eNeuro最新文献

Alpha peak frequency (APF) is defined as a prominent spectral peak within the 8-12 Hz frequency range. Typically, an individual's alpha frequency is regarded as a stable neurophysiological marker. A wealth of recent evidence, however, indicates that APF shifts within short timescales in relation to task demands and even spontaneously so. Further, brain stimulation studies often report shifts in APF both within and between experimental sessions, directly contradicting the idea of a stable APF. To characterize the nonstationarities in spectral parameters, we estimated APFs from 1 s epochs of resting-state magnetoencephalography (MEG) recordings from healthy adults of either sex. To enhance signal-to-noise ratio, without compromising on temporal resolution, we averaged power spectra within parcelled regions. Our findings indicate that variation in APFs exacerbates along the posterior-to-anterior cortical plane, i.e., from the occipital to the frontal cortices. Further, by comparisons with amplitude-matched simulated signals, we demonstrated that the observed gradient is not attributable to measurement noise. Across the cortex, APFs showed poor temporal reliability, raising the question of whether APFs are more like a transient state than a trait. In general, our study elucidates the dynamic characteristics of alpha oscillations and reveals systematic regional differences which are, in part, shaped by underlying signal-to-noise ratio inherent to MEG recordings.

Bimanual coordination, fundamental to human motor control, typically involves the execution of different functions by the two limbs (e.g., opening a jar). Previous research has largely investigated bimanual control through simple coordination tasks in which the limbs perform similar movements (e.g., finger tapping); however, few studies have specifically examined coordination when the two limbs perform different yet complementary functions. In the current study, participants performed point-to-point movements of a rectangular cursor, where one limb controlled cursor trajectory and the other rotated a knob to match a target orientation. Participants (N = 116, 76 female, 1 nonbinary; 92% right-handed) were divided into four groups and completed the task with a visual feedback gain perturbation (an increase or decrease) applied either to the cursor trajectory or orientation. Our results showed rapid adaptation to perturbations of visual feedback of the movement trajectory, affecting both the perturbed limb controlling the trajectory and the unperturbed limb controlling the orientation. Conversely, perturbation to the visual orientation feedback primarily only influenced the perturbed limb controlling orientation, with minimal impact on movement trajectory metrics. Importantly, these results were independent of reaching amplitude, duration, and limb dominance. In addition, we assessed the temporal coordination between the two limbs and found that perturbations in visual trajectory feedback led to significant changes in limb coordination, whereas no notable difference was observed for perturbations of orientation. These findings indicate asymmetries in bimanual motor recalibration dependent on the perturbed aspect of visual feedback (orientation vs trajectory), suggesting differences in underlying neural mechanisms and interhemispheric communication.

While the most common statistical tests assume that the error of the dependent variable follows a normal distribution, dependent variables in translational neuroscience studies often fail to meet this assumption. Common statistical tests like the t test and ANOVA are based on the normality assumption, but quite often these tests are used without checking whether the dependent variable meets the normality assumption which can lead to erroneous interpretations and conclusions about observed associations. There is a significant need for the neuroscience community to utilize nonparametric statistics, particularly for regression analyses. Neuroscientists can greatly enhance the rigor of their analyses by understanding and utilizing nonparametric regression techniques that provide robust estimates of associations when data are skewed. This commentary will discuss and demonstrate analytic techniques that can be used when data do not meet the assumption of normality.

Repetitive mild traumatic brain injury (rmTBI) is a major contributor to long-term neurological dysfunction, yet many preclinical models lack precise control and quantification of biomechanical forces across impacts. We developed a reproducible, closed-skull mouse model of rmTBI using a custom-built weight-drop apparatus featuring a solenoid-based rebound arrest system, integrated high-speed videography, and accelerometry to track head kinematics during impact. Adult male and female mice received either a single impact or nine daily impacts. Linear and angular acceleration data were analyzed alongside behavioral and histological outcomes. Our apparatus delivered consistent impact and velocity forces with minimal intersubject variability. Additionally, the animals experienced consistent linear and angular acceleration as measured using high-speed video capture. These impacts did not cause skull fracture or acute vascular hemorrhage, but impacted animals had increased return of righting reflex time, consistent with mild, concussion-like symptoms. Behavioral testing revealed reduced performance of rmTBI-affected mice in an olfaction-mediated foraging task (buried food task), particularly at later timepoints, consistent with progressive olfactory impairment. Immunohistochemical analysis of Iba1 and CD68 in the brain demonstrated sex-dependent microglial activation, with males showing higher expression levels in both single- and nine-impact models. Among the brain regions investigated, microglial activation was most pronounced in the corpus callosum, neocortex, and olfactory tubercle. These findings underscore the importance of including sex as a biological variable in rmTBI research and support the utility of this model for probing injury thresholds, regional vulnerability, and potential therapeutic interventions in repetitive head trauma.

Perinatal exposure to the organophosphorus insecticide chlorpyrifos (CPF) is associated with an increased incidence of neurodevelopmental disorders, such as autism spectrum disorder. While these behavioral detriments have been modeled in rodents, the underlying functional alterations in the developing brain are largely unknown. Previous reports using a rat model have identified alterations to both inhibitory synaptic transmission and serotonergic (5-HT) receptor binding in the cortex following developmental CPF exposure. Here, we use a rat model of gestational CPF exposure to investigate whether this altered inhibitory activity is driven by increased spontaneous firing of inhibitory interneurons and altered 5-HT receptor expression. Using cell-attached ex vivo electrophysiology in young rats of both sexes, we identified a significant increase in the number of spontaneously firing neurons in the somatosensory cortex of CPF-exposed offspring. Analysis of action potential metrics identified a subset of these neurons as fast-spiking parvalbumin (PV) interneurons. Immunohistochemical labeling of c-Fos, a marker of neuronal activity, further revealed a pronounced increase in activity of neurons of the somatosensory cortex in both juvenile and adult rats that had been gestationally exposed to CPF. Finally, RNAscope in situ hybridization showed an increase in the expression of the inhibitory receptor 5-HT_1B in PV neurons of male offspring. The preliminary data reported here suggest that gestational exposure to CPF may result in persistent hyperexcitation of the somatosensory cortex. These neurophysiological effects may contribute to the established behavioral outcomes resulting from gestational exposure to CPF and offer guidance for novel preventative interventions.

Sulf1 is an extracellular sulfatase that regulates cell signaling by removing 6-O-sulfates from heparan sulfate. Although the roles of Sulf1 in neural development have been studied extensively, its functions in the adult brain remain largely unknown. Here, we report the effects of Sulf1 disruption on the neuronal properties of the medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell, one of the regions highly expressing Sulf1 We separately labeled MSNs expressing dopamine D1 receptors (D1-MSNs) or D2 receptors (D2-MSNs) by injecting adult male Drd1-Cre and Drd2-Cre mice with a Cre-dependent AAV vector expressing a red fluorescent protein, mCherry, and examined their electrophysiological properties by means of whole-cell patch-clamp recording. In the D2-MSNs, Sulf1 disruption led to drastic changes in neural firing responses to depolarizing current injections: in the Sulf1 knock-out mice, the rheobase was smaller than in the wild-type mice, but the number of action potentials elicited by depolarization did not increase at larger current injections. In the D1-MSNs, Sulf1 disruption resulted in more depolarized resting membrane potentials and increase in the AMPA/NMDA ratio. These results suggest that Sulf1 is essential for regulation of neuronal excitability and glutamatergic transmission of NAc MSNs in adult mice and implicate the potential roles of Sulf1 in NAc circuit activity, reward-aversion behaviors, and psychiatric disorders such as schizophrenia and drug addiction.

We studied the role of movement and outcome information in forming metacognitive representations of agency. Human participants (N = 40; 25 female, 15 male, 0 diverse) completed a goal-oriented task: a semivirtual version of a ball-throwing game. In two conditions, we manipulated either the visual representation of the throwing movement or its proximal outcome (the resulting ball trajectory). We measured participants' accuracy in a discrimination agency task, as well as confidence in their responses and tested for differences in the electrophysiological (EEG) signal using mass linear mixed-effect modeling. We found no mean differences between participants' metacognitive efficiency between conditions. However, through exploratory analyses, we found that metacognitive sensitivity did not correlate between the two conditions and that the EEG signal differed between the two conditions during the agency discrimination task. We cautiously interpret these results as suggesting that although both movement and outcome information contribute to participants' sense of agency, they may do so through distinct processes. These findings highlight the need for further research examining the potential neurophysiological differences corresponding to the conceptual distinction between bodily and external agency.

Decoding algorithms provide a powerful tool for understanding the firing patterns that underlie cognitive processes such as motor control, learning, and recall. When implemented in the context of a real-time system, decoders also make it possible to deliver feedback based on the representational content of ongoing neural activity. That, in turn, allows experimenters to test hypotheses about the role of that content in driving downstream activity patterns and behaviors. While multiple real-time systems have been developed, they are typically implemented with a compiled programming language, making them more difficult for users to quickly adapt for new experiments. Here we present a software system written in the widely used Python programming language to facilitate rapid experimentation. Our solution implements the state space based clusterless decoding algorithm for an online, real-time environment. The parallelized application processes neural data with temporal resolution of 6 ms and median computational latency <50 ms for medium- to large-scale (32+ tetrodes) rodent hippocampus recordings without the need for spike sorting. It also executes auxiliary functions such as detecting sharp wave ripples from local field potential data. Even with an interpreted language, the performance is similar to state-of-the-art solutions that use compiled programming languages. We demonstrate this real-time decoder in a rat behavior experiment in which the decoder allowed closed-loop neurofeedback based on decoded hippocampal spatial representations. Overall this system provides a powerful and easy-to-modify tool for real-time feedback experiments.

Mice offer a wealth of opportunities for investigating brain circuits regulating multiple behaviors, largely due to their genetic tractability. Social behaviors are translationally relevant, considering both mice and humans are highly social mammals, and human social behavior disruptions are key symptoms of myriad neuropsychiatric disorders. Stresses related to social experiences are particularly influential in the severity and maintenance of neuropsychiatric disorders like anxiety disorders and trauma and stressor-related disorders. Yet, induction and study of social stress in mice has disproportionately focused on males, influenced heavily by their inherent territorial nature. Social target-instigated stress (i.e., defeat), while ethologically relevant, is quite variable and predominantly specific to males, making rigorous and sex-inclusive studies challenging. In pursuit of a controllable, consistent, high-throughput, and sex-inclusive method for social stress elicitation, we modified a paradigm to train male and female F1 129S1/SvlmJ × C57BL/6J mice to associate (via classical conditioning) same or different sex C57BL/6J targets with a mild, aversive stimulus. While further paradigm optimization is required, social interaction testing 24 h after conditioning indicates males socially conditioned better to male targets by exhibiting reduced social interaction, whereas females appeared not to form social stimulus associations. Serum corticosterone levels inversely corresponded to social avoidance after different sex, but not same sex, conditioning, suggesting corticosterone-mediated arousal influences cross-sex interactions. These rigorously controlled null outcomes align with past pursuits' limited success in creating a sex-inclusive social stress paradigm.

Olfaction is the dominant sensory modality in rodents. It can be used to assess behavioral phenomena including stress, learning and memory, and social investigation, and impaired olfaction is implicated in several neurological disorders. Paradigms such as the olfactory habituation/dishabituation (OHD) task can assess olfactory perception, memory, and motivation. However, these tasks require manual stimulus presentation, introducing variability and making them labor-intensive. Olfactometers allow automated stimulus delivery, but the OHD task has not yet been adapted for use with an olfactometer. Additionally, current olfactometer designs require proprietary software or components that are difficult to obtain/fabricate and commercial units are expensive. As a result, these apparatuses have not been widely implemented. Here, we describe the design and assembly of the Odor Delivery Optimization Research System (ODORS), an economical, modular, and open-source olfactometer for use in rodents, and describe a variant of the OHD task that can be automated using this apparatus. The design is based on five principles: (1) familiar layout and function; (2) use of inexpensive, readily available components; (3) easily integrated, modular design; (4) real-time assessment of odorant levels; and (5) the ability to test tethered and untethered rodents in optogenetic and electrophysiological experiments. Male and female C57BL/6NCrl mice performing OHD in the ODORS exhibit the characteristic habituation to repeated presentations of an odor and dishabituation to the first presentation of a novel odor. As a result, we suggest that the ODORS makes improved olfactory testing accessible to many labs and offers a major refinement over existing OHD testing paradigms.