European Journal of Neuroscience最新文献

Anxiety disorders are the most common mental illnesses — afflicting 19% of Americans every year and 31% within their lifetimes — yet diagnoses remain based on symptom checklists because existing technologies have yet to produce biomarkers sufficiently robust for clinical use. Some techniques provide superior spatial resolution of deep brain regions implicated in anxiety but have poor time resolution; while others measure signals in real time but lack spatial resolution. Often, the goal of probing deep brain regions in humans for anxiety research is to measure a putative analogue of a mammalian brain rhythm linked to behaviour that is suggestive of anxiety. This 4–12 Hz, 1–2 mV, behaviourally modulated, nearly sinusoidal “hippocampal theta rhythm” (hTheta) is one of the largest normal extracellular synchronous signals in mammals and although it has been linked to anxiety processes, its function remains unclear. This paper reviews the literature on hTheta as it relates to anxiety and sensory, in particular vestibuloacoustic, signals, concludes that hTheta can modulate sensory signals during anxiety and posits that such modulation of vestibular signals may be an anxiety biomarker that could be detected non-invasively in humans.

Binaural unmasking is a remarkable phenomenon that it is substantially easier to detect a signal in noise when the interaural parameters of the signal are different from those of the noise – a useful mechanism in so-called cocktail party scenarios. In this study, we investigated the effect of binaural unmasking on neural tracking of the speech envelope. We measured EEG in 8 participants who listened to speech in noise at a fixed signal-to-noise ratio, in two conditions: one where speech and noise had the same interaural phase difference (both speech and noise having an opposite waveform across ears, SπNπ), and one where the interaural phase difference of the speech was different from that of the noise (only the speech having an opposite waveform across ears, SπN). We measured a clear benefit of binaural unmasking in behavioural speech understanding scores, accompanied by increased neural tracking of the speech envelope. Moreover, analysing the temporal response functions revealed that binaural unmasking also resulted in decreased peak latencies and increased peak amplitudes. Our results are consistent with previous research using auditory evoked potentials and steady-state responses to quantify binaural unmasking at cortical levels. Moreover, they confirm that neural tracking of speech is associated with speech understanding, even if the acoustic signal-to-noise ratio is kept constant. From a clinical perspective, these results offer the potential for the objective evaluation of binaural speech understanding mechanisms, and the objective detection of pathologies sensitive to binaural processing, such as asymmetric hearing loss, auditory neuropathy and age-related deficits.

This study aims to investigate the value of basal ganglia and limbic/paralimbic networks alteration in identifying preschool children with ASD and normal controls using diffusion basis spectrum imaging (DBSI). DBSI data from 31 patients with ASD and 30 NC were collected in Hunan Children's Hospital. All data were imported into the post-processing server. The most discriminative features were extracted from the connection, global and nodal metrics separately using the two-sample t-test. To effectively integrate the multimodal information, we employed the multi-kernel learning support vector machine (MKL-SVM). In ASD group, the value of global efficiency, local efficiency, clustering coefficient and synchronization were lower than NC group, while modularity score, hierarchy, normalized clustering coefficient, normalized characteristic path length, small-world, characteristic path length and assortativity were higher. Significant weaker connections are mainly distributed in the limbic/paralimbic networks. The model combining consensus connection, global and nodal graph metrics features can achieve the best performance in identifying ASD patients, with an accuracy of 96.72%.The most specific brain regions connection weakening associated with preschool ASD are predominantly located in limbic/paralimbic networks, suggesting their involvement in abnormal brain development processes. The effective combination of connection, global and nodal metrics information by MKL-SVM can effectively distinguish patients with ASD.

While pictures share global similarities with the real-world objects they depict, the latter have unique characteristics going beyond 2D representations. Due to its three-dimensional presentation mode, Virtual Reality (VR) is increasingly used to further approach real-world visual processing, yet it remains unresolved to what extent VR yields process comparable to real-world processes. Consequently, our study examined visuospatial processing by a triangular comparison of 2D objects, virtual 3D objects and real 3D objects. The theta band response (TBR) was analysed as an electrophysiological correlate of visual processing, allowing for the differentiation of predominantly stimulus-driven processes mirrored in the evoked response and internal, complex processing reflected in the induced response. Our results indicate that the differences between conditions driven by sensory features go beyond a binary division into 2D and 3D materials but are based on further sensory features: The evoked posterior TBR differentiated between all conditions but revealed fewer differences between processing of real-world and VR objects. Moreover, the induced midfrontal TBR indicated higher cognitive load for 2D objects compared to VR and real-world objects, while no difference between both latter conditions was revealed. In conclusion, our results demonstrate that the transferability of 2D- and VR-based findings to real-world processes depends to some degree on whether predominantly sensory stimulus features or higher cognitive processes are examined. Yet although VR and real-world processes are not to be equated based on our results, their comparison yielded fewer significant differences relative to the PC condition, advising the use of VR to examine visuospatial processing.

This study aimed to explore the interaction between the expression of neuronal HIF-1α in the mediobasal hypothalamus and food intake, glycolipid metabolism and body weight (BW) in mice consuming high-fat diet (HFD). In HIF-1α^flox/flox mice, AAV-hSyn-GFP (NC group) or AAV-hSyn-cre-GFP (KD group) virus was injected into medial base of the hypothalamus. Frozen brain tissue sections confirmed the presence of the virus within the hypothalamus of mice after 28 days of AAV injection, including reporter signals within the arcuate nucleus, dorsomedial hypothalamic nucleus (DMH) and ventromedial hypothalamus (VMH). Consistently, the levels of HIF-1α mRNA in the ventral hypothalamus were significantly lower in the KD group compared to the NC group. These KD mice also demonstrated significantly increased food intake, body weight (BW), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum insulin, combined with higher blood glucose, compared to NC animals. However, the levels of triglycerides and FFA were similar in both groups. Significant differences in p-Akt levels were not observed in the skeletal muscle, liver or epididymal fat in KD mice after insulin injection. In conclusion, the knockdown of HIF-1α within the neurons of mediobasal hypothalamus results in an increase in the appetite of mice fed with HFD, which in turn leads to a significant dysregulation of lipid and glucose metabolism and a corresponding increase in weight. Therefore, the neuronal HIF-1α expression in the mediobasal hypothalamus may be a critical regulator of glycolipid metabolism and body weight control when a high-fat diet is consumed.

Childhood trauma has a well-established negative impact on mental health outcomes across the lifespan. Cumulative evidence suggests an intergenerational transmission of trauma to descendants. In this way, considering the child's COMT Val¹⁵⁸Met (rs4680: G > A) variant, the study aims to investigate the interactive effect of maternal childhood trauma on the emotional/behavioural problems of their offspring in preschoolers age (4–5 and 11 years old) from a population-based dyad of pregnant adolescent women. The behaviour problems of 310 children were assessed using the Child Behaviour Checklist (CBCL) instrument, and maternal trauma was assessed with the Child Trauma Questionnaire (CTQ) between the 20 to 22° gestational weeks. Maternal childhood trauma increases the risk for all emotional/behavioural problems in the offspring, and no direct association between the child's Val¹⁵⁸Met genotypes with emotional/behavioural problems. Interestingly, in moderation analysis adjusted by sex, age and skin colour, children of mothers exposed to childhood trauma, carrying the Val/Met genotype, are less likely to develop externalising (p = .020) and total problems (p = .041) when compared to homozygous (Val/Val and Met/Met). Thus, our findings reinforce evidence on the intergenerational impact of maternal trauma on emotional/behavioural problems and demonstrate that this risk is influenced by the genetic background of the individual, varying according to the functional COMT genotype, which confers a protective profile for the development of externalising and total problems.

Based on motor symptoms, Parkinson's disease (PD) can be classified into tremor dominant (TD) and postural instability gait difficulty (PIGD) subtypes. Few studies have examined cortical complexity differences in PD motor subtypes. This study aimed to investigate differences in cortical complexity and grey matter volume (GMV) between TD and PIGD. We enrolled 36 TD patients, 27 PIGD patients and 66 healthy controls (HC) from the PPMI (Parkinson's Progression Markers Initiative) database. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) were utilized to assess differences in GMV, cortical thickness and cortical complexity. The structural MRI data of participants was analysed using CAT12/SPM12 (p < 0.05, FDR corrected). Additionally, correlations between clinical data and structural changes were examined (p < 0.05, Holm-Bonferroni corrected). In comparison to both HC and TD groups, PIGD patients exhibited a significant fractal dimension (FD) decrease in many cortical regions. A significant negative correlation between age and FD was observed in the left insula for the PIGD patients and in the bilateral insula for the TD patients. However, no significant differences were found in GMV, cortical thickness or other complexity indices. Altered FD in the bilateral insula indicates that postural instability and gait disturbances may result from a failure to integrate information from various structures, whereas parkinsonian rest tremor is not associated with this integration. Also, widespread decreases in cortical FD demonstrate that FD is more sensitive than other complexity measures and can serve as a novel biomarker for identifying subtle changes in cortical morphology in the PIGD subtype.

Dopaminergic nigrostriatal denervation in Parkinson's disease (PD) disrupts the functional balance between striatal projecting neurons, leading to aberrant activity in the cortico-basal ganglia circuit and characteristic motor symptoms. While genetic and toxin-based animal models are commonly used to mimic PD pathology and behaviour, they have limitations when combined with circuit manipulation tools. This highlights the need for complementary approaches, particularly when combined with viral-based circuit targeting of specific neuronal subpopulations involved in PD circuit dysfunction. Here, we pursue a pharmacological approach targeting dopamine D1 or D2 receptors to induce dopamine deprivation and to replicate key motor symptoms in PD. We demonstrate a clear dose-dependent induction of parkinsonian motor behaviour by both a dopamine D1 receptor antagonist (SCH23390) and a D2 receptor antagonist (haloperidol). The motor phenotype is evaluated by considering relevant motor metrics in an open-field maze platform. The proposed parkinsonian pharmacological model constitutes an acute, flexible approach, which allows parallel brain circuit manipulations.

Reciprocal structure–function relationships underlie both healthy and pathological behaviours in complex neural networks. Thus, understanding neuropathology and network dysfunction requires a thorough investigation of the complex interactions between structural and functional network reconfigurations in response to perturbation. Such adaptations are often difficult to study in vivo. For example, subtle, evolving changes in synaptic connectivity, transmission and the electrophysiological shift from healthy to pathological states, for example alterations that may be associated with evolving neurodegenerative disease, such as Alzheimer's, are difficult to study in the brain. Engineered in vitro neural networks are powerful models that enable selective targeting, manipulation and monitoring of dynamic neural network behaviour at the micro- and mesoscale in physiological and pathological conditions. In this study, we engineered feedforward cortical neural networks using two-nodal microfluidic devices with controllable connectivity interfaced with microelectrode arrays (mMEAs). We induced P301L mutated tau protein to the presynaptic node of these networks and monitored network dynamics over three weeks. Induced perturbation resulted in altered structural organization and extensive axonal retraction starting in the perturbed node. Perturbed networks also exhibited functional changes in intranodal activity, which manifested as an overall decline in both firing rate and bursting activity, with a progressive increase in synchrony over time and a decrease in internodal signal propagation between pre- and post-synaptic nodes. These results provide insights into dynamic structural and functional reconfigurations at the micro- and mesoscale as a result of evolving pathology and illustrate the utility of engineered networks as models of network function and dysfunction.