eNeuro最新文献

Facial paralysis is characterized by an injury to the facial nerve, causing the loss of the functions of the structures that it innervates, as well as changes in the motor cortex. Current models have some limitations for the study of facial paralysis, such as movement restriction, the absence of studying awake animals in behavioral contexts, and the lack of a model that fully evaluates facial movements. The development of an algorithm capable of automatically inferring facial paralysis and overcoming the existing limitations is proposed in this work. In C57/BL6J mice, we produced both irreversible and reversible facial paralysis. Video recordings were made of the faces of paralyzed mice to develop an algorithm for detecting facial paralysis applied to mice, which allows us to predict the presence of reversible and irreversible facial paralysis automatically. At the same time, the algorithm was used to track facial movement during gustatory stimulation and extracellular electrophysiological recordings in the anterolateral motor cortex (ALM). In the basal state, mice can make facial expressions, whereas the algorithm can detect this movement. Simultaneously, such movement is correlated with the activation in the ALM. In the presence of facial paralysis, the algorithm cannot detect movement. Furthermore, it predicts that the condition exists, and the neuronal activity in the cortex is affected with respect to the evolution of facial paralysis. This way, we conclude that the facial paralysis algorithm applied to mice allows for inferring the presence of experimental facial paralysis and its neuronal correlates for further studies.

In models of visual spatial attention control, it is commonly held that top-down control signals originate in the dorsal attention network, propagating to the visual cortex to modulate baseline neural activity and bias sensory processing. However, the precise distribution of these top-down influences across different levels of the visual hierarchy is debated. In addition, it is unclear whether these baseline neural activity changes translate into improved performance. We analyzed attention-related baseline activity during the anticipatory period of a voluntary spatial attention task, using two independent functional magnetic resonance imaging datasets and two analytic approaches. First, as in prior studies, univariate analysis showed that covert attention significantly enhanced baseline neural activity in higher-order visual areas contralateral to the attended visual hemifield, while effects in lower-order visual areas (e.g., V1) were weaker and more variable. Second, in contrast, multivariate pattern analysis (MVPA) revealed significant decoding of attention conditions across all visual cortical areas, with lower-order visual areas exhibiting higher decoding accuracies than higher-order areas. Third, decoding accuracy, rather than the magnitude of univariate activation, was a better predictor of a subject's stimulus discrimination performance. Finally, the MVPA results were replicated across two experimental conditions, where the direction of spatial attention was either externally instructed by a cue or based on the participants' free choice decision about where to attend. Together, these findings offer new insights into the extent of attentional biases in the visual hierarchy under top-down control and how these biases influence both sensory processing and behavioral performance.

Early psychosis (EP) is a critical period for psychotic disorders during which the brain undergoes rapid and significant functional and structural changes(Shinn et al., 2017). The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in health and disease. Here we focus on HCP-EP subjects (i.e., those within five years of the initial psychotic episode) to determine macro- and micro-structural alterations in EP (HCP-EP sample, n=179: EP, n=123, Controls, n=56) and their association with clinical outcomes (i.e., symptoms severity) in HCP-EP. We carried out analyses of Deformation-Based-Morphometry (DBM), scalar indices from the Diffusion Tensor Imaging (DTI), and Tract-Based Spatial Statistics (TBSS). Lastly, we conducted correlation analyses focused on the midbrain (DBM and DTI) to examine associations between its structure and clinical symptoms. Our results show that the midbrain displays robust alteration in its structure (DBM and DTI) in the voxel-based analysis. Complimentary alterations were also observed for the hippocampus and putamen. A seed-based analysis centered around the midbrain confirms the voxel-based analysis of DBM and DTI. TBSS displays structural differences within the midbrain and complementary alterations in the corticospinal tract and cingulum. Correlations between the midbrain structures and behavior showed that the quantified features correlate with cognition and clinical scores. Our findings contribute to understanding the midbrain-focused circuitry involvement in EP and provide a path for future investigations to inform specific brain-based biomarkers of EP.Significance statement Psychotic disorders are preceded by a critical period known as early psychosis (EP), where detection and effective interventions could substantially improve symptoms and have the potential to modify the subsequent disease course. However, early biomarkers of the disease are not established, and the current clinical MRI practices do not contribute to diagnosis or treatment. Therefore, identifying critical and comprehensive features of brain alteration (e.g., via multimodal MRI approaches) for EP is a high priority for the field to determine future impactful biomarkers. The HCP-EP provides a refined, high-quality, and specific dataset focusing on the EP period (i.e., those within five years of the initial psychotic episode), which we focus on to provide insights into putative early targets of EP.

While ketamine, an NMDA receptor antagonist, is effective in treating major depression, studies have not addressed the safety of repeated ketamine infusions in depressed patients with comorbid alcohol use disorder (AUD). In this study, we aimed to determine whether a history of chronic social isolation and alcohol exposure alter the reinforcing properties of ketamine in male and female rats. Rats were pair-housed or socially isolated for 12 weeks and underwent intermittent access to 20% alcohol. Subsequently, rats underwent intravenous ketamine self-administration under a fixed ratio 1 schedule, followed by extinction training and one session of cue-induced reinstatement. Dendritic spine morphology was examined in the nucleus accumbens, an important area implicated in reward and motivation. Our results show that females self-administered more ketamine than males, a history of alcohol increased ketamine intake in females, and a history of isolation or alcohol independently increased ketamine intake in males. All experimental groups showed similar extinction patterns and reinstatement to ketamine cues. A pattern emerged similar to ketamine self-administration behaviors, where isolation increased the number of immature spines in males, a change that was attenuated in isolated alcohol drinkers, and a history of alcohol increased the number of immature spines in females. Our results suggest that a history of isolation and alcohol modulate the reinforcing properties of ketamine in a sex-dependent manner. This underscores the importance of considering sex differences and a history of alcohol use when employing ketamine to treat various psychopathologies, including major depression.

Transgenic mice provide unprecedented access to manipulate and visualize neural circuits; however, those on a C57BL/6 background develop progressive hearing loss, significantly confounding systems-level and behavioral analysis. While outbreeding can limit hearing loss, it introduces strain variability and complicates the generation of complex genotypes. Here, we propose an approach to preserve hearing by crossing transgenic mice with congenic B6.CAST-Cdh23^{Ahl +} mice, which maintain low-threshold hearing into adulthood. Widefield and two-photon imaging of the auditory cortex revealed that 2.5-month-old C57BL/6 mice exhibit elevated thresholds to high-frequency tones and widespread cortical reorganization, with most neurons responding best to lower frequencies. In contrast, Ahl+ C57BL/6 mice exhibited robust neural responses across tested frequencies and sound levels (4-64 kHz, 30-90 dB SPL) and retained low thresholds into adulthood. Our approach offers a cost-effective solution for generating complex genotypes and facilitates more interpretable systems neuroscience research by eliminating confounding effects from hearing loss.

Functional ultrasound (fUS) imaging is a well-established neuroimaging technology that offers high spatiotemporal resolution and a large field of view. Typical strategies for analyzing fUS data comprise either region-based averaging, typically based on reference atlases, or correlation with experimental events. Nevertheless, these methodologies possess several inherent limitations, including a restricted utilization of the spatial dimension and a pronounced bias influenced by preconceived notions about the recorded activity. In this study, we put forth single-voxel clustering as a third method to address these issues. A comparison was conducted between the three strategies on a typical dataset comprising visually evoked activity in the superior colliculus in awake mice. The application of single-voxel clustering yielded the generation of detailed activity maps, which revealed a consistent layout of activity and a clear separation between hemodynamic responses. This method is best considered as a complement to region-based averaging and correlation. It has direct applicability to challenging contexts, such as paradigm-free analysis on behaving subjects and brain decoding.

The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to quantify calcium signaling in macrophages revealed these cells respond directly and indirectly to a wide variety of neuromodulators, including pre- and postganglionic transmitters and systemic hormones. Purinergic agonists, histamine, acetylcholine, and bradykinin rapidly and reversibly increased intracellular calcium. These results are consistent with a substantial resident population of innate immune cells in the adrenal medulla. Their close association with chromaffin cells and the preganglionic input suggests they may regulate sympatho-adrenal activity and thus the strength of the fight-or-flight response.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available. Furthermore, age-related hearing damage can comprise various aspects (e.g., hair cell damage, CS) that each can play a role in impaired sound perception. To explore the link between cochlear damage and speech intelligibility deficits, this study examines the role of CS for word recognition among older listeners. We first validated an envelope-following response (EFR) marker for CS using a Budgerigar model. We then applied this marker in human experiments, while restricting the speech material's frequency content to ensure that both the EFR and the behavioral tasks engaged similar cochlear frequency regions. Following this approach, we identified the relative contribution of hearing sensitivity and CS to speech intelligibility in two age-matched (65-year-old) groups with clinically normal (n = 15, 8 females) or impaired audiograms (n = 13, 8 females). Compared to a young normal-hearing control group (n = 13, 7 females), the older groups demonstrated lower EFR responses and impaired speech reception thresholds. We conclude that age-related CS reduces supra-threshold temporal envelope coding with subsequent speech coding deficits in noise that cannot be explained based on hearing sensitivity alone.

Acute ischemic stroke (AIS) is a severe neurological disease associated with Th17/Treg cell imbalance and dysregulation of the Wnt/β-catenin signaling pathway. This study investigates whether miR-155 inhibition can activate Wnt/β-catenin signaling, improve Th17/Treg balance, and provide neuroprotection against stroke. We conducted a multilevel experimental design, including high-throughput sequencing, bioinformatics analysis, in vivo mouse models, and in vitro cell experiments. High-throughput sequencing revealed significant differential gene expression between the miR-155 antagomir-treated and control groups (BioProject: PRJNA1152758). Bioinformatics analysis identified key genes linked to Wnt/β-catenin signaling and Th17/Treg imbalance. In vitro experiments confirmed that miR-155 inhibition activated Wnt/β-catenin signaling and improved Th17/Treg ratios. In vivo studies demonstrated that miR-155 antagomir treatment provided significant neuroprotection against AIS. These findings suggest that targeting miR-155 could be a promising therapeutic strategy for stroke by modulating immune balance and key signaling pathways.

Hearing impairment (HI) disrupts social interaction by hindering the ability to follow conversations in noisy environments. While hearing aids (HAs) with noise reduction (NR) partially address this, the "cocktail-party problem" persists, where individuals struggle to attend to specific voices amidst background noise. This study investigated how NR and an advanced signal processing method for compensating for nonlinearities in Electroencephalography (EEG) signals can improve neural speech processing in HI listeners. Participants wore HAs with NR, either activated or deactivated, while focusing on target speech amidst competing masker speech and background noise. Analysis focused on temporal response functions to assess neural tracking of relevant target and masker speech. Results revealed enhanced neural responses (N1 and P2) to target speech, particularly in frontal and central scalp regions, when NR was activated. Additionally, a novel method compensated for nonlinearities in EEG data, leading to improved signal-to-noise ratio (SNR) and potentially revealing more precise neural tracking of relevant speech. This effect was most prominent in the left-frontal scalp region. Importantly, NR activation significantly improved the effectiveness of this method, leading to stronger responses and reduced variance in EEG data and potentially revealing more precise neural tracking of relevant speech. This study provides valuable insights into the neural mechanisms underlying NR benefits and introduces a promising EEG analysis approach sensitive to NR effects, paving the way for potential improvements in HAs.