Cerebellar Computation & Motor Control

Human cerebellum and ventral tegmental area interact during extinction of learned fear

Mon, 13 Jul 2026 00:00:00 GMT

Abstract The key elements for fear extinction learning are unexpected omissions of expected aversive events, which are considered to be rewarding. Given its reception of reward information, we tested the hypothesis that the cerebellum contributes to reward-like prediction error processing driving extinction learning via its connections with the ventral tegmental area (VTA). Forty-three young and healthy participants performed a three-day fear conditioning paradigm in a 7T MR scanner. The cerebellum and VTA were active during unexpected omissions of aversive unconditioned stimuli in the initial extinction trials and in other learning phases, in line with the proposed role of prediction-error processing. Increased functional connectivity was observed between the cerebellum and VTA, indicating that they are functionally coupled during fear extinction learning. These results suggest that an interaction between the cerebellum and VTA should be incorporated into the existing model of the fear extinction network.

Tiny visual latencies can profoundly impair implicit sensorimotor learning

Thu, 08 May 2025 00:00:00 GMT

Short sub-100 ms visual feedback latencies are common in many types of human-computer interactions yet are known to markedly reduce performance in a wide variety of motor tasks from simple pointing to operating surgical robotics. It remains unclear, however, whether these latencies impair not only skilled motor performance but also the implicit sensorimotor learning that underlies its acquisition. Inspired by neurophysiological findings showing that cerebellar LTD and cortical LTP would both be disrupted by sub-100 ms latencies, we hypothesized that implicit sensorimotor learning may be particularly sensitive to these short latencies. Remarkably, we find that improving latency by just 60 ms, from 85 to 25 ms in continuous-feedback experiments, increases implicit learning by 50% and proportionally decreases explicit learning. This resulted in a dramatic reorganization of sensorimotor memory from a 45/55 to a 70/30 implicit/explicit ratio. This 70/30 ratio is more than double that observed in any previous study examining the effect of latency on sensorimotor learning, including a recent study which provided time-advanced visual feedback, suggesting that the low-latency continuous visual feedback we provided is critical for efficiently driving implicit learning. We go on to show that implicit sensorimotor learning is considerably more sensitive to latencies in the sub-100 ms range than to higher latencies, in line with the latency-specific neural plasticity that has been observed. This suggests a clear benefit for latency reduction in computer-based training that involves implicit sensorimotor learning and that across-study differences in computer-based experiments that have examined implicit sensorimotor learning might be explained by differences in unmeasured feedback latencies.

Coincidence detection between apical and basal dendrites drives STDP in cerebellar Golgi cells

Sun, 11 May 2025 00:00:00 GMT

Cerebellar Golgi cells (GoCs), segregate parallel fiber (pf), and mossy fiber (mf) inputs on apical and basal dendrites. Computational modeling predicted that this anatomical arrangement, coupled with a specific ionic channel localization, could be instrumental to drive STDP at mf-GoC synapses. Here, we test this hypothesis with GoC patch-clamp recordings in acute mouse cerebellar slices. Repeated mf-pf pairing on the theta-band within a ± 50 ms time window induces anti-symmetric Hebbian-STDP, with spike-timing long-term potentiation or depression (st-LTP or st-LTD) occurring when action potentials (APs) elicited by pf stimulation follow or precede the activation of mf synapses, respectively. Mf-GoC STDP induction requires AP backpropagation from apical to basal dendrites, NMDA receptor activation at mf-GoC synapses, and intracellular calcium changes. Importantly, STDP is inverted by inhibitory control. Thus, experimental evidence confirms and extends model predictions suggesting that GoC STDP can bind molecular layer to granular layer activity, regulating cerebellar computation and learning.

Ca2+-pumping by PMCA-neuroplastin complexes operates in the kiloHertz-range

Wed, 20 Aug 2025 00:00:00 GMT

Abstract Ca 2+ -ATPases in the plasma membrane extrude Ca 2+ ions from the cytosol to the extracellular space thereby terminating Ca 2+ -signals and controlling Ca 2+ -homeostasis in any type of cell. Recently, these Ca 2+ -pumps have been identified as protein complexes of the transporting subunits PMCAs1-4 and the single-span membrane proteins Neuroplastin (NPTN) or Basigin that are obligatory for efficient trafficking of the pump complexes to the surface membrane. Quantitative investigation of the pumping velocity controlling the time course of Ca 2+ -signals, however, has remained unresolved. Here we show, using Ca 2+ -activated K + channels as fast native reporters of intracellular Ca 2+ concentration(s) together with membrane-tethered fluorescent Ca 2+ -indicators, that under cellular conditions PMCA2-NPTN complexes can clear Ca 2+ in the low millisecond-range. Computational modeling exploiting EM-derived densities of Ca 2+ -source(s) and Ca 2+ -transporters in freeze-fracture replicas translated these fast kinetics into transport rates for individual PMCA2-NPTN pumps of more than 5000 cycles/s. Direct comparison with the Na + /Ca 2+ -exchanger NCX2, an alternate-access transporter with established cycling rates in the kHz range, indicated similar efficiencies in Ca 2+ -transport. Our results establish PMCA2-NPTN complexes, the most abundant Ca 2+ -clearing tool in the mammalian brain, as transporters with unanticipated high cycling rates and demonstrate that under cellular conditions ATPases may operate in the kHz-range.

Independence and coherence in temporal sequence computation across the fronto-parietal network

Thu, 11 Jun 2026 00:00:00 GMT

Time processing requires distributed and coordinated cortical dynamics. Flexible yet robust temporal representations can arise from two distinct computational modes: a coherence mode, where multiple cortical areas hold the same elapsed-time estimate, and an independence mode, where each area maintains its own local estimate. However, how the brain switches between these modes has remained unknown. Using mesoscale two-photon calcium imaging, we simultaneously recorded neuronal populations in the secondary motor cortex (M2) and posterior parietal cortex (PPC) of mice performing a novel alternating-interval timing task. Both areas encoded elapsed time through similar high-dimensional sequential activity. Decoding analyses revealed that the fronto-parietal network has both independent and coherent temporal codes. Communication-subspace analysis showed that temporal information was distributed across multiple low-variance subspaces, whereas the largest subspace preferentially encoded behaviour. A twin recurrent neural network (RNN) model with sparse inter-RNN connections and shared high-variance noise reproduced these experimental findings. Moreover, perturbations applied along the dominant shared subspace paradoxically enhanced independence between the two networks. Through a mathematical formalization based on the local Lyapunov exponents, we uncovered how perturbations along different subspaces selectively evoke either independent or coherent communication mode. Together, these results reveal a principle by which fronto-parietal circuits achieve robust yet flexible computation through the interplay of sparse coupling and shared global fluctuations.

Subthreshold violations of trajectory predictions are sensitive to TMS of cerebellum Crus I/II

Mon, 20 Jul 2026 00:00:00 GMT

Abstract Temporal prediction can help to follow a trajectory. In case of an error, the prediction can be adjusted. However, processing the error and adjusting the prediction can take time. What happens immediately after a prediction error, and can the processing of the prediction be modulated? We use a newly found illusion based on moving squares and requiring trajectory regularity to be elicited. We examined the conscious consequences of a sub-threshold manipulation of the square trajectories, and transcranial magnetic stimulation (TMS) on the cerebellum (right CRUS I/II) to study the modulation of the processing of the trajectory manipulations. The TMS was a typical intermittent theta-burst stimulation, but only one sequence of around 3 minutes, compared with a placebo stimulation. The trajectory manipulation had a reliable effect on the illusion, even though the illusion emerged within less than 100 ms after the trajectory manipulation. The results suggest that the prediction is temporarily stopped after the trajectory change. The illusion was accompanied by EEG signals whose amplitude was modulated by TMS on the cerebellum, at least in those participants who received verum TMS after having performed the task three times. Those EEG signals resembled a late LPP (Late Positive Potential). As LPP spontaneously decreased over time, the results suggest the effect of TMS may represent a reinstation of the EEG consequences of the prediction error, i.e., a modulation of its significance.

Structured sampling of molecularly classified mossy fiber inputs by cerebellar granule cells

Mon, 22 Jun 2026 00:00:00 GMT

The cerebellar granule cell layer receives mossy fiber inputs from diverse brain regions, yet the principles governing how individual granule cells sample distinct types of inputs remain poorly understood. Using a volumetric correlated light and electron microscopy (vCLEM) dataset from an adult female mouse cerebellum, in which VGluT1-positive and VGluT1-negative mossy fiber terminals are molecularly distinguished, we reconstructed granule cell and mossy fiber connectivity to examine input selection rules. We constructed spatially constrained null models to simulate sampling during adulthood and development. Granule cell-centered analysis showed that granule cells shared less innervation from the same mossy fiber than expected by chance. Moreover, subpopulations of granule cells preferentially sample either VGluT1-positive or VGluT1-negative mossy fibers. In contrast, mossy fiber-centered analysis showed that individual terminals distributed their outputs across granule cells in a pattern consistent with random sampling. However, sampling in the adult state was more selective than in developmental simulations. Together, our findings demonstrated structured, non-random sampling of cerebellar VGluT1-positive and VGluT1-negative mossy fiber inputs and provide a framework for understanding how granule cells integrate molecularly distinct inputs to support cerebellar computation.

Dentate Nucleus Deep Brain Stimulation for Spinocerebellar Ataxia: Results of a 6‐Month Follow‐Up

Sat, 08 Nov 2025 00:00:00 GMT

BACKGROUND: Spinocerebellar ataxia (SCA) is a genetically heterogeneous neurodegenerative disorder with no effective treatments. Although noninvasive cerebellar neuromodulation has shown positive outcomes, invasive approaches such as deep brain stimulation (DBS) remain inadequately evaluated in SCA. OBJECTIVES: This study assessed the treatment outcomes of DBS targeting the cerebellar dentate nucleus (DN) in SCA patients over a 6-month follow-up. METHODS: Six patients with heterogeneous SCA underwent bilateral DN-DBS. The stimulation parameters were programmed iteratively, and ataxia symptoms were evaluated at predefined intervals using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). RESULTS: Individualized appropriate stimulation parameters (current, frequency, and pulse width) were established. At the 6-month follow-up, the SARA scores decreased by 43% (P = 0.014) and the ICARS scores by 51% (P = 0.013) compared with baseline. CONCLUSIONS: These findings provide evidence for the potential therapeutic efficacy of DN-DBS in SCA and offer preliminary insights for stimulation parameter programming. © 2025 International Parkinson and Movement Disorder Society.

Intrinsic brain network dynamics modulated by neural stimulation to cerebellum

Thu, 01 Jan 2026 00:00:00 GMT

Abstract The cerebellum, with its distinctive architecture and extensive cortical connections, has long been recognized for its highly structured interconnectivity with the cortex and has been proposed as part of a larger circuit that shapes brain network dynamics. Here, we evaluate dynamic network reconfigurations in resting-state fMRI connectivity pre- and post-noninvasive inhibitory repetitive transcranial magnetic stimulation targeting the right Crus I of the cerebellum. Using dynamic community detection to evaluate the stimulation’s effect on modular network structures, we characterize the network properties by which cerebellar stimulation spreads through the cortex. We find that: (a) the flexibility, or the likelihood of network nodes to change module allegiances, increased post stimulation; (b) the dynamic patterns by which module allegiances emerged and evolved were highly individual and did not follow a single functional prototype; and (c) the cerebellar nodes had connectivity properties of integrators for distinct network modules. These results are consistent with the idea that cerebellum is pivotal in modulating distributed cortical activity by restructuring the integration and segregation of neural networks. This integrative capacity of the cerebellum may underlie its proposed role in coordinating neural systems, including those supporting higher cognitive function.

Multimodal Imaging Investigation of the Dentato‐Thalamo‐Cortical Pathway in Friedreich's Ataxia

Wed, 21 Jan 2026 00:00:00 GMT

BACKGROUND: Friedreich's ataxia (FRDA) is a spinocerebellar neurodegenerative disorder. The dentato-thalamo-cortical (DTC) pathway, an important cerebellar output involved in motor control, plays a crucial role in the neural mechanisms underlying ataxia symptoms in FRDA. OBJECTIVE: The aim was to quantify regional alterations in structure, connectivity, function, and neurometabolism along the DTC pathway in FRDA patients using multimodal magnetic resonance imaging (MRI). METHODS: Twenty-two individuals with FRDA and 22 healthy controls underwent a brain MRI. Volumetry, amplitude of low-frequency fluctuation of resting-state functional MRI data, and phosphorus MR spectroscopy were used to assess key regional changes along the DTC pathway. Diffusion tractography and dynamic causal model (DCM) were adopted to investigate microstructural integrity and effective connectivity of the DTC pathway, respectively. Associations with clinical parameters, including ataxia severity, were also tested. RESULTS: Compared to controls, FRDA patients exhibited reduced volumes and adenosine triphosphate levels in the bilateral dentate nuclei and right motor cortex, as well as elevated glycerophosphoethanolamine levels in thalami and the left motor cortex. In FRDA patients, fractional anisotropy was decreased in the dentatothalamic sections of the DTC tract and correlated negatively with ataxia severity. Additionally, DCM revealed elevated excitatory connectivity from the right thalamus to the left dentate nucleus in FRDA patients, showing a U-shaped association with ataxia scores. CONCLUSIONS: This study provides multimodal imaging evidence for comprehensive alterations along the DTC pathway in FRDA, including first insights into energy metabolism and effective connectivity. A better pathophysiological understanding of early metabolic and dynamic pathway disruptions might inform potential neuromodulatory interventions targeting this pathway. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Modeling human visuomotor adaptation with a disturbance observer framework

Wed, 04 Feb 2026 00:00:00 GMT

A fundamental problem of visuomotor adaptation research is to understand how the brain is capable to asymptotically remove a predictable exogenous disturbance from a visual error signal using limited sensor information by re-calibration of hand movement. From a control theory perspective, the most striking aspect of this problem is that it falls squarely in the realm of the internal model principle of control theory. Despite this fact, the relationship between the internal model principle and models of visuomotor adaptation is currently not well developed. This paper aims to close this gap by proposing an abstract discrete-time state space model of visuomotor adaptation based on the internal model principle. The proposed DO Model, a metonym for its most important component, a disturbance observer, addresses key modeling requirements: modular architecture, physically relevant signals, parameters tied to atomic behaviors, and capacity for abstraction. The two main computational modules are a disturbance observer, a recently developed class of internal models, and a feedforward system that learns from the disturbance observer to improve feedforward motor commands.

Consensus Paper: Models of Cerebellar Functions

Mon, 09 Feb 2026 00:00:00 GMT

For a long time, from the nineteenth century to most of the twentieth century, the cerebellum was thought to be an organ that regulates movement. Towards the end of the twentieth century, the brain functions associated with the cerebellum began to extend beyond motor control. Now, there is a consensus that the cerebellum is involved not only in motor functions but also in the most basic autonomic functions and the most complex cognitive and emotional functions, with a focus on predictions and internal models. A new functional model of the cerebellum is needed to explain all layers of brain functions by extending predictive computations in the cerebellum. On the other hand, the cerebellum and the basal ganglia were believed to be independent and complementary motor centers that lacked direct neural connections. For example, in neurophysiology classes in the 1980s, the characteristics of cerebellar ataxia were summarized as hyperkinetic and hypotonia, while the characteristics of Parkinson's disease (traditionally classified as "basal ganglia disorder") were summarized as hypokinetic and hypertonia, and therefore their functions were assumed at opposite poles, without interactions between the two main subcortical systems. The cerebellum and the basal ganglia were also assigned contrasting models regarding their learning mechanisms. Namely, the cerebellum was assumed to employ supervised learning with error signals, while the basal ganglia were assumed to employ reinforcement learning with reward prediction errors. However, recent neuroanatomical studies have demonstrated a number of novel connections between them, questioning their independence. Moreover, recent single-neuron recording and inactivation studies provided evidence that the cerebellum may also be involved in reinforcement learning. The cerebellum is neither independent of the basal ganglia nor exclusively specialized for supervised learning. We now need a new, general model to explain the contradiction between the known uniformity of the cerebellar cortex's structure and the newly added diversity of brain functions to which the cerebellum contributes. This consensus paper summarizes many of the seeds of such a new theory. The panel of experts (1) highlights the importance of the anatomical connectivity between cerebellar circuitry and basal ganglia, (2) points out that the anatomy of the cerebellum is unique and allows predictive computations in motor and extra-motor domains such as cognition, affect, social interactions and reward processes, (3) underlines the need to further elucidate the nature of interactions between cerebellar cortex and cerebellar nuclei to better understand cerebellar and psychiatric disorders and (4) suggests that common operations may underlie the motor and non-motor functions of the cerebellar circuitry. Cerebellar models remain a major topic of research to improve our understanding of the numerous cerebellar activities and to better understand the complexity of cerebellar disorders.

Value of MRI Outcomes for Preventive and Early‐Stage Trials in Spinocerebellar Ataxias 1 and 3

Tue, 10 Feb 2026 00:00:00 GMT

OBJECTIVE: To examine the value of MRI outcomes as endpoints for preventive and early-stage trials of two polyglutamine spinocerebellar ataxias (SCAs). METHODS: A cohort of 100 participants (23 SCA1, 63 SCA3, median Scale for the Assessment and Rating of Ataxia (SARA) score = 5, 42% preataxic, and 14 gene-negative controls) was scanned at 3T up to 6 times (median follow-up 3 years) in the READISCA study. Structural, microstructural, and neurochemical outcomes were assessed for sensitivity to change. Associations between change in MR and clinical and patient-reported outcomes were evaluated. Sample sizes were estimated for preventive trials (at preataxic stage) and early-stage trials using the most sensitive outcomes. RESULTS: Infratentorial volumes, middle cerebellar peduncle (MCP) diffusivities and select neurochemical outcomes were more sensitive to change than SARA in both SCAs with moderate-to-high effect sizes (Cohen's d ≥ 0.5). The pons volume was the most sensitive outcome at both preataxic (d = 1.09) and ataxic (d = 1.48) stages. The most sensitive MR measures overlapped between genotypes, except that SCA1 showed faster progression in the cerebellum and SCA3 in the pons. Changes in MCP diffusivities and pontine neurochemical measures were associated with changes in SARA and FARS-ADL (|r| = 0.28-0.47). INTERPRETATION: The estimated sample sizes to detect a 50% reduction in progression with 80% power using the pons volume as primary outcome measure indicate the feasibility of preventive trials (n = 73 per arm in a 1-year trial) in common SCAs and predict a 6-fold reduction in required sample sizes relative to SARA in early interventional trials. These findings support the use of MRI endpoints in early-stage SCA trials.

Predictive processes linking sense of agency and fatigue: a novel allostatic framework

Thu, 02 Apr 2026 00:00:00 GMT

The sense of agency and the experience of fatigue are usually treated as separate constructs: one concerning perceived control over action, the other reflecting subjective energetic state. However, both rely on how the brain predicts, evaluates, and updates information about the body and its actions. Despite this conceptual proximity, the two phenomena have rarely been examined together, and no unified framework currently explains why changes in perceived control and perceived effort so often co-occur. The aim of this review was to provide such integrative framework. We first examined behavioral, clinical, and neuroimaging evidence indicating that both agency and fatigue rely on the precision of anticipatory models that guide action and bodily regulation. When predictions align with incoming sensory and interoceptive signals, individuals experience a stable sense of control and low perceived effort. When these predictions become imprecise or mismatched, disruptions can arise in both domains. We then evaluated existing theoretical models for agency and fatigue and highlighted the limitations of accounts that treat the two phenomena independently or assume unidirectional relationships. Building on these limitations, we propose an allostasis-based model in which agency and fatigue emerge from the same anticipatory system governing energy regulation. In this view, perturbations in prediction can propagate across systems, producing parallel disruption in perceived control and effort. This new integrative perspective underscores the need for research designs that assess agency and fatigue jointly and provides a conceptual foundation for understanding their co-occurrence across healthy and clinical populations.

Cerebellar Time and Relative Time: A Comparator-Based Dynamical Timing Model and its Relevance to Psychopathology and Therapies

Tue, 14 Apr 2026 00:00:00 GMT

Time perception is fundamental to adaptive behavior, providing the scaffold for prediction, coordination, and learning. The cerebellum has long been recognized as a core hub for interval timing, yet its role extends beyond motor control to perceptual chronometry, reinforcement learning, and affective regulation. Here we introduce a novel framework, a Comparator-Based Dynamical Timing (CDT) model which describes distortions of subjective time as transformations that yield compression, dilation, and changes in temporal precision. In this account, subjective time is scaled by a gain factor κ. When κ > 1, subjective time dilates; when κ < 1, subjective time compresses. We synthesize convergent evidence from cerebellar anatomy, physiology, and computational modeling, and show how time distortions in psychiatric, neurodegenerative and neurodevelopmental disorders can be interpreted in the context of altered cerebellar temporal processing. We argue that cerebellar circuits operate in concert with cortical and basal ganglia oscillators in a comparator role, minimizing temporal deviation and maximizing precision. We propose that dysfunction across these interconnected networks contributes to distortions in subjective time perception observed in schizophrenia, bipolar disorder, depression, anxiety, post-traumatic stress disorder, autism spectrum disorder), and motor and movement disorders including Parkinson’s Disease. This framework provides a quantitative tool to predict and monitor the progression of psychiatric and neurodevelopmental/neurodegenerative disorders characterized by disrupted timing networks. Beyond diagnostic utility proposing an EEG-informed approach to track deviations in time perception, it also offers a translational platform for testing novel interventions, including non-invasive neuromodulation such as transcranial magnetic stimulation.

Association Between Cerebellar Metabolic Markers and Activities of Daily Living in Patients With Spinocerebellar Ataxia Type 3

Wed, 01 Apr 2026 00:00:00 GMT

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder that results in the impaired ability to perform activities of daily living (ADLs). However, there is a lack of objective neuroimaging indices to assess functional decline. In this study, we investigated the association between cerebellar metabolic rate as detected by magnetic resonance spectroscopy (MRS) and ADL performance in patients with SCA3. METHODS: A total of 23 SCA3 patients underwent multivoxel MRS scans of the cerebellar cortex, dentate nucleus, and vermis and were analyzed for associations between the metabolic ratio and the ability to perform activities of daily living (ADL). Metabolic ratios were quantified and correlated with Barthel Index scores. The predictive value of metabolic ratio was assessed using multiple regression and least absolute shrinkage and selection operator (LASSO) analysis. RESULTS: Our results showed that the NAA/Cr and Cho/Cr ratios in all three brain regions were significantly correlated with higher Barthel Index scores (r = 0.66), indicating a link between neuronal integrity, membrane metabolism, and functional independence. Regression analyses confirmed these associations, and the exploratory LASSO analysis suggested that the combined markers may have potential predictive value in patients' daily lives. CONCLUSION: Cerebellar NAA/Cr and Cho/Cr ratios may serve as candidate neuroimaging biomarkers of functional status in patients with SCA3. These preliminary results warrant validation in future studies using advanced MRS quantitative analysis.

Spinocerebellar Ataxia Type 23 (SCA23): A Rare Cause of SCA in the Americas

Mon, 20 Apr 2026 00:00:00 GMT

Spinocerebellar ataxia type 23 (SCA23) is a rare autosomal dominant hereditary ataxia caused by a pathogenic variant in the PDYN gene. It usually presents in adulthood, with a mean age of onset around 43 ± 15 years (reported range: 10–73 years), and progresses slowly with cerebellar symptoms. We report a case of a Brazilian 25-year-old female patient whose symptoms began at 19 years of age, characterized by progressive dysarthria, tremor, dysphagia, and gait disturbance. She had no relatives with similar symptoms. The initial genetic ataxia panel, which included the most prevalent hereditary ataxia genes, was negative. Subsequent next-generation sequencing identified a pathogenic variant in the PDYN gene, confirming the diagnosis of SCA23. Brain MRI demonstrated significant cerebellar atrophy. The patient was referred to a multidisciplinary rehabilitation group with emphasis on functional rehabilitation of gait and dysphagia. This case is notable for the rarity of SCA23 in the Americas, the relatively young age at onset compared with the reported mean age in the literature, while still remaining within the previously described age range, and the absence of a family history of ataxia or other neurological symptoms, despite SCA23 having an autosomal dominant inheritance pattern.

Sensory basis of speech motor learning and memory

Fri, 24 Apr 2026 00:00:00 GMT

Changes to speech offer a quantifiable means to assess speech motor learning, and the resulting memory is thought to be motor in nature. Here, we evaluate this idea and show instead that memory for speech movements has a sensory basis. Speech motor learning, using altered auditory feedback, provides an experimental model to address this question as it involves auditory, somatosensory, and motor components to learning. Transcranial magnetic stimulation was used to disrupt auditory (superior temporal gyrus, STG), posterior somatosensory (S1), or motor (M1) cortex following speech motor learning. Retention tests were conducted 24 h later. It was found that following disruption of either STG or S1, motor memory retention was impaired whereas disruption of M1 led to retention that was no different than that of a no TMS control condition. The effects of disruption were specific to speech motor learning and did not interfere with speech production per se. Taken together, the findings support the notion that plasticity in the sensory cortex, both auditory and somatosensory, is necessary for speech motor learning and memory. In speech, changes to sensory systems enable the production of newly learned movements.

Serum Neurofilament Light Chain and GFAP Levels Are Associated with Structural Brain Connectivity in Parkinson’s Disease

Tue, 28 Apr 2026 00:00:00 GMT

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and widespread alterations in brain networks. Circulating biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect neuroaxonal damage and astroglial activation, respectively, but their relationship with large-scale brain connectivity remains poorly understood. Seventy-three PD patients and thirty-four healthy controls underwent diffusion magnetic resonance imaging. Whole-brain tractography was used to reconstruct structural connectivity networks, and graph-theoretical measures were derived. Serum NfL and GFAP levels were quantified, and their associations with network metrics and clinical variables were assessed. PD patients showed significant alterations in global and nodal network organization compared to controls. Higher NfL and GFAP levels were associated with reduced global clustering coefficient and efficiency, as well as increased path length and modularity. At the regional level, higher biomarker levels were associated with reduced network measures in the right thalamus and right cerebellar cortex. No significant associations were observed in healthy controls. These findings demonstrate that circulating biomarkers of neurodegeneration are linked to both global and regional disruptions of structural brain connectivity in PD, supporting the integration of blood-based biomarkers and connectomics to better characterize disease-related network alterations.

Age‐Related Low Frequency Amplitude Differences in Resting‐State Blood Oxygenation Level‐Dependent Signal in the Cerebellum

Fri, 01 May 2026 00:00:00 GMT

There is a growing interest to study cerebellar contributions to aging outside of traditional sensory processing and motor tasks. While cerebellar aging analyses typically utilize functional connectivity (FC) to study functional differences with age, this study aimed to identify a marker of healthy aging based on resting state blood oxygenation level dependent (BOLD) signal dynamics in the cerebellum. To do this, we investigated both Amplitude of Low Frequency Fluctuations (ALFF) and fractional ALFF (fALFF), semi-quantitative metrics of the strength of the BOLD signal. We found that fALFF is a highly repeatable metric of cerebellar function that demonstrates a significant increase in BOLD signal fluctuations at 0.008-0.1 Hz in cerebellar regions Crus I and II with aging. Furthermore, cerebellar fALFF of these regions was associated with FC to cortical regions across separate scanning sessions. These results highlight age-related differences in spontaneous cerebellar dynamics, particularly in regions tied to the frontal cortex, motivating the use of fALFF as a potential biomarker of healthy aging and motivate the need to incorporate the cerebellum in existing models of brain network changes with age.

Cerebellar growth is associated with domain-specific cerebral maturation and socio-linguistic behavior

Wed, 13 May 2026 00:00:00 GMT

The cerebellum's involvement in cognitive functions is increasingly recognized, yet its developmental contribution to cognition remains poorly understood. The cerebellum undergoes rapid development in early life, paralleling major cognitive and behavioral changes. Although clinical studies have linked early cerebellar disruptions to profound developmental deficits, it remains largely unclear how typical cerebellar maturation supports the development of cognitive functions and how it interacts with broader cerebral development. Here, we apply a normative modeling framework to map cerebellar volumetric growth from age one to young adulthood (N = 751; ages 1-21 years). Using both lobular and functional cerebellar parcellations, we characterize typical cerebellar development from late infancy and its relationship to cerebral development and behavioral performance in childhood through adulthood. Across parcellations, association areas consistently show steeper growth trajectories than sensorimotor areas. Cerebellar and cerebral areas with similar functional roles demonstrate coordinated maturation, and volumetric growth in the posterior cerebellum relates to individual differences in socio-linguistic behaviors. These findings establish a comprehensive reference for typical cerebellar development, highlight cerebellar co-maturation with the cerebral cortex, and underscore the cerebellum's role in supporting the development of cognitive functions.

Synchronous climbing fiber activity enables instructive signaling for cerebellar learning through modulation of disinhibitory circuits

Thu, 14 May 2026 00:00:00 GMT

Motor learning relies on signals that instruct adaptive plasticity following errors. In the cerebellum, climbing fibers (CFs) provide these instructions to Purkinje cells (PCs). Yet CFs fire continuously, even without errors, requiring molecular layer interneuron (MLI) inhibition of PCs to counteract CF excitation and prevent maladaptive plasticity. Here, to identify how this regulatory inhibition is contextually suppressed to selectively permit error-driven learning in mice, we combined connectomics, functional recordings, computational modeling and behavioral manipulations. We discovered that CFs target not only PCs but also a specific MLI subtype that inhibits PC-targeting MLIs, creating serial disinhibition. These disinhibitory MLIs integrate multiple CFs, causing increased activation with CF synchrony. This stronger disinhibitory drive allows larger CF-evoked calcium responses in PCs. Disruption of MLI-to-MLI inhibition prevents CF-instructed motor learning, confirming the necessity of this disinhibitory pathway. Therefore, population synchrony selectively enables CF-driven plasticity through disinhibitory network interactions, demonstrating that instructive signaling is a product of circuit-level processing. Combining connectomics, physiology and behavior, this study shows how the cerebellum decides when to learn. Synchronized climbing-fiber error signals lift an inhibitory signal gate on Purkinje cells, enabling synaptic plasticity and motor adaptation.

Inhibitory Circuits of the Sensorimotor Network are Not Modulated By Cerebellar Transcranial Direct Current Stimulation in Isolated Cervical Dystonia

Sat, 16 May 2026 00:00:00 GMT

Impaired cerebellar influence on motor cortical excitability and plasticity has been reported in cervical dystonia (CD) patients, accompanied by the absence of cerebellar brain inhibition (CBI). Polarity-specific modulation of CBI in healthy individuals using cerebellar transcranial direct current stimulation (ctDCS) suggested that ctDCS could normalize abnormal cerebellar output and improve clinical symptom severity in CD. The objective of this study was to determine whether anodal or cathodal ctDCS can modulate neurophysiological parameters of cortico-cortical, cerebello-cortical or afferent inhibition and improve motor symptom severity in CD patients. Fifteen patients with isolated CD participated in a randomized, double-blinded crossover study consisting of three sessions of anodal, cathodal, or sham ctDCS. Before and after each intervention, motor symptom severity and inhibitory circuits of the sensorimotor network were investigated using transcranial magnetic stimulation (TMS), including short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI) and CBI. Baseline TMS measurements showed inhibitory influence of SICI (p < 0.001) and SAI (p < 0.001) in CD patients, whereas CBI had no inhibitory effect (p = 0.281). The different ctDCS interventions caused no significant modulation in any of the inhibitory TMS paradigms investigated. Similarly, motor symptom severity remained unchanged after the ctDCS interventions. A single session of ctDCS was not effective to modulate inhibitory circuits of the sensorimotor network in isolated CD patients. Future studies focusing on repetitive ctDCS interventions or multifocal stimulation protocols are needed to assess the influence on network excitability and connectivity as well as on motor symptoms.

Assessing subcortical, brainstem and cerebellar metabolic patterns using [18F]FDG PET-CT imaging in dementia with Lewy bodies

Mon, 08 Jun 2026 00:00:00 GMT

Abstract Purpose Numerous clinical features of Dementia with Lewy Bodies (DLB) are attributed to dysfunction in subcortical anatomy. Despite this, [ 18 F]FDG PET imaging as a diagnostic tool for DLB largely relies on the metabolic signature of the occipital lobe, precuneus, and posterior cingulate cortex. This study aimed to assess subcortical brain metabolism in patients with DLB using [ 18 F]FDG PET imaging. Methods Patients diagnosed with probable DLB were included from both a prospectively maintained regional database ( n = 33), and the ADNI database ( n = 43). Using statistical parametric mapping (SPM) analysis, metabolic activity was compared with a cohort of subjects exhibiting normal brain metabolism ( n = 19). A sub-analysis was conducted with disease progression included as a covariate. Results Hypermetabolism was observed in various subcortical regions, notably in the dentate nucleus, anterolateral thalamus, and regions of the superior cerebellar peduncle. Increased metabolism was also detected in the mesencephalic tectum, likely representing heightened activity in the superior colliculus. All findings were reproduced in the ADNI cohort and were found to be dependent on the DLB disease stage. Additionally, the well-established cortical hypometabolic signature of DLB pathology was evident, validating our methods and findings. Conclusion Increased metabolic activity is evident in a variety of brainstem, cerebellar, and subcortical regions in patients with DLB. The dentatorubrothalamic tract, in particular, emerges as a structure of interest that connects these structures and potentially helps in understanding DLB pathophysiology. Correction for disease stage eliminated this pattern, suggesting a driver associated with disease progression.

Driving Cerebellar Theta Oscillations Interferes With Voluntary Neck Movements in Cervical Dystonia

Wed, 10 Jun 2026 00:00:00 GMT

BACKGROUND: Cervical dystonia (CD) is a movement disorder with a complex pathophysiology, including cerebellar abnormalities. Transcranial alternating current stimulation (tACS), a noninvasive neuromodulation technique capable of entraining brain oscillations, can transiently modulate neuronal activity and enhance resonant rhythms. OBJECTIVE: The aim of this study was to explore whether cerebellar tACS delivered at specific cerebellar-resonant frequencies modifies fast voluntary neck movements in patients with CD and whether botulinum toxin (BoNT) therapy influences tACS effects. METHODS: Eighteen patients with CD, predominantly exhibiting the torticollis phenotype, were included. Fast voluntary neck movements were objectively assessed using motion analysis during two experimental sessions: (1) pre-BoNT and (2) 1 month after BoNT. Cerebellar tACS was applied at theta (θ), beta (β), and gamma (γ) frequencies, along with sham stimulation, while patients performed fast neck movements. Peak angular velocity and angular amplitude of both prodystonic and antidystonic movements were measured. RESULTS: In the OFF-BoNT state, neck (antidystonic) movements' velocity and amplitude decreased with θ-tACS, particularly when stimulation was applied to the cerebellar hemisphere ipsilateral to the side of torticollis. BoNT ameliorated movement velocity and amplitude, but it did not change the detrimental effect of cerebellar θ oscillations on antidystonic movements. CONCLUSIONS: Driving cerebellar θ oscillations interferes with the execution of fast voluntary neck movements in CD, and BoNT therapy does not influence this effect. These findings support the view of dystonia as a network disorder in which the cerebellum plays a key role. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neuroplasticity in Spinal Circuits Mediated by Sexual Experience and Cerebellar Lobules

Thu, 11 Jun 2026 00:00:00 GMT

Objective: We aimed to determine whether sexual experience modulates the soleus H-reflex in male rats and to assess the specific contribution of vermis lobules 6a and 7 to cerebellar-dependent spinal plasticity. Methods: Thirty-six male Wistar rats were divided into sexually inexperienced (SI) and sexually experienced (SE) groups and assigned to one of three cerebellar conditions: intact control, lobule 6a lesion, or lobule 7 lesion. SE rats underwent repeated mating sessions until they achieved efficient copulatory performance. Subsequently, targeted electrolytic lesions were made, and electromyographic recordings of the soleus H-reflex were obtained under urethane anesthesia to quantify H-wave amplitude and temporal parameters. Results: The global linear mixed model yielded no significant main effects of sexual experience, cerebellar condition, or their interaction on H-wave amplitude. Planned contrasts revealed a near-significant trend toward higher H-wave amplitude in sexually experienced intact animals compared with inexperienced controls (p = 0.061, Cohen’s d = 0.592, 95% CI [−1.44, 0.04] V), and significant amplitude reductions following lobule 6a (p = 0.029, d = 1.450, 95% CI [0.13, 2.33] V) and lobule 7 (p = 0.002, d = 2.256, 95% CI [0.74, 3.08] V) lesions specifically in sexually experienced animals. Neither sexual experience nor lesions significantly affected H-wave latency or duration, suggesting that modulation primarily targets synaptic excitability rather than axonal conduction. M-wave latency showed a significant effect of sexual experience (p = 0.026, d = 1.405, 95% CI [0.03, 0.45] ms). Conclusions: Sexual experience appears to be associated with cerebellar-dependent modulation of soleus H-reflex excitability; lobules 6a and 7 of the cerebellar vermis contribute to this effect specifically in experienced animals. Shorter M-wave latency in experienced animals suggests parallel peripheral motor reorganization. Adequately powered confirmatory studies are needed to characterize the mechanisms underlying this association.

Cerebellar Kv2.1 downregulation, cytoarchitectural alterations, and persistent motor impairments following subchronic phencyclidine exposure

Fri, 12 Jun 2026 00:00:00 GMT

Dysfunction of the cerebellum is increasingly recognised as a contributor to schizophrenia. As one of the most ubiquitous voltage-gated potassium channels in the brain, the expression and function of Kv2.1 remains underexplored in the cerebellum, and its potential involvement in cerebellar pathophysiology in schizophrenia is unknown. Here, we characterised the expression pattern of Kv2.1 in the cerebellar cortex and examined its changes, along with cerebellar cytoarchitecture, in a subchronic phencyclidine male mouse model of schizophrenia. Behavioural performance was assessed throughout phencyclidine treatment and during a one-week washout using the horizontal bar, vertical pole, and beam walk tests, focusing on indices of fine motor coordination and balance. Significant alterations emerged during treatment. Notably, four parameters, the number of swings on the bar, time to complete the T-turn, time to cross the beam, and number of foot slips, remained impaired after washout, indicating persistent deficits in motor coordination and balance. Fluorescence imaging showed Kv2.1 expression on the soma, proximal dendrite, and axon initial segment of Purkinje cells, and in granule cell somata and dendrites. After washout, Western blot revealed reduced cerebellar Kv2.1 levels, corroborated by fluorescence analyses showing downregulation in both Purkinje and granule cells. In addition, cytoarchitectural changes were detected, including globally reduced Purkinje cell soma size and a hemisphere-specific decrease in NeuN-positive granule cell density. Overall, this study provides a descriptive account of cerebellar cytoarchitectural and Kv2.1 expression changes, alongside persistent motor impairments, associated with subchronic phencyclidine exposure, warranting future studies on mechanistic links between cerebellar neuropathology and behavioural performance.

Behavioral correlates of Purkinje cell ensemble covariance

Fri, 19 Jun 2026 00:00:00 GMT

Purkinje cells (PCs) mediate adaptive cerebellar output through inhibitory control of the cerebellar nuclei. Because many PCs converge, their influence on target neurons likely depends on population activity. However, despite a large literature on individual PC relationships with behavior, little is known about how multiple PCs collaborate to influence movement. In simultaneously recorded PCs during mouse forelimb reach behavior, we found that different kinematic variables correlated either with PC firing rates or covariance: reach velocity and deceleration correlated with firing rates, while the coordination of these kinematic variables, which influences reach amplitudes, was related to covariance. In a model, physiological levels of PC covariance elevated nuclear firing rates, which could promote faster reach deceleration than the same conditions with low covariance. These findings suggest a role for coherent PC population activity to coordinate movement. Little is known about how cerebellar population activity controls movements in ways distinct from individual neuron correlations. Here the authors show that Purkinje neuron population covariance uniquely influences motor coordination in mice.

Synaptophysin density underestimates synapse counts in the human brain – An anatomical study on synaptoporin protein expression

Tue, 23 Jun 2026 00:00:00 GMT

Synaptoporin (SPO; synaptophysin II) has classically been described as a presynaptic vesicle protein enriched in the hippocampal mossy fiber pathway, distinguishing it from the ubiquitously expressed synaptophysin I (SYP). However, its distribution and synapse-type specificity in the human brain have not been studied yet. Here, we comprehensively mapped SPO protein expression across multiple human brain regions using immunofluorescence staining of post mortem tissue and biochemical analysis of brain lysates. We identified high SPO protein expression in the hippocampus, cerebral cortex, and dorsal horn of the spinal cord; moderate expression in the cerebellum and amygdala; and low levels in the putamen. The analyzed brainstem regions and the thalamus were devoid of SPO. Notably, SPO was present in distinct components of the human auditory pathway, mirroring rodent patterns. Colocalization analyses revealed largely separate distributions of SPO and SYP, challenging the concept of SYP as 'pan-synaptic' marker. In the cerebral cortex, a region with pronounced SPO expression, SYP-based synapse quantification underestimated total synapse numbers by up to 35%, a result replicated across independent brain tissue sources. SPO puncta were associated with both excitatory and inhibitory synaptic markers, reflecting the highly heterogeneous human synaptome. Collectively, these findings demonstrate that SYP-only assays overlook a substantial subset of synapses and they highlight the combinatorial complexity of vesicle protein expression in the human brain. This work establishes SPO as a critical determinant of synaptic diversity and can serve as reference to identify vulnerable synaptic subtypes in neurodegenerative diseases.

Anticipation strategies of motor control in children and adolescents with cerebellar pathologies and typical development: a dual task paradigm

Wed, 24 Jun 2026 00:00:00 GMT

Background: Besides ataxia, cerebellar pathologies are often associated with neuropsychological deficits, particularly in executive attention. The cerebellum is considered a key hub of the predictive brain network, interacting with prefrontal and parietal areas through the basal ganglia. Anticipating the sensory consequences of motor actions and comparing them with actual feedback supports feedforward control, improving coordination, processing speed, and reducing errors. It also contributes to integrating subcortical-cortical networks during dual-task conditions. We hypothesized that impaired anticipatory strategies contribute to motor control deficits in cerebellar patients. Specifically, fine upper-limb motor control would worsen when combined with concurrent neuropsychological and cerebellar tasks (verbal anticipation and timing), compared with a working memory task or a single motor task. Therefore, we aimed to investigate dual-task abilities in cerebellar patients. Method: In total, 24 participants affected by cerebellar pathologies (mean age was 13y 1 m; 16 females) and 24 participants with typical development (mean age was 13y 1 m; 14 females) were required to execute a single visuo-motor precision task (single task condition) alone and with concurrent verbal anticipation, verbal timing, and verbal nBack tasks. Execution time and accuracy were analyzed as dependent variables combined in a single index [Inverse Efficacy, IE = RT/(1-pE)] and separately. Results: The results showed that the dual-task condition negatively affects the fine motor control of the upper limb in the two groups. A significant negative effect of the anticipation task was found for both the cerebellar and control groups. The cerebellar group presented a significant negative effect on the nBack task as well. Discussion: The results are consistent with the models describing the cerebellum as a key hub in anticipatory control, probably through predictive network synchronization. The anticipatory control is a damaged component in the control deficit of cerebellar patients. Finally, the cerebellar role in synchronizing the different cerebral networks involved in dual-task processing is strengthened. This study underlines the crucial role of anticipatory and feedforward mechanisms in motor control of both typically developed children and those with cerebellar pathologies and defines the importance of predictive neuropsychological skills in cognitive and motor fluidity.

Chronic pantoprazole exposure induces behavioral deficits and region‑specific molecular changes in the rat motor cortex and cerebellum

Thu, 25 Jun 2026 00:00:00 GMT

Proton pump inhibitors are widely used, but their long‑term effects on the central nervous system are not well understood. In this study, we investigated whether chronic pantoprazole use alters sensorimotor function, oxidative stress, inflammatory response, and apoptosis in the motor cortex and cerebellum. Twenty‑one female Wistar rats were randomized to control (C), gavage control (GC), or pantoprazole (P; 20 mg/kg/day for 12 weeks) groups. Sensorimotor coordination (rotarod), water‑maze swim velocity, and open‑field locomotion were assessed as behavioral parameters. The cortical and cerebellar tissues were analyzed by Enzyme‑Linked Immunosorbent Assay (ELISA) for apoptosis, inflammation, and oxidative stress. Pantoprazole impaired sensorimotor coordination compared to both control groups. However, its effects on swim velocity and locomotor activity were primarily significant when compared to the naive control group, suggesting that gavage‑related stress may have contributed to these behavioral outcomes. Bcl‑2‑associated X protein (BAX) and Bcl‑2 associated agonist of cell death (BAD) protein levels and the BAX/Bcl‑2 ratio increased with pantoprazole, particularly in the motor cortex, indicating enhanced pro‑apoptotic activity. While tumor necrosis factor levels did not change, interleukin (IL)‑6 and IL‑1β levels were significantly higher in the cerebellum, suggesting neuroinflammatory activation associated with both pantoprazole and gavage‑induced stress. Furthermore, oxidative stress analyses revealed elevated malondialdehyde and oxidative stress index levels, as well as increased total antioxidant status, in specific regions, suggesting an imbalance between oxidative and antioxidant responses. Chronic pantoprazole administration resulted in modest motor deficits and region‑specific molecular alterations, including a pro‑apoptotic shift in the motor cortex. In addition, an inflammatory/compensatory antioxidant response in the cerebellum was observed due to both gavage‑induced stress and pantoprazole administration. These findings highlight the need for further studies on dose‑response, reversibility, and synaptic consequences, and suggest the importance of considering the risks of prolonged proton pump inhibitors exposure.

Biochemical Pathways of Neuroplasticity in Sport Skill Acquisition: From Neuroscience to Coaching Practice

Tue, 30 Jun 2026 00:00:00 GMT

Background/Aim: Motor skill acquisition is the foundation of athletic performance, from the novice learning a new technique to the elite athlete executing complex movements automatically under pressure. Although classical models have defined the neural substrates of motor control—the cerebellum for error correction, the basal ganglia for action selection, and the primary motor cortex (M1) for execution—emerging evidence suggests that motor learning is the result of the dynamic interaction of multiple parallel processes rather than a linear hierarchy. This narrative review integrates classical neuroanatomical knowledge with contemporary findings on multisite plasticity, with a particular focus on sport-specific adaptations. Methods: We examined three core learning mechanisms operating in parallel: error-based learning (cerebellar-dependent, driven by sensory prediction errors), reinforcement learning (striatal-dependent, driven by reward prediction errors and dopamine), and use-dependent learning (cortical-dependent, driven by mere repetition). We also summarize the biochemical pathways supporting these learning processes, including glutamatergic LTP-like cortical plasticity, cerebellar mGluR1–PKC–LTD signaling, dopaminergic corticostriatal plasticity, BDNF–TrkB-dependent neurotrophic mechanisms, growth-factor signaling, and exercise-induced muscle–brain communication. Results: We then propose a spatiotemporal model in which the relative contribution of each network shifts dynamically across the three stages of skill acquisition, from the early cognitive/strategic phase to the late automatic phase characteristic of elite performance. At the molecular level, these stage-dependent adaptations are supported by synaptic strengthening and weakening mechanisms, reward-dependent dopamine signaling, neurotrophic and growth-factor-mediated remodeling, and peripheral metabolic/myokine signals that modulate brain plasticity during training and recovery. Special attention is given to contextual and sport-specific adaptations, using the paradigmatic example of elite swimmers who demonstrate enhanced short-interval intracortical inhibition (SICI) selectively in the aquatic environment, reflecting long-term sport-induced neuroplasticity. Conclusions: Understanding these dynamic network mechanisms has direct implications for coaching, training periodization, and the development of targeted neuromodulatory interventions to accelerate skill acquisition and optimize athletic performance.

Adipose-Derived Mesenchymal Stem Cells Improve Motor Function and Reduce Neuroinflammation and Mutant Ataxin-3 Protein Levels in SCA3 Mice

Thu, 02 Jul 2026 00:00:00 GMT

The CAG expansion in the ataxin-3 (ATXN3) protein is the underlying cause of Spinocerebellar Ataxia Type 3 (SCA3), a polyglutamine disease.The aggregation of mutant ATXN3 protein is hypothesized to contribute to neuronal dysfunction, neurodegeneration, or neuroinflammation.Mesenchymal stem cells have pleiotropic therapeutic properties, and adipose-derived mesenchymal stem cells (ADMSC) have been shown to be safe and well-tolerated in SCA3 patients.In this study, we evaluated the therapeutic effects of ADMSC in SCA3 mice.In a mouse model of SCA3, the Purkinje-cell-specific L7 promoter drives the expression of a truncated form of human ataxin-3 with 69 glutamine repeats.SCA3 mice exhibited cerebellar Purkinje cell degeneration, reduced myelination, and increased gliosis; pathological features also observed in SCA3 patients.SCA3 mice received repeated intravenous administrations of ADMSC, and efficacy was assessed by rotarod performance, molecular and pathological changes, and serum neurofilament light chain (NfL) levels.ADMSC-treated SCA3 mice showed significant improvements in rotarod performance, a reduction in accumulated toxic mutant ATXN3-69Q protein in Purkinje cells, decreased demyelination, and alleviation of neuroinflammatory and systemic inflammatory responses during disease progression.Furthermore, NfL levels, a potential biomarker for SCA3 disease progression, were inversely correlated with the rotarod performance.Based on these findings, we conclude that ADMSC enhance motor function in SCA3 mice by reducing neuroinflammation, demyelination and aggregated mutant ataxin-3 protein levels in Purkinje cells.ADMSC have the potential to serve as a disease-modifying therapy for SCA3 patients.

Light-activated insulin receptor modulates neuronal plasticity and cerebellar-driven behavior

Wed, 01 Jul 2026 00:00:00 GMT

We have developed an optogenetic tool called InLOV-an insulin receptor fused to a LOV domain-that enables activation of the insulin receptor signaling pathway via light-induced phosphorylation of its intracellular domains. Light activation of InLOV promotes insulin-induced neuronal plasticity in the mouse cerebellum and enhances cerebellar-driven self-motion behavior. Thus, InLOV enables optogenetic modulation of insulin receptor phosphorylation, opening new possibilities for disease modeling and therapeutic strategies for pathological insulin signaling in humans.

EXPRESS: Paroxysmal Dyskinesia like movement disorder in a Ragdoll cat following a rostral cerebellar infarct

Fri, 03 Jul 2026 00:00:00 GMT

Case summary A 6-year-8-month-old neutered male Ragdoll cat was investigated for peracute right-sided neurological deficits consistent with a C1–C5 myelopathy. Initial MRI identified an intramedullary lesion at C2, most consistent with ischaemic myelopathy. The cat improved with physiotherapy; however, on day 21, it developed recurrent episodes of abnormal limb posturing and involuntary movements. Episodes comprised segmental dystonia with a spreading pattern, preserved consciousness, and no consistent autonomic signs, supporting a paroxysmal dyskinesia (PD)-like movement disorder rather than epileptic seizures. Brain MRI performed on day 24 identified a focal wedge-shaped lesion in the rostroventral right cerebellar hemisphere within the territory of the rostral cerebellar artery, consistent with a subacute infarct. Additional findings, including renal infarction supported multifocal thromboembolic disease. The temporal association between cerebellar infarction and onset of paroxysmal episodes supported a diagnosis of secondary PD. Clopidogrel was initiated. Further episodes occurred 46 and 87–90 days later; the latter cluster coincided with the presence of two visiting dogs. Two episodes were associated with owner-reported nystagmus alongside PD signs consistent with those observed previously. Relevance and novel information This report describes a novel PD-like movement disorder associated with cerebellar infarction in a cat. Unlike most reported feline PD cases, which are idiopathic or metabolic (hyperthyroidism), it supports a structural cerebrovascular aetiology involving cerebellar motor networks. Although causality cannot be definitively established, the findings support emerging concepts that paroxysmal dyskinesia may arise from dysfunction within distributed motor networks, including cerebellar–thalamo–cortical pathways, rather than being exclusively attributable to basal nuclei circuitry.

Efficacy and Safety of Transcranial Direct Current Stimulation on Multiple Health Outcomes in Neurological Disorders: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials

Mon, 15 Jun 2026 00:00:00 GMT

BACKGROUND: Neurological disorders are a leading cause of disability worldwide. Transcranial direct current stimulation (tDCS) is a promising therapeutic tool for neurological disorders. However, a consensus on clinical recommendations for using tDCS in patients with neurological disorders is lacking. In this umbrella review, we aimed to establish evidence-based guidance for using tDCS to treat neurological disorders. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 2020. PubMed/MEDLINE, Embase, the Cochrane Library, the Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were systematically searched to identify and evaluate existing systematic reviews and meta-analyses on the use of tDCS for neurological disorders. Quality was assessed using the Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. The Hartung-Knapp-Sidik-Jonkman random effects model was employed for reanalysis. RESULTS: A total of 17 systematic reviews and meta-analyses encompassing 358 randomized controlled trials and 7160 participants were analyzed. tDCS demonstrated efficacy across seven distinct health conditions, including stroke, Parkinson's disease, Alzheimer's disease, cerebellar ataxia, fibromyalgia, disorders of consciousness, and migraine. Adverse effects were rarely reported, with the exception of mood changes associated with fibromyalgia. Our results indicated that tDCS significantly improved 34 distinct health outcomes related to these conditions. CONCLUSIONS: We found that tDCS may be a promising treatment for neurological disorders, with mild and infrequent adverse effects. Further studies are warranted to validate the therapeutic potential of tDCS in the reported neurological conditions, investigate additional neurological health outcomes, and explore the underlying mechanisms of tDCS effects. The PROSPERO Registration: CRD42024589432, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024589432.

Brain organoids and brain disease organoids modeling in the age of artificial intelligence

Wed, 01 Jul 2026 00:00:00 GMT

Abstract The human brain governs bodily functions with exceptional complexity, yet neuroscience research is hindered by limited access to authentic human tissues, restricted availability of region-specific specimens, and a lack of physiologically relevant experimental models. Brain organoids and disease-specific brain organoids have emerged as transformative research platforms to address these bottlenecks. This review systematically summarizes advances in normal brain organoids, including cortical, cerebellar, meningeal, cerebrovascular, and blood–brain barrier models, as well as disease organoids recapitulating glioma, neurodegeneration, psychiatric disorders, neurodevelopmental defects, epilepsy, stroke and other neurological conditions. We highlight seven key translational advances of brain organoids in targeted therapy development, drug discovery and repurposing, brain–organ crosstalk, tumor brain metastasis, and longevity research. We further discuss the frontier interplay between carbon-based brain organoids and silicon-based artificial intelligence. Integrating stem cell biology, tissue engineering and clinical neuroscience, brain organoids greatly advance mechanistic research of neurological diseases and provide promising platforms for personalized medicine and regenerative therapeutics.

Polarity-dependent modulation of sensory circuits by cerebellar tDCS: local and distant effects

Thu, 09 Jul 2026 00:00:00 GMT

Cerebellar transcranial direct current stimulation (Cb-tDCS) is a promising tool for non-invasive modulation of cerebellar function and is under investigation for treating cerebellum-related disorders. However, its local and remote effects on sensory processing remain poorly understood. We investigated the immediate and long-term effects of Cb-tDCS on sensory-evoked responses in the cerebellum and primary somatosensory cortex (S1) of awake mice. Sensory-evoked potentials (SEPs) were recorded in Crus I/II and S1 during and after short (15 s) or long (20 min) sessions of anodal or cathodal Cb-tDCS. In addition, vGLUT1 and GAD65-67 immunoreactivity were quantified, and spectral changes in local field potentials were assessed. Anodal and cathodal Cb-tDCS respectively induced an immediate increase and decrease in the trigeminal component in Crus I/II but no aftereffects were observed 20 min post-stimulation. In S1, Cb-tDCS resulted in polarity and intensity-dependent modulation of the N1 component during stimulation, which was opposite to the changes induced in Crus I/II, as well as a polarity-dependent modulation after stimulation. In addition, anodal Cb-tDCS was associated with reduced GAD65-67 immunoreactivity in S1, whereas vGLUT1 remained unchanged. While power spectrum analysis revealed no changes in Crus I/II, Cb-tDCS induced polarity-dependent post-stimulation changes in S1 spectral power, with higher values after cathodal stimulation. These findings show that Cb-tDCS differentially modulates sensory processing in cerebellar and cortical circuits. While cerebellar effects are mainly transient, stimulation induces longer-lasting changes in the remote cortical area investigated, S1. This underscores the need to consider both local and distant network effects when applying Cb-tDCS in translational and clinical settings.

The Silent Triangle Speaks: Hypertrophic Olivary Degeneration Unveiled

Sat, 11 Jul 2026 00:00:00 GMT

Background: Hypertrophic olivary degeneration is an uncommon form of trans synaptic degeneration affecting inferior olivary nucleus. It mostly develops secondary to a destructive lesion involving the Guillain?Mollaret pathway. It presents with symptomatic palatal tremor, less frequently can cause dentatorubral tremor (Holmes tremor). In some cases, these tremors may also involve facial muscles, diaphragm, or muscles of the tongue and larynx.HOD commonly develops secondary to a focal lesion like haemorrhage, infarction, tumours, infection, inflammatory conditions, trauma, or post-surgical. In rare cases, HOD has been documented to be idiopathic. Case presentation: We present a case of a 29-year-old male with complaints of diplopia, syncopal attacks. On physical examination, ocular tremors was seen. Patient had no significant past medical history. There was no history of trauma, neurosurgical interventions.

Anatomical and Histological Characterization of Brain in the Long-legged Buzzard (Buteo rufinus)

Mon, 13 Jul 2026 00:00:00 GMT

This study was conducted to determine the macroscopic and light microscopic characteristics of the brain of the long-legged buzzard (Buteo rufinus), a diurnal bird of prey. The study utilized five adult long-legged buzzard that were brought to the Yozgat Directorate of Nature Conservation and National Parks and the Afyon Kocatepe University Wildlife Rescue and Rehabilitation Center as injured but could not be saved. The brain tissues of the long-legged buzzard were subjected to macroscopic and light microscopic examinations. Macroscopically, the pear-shaped brain was observed to have a smooth surface characteristic of birds. The olfactory bulbs were identified as having a reduced structure in the rostroventral region. A highly developed optic lobe was detected. It was determined that the cerebellum was large and laterally flattened, with 11 to 13 cerebellar folia separated by the fissura cerebelli. During light microscopic examination, it was observed that the cerebral cortex is enveloped externally by the pia mater and does not exhibit the typical laminar organization seen in mammals. The cerebellum was found to consist of three typical layers: the molecular layer on the outside, the Purkinje cell layer in the middle, and the granular layer on the inside. In the medulla oblongata, the pia mater, pyramidal cells, and glial cells were distinguished, while the optic lobe was found to consist of medium-sized spherical neurons and pyramidal cells, containing a small number of glial cells. The findings provide comprehensive neuroanatomical data on the brain structure of the long-legged buzzard and contribute to the comparative brain morphology and histology of diurnal birds of prey.

Advances in the Comprehensive Tree Shrew Brain Atlas

Tue, 14 Jul 2026 00:00:00 GMT

The tree shrew is a small mammal characterized by a short gestation period, a relatively short lifespan, and low maintenance costs. It exhibits a close genetic relationship with primates and humans. The tree shrew possesses an eight-layered neocortex, limited cortical gyrification, an expanded subventricular zone, and sensory, visual, and motor cortices that resemble those of primates, along with comparable neurotransmitter systems, cognitive potential, and neural flexibility. These features render it a promising animal model for neurological disease research. A comprehensive understanding of its brain morphology, neural projections, neural circuits, and neuronal diversity is crucial both in terms of elucidating normal brain function and in order to establish this species as a reliable model in investigations of the mechanisms underlying neural injury and neurodegenerative diseases. Currently, studies on tree shrew brain development remain limited. This review presents a comprehensive summary of two-dimensional (2D) and three-dimensional (3D) comparative anatomical studies based on brain region localization, histological section staining, and MRI-derived brain imaging data in the tree shrew. It also analyzes the developmental characteristics of neural progenitor cells in this species. Furthermore, the review compares brain atlases of mice, non-human primates (NHPs), humans, and tree shrews generated using single-cell sequencing and spatial transcriptomic technologies. Finally, it outlines future research directions that emphasize the importance of integrating morphology and functional neuroimaging data with multi-omics data to construct a multimodal, four-dimensional (4D) brain development atlas of the tree shrew.

Synaptic Ca2+ channels and neurexins are linked through direct and indirect binding complexes

Wed, 15 Jul 2026 00:00:00 GMT

Abstract Rapid release of neurotransmitters from presynaptic boutons is essential for brain function and is triggered by Ca 2+ influx through voltage-gated calcium channels (VGCCs), which consist of an α1 pore-forming subunit, intracellular β subunits, and mostly extracellular α2δ auxiliary subunits. Neurexins (Nrxn) regulate neurotransmission and presynaptic Ca 2+ influx, but the physical interactions with VGCC subunits remain unknown. Here, we examined these interactions in recombinant VGCC-Nrxn complexes using a nanobody-based co-precipitation system. We found that the α2δ-1 and α2δ-3 variants bind to the α1 pore-forming subunits of Ca V 2.1- and Ca V 2.2-type VGCCs with distinct preferences, whereas Nrxn1α and Nrxn1β do not directly interact with α1. Since Nrxn1α binds both α2δ variants but Nrxn1α/α2δ complexes do not include α1, mobile α2δ subunits may dynamically toggle between Nrxn1α and the Ca V core. Additionally, Nrxn1α associates with α1 subunits independently of α2δ through the intracellular scaffold protein Mint2, which enhances Nrxn1α/α2δ complex formation by inhibiting full glycosylation of α2δ. Extracellularly shorter Nrxn1β cannot bind α2δ but can indirectly associate with Ca V 2 α1 pore-forming subunits via either Mint2 or CASK proteins. Therefore, our findings reveal distinct molecular complexes through which αNrxn and βNrxn variants interact with VGCC subunits to regulate presynaptic Ca 2+ influx. (196 words)

Toxicological assessment of the hydroethanolic extract of Sterculia setigera leaves', a neuroactive medicinal plant of Togolese flora

Wed, 15 Jul 2026 00:00:00 GMT

Background: Sterculia setigera is a plant used in traditional medicine for many purposes. We previously reported that its dry hydroethanolic leaf extract (SSE) protected cerebellar granule neurons and PC12 cells against H₂O₂, 6-OHDA, and serum deprivation-induced cell death, and mitigated ethanol neurotoxicity in the cerebellar cortex of neonatal Wistar rats while preserving motor coordination. This study aims to establish the toxicological profile of Sterculia setigera leaves' hydroethanolic extract, using appropriate in vitro and in vivo models. Methods : The brine shrimp (Artemia salina) lethality assay served as a cytotoxicity test (in vitro model). An acute oral toxicity test was conducted according to OECD TG 423 (2000 mg/kg). The repeated dose oral toxicity of 28 days was performed following the OECD TG 407 (100, 200, and 400 mg/kg) on Wistar rats. Results: The 50% lethal concentration (LC50) was 1.84 mg/mL. Based on acute oral toxicity, the LD50 value of the extract was up to 2000 mg/kg of body weight. The 28-day repeated oral administration of Sterculia setigera leaves hydroethanolic extract did not provoke negative effects on rats, as they were safe based on body and organ weight, hematological, biochemical, and histopathological results. Conclusion : These results indicate that the dry hydroethanolic extract of S. setigera leaves did not provoke adverse effects that can lead to death or internal histological lesions in Wistar rats after 28-day oral administration. Keywords: Sterculia setigera; cytotoxicity; Artemia salina; toxicological profile

Chemogenetic Activation of LC Noradrenergic Afferents Facilitates Cerebellar CF–PC LTD via Presynaptic α2A–AR/CDK5/PKA Signaling

Fri, 17 Jul 2026 00:00:00 GMT

Cerebellar climbing fiber–Purkinje cell (CF–PC) long-term depression (LTD) plays a critical role in motor learning and is modulated by locus coeruleus (LC) noradrenergic afferents via distinct adrenergic receptor (AR) subtypes. Nevertheless, the mechanisms underlying LC noradrenergic neuron-mediated regulation of CF–PC LTD remain poorly understood. Here, we investigated the effects of chemogenetic activation of LC noradrenergic afferents on CF–PC LTD in cerebellar slices from dopamine β-hydroxylase (DBH)-Cre mice using electrophysiology, glutamate sensor imaging, immunofluorescence and pharmacological approaches. Tetanic stimulation (5 Hz) of CFs induced CF–PC LTD under control conditions, and this LTD was enhanced by chemogenetic activation of LC noradrenergic afferents. Blockade of group I metabotropic glutamate receptors (mGluR1) abolished LTD under control conditions, whereas chemogenetic activation of LC noradrenergic afferents triggered a novel form of CF–PC LTD accompanied by an increased N2/N1 ratio. With mGluR1 blocked, chemogenetic activation of LC noradrenergic afferents failed to trigger the novel CF–PC LTD following blockade of α2-AR or α2A-AR, but not α2B-AR or α2C-AR. Importantly, chemogenetic activation of LC noradrenergic afferents triggered LTD of glutamate fluorescence at CF terminals, which was abolished by blockade of α2-AR or α2A-AR, but not α2B-AR or α2C-AR. Notably, inhibition of either cyclin-dependent kinase 5 (CDK5) or presynaptic, but not postsynaptic, protein kinase A (PKA) completely abolished the CF–PC LTD triggered by chemogenetic activation of LC noradrenergic afferents in mouse cerebellar slices. Immunofluorescence results showed robust α2A-AR expression throughout the cerebellar molecular layer, with intense signals along PC dendrites and clear colocalization with vesicular glutamate transporter 2 (vGluT2) at cerebellar CF terminals. These results indicate that activation of LC noradrenergic afferents potentiates CF–PC LTD by triggering Glu-LTD at CF terminals through the α2A-AR/CDK5/PKA signaling cascade in the mouse cerebellar cortex.

Brain structure abnormalities in neurodevelopmental synaptopathies

Wed, 01 Jul 2026 00:00:00 GMT

Advanced brain imaging studies have been scarcely reported in neurodevelopmental encephalopathies. In this study we assess structural brain alterations in three rare neurogenetic disorders primarily affecting glutamatergic neurotransmission, aiming to identify shared and disease-specific neuroanatomical patterns and their clinical correlations. A cohort of patients with SYNGAP1 ( n = 19), GRIN gene family (n = 19), and STXBP1 ( n = 10) mutations underwent magnetic resonance imaging. Advanced segmentation tools were used to extract regional brain volumes. Volumetric differences between patient and age-matched normative reference templates were assessed using parametric and non-parametric tests, depending on data distribution, and ANCOVA was used to adjust between covariates. Associations with clinical symptoms were evaluated using the appropriate correlation tests. In our cohort, we found that patients exhibited statistically significant and consistent shared differences in brain tissue volumes compared to age-matched templates, including larger volumes in the basal ganglia, thalamus, ventricles, and certain cortical regions, alongside reductions in total white matter, cerebellar, and limbic structures (amygdala and parahippocampal gyrus). Clinically, ventricular enlargement correlated positively with the severity of intellectual disability, language impairment, and motor dysfunction, while total intracranial volume showed negative correlations with these same domains. Distinctive trends included supplementary motor cortex enlargement and cerebellar volume deficit in STXBP1, while amygdala volume deficit was most prominent in SYNGAP1 and GRINpathies. In conclusion, the study suggests the presence of shared and disease-specific brain alterations in SYNGAP1, GRINpathies, and STXBP1 disorders. Overall, brain volumetry may represent a useful exploratory tool, contributing to a more detailed characterization of these diseases while offering insights beyond conventional radiological assessment.

Cerebellar Transcranial Alternating Current Stimulation: Frequency-Specific Modulation of Human Gait

Mon, 20 Jul 2026 00:00:00 GMT

Coordinated locomotion depends on rhythmic neural interactions, with the cerebellum contributing to movement timing and scaling. However, how cerebellar oscillatory dynamics influence human gait remains unclear, despite its relevance for motor learning and rehabilitation. We hypothesized two frequency-dependent effects: (i) gait-matched cerebellar transcranial alternating current stimulation (c-tACS) would produce stronger phase alignment than sham and selectively affect temporal rather than spatial gait parameters; and (ii) higher-frequency stimulation would preferentially modulate spatial gait parameters without consistent phase alignment with the ongoing locomotor rhythm. To test this, fifteen healthy adults received randomized bilateral c-tACS at their individual gait-cycle frequency (iGCF), iGCF ± 10% offsets, individual step frequency (iSF), a harmonic in alpha range (iGCF×10), 50 Hz (gamma), and sham. Head-mounted accelerometry recorded kinematics of continuous walking and a stop-and-go task. Phase synchrony between stimulation and gait periodicity was quantified using the debiased phase-locking value (dPLV). 50 Hz c-tACS increased gait velocity and stride length without altering cadence or stride time, indicating selective modulation of spatial gait parameters. In contrast, gait-matched stimulation (iGCF, iSF) produced strong stimulation-gait phase alignment but did not enhance temporal gait parameters beyond sham, arguing against entrainment-specific behavioral effects. dPLV declined with iGCF ± 10% during continuous walking, whereas a transient increase at iGCF-10% during stop-and-go was not specific to active stimulation. These findings support frequency-dependent effects of c-tACS on locomotion and refine the mechanistic understanding of how rhythmic cerebellar stimulation interacts with gait control, with potential implications for targeted neuromodulation.

Identification of a novel glutamate receptor 2 mutation in mice presenting progressive cerebellar ataxia

Mon, 20 Jul 2026 00:00:00 GMT

Ataxia is a condition characterized by impaired coordination of movements due to dysfunction of the cerebellum or related neural circuits. Here, we describe a mouse colony exhibiting progressive ataxia that arose spontaneously, which we have designated td. Whole genome sequencing and gene mapping revealed a 0.2 Mb tandem duplication involving exons 3 and 4 of the Grid2 gene, leading to premature termination of translation and reduced mRNA expression. Consistent with previous reports, our findings indicate that both structural and transcriptional abnormalities of Grid2 contribute to the observed phenotype. Notably, this type of variant in the Grid2 gene has not been identified. We observed atrophy of the granular and molecular layers and neuroinflammation in the granular layer of the td cerebellum, consistent with the role of Grid2 in Purkinje cell dendrites. Together, these findings establish td as a novel Grid2 mutant mouse model exhibiting cerebellar neurodegeneration.

Differentially Methylated Regions in Human Rhombic Lip Compartments Are Enriched in Putative Active Enhancers, Human Accelerated Regions, and Medulloblastoma Copy Number Aberrations

Tue, 21 Jul 2026 00:00:00 GMT

The cerebellar rhombic lip (RL) of the prenatal hindbrain is a progenitor niche essential for cerebellar glutamatergic neurogenesis. Humans demonstrate a structural elaboration of this niche with a rhombic lip subventricular zone (RL-SVZ). Disruption of this zone causes cerebellar malformations and tumors, yet its gene regulatory networks are poorly understood. We present a predicted gene regulatory network for the human RL inferred from epigenomic maps of the developing human cerebellum. We generated DNA methylomes from microdissected mid-gestation human RL ventricular zone (RL-VZ) and RL-SVZ (N = 9; 15-16 post-conception weeks) using low-input Enzymatic MethylSeq, and profiled histone marks of active promoters and enhancers in whole fetal cerebellum (N = 6; 14 and 18 weeks). Transition from RL-VZ to RL-SVZ is accompanied by widespread hypomethylation, including 9,855 differentially methylated regions (DMRs) enriched for binding sites of ATOH1, NEUROD1/2, and HMGA1. Of these, 88.9% are hypomethylated in RL-SVZ, enriched in active enhancers and human accelerated regions, and depleted at promoters. By integrating DMRs with bulk tissue histone maps as well as single-cell chromatin accessibility and transcriptomic maps of the mid-gestation cerebellum, we inferred over 100,000 transcription factor-enhancer-gene links. Twenty-five DMRs overlap human accelerated regions near genes implicated in intellectual disability, autism spectrum disorder, and neurological deficits. DMRs are also enriched in copy-number aberrations in medulloblastoma, with ~ 25% overlapping known aberrant regions, nominating disrupted promoters and enhancers. These data provide a framework for interpreting non-coding variation in human cerebellar development and disease.

Reference morphometric parameters of cerebellar cortical neurons in domestic birds: a comparative histomorphometric study

Fri, 10 Jul 2026 00:00:00 GMT

Domestic birds are characterized by a highly developed functional organization of the central nervous system, which has evolved as an adaptation to complex sensorimotor activity, spatial orientation, and diverse locomotor patterns. One of the principal integrative centers of the brain is the cerebellum, whose morphofunctional status is determined by the cytoarchitectonic organization of its cortex and the quantitative characteristics of its neuronal populations. Despite the considerable number of studies devoted to cerebellar morphology, comparative histomorphometric characteristics of cerebellar cortical neurons in domestic birds remain insufficiently investigated, highlighting the relevance of the present study. The aim of this study was to establish reference morphometric parameters of cerebellar cortical neurons in domestic birds and to determine their species-specific characteristics based on a comparative histomorphometric analysis. The study was conducted on the cerebella of clinically healthy sexually mature domestic chickens (Gallus gallus domesticus), turkeys (Meleagris gallopavo), domestic ducks (Anas platyrhynchos domesticus), and domestic geese (Anser anser domesticus). Histological, neurohistological, morphometric, and statistical methods were employed for morphological evaluation. The cerebellar cortex of all examined species exhibited the typical trilaminar organization; however, significant interspecies differences were observed in the morphometric characteristics of neurons within the ganglionic (Purkinje cell) layer. The largest neuronal perikaryon volume was recorded in turkeys (1423.86 ± 81.60 µm³), followed by geese (1315.22 ± 88.53 µm³) and ducks (1139.49 ± 88.79 µm³), whereas the smallest value was observed in chickens (713.95 ± 68.58 µm³). Nuclear volume varied to a lesser extent and showed no statistically significant interspecies differences (P > 0.05). In contrast, the nuclear-to-cytoplasmic ratio demonstrated species-specific variability, with the highest value observed in ducks (0.087 ± 0.013), followed by turkeys (0.083 ± 0.024) and geese (0.079 ± 0.013), while chickens exhibited a significantly lower ratio (P < 0.001). The obtained findings expand current knowledge of the structural organization of the cerebellar cortex in domestic birds, provide reference histomorphometric parameters of cerebellar neurons, and may serve as a normative basis for comparative anatomical, histological, experimental morphological, and forensic veterinary investigations.