In our continuous drive to increase the standards of statistical rigor in neuroscience, we, at eNeuro , have launched a series of initiatives aimed at refining how statistics are employed, reported, and interpreted in neuroscience (Bernard, 2019, 2021; Calin-Jageman and Cumming, 2019). The drive toward this enhancement stems, in part, from the ongoing challenge of reproducibility—a cornerstone of scientific integrity that, unfortunately, has been undermined by gaps in statistical literacy (Bernard, 2023). Statistics, a discipline with its unique complexities and nuances, extends far beyond mere number-crunching. My personal journey from grasping basic statistical concepts to applying …

The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino–parabrachio–amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce afterdischarges that outlast the stimulus. Using ex vivo slice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitabilit...

Spontaneous eye blinking is gaining popularity as a proxy for higher cognitive functions, as it is readily modulated by both environmental demands and internal processes. Prior studies were impoverished in sample size, sex representation, and age distribution, making it difficult to establish a complete picture of the behavior. Here we present eye-tracking data from a large cohort of normative participants ( n  = 604; 393 F; aged 5–93 years) performing two tasks: one with structured, discrete trials (interleaved pro-/anti-saccade task, IPAST) and one with a less structured, continuous organization in which participants watch movies (free-viewing; FV). Sex- and age-based analyses revealed that females had higher blink rates between the ages of 22 and 58 years in the IPAST and 22 and 34 years in FV. We derived a continuous measure of blink probability to reveal behavioral changes driven by stimulus appearance in both paradigms. In the IPAST, blinks were suppressed near stimulus appearance, particularly on co...

The neural mechanisms underlying the exogenous coding and neural entrainment to repetitive auditory stimuli have seen a recent surge of interest. However, few studies have characterized how parametric changes in stimulus presentation alter entrained responses. We examined the degree to which the brain entrains to repeated speech (i.e., /ba/) and nonspeech (i.e., click) sounds using phase-locking value (PLV) analysis applied to multichannel human electroencephalogram (EEG) data. Passive cortico-acoustic tracking was investigated in N  = 24 normal young adults utilizing EEG source analyses that isolated neural activity stemming from both auditory temporal cortices. We parametrically manipulated the rate and periodicity of repetitive, continuous speech and click stimuli to investigate how speed and jitter in ongoing sound streams affect oscillatory entrainment. Neuronal synchronization to speech was enhanced at 4.5 Hz (the putative universal rate of speech) and showed a differential pattern to that of clicks,...

The preBötzinger complex (preBötC), located in the medulla, is the essential rhythm-generating neural network for breathing. The actions of opioids on this network impair its ability to generate robust, rhythmic output, contributing to life-threatening opioid-induced respiratory depression (OIRD). The occurrence of OIRD varies across individuals and internal and external states, increasing the risk of opioid use, yet the mechanisms of this variability are largely unknown. In this study, we utilize a computational model of the preBötC to perform several in silico experiments exploring how differences in network topology and the intrinsic properties of preBötC neurons influence the sensitivity of the network rhythm to opioids. We find that rhythms produced by preBötC networks in silico exhibit variable responses to simulated opioids, similar to the preBötC network in vitro. This variability is primarily due to random differences in network topology and can be manipulated by imposed changes in network connect...

Problematic alcohol consumption is associated with deficits in decision-making and alterations in prefrontal cortex neural activity likely contribute. We hypothesized that the differences in cognitive control would be evident between male Wistars and a model of genetic risk: alcohol-preferring P rats. Cognitive control is split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus, whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol seeking whereas P rats would show reactive control over alcohol seeking. Neural activity was recorded from the prefrontal cortex during an alcohol seeking task with two session types. On congruent sessions, the conditioned stimulus (CS+) was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, made more incorrect approaches during incongruent sessions,...

The motor cortex comprises the primary descending circuits for flexible control of voluntary movements and is critically involved in motor skill learning. Motor skill learning is impaired in patients with Parkinson's disease, but the precise mechanisms of motor control and skill learning are still not well understood. Here we have used transgenic mice, electrophysiology, in situ hybridization, and neural tract-tracing methods to target genetically defined cell types expressing D1 and D2 dopamine receptors in the motor cortex. We observed that putative D1 and D2 dopamine receptor-expressing neurons (D1+ and D2+, respectively) are organized in highly segregated, nonoverlapping populations. Moreover, based on ex vivo patch-clamp recordings, we showed that D1+ and D2+ cells have distinct morphological and electrophysiological properties. Finally, we observed that chemogenetic inhibition of D2+, but not D1+, neurons disrupts skilled forelimb reaching in adult mice. Overall, these results demonstrate that dopami...

The cortical visual area, V4, has been considered to code contours that contribute to the intermediate-level representation of objects. The neural responses to the complex contour features intrinsic to natural contours are expected to clarify the essence of the representation. To approach the cortical coding of natural contours, we investigated the simultaneous coding of multiple contour features in monkey ( Macaca fuscata ) V4 neurons and their population-level representation. A substantial number of neurons showed significant tuning for two or more features such as curvature and closure, indicating that a substantial number of V4 neurons simultaneously code multiple contour features. A large portion of the neurons responded vigorously to acutely curved contours that surrounded the center of classical receptive field, suggesting that V4 neurons tend to code prominent features of object contours. The analysis of mutual information (MI) between the neural responses and each contour feature showed that most ...

Touch sensation from the glabrous skin of the hand is essential for precisely controlling dexterous movements, yet the neural mechanisms by which tactile inputs influence motor circuits remain largely unexplored. By pairing air-puff tactile stimulation on the hand's glabrous skin with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), we examined the effects of tactile stimuli from single or multiple fingers on corticospinal excitability and M1's intracortical circuits. Our results showed that when we targeted the hand's first dorsal interosseous (FDI) muscle with TMS, homotopic (index finger) tactile stimulation, regardless of its point (fingertip or base), reduced corticospinal excitability. Conversely, heterotopic (ring finger) tactile stimulation had no such effect. Notably, stimulating all five fingers simultaneously led to a more pronounced decrease in corticospinal excitability than stimulating individual fingers. Furthermore, tactile stimulation significantly increased intr...

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate ( Macaca mulatta ) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These “V1-bypassing” projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extr...