Vestibular research is essential for understanding and treating disorders such as vertigo and Meniere's disease. The vestibulo-ocular reflex (VOR) is a key method for assessing vestibular function and an essential tool for diagnosing vertigo. Traditionally, the VOR comprises angular VOR (aVOR) and translational VOR (tVOR), which originate from the vestibular semicircular canals (SCCs) and otolith organs, respectively. VOR consists of both fast-phase and slow-phase eye movements, which functionally interact to contribute to gaze control. However, to calculate the gain and phase parameters of the VOR, it is common practice to exclude fast-phase information superimposed on slow-phase eye movements. As a result, the information contained in the fast phase has not been fully utilized. OVAR is primarily used to evaluate otolith function, as there is no SCC input during its steady state. It is widely accepted that fast-phase nystagmus (FPN) during OVAR is generated by periodic otolith inputs via the central vesti...

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][1]). 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 5 years of the initial psychotic episode) to determine macro- and microstructural 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 analy...

Human brain banks are essential for studying a wide variety of neurological and neurodegenerative diseases, yet the variability in postmortem interval (PMI)—the time from death to tissue preservation—poses significant challenges due to rapid cellular decomposition, protein alterations, and RNA degradation. Furthermore, the postmortem transcriptomic alterations occurring within distinct cell types are poorly understood. In this study, we analyzed the effect of a 3 h postmortem interval on single-nucleus RNA signatures in the brains of wild-type (WT) and PS19 mice, a common model of tauopathy. We observed that basic quality control metrics (such as the number of genes and reads per cell), total nuclei counts, and RNA integrity number (RINe) remained consistent across all samples, regardless of PMI or genotype. However, a 3 h PMI diminished the number of genes differentially expressed between PS19 and WT mice, suggesting an impact of delayed processing on the detection of disease-specific transcriptomic signa...

Alpha (8–12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram (EEG)/magnetoencephalogram and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG–fMRI data acquired before and after alpha-frequency transcranial alternating current stimulation ( α -tACS) and observed that α -tACS tightened the dynamic coupling between spontaneous fluctuations in alpha power and DMN connectivity (especially, in the posterior DMN, between the posterior c...

Binocular disparity is used for perception and action in three dimensions. Neurons in the primary visual cortex respond to binocular disparity in random dot patterns, even when the contrast is inverted between eyes (false depth cue). In contrast, neurons in the ventral stream largely cease to respond to false depth cues. This study evaluated whether GABAergic inhibition is involved in suppressing false depth cues in the human ventral visual cortex. We compared GABAergic inhibition (GABA+) and glutamatergic excitation (Glx) during the viewing of correlated and anticorrelated binocular disparity in 18 participants using single-voxel proton magnetic resonance spectroscopy. Measurements were taken from the early visual cortex (EVC) and the lateral occipital cortex (LO). Three visual conditions were presented per voxel location: correlated binocular disparity, anticorrelated binocular disparity, or a blank gray screen with a fixation cross. To identify differences in neurochemistry, GABA+ or Glx levels were com...

Evolutionary pressures adapted insect chemosensation to their respective physiological needs and tasks in their ecological niches. Solitary nocturnal moths rely on their acute olfactory sense to find mates at night. Pheromones are detected with maximized sensitivity and high temporal resolution through mechanisms that are mostly unknown. While the inverse topology of insect olfactory receptors and heteromerization with the olfactory receptor coreceptor suggest ionotropic transduction via odorant-gated receptor–ion channel complexes, contradictory data propose amplifying G-protein–coupled transduction. Here, we used in vivo tip-recordings of pheromone-sensitive sensilla of male Manduca sexta hawkmoths at specific times of day (rest vs activity). Since the olfactory receptor neurons distinguish signal parameters in three consecutive temporal windows of their pheromone response (phasic; tonic; late, long-lasting), respective response parameters were analyzed separately. Disruption of G-protein–coupled transdu...

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. For instance, the deletion of RhoA and phosphatase and tensin homolog ( Pten ) (an extrinsic and intrinsic modulating factor, respectively) in corticospinal neurons (CSNs) promotes axon sprouting after thoracic SCI; however, it is unable to restore motor function. Here, we examine the effects of combining RhoA/Pten deletion in CSNs with chemogenetic neuronal stimulation on axonal growth and motor recovery after SCI in mice. We find that this combinatorial approach promotes greater axonal growth and presynaptic bouton formation in CSNs within the spinal cord compared with RhoA ; Pten deletion alone. Furthermore, chemogenetic neuronal stimulation of RhoA ; Pten -deleted CSNs improves forelimb performance in behavioral tasks after SCI compared with RhoA ; Pten deletion alone. These results demonstrate that combination therapies pairing genetic modifications with neuro...

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...

Maintenance of normal structure of the enteric nervous system (ENS), which regulates key gastrointestinal functions, requires robust homeostatic mechanisms, since by virtue of its location within the gut wall, the ENS is subject to constant mechanical, chemical, and biological stressors. Using transgenic and thymidine analog-based experiments, we previously discovered that neuronal turnover—where continual neurogenesis offsets ongoing neuronal loss at steady state—represents one such mechanism. Although other studies confirmed that neuronal death continues into adulthood in the myenteric plexus of the ENS, the complicated nature of thymidine analog presents challenges in substantiating the occurrence of adult neurogenesis. Therefore, it is vital to employ alternative, well-recognized techniques to substantiate the existence of adult enteric neurogenesis in the healthy gut. Here, by using established methods of assessing nuclear DNA content and detecting known mitotic marker phosphor-histone H3 (pH3) in Hu+...

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 anal...