European Journal of Neuroscience最新文献

Word problems are essential for math learning and education, bridging numerical knowledge with real-world applications. Despite their importance, the neural mechanisms underlying word problem solving, especially in children, remain poorly understood. Here, we examine children's cognitive and brain response profiles for arithmetic word problems (AWPs), which involve one-step mathematical operations, and compare them with nonarithmetic word problems (NWPs), structured as parallel narratives without numerical operations. Behavioural results suggested that AWP performance was associated with both reading comprehension and arithmetic fluency, whereas NWP performance correlated only with reading comprehension. Neuroimaging results revealed distinct neural substrates: AWP solving primarily activated the anterior insula, middle frontal gyrus and intraparietal sulcus, whereas NWP solving engaged in the inferior frontal gyrus, middle temporal gyrus and angular gyrus. Critically, we observed a developmental shift: Children showed heightened prefrontal activation during AWP solving, contrasting with increased posterior parietal engagement in adults. Moreover, although adults demonstrated brain–behaviour associations, with slower AWP solving linked to stronger parietal activation, this relationship was absent in children. Taken together, these findings suggest that AWP solving recruits specialized arithmetic brain circuits that undergo a frontal-to-parietal trajectory. Our study thus provides a neurological basis for AWP solving in children, emphasizing the crucial role of the fronto-insular-parietal network. These insights into brain-based contributions to developmental differences may guide the development of targeted remediation strategies and educational interventions tailored to individual learning needs.

Chronic migraine (CM) is the ultimate and most burdensome form of the transformation from episodic migraine (EM), called chronification. The mechanism behind migraine chronification is poorly known and difficult to explore as CM has the same spectrum of pathogenesis as EM and the EM-CM transition is bidirectional. Central sensitization (CS) is a key phenomenon in migraine: its mechanisms include disturbed neural plasticity, which is the ability of the nervous system to adapt to endo- and exogenous changes. Cutaneous allodynia, a maker of central sensitization, may be an easy-to-determine marker of the EM-CM transition. Pituitary adenylate cyclase-activating peptide, a pro-inflammatory, vasodilatory and pain-producing neuropeptide, which has been proposed as an alternative to CGRP target in migraine, was shown to improve CS by regulating synaptic plasticity in the trigeminal nucleus caudalis in CM rats. Oxytocin and its receptor were found to influence CS through modulating synaptic plasticity in CM mice. Similar results were obtained for ephrin type-B receptor and its ligands. These and other studies suggest that neural plasticity may be important in CM pathogenesis. Still, its involvement in migraine chronification requires further studies which should include patients/animals with EM and CM. In this narrative/hypothesis paper, we review the current literature on the molecular mechanisms of CM pathogenesis and try to link them with neural plasticity and central sensitization to support the hypothesis that it is a key element in migraine chronification.

New therapeutic agents developed for treating neurological disorders are often tested successfully on rodents. Testing in an appropriate large animal model where there is longer lifespan and comparable brain size to humans should improve translational success and is frequently expected by regulatory bodies. In this project, we aimed to establish a novel sheep model of Parkinson's disease as a large-brained experimental model for translational research. Our objective was to create a sheep model of Parkinson's disease by unilaterally infusing the neurotoxin 6-hydroxydopamine into the substantia nigra pars compacta. This approach, previously used to induce parkinsonism in rat and non-human primate models, causes dopaminergic imbalance and induces rotational behaviour in quadrupeds challenged with dopaminergic receptor agonists. In the present sheep study, the mixed dopamine receptor agonist apomorphine, 0.25 mg/kg, and dopamine D2 agonist ropinirole, 0.16 mg/kg, were used to induce rotational behaviour and confirm dopamine depletion. Behavioural signs were then measured and characterised in the field using automated movement tracking with simultaneous video recordings. Post-mortem, the extent of the 6-hydroxydopamine lesions was evaluated through tyrosine hydroxylase immunohistochemistry and quantifying levels of catecholamines (dopamine, 3,4-dihydroxyphenylacetic acid and homovanilic acid) quantified using high-performance liquid chromatography. Our new sheep model of Parkinson's disease using 6-hydroxydopamine is safe and offers a number of regulatory, ethical and financial advantages over non-human primate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine models. It provides a platform to evaluate novel antiparkinsonian agents and medical devices in a large brain with the promise of greater success for translation into clinical application.

The occurrence and persistence of tinnitus result from the interaction of multiple neural networks. This study aims to explore the alterations in brain network topology associated with the transition of tinnitus from recent-onset to chronic. Twenty-eight patients with chronic tinnitus, 28 patients with recent-onset tinnitus and 28 sex- and age-matched healthy controls (HC) were enrolled in this study. We performed a graph theory analysis to identify aberrant brain network topologies and calculated the correlation between differential brain regions and clinical indicators. Compared with the recent-onset tinnitus group, patients with chronic tinnitus showed decreased global efficiency (Eg, decreased by 3.7%, p < 0.001), local efficiency (Eloc, decreased by 1.8%, p = 0.031) and small-worldness (decreased by 13.8%, p = 0.007) and increased characteristic path length (Lp, increased by 6.8%, p = 0.001). Additionally, ANOVA revealed significant differences in the AUC of degree centrality (DC), nodal efficiency (Ne), nodal clustering coefficient (NCp) and nodal local efficiency (Nle) among the three groups in brain regions such as the superior temporal gyrus, inferior temporal gyrus, anterior cingulate cortex, precuneus, middle occipital gyrus, inferior occipital gyrus, fusiform gyrus, cuneus and putamen (q < 0.05, FDR corrected). Notably, several of these regions were associated with tinnitus duration, distress and loudness. The topological properties of several brain networks were altered in patients with chronic tinnitus compared to those with recent-onset tinnitus, providing new insights into the neural mechanisms of tinnitus chronification. These findings could inform the development of targeted interventions aimed at mitigating the progression from recent-onset to chronic tinnitus.

Movement disorders such as Parkinson's disease (PD) and cervical dystonia (CD) are associated with abnormal neuronal activity in the globus pallidus internus (GPi). Reduced firing rate and presence of spiking bursts are typical for CD, whereas PD is characterized by high frequency tonic activity. This research aims to identify the most important pallidal spiking parameters to classify these conditions. We analysed the single unit activity of the globus pallidus externus (GPe) and internus (GPi) in 11 CD and 10 PD patients who underwent standard-of-care DBS implantation. We compared firing rate, firing pattern and oscillatory characteristics of tonic, burst and pause cells and used logistic regression and random forest models to classify patients according to their pallidal activity. In the GPi, we discovered prevalence of high firing rate tonic cells in patients with PD, whereas in dystonia, burst neurons with high firing rate were predominant. GPi pause cells were mostly observed in CD patients and exhibited less spike variability compared to PD. Characteristics of neurons and their distribution in the GPe was similar. Logistic regression and random forest models identified spike variability and randomness as the key features for distinguishing between PD and CD, instead of firing rate or oscillation properties. Our study demonstrates that pallidal activity can predict PD and CD with high accuracy. Burst dynamics and characteristics of spiking randomness including entropy appear to be the most meaningful reflections of the neurophysiology of studied diseases.

Combination of structural and functional brain connectivity methods provides a more complete and effective avenue into the investigation of cortical network responses to traumatic brain injury (TBI) and subtle alterations in brain connectivity associated with TBI. Structural connectivity (SC) can be measured using diffusion tensor imaging to evaluate white matter integrity, whereas functional connectivity (FC) can be studied by examining functional correlations within or between functional networks. In this study, the alterations of SC and FC were assessed for TBI patients, with and without chronic symptoms (TBIcs/TBIncs), compared with a healthy control group (CG). The correlation between global SC and FC was significantly increased for both TBI groups compared with CG. SC was significantly lower in the TBIcs group compared with CG, and FC changes were seen in the TBIncs group compared with CG. When comparing TBI groups, FC differences were observed in the TBIcs group compared with the TBIncs group. These observations show that the presence of chronic symptoms is associated with a distinct pattern of SC and FC changes including the atrophy of the SC and a mixture of functional hypoconnectivity and hyperconnectivity, as well as loss of segregation of functional networks.