European Journal of Neuroscience最新文献

This study aimed to investigate the topological properties of brain functional networks in patients with tinnitus of varying durations. A total of 51 tinnitus patients (divided into recent-onset tinnitus (ROT) and persistent tinnitus (PT) groups) and 27 healthy controls (HC) were recruited. All participants underwent resting-state functional MRI and audiological assessments. Graph theory was used to examine brain network topology.

The results showed that the ROT group exhibited lower clustering coefficient, gamma, sigma and local efficiency compared to both the HC and PT groups (all P < 0.05). Significant reductions in nodal clustering coefficient and local efficiency were found in the left caudate nucleus and left olfactory cortex, while increased nodal centralities were observed in the left orbital middle frontal gyrus and left postcentral gyrus in ROT patients (all P < 0.05). Furthermore, the ROT group had decreased nodal clustering in the right lenticular putamen and reduced nodal efficiency in the left olfactory cortex compared to both PT patients and HCs (all P < 0.05).

Additionally, PT patients showed weaker functional connectivity between the subcortical and occipital lobe modules, as well as between the prefrontal and intra-frontal modules, compared to ROT patients. However, intra-module connectivity in the subcortical module was stronger in PT patients than in HCs.

These findings suggest that recent-onset tinnitus is associated with alterations in brain network topology, but many of these changes are restored with the persistence of tinnitus.

Staining brain slices with acetoxymethyl ester (AM) Ca²⁺ dyes is a straightforward procedure to load multiple cells, and Fluo-4 is a commonly used high-affinity indicator due to its very large dynamic range. It has been shown that this dye preferentially stains glial cells, providing slow and large Ca²⁺ transients, but it is questionable whether and at which temporal resolution it can also report Ca²⁺ transients from neuronal cells. Here, by electrically stimulating mouse hippocampal slices, we resolved fast neuronal signals corresponding to 1%–3% maximal fluorescence changes. Specifically, by recording Ca²⁺ fluorescence at 2000 frames/s from multiple sites both in the CA3 and in the CA1 regions, we observed that the signal measured near the stimulating electrode, positioned on the mossy fibre pathway, was not blocked by perfusion with 10 μM NBQX and 50 μM AP5, preventing excitatory synaptic transmission. In contrast, this signal was fully blocked by additional perfusion with 1 μM tetrodotoxin, inhibiting voltage-gated Na⁺ channels and neuronal action potentials. We also present recordings obtained in the presence of 10 μM of the GABA_A receptor antagonist bicuculline, or of 50 μM of the voltage-gated K⁺ channel inhibitor 4-aminopyridine, exhibiting a wide propagation of the signal from CA3 to CA1 regions under conditions that mimic epileptic seizures. Altogether, while Fluo-4 AM remains a preferable indicator for reporting Ca²⁺ signals from astrocytes at slow temporal resolution, we demonstrated that it can be also utilised for analysing fast neuronal network activity elicited by electrical stimulation in brain slices.

Anxiety is one of the most common and debilitating mental health disorders, and is related to changes in interoception (perception of bodily states). While anxiety is more prevalent in women than men, gender differences in interoception-anxiety associations are often overlooked. Here, we examined gender-specific relationships between anxiety and interoception in the breathing domain, utilising multicentre data pooled from four study sites (N = 175; 51% women). State anxiety scores were quantified via the Spielberger State–Trait Anxiety Inventory, and breathing-related interoceptive dimensions via an inspiratory load task to quantify sensitivity, decision bias, metacognitive bias (confidence in interoceptive decisions), and metacognitive insight (congruency between performance and confidence). Regression analyses revealed a significant negative relationship between state anxiety and metacognitive bias (β = −0.28; p = 0.01) and insight (β = −0.09; 95% highest density interval [HDI] in a hierarchical Bayesian regression = [−0.18, −0.004]) across the whole sample, while state anxiety did not relate to interoceptive sensitivity nor decision bias. While no mean interoceptive effects relating to gender were observed, the relationship between anxiety and metacognitive insight towards breathing was driven by women (women: β = −0.18; HDI = [−0.31, −0.05]; men: β = 0.02; HDI = [−0.12, 0.15]) with a significant interaction effect (β difference = −0.20; HDI = [−0.37, −0.01]), which did not hold for trait anxiety nor depression measures. In summary, state anxiety was associated with decreased metacognitive bias across all participants, while decreased interoceptive insight was only associated with anxiety in women but not men. Therefore, treatment programmes focusing on interoceptive metacognitive bias may be useful for all anxiety patients, while interoceptive insight might represent a specific treatment target for women with anxiety.

Through the lens of preclinical research on substance use disorders (SUD), I propose a reflection aimed at re-evaluating animal models in neuroscience, with a focus on ecological relevance. While rodent models have provided valuable insights into the neurobiology of SUD, the field currently faces a validation crisis, with findings often failing to translate into effective human treatments. Originally designed to address the lack of reproducibility in animal studies, the current global gold standard of rigorous standardization has led to increasingly controlled environments. This growing disconnection between laboratory settings and real-world scenarios exacerbates the validation crisis. Rodent models have also revealed various environmental influences on drug use and its neural mechanisms, highlighting parallels with human behaviour and underscoring the importance of ecological relevance in behavioural research. Drawing inspiration from inquiries in ethology and evolutionary biology, I advocate for incorporating greater environmental complexity into animal models. In line with this idea, the neuroethological approach involves studying spontaneous behaviours in seminatural habitats while utilizing advanced technologies to monitor neural activity. Although this framework offers new insights into human neuroscience, it does not adequately capture the complex human conditions that lead to neuropsychiatric diseases. Therefore, preclinical research should prioritize understanding the environmental factors that shape human behaviour and neural architecture, integrating these insights into animal models. By emphasizing ecological relevance, we can achieve deeper insights into neuropsychiatric disorders and develop more effective treatment strategies. This approach highlights significant benefits for both scientific inquiry and ethical considerations. The controlled environment is a chimera; it is time to rethink our models. Here, I have chosen the prism of preclinical research on SUD to present, in a nonexhaustive manner, advances enabled by the use of rodent models, the crises faced by animal experimentation, the reflections and responses provided by laboratories, to finally propose rethinking our models around questions of ecological relevance, in order to improve both ethics and scientific quality. Although my discussion is illustrated by the situation in preclinical research on SUD, the observation drawn from it and the proposals made can extend to many other domains and species.

Resting-state functional connectivity analyses have been used to examine synchrony in neural networks in substance use disorders (SUDs), with the default mode network (DMN) one of the most studied. Prior research has generally found less DMN synchrony during use and greater synchrony during cessation, although little research has utilized this method with opioid use. This study examined resting brain activity in treatment-seeking persons who use opioids at two points—when using opioids and when opioid-free—to determine whether the DMN exhibits different levels of connectivity during opioid use and cessation and whether differences in connectivity predict subsequent relapse. The sample included 11 participants who met DSM-5 criteria for opioid use disorder and initiated buprenorphine treatment following fMRI scans that were approximately 3 days apart. Results showed greater functional connectivity in the DMN and the rIFG of the salience network (SN) when participants were abstaining than when actively using opioids. These changes in connectivity predicted 76.2% of the variance in withdrawal symptom severity, with the DMN nodes accounting for an additional 30.9%. Findings warrant further longitudinal exploration of the role of DMN connectivity and its interactions with other networks in relation to abstinence and withdrawal status and examination of its utility as a prognostic marker of cessation or relapse.

Animal models have been crucial for scientific development, allowing researchers to understand the underlying mechanisms of various human conditions, and are far from becoming obsolete in scientific research. However, the ethics of animal experimentation has been a prevalent question between both experts and nonexperts. This essay tackles the advantages and disadvantages of the usage of animal models while delving into new alternatives that have emerged in light of contemporary science.

Previous research demonstrated that transcranial alternating current stimulation (tACS) can induce phosphene perception. However, tACS involves rhythmic changes in the electric field and alternating polarity (excitatory vs. inhibitory phases), leaving the precise mechanism behind phosphene perception unclear. To disentangle the effects of rhythmic changes from those of alternating polarity, this study employs oscillatory transcranial direct current stimulation (otDCS), in which the current oscillation remains confined to either a positive or negative polarity, thereby eliminating the influence of polarity switching. We applied scalp electrical stimulations using both polarity-switching (tACS) and non-polarity-switching (otDCS) methods, with anodal or cathodal polarities, targeting the occipital lobe. All stimulations were performed using sinusoidal or amplitude modulation (AM) waveforms at threshold or suprathreshold intensities. Our results show that tACS results in faster response times compared to cathodal otDCS, but not anodal otDCS, while anodal otDCS elicits greater brightness perception than both cathodal otDCS and tACS. Additionally, AM frequency induced a higher threshold than the sinusoidal frequency, and response times were slower in the AM condition across all positive, negative, and polarity-switching stimulations. However, stimulation intensity in the anodal AM condition could influence speed ratings, unlike in cathodal or tACS conditions. Our findings reveal that both tACS and otDCS induce phosphenes, with significant differences between polarities and current oscillation types, indicating that both mechanisms are critical in phosphene induction. This study provides evidence linking phosphene occurrence to oscillatory current activity and highlights the robustness and impact of AM coding in visual perception.