanisms underlying synaptic plasticity are still under intense investigation. Long-ter...
Synaptic transmission between specific connection motifs undergoes plastic changes during the learning process; however, the exact mechanisms underlying synaptic plasticity are still under intense investigation. Long-term potentiation (LTP) of synaptic transmission is a widely used cellular model of synaptic plasticity occurring during learning. Here, we focused on studying LTP at excitatory synapses on layer (L) 2/3 vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) in the mouse somatosensory (barrel) cortex. LTP was induced by a pairing protocol of postsynaptic depolarization with extracellular stimulation in acute brain slices of young mice (P21-P28). The pairing protocol evoked LTP in L2/3 VIP-INs under control conditions; however, pharmacological blockade of GABAaR inhibition enhanced LTP. Next, we found that LTP in L2/3 VIP-INs is dependent on metabotropic glutamate receptor type 1 (mGluR-1) and L-type voltage-gated calcium channels (L-type VGCCs) but not on NMDARs or mGluR-5. Here, mGluR-1 acts through a G-protein-coupled signaling pathway and Src-family kinases, independently of transient receptor potential channels (TRPCs). Analyses of the paired-pulse ratio (PPR) and coefficient of variation (CV) indicate a presynaptic locus of LTP expression. Presynaptic expression of LTP in VIP-INs relies on retrograde signaling through endocannabinoids (eCBs) but not on brain-derived neurotrophic factor (BDNF). In conclusion, we dissected the mechanisms of LTP induction and expression at excitatory inputs to L2/3 VIP-INs in the mouse barrel cortex. LTP at excitatory synapses on VIP-INs might serve as a positive feedback for enhanced VIP-IN-mediated inhibition of SST-INs, leading to disinhibition of excitatory neurons from SST-IN inhibition during the learning process.
Extracellular Diffusion of Tau Protein Is Slower Than Similar-Sized IgG Protein and Dextran Polysaccharide in Entorhinal Cortex but Not in Prefrontal Cortex.
Rubin M, Naik-Talapadatur A, Majerova P … +3 more , Hrabe J, Kovac A, Hrabetova S
Eur J Neurosci · 2026 Mar · PMID 41816971 · Publisher ↗
In brain's extracellular space (ECS), proteins form an important part of endogenous macromolecular traffic. Each protein has unique diffusion characteristics governed by its size and, potentially, by charge-based interac...
In brain's extracellular space (ECS), proteins form an important part of endogenous macromolecular traffic. Each protein has unique diffusion characteristics governed by its size and, potentially, by charge-based interactions with extracellular matrix. The goal of this study was to provide quantitative data for extracellular diffusion of a human full-length Tau protein (Tau), a large intrinsically disordered protein with positively charged domains including specific heparan sulfate binding sites, in entorhinal cortex (EC) and prefrontal cortex (PFC), two brain regions affected by tauopathies. To this end, diffusion measurements with integrative optical imaging method in agarose gel and acute mouse brain slices determined diffusion permeability in the ECS of these two brain regions for Tau and for several control macromolecules: weakly negatively charged immunoglobulin G, neutral apolipoprotein E with a heparan sulfate binding site, and neutral or positively charged dextran polysaccharides. We found that diffusion permeability for Tau was similar in PFC and EC. In contrast, all other macromolecules were less hindered in EC with the exception of the positively charged dextran, suggesting that charge-based interactions between Tau and negatively charged extracellular matrix retard its extracellular diffusion. In conclusion, the extracellular diffusion of Tau in the EC is exceptionally slow in comparison to the other proteins and neutral dextrans. EC is the brain region linked to an onset of Alzheimer's disease, and the elements of extracellular microenvironment that govern Tau diffusion inside it will affect both its distribution and its clearance and could therefore play an important role in tauopathies such as the Alzheimer's disease.
Region and Cell-Selective Induction of Zbtb16/Plzf by Multiple Stressors in the Adult Murine Hypothalamus.
Roueinfar M, Mohammadzadeh P, Schwerdtfeger LA … +2 more , Handa RJ, Tobet SA
Eur J Neurosci · 2026 Mar · PMID 41816969 · Full text
Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that regulates responses related to feeding, reproduction, and aggression, among other homeostatic functions. Stressors significantl...
Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system that regulates responses related to feeding, reproduction, and aggression, among other homeostatic functions. Stressors significantly impact gene expression along the HPA axis and in hypothalamic nuclei that drive it, including the paraventricular nucleus (PVN). To identify genetic regulators of stress responses in the PVN, adult mice underwent 2 h of multi-modal stress before gene expression profiles were analyzed using bulk RNA sequencing. A transcription factor zinc finger and BTB domain containing 16 (Zbtb16), also known as PLZF, was identified as a stress responsive, glucocorticoid receptor (GR) target in the PVN. Zbtb16 mRNA expression was increased by two-fold in male and female mice within 2 h of restraint stress or injection of a synthetic glucocorticoid, dexamethasone (DEX). Immunohistochemistry (IHC) confirmed Zbtb16 protein expression and localization in the PVN following 20 min of restraint stress and 4 h of recovery. Cellular analyses revealed that Zbtb16 was highly expressed in CRH neurons in the PVN, neurons routinely activated post-stress as indicated by colocalization with c-FOS. Adult mice were also exposed to an immune stress by injection of tumor necrosis factor alpha (TNFα) to assess Zbtb16 regulation. Expanded analyses indicated that the cell specificity of Zbtb16 expression was region-specific, colocalizing with CRH neurons in the mid-PVN but more in astrocytes surrounding the PVN. These findings identify Zbtb16 as a glucocorticoid- and cytokine-inducible transcriptional regulator with region- and cell type-specific roles in PVN stress circuitry.
Correction to "Bi-Cephalic Self-Attended Model to Classify Parkinson's Disease Patients With Freezing of Gait".
Eur J Neurosci · 2026 · PMID 41808550 · Publisher ↗
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Sensory Experience and Motor Signals Shape Auditory Processing in an Independent Manner.
Buaron B, Mukamel R
Eur J Neurosci · 2026 · PMID 41805065 · Full text
Voluntary actions are usually accompanied by sensory consequences that evoke neural responses in relevant sensory regions. These responses are different when compared to those evoked by otherwise identical physical stimu...
Voluntary actions are usually accompanied by sensory consequences that evoke neural responses in relevant sensory regions. These responses are different when compared to those evoked by otherwise identical physical stimulation not associated with preceding actions (sensory attenuation). A common model suggests that sensory attenuation is caused by efference signals associated with the binding of actions with sensory outcomes. Nevertheless, the information encoded in such signals is debated, with some theories suggesting they convey predictive information while others suggest they convey global motor information regardless of outcome expectations. To address this debate, we recorded EEG data, while participants (n = 30) learned to associate motor or visual cues with corresponding tones. Following eight cue-outcome presentations, participants successfully learned the association (> 84% correct). At the neural level, the amplitude of auditory-evoked responses (N100) decreased during learning, as experience with cues and tones was gained. In addition, N100 amplitude was attenuated when preceded by motor vs. visual cues (sensory attenuation). Most importantly, we did not find an interaction effect between learning phase and cue type, suggesting a similar magnitude of sensory attenuation throughout learning. Moreover, we find significant sensory attenuation even before tone-specific expectations were formed. Thus, our results suggest that the magnitude of sensory attenuation is invariant to short-term experience with specific action-outcome contingency. Exploratory time-frequency analysis suggests experience affects EEG signals prior to tone onset and earlier than motor signals. Together, our results are consistent with models suggesting a distinct influence of action on sensory processing that is independent of experience.
Cortical Brain Activation During Robot-Assisted Gait in Humans With Acute and Chronic Spinal Cord Injury: A Functional Near-Infrared Spectroscopy Study.
Donati ARC, Coelho DB, Sato JR … +2 more , Fregni F, Battistella LR
Eur J Neurosci · 2026 Mar · PMID 41805031 · Full text
Most treatments being developed to regain motor function following spinal cord injury (SCI) presuppose that brain motor functions remain intact. To examine this assumption, this study aims to analyze residual neurologica...
Most treatments being developed to regain motor function following spinal cord injury (SCI) presuppose that brain motor functions remain intact. To examine this assumption, this study aims to analyze residual neurological functions during assisted robotic gait in individuals with SCI comparing blocks (gait × resting), time after SCI (acute × chronic), injury level (paraplegic × tetraplegic), and ASIA scale (ASIA C × D). The hemodynamic functions were analyzed using functional near-infrared spectroscopy (fNIRS) in 23 individuals (11 acute, 12 chronic; ASIA Impairment Scale grade C: 10, D: 13; paraplegia: 15, tetraplegia: 8) while performing an assisted robotic gait task (Lokomat). Brain areas analyzed included supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1). Blocks (robotic gait × resting), acute × chronic, paraplegic × tetraplegic, and ASIA C × ASIA D groups were compared. For the block comparison, there was a significant difference in SMA and M1, with higher oxyhemoglobin values in the robotic gait task compared to resting. For the comparison between groups, there was a significant difference in M1, with higher oxyhemoglobin values in the chronic group compared to the acute group. The individuals with paraplegia exhibited greater activity in M1 than those with tetraplegia during the robotic gait task. These results demonstrate the plasticity and adaptability of brain motor cortex areas even during the chronic phase after SCI. The brain motor cortex activity during a walking motor task reinforces the importance of analyzing residual neurological function after SCI.
Association of Bassoon (BSN) Gene Mutations With Gait and Motor Impairments in Parkinson's Disease.
Kukkle PL, Panikkaveettil Kaladiyil A, Geetha TS … +22 more , Menon R, Kandadai RM, Goyal V, Desai SD, Joshi D, Kumar H, Wadia PM, Mukherjee A, Kumar N, Mehta S, Chargulla S, Murugan S, Shah HS, Paramanandam V, Chandarana M, Yadav R, Dhamija RK, Pal PK, Biswas A, Gupta R, Borgohain R, Ramprasad VL
Eur J Neurosci · 2026 Mar · PMID 41802976 · Publisher ↗
Parkinson's disease (PD) is a neurodegenerative syndrome with diverse biological drivers, where gait and balance dysfunction remain among the most disabling and least understood symptoms. Bassoon (BSN), a presynaptic act...
Parkinson's disease (PD) is a neurodegenerative syndrome with diverse biological drivers, where gait and balance dysfunction remain among the most disabling and least understood symptoms. Bassoon (BSN), a presynaptic active-zone organizer, has been implicated in various parkinsonian disorders. Here, we report the impact of BSN mutations on motor symptoms, especially gait-related symptoms, in PD patients. Our study included 110 patients carrying BSN mutations in a cohort of 668 South Asian early-onset PD (age of onset < 50 years). Clinical motor features were compared between variant carriers and noncarriers. Computational tools (CADD, PolyPhen-2, I-Mutant2.0 and ConSurf) predicted deleteriousness of individual mutations, whereas GeneMANIA and STRING speculated Bassoon's functional interactions. Subjects carrying BSN variants exhibited significantly increased burden of motor-related symptoms (p = 0.036). Freezing of gait (FOG) and shuffling gait (SG) were significantly more prevalent in BSN mutation carriers (p = 0.03). Presence of BSN mutation correlated with an increased disease stage, an effect driven by FOG and SG (p = 0.012). Rare BSN mutations (MAF < 0.1%) clustered in the Bassoon C-terminal region (aa 3500-3800), at a threefold frequency than expected (p < 0.01), implying a hotspot. In silico analysis identified seven likely pathogenic variants (P171L, A852T, P988A, R1015H, R2561H, R3400W and L3561P). Predictive analyses implicated BSN in axonal transport, presynaptic proteostasis and neurotransmitter release in dopaminergic/cholinergic neurons. Our findings put forth BSN mutations as a potential genetic risk factor for PD-related motor and gait dysfunction, warranting further research in this respect.
Cell Type-Specific Encoding of Cocaine-Conditioned Responses in the Lateral Preoptic Area.
Mejaes JI, Rajendran R, Sayed K … +3 more , Yecham P, Bernstein A, Barker DJ
Eur J Neurosci · 2026 Mar · PMID 41795287 · Full text
The lateral preoptic area (LPO) is a functionally heterogeneous hypothalamic structure that is increasingly recognised for its role in motivated and drug-seeking behaviours. Although prior studies have shown that LPO neu...
The lateral preoptic area (LPO) is a functionally heterogeneous hypothalamic structure that is increasingly recognised for its role in motivated and drug-seeking behaviours. Although prior studies have shown that LPO neurons exhibit diverse activity patterns during cocaine self-administration, the specific contributions of glutamatergic and GABAergic populations to conditioned responses to cocaine remain unclear. In this study, we recorded the activity of LPO glutamatergic (vglut2-expressing) and GABAergic (vgat-expressing) neuronal subpopulations during cocaine conditioning to identify how these cell types respond to drug-associated cues in awake, behaving mice. Our results revealed that, after cocaine conditioning, both glutamatergic and GABAergic populations showed reduced activity upon entry into the cocaine-paired chamber. However, only glutamatergic neurons exhibited increased activity when mice entered the saline-paired chamber. The magnitude of these activity changes was also correlated with behavioural outcomes: reduced GABAergic activity was associated with greater preference for the cocaine-paired chamber, whereas stronger glutamatergic responses were associated with greater preference for the saline-paired chamber. These findings indicate that LPO GABAergic and glutamatergic neurons exhibit distinct, cell type-specific patterns during cocaine-conditioned place preference. Rather than indicating opposing motivational states, the results highlight that LPO activity relates to conditioned behaviours in a cell type- and context-dependent manner. By linking activity in glutamatergic and GABAergic neurons with conditioned responses, this work provides initial evidence for how LPO circuits may contribute to drug-associated learning.
The Effects of Maturation and Dyslexia Risk on Neural Speech-Sound Encoding and Discrimination at Preschool Stage.
Navarrete-Arroyo S, Nie P, Virtala P … +1 more , Kujala T
Eur J Neurosci · 2026 Mar · PMID 41795283 · Full text
Event-related potentials (ERPs), and particularly change-elicited mismatch responses (MMRs), are valuable tools for assessing early speech processing and promising markers of dyslexia risk. Yet, their maturation during t...
Event-related potentials (ERPs), and particularly change-elicited mismatch responses (MMRs), are valuable tools for assessing early speech processing and promising markers of dyslexia risk. Yet, their maturation during the preschool stage remains poorly characterized. We determined the typical elicitation of ERPs and MMRs to speech sounds at preschool age (4-5 years), their maturation from early childhood (28 months) to preschool age, and the impact of dyslexia risk on them. To this end, we recorded obligatory ERPs to a repeating pseudoword and MMRs to five deviances at 4-5 years and compared them with a previously reported follow-up at 28 months, in subgroups with versus without dyslexia risk in a large sample (n ~ 150). In the full sample, including both control and at-risk children, the 4- to 5-year obligatory ERPs showed a P1-N2 pattern, while the MMRs included a mismatch negativity (MMN) followed by a late discriminative negativity (LDN). From 28 months to 4-5 years, P1 amplitude increased and latency decreased, whereas the N2 amplitude increased. MMN and LDN amplitudes increased and LDN latency decreased with age, whereas a positive MMR reported at 28 months was no longer evident at 4-5 years. Crucially, at-risk children exhibited reduced MMN amplitudes at 4-5 years across deviants, suggesting deficient speech discrimination. Changes from 28 months to 4-5 years were similar in both subgroups. These findings establish a solid description of typical/atypical neural speech-sound processing during preschool years, serving as a reference for future studies including interventions or clinical groups.
Action or Stimulus: Individual Beliefs About Learned Associations Influence the Processing of Immediate and Delayed Feedback.
Albrecht C, Ghio M, Bellebaum C
Eur J Neurosci · 2026 Mar · PMID 41793036 · Full text
Feedback learning seems to involve two systems, the striatal reward system and the medial temporal lobe (MTL), which have both been linked to event-related potential (ERP) components such as the feedback-related negativi...
Feedback learning seems to involve two systems, the striatal reward system and the medial temporal lobe (MTL), which have both been linked to event-related potential (ERP) components such as the feedback-related negativity (FRN)/N2, overlapped by a reward positivity (RewP), and the N170, respectively. In this study, we tested the hypothesis that the former system is more involved in associating the feedback with previous actions and the latter in associating the feedback with previous stimuli. More specifically, we hypothesized that the engagement of these systems depends on individual beliefs in credit assignment, that is, whether participants linked the feedback they received to actions or stimuli, possibly modulated by feedback timing. Electroencephalography (EEG) data were recorded from 43 participants performing an ambiguous feedback-learning task, in which feedback could be attributed to either a performed action or a selected stimulus, according to the instruction. As revealed by an Action Index derived from behavioral data, the focus on stimulus-feedback associations was generally stronger than that on action-feedback associations. We found that both FRN/N2 and N170 were influenced by individual beliefs about learned associations, with the FRN/N2 showing stronger feedback valence coding across feedback delays when participants took action-feedback associations into account. Also prediction error coding in the N170 was more pronounced for stronger action-feedback association learning. The results seem to suggest that both learning systems are recruited, at least to some extent, when action-feedback and stimulus-feedback associations are considered simultaneously.
Mitochondrial-Derived Vesicles: An Emerging Whisperer in Neurological Disorders.
Abuelezz NZ, Nasr FE, El Aziz AEA … +2 more , Ahmed MK, El Sayed NS
Eur J Neurosci · 2026 Mar · PMID 41789494 · Publisher ↗
Mitochondrial dysfunction is a pivotal feature in the pathogenesis of various neurological and neurodegenerative disorders. The brain, with its high metabolic demands, is particularly vulnerable to impaired mitochondrial...
Mitochondrial dysfunction is a pivotal feature in the pathogenesis of various neurological and neurodegenerative disorders. The brain, with its high metabolic demands, is particularly vulnerable to impaired mitochondrial function, leading to oxidative stress, disturbed calcium homeostasis, and hyperactivated microglial responses. Mitochondrial disturbances majorly contribute to neuronal damage, synaptic dysfunction, and cognitive decline, making mitochondria a crucial target for therapeutic intervention in brain disorders. In this context, mitochondrial-derived vesicles (MDVs) are increasingly emerging as a novel aspect of mitochondrial biology with significant implications for brain health and disease. Prior to mitophagy, MDVs are released from stressed mitochondria, incorporating either healthy or damaged mitochondrial components as an earlier defense mechanism to maintain mitochondrial integrity and homeostasis. Furthermore, MDVs contribute to intercellular communication and extracellular neuroinflammation signaling, potentially influencing the progression of neurological disorders. This review provides a thorough overview of MDVs' subpopulations, highlighting the most recently reported MDVs roles across multiple neurological disorders and exploring their potential in diagnostic and therapeutic settings. Additionally, we further analyze the current limitations that hinder broader clinical applications of MDVs and present future perspectives and key recommendations to overcome these obstacles, aiming to enhance their effectiveness in diagnosis, therapy, and brain-targeted drug delivery.
A Rapid fMRI Paradigm for Localisation of the Language Network.
Jain S, Stamatakis EA, Price SJ
Eur J Neurosci · 2026 Mar · PMID 41789440 · Full text
Language assessment using imaging remains an arduous task due to the complexity of the language network. Given the complex neural instantiation of the language function, structural imaging is insufficient in determining...
Language assessment using imaging remains an arduous task due to the complexity of the language network. Given the complex neural instantiation of the language function, structural imaging is insufficient in determining the extensive network of relevant cortical and subcortical areas in patients with intrinsic brain tumours. Functional magnetic resonance imaging (fMRI) provides a non-invasive method for the localisation of language-dominant areas using task-specific brain activation maps. In this study, the authors provide the results of a rapid four-task-based fMRI paradigm that can be used to determine an individual's specific language network. Fifteen participants were recruited prospectively for this study. A 10-min pre-scan preparation was done with each participant prior to the scan on the various tasks they were expected to complete during the fMRI scan. The following four tasks were conducted: covert naming, overt naming, sentence completion and pyramids and palm trees test (PPTT). The average time taken for all four tasks was 25.9 ± 1.8 min (23-31 min). All tasks were successfully completed in less than 30 min for all but one volunteer (31 min). Subject specific task-based fMRI maps were generated for each task, providing overall insights into the bilaterally represented language network. Tasks were completed in a reasonable time duration, providing maximal information that can be translated into intraoperative testing during awake surgeries. Further research is needed to understand any limitations of this type of testing in patients with pre-existing neurological deficits and brain lesions.
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