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 out...

Investigations into the neural basis of behavior frequently employ calcium imaging to measure neuronal activity. Across studies, however, seemingly reasonable but highly diverse methodological choices are typically made to assess the selectivity of individual neurons to task states. Here, we examine systematically the effect of parameter choices, along the pipeline from data acquisition through statistical testing, on the inferred encoding preferences of individual neurons. We use, as an experimental testbed, calcium imaging in the medial prefrontal cortex of freely behaving mice engaged in a classic exploration-avoidance task with animal-controlled state transitions, namely, navigation in the elevated zero maze. We report that most of the key parameters in the pipeline substantially impact the inferred selectivity of neurons and do so in distinct ways. Using novel accuracy and robustness metrics, we directly compare the quality of inference across combinations of parameter levels and discover an optimal c...

In a dense-sampling resting–state functional magnetic resonance imaging study, Wang et al. (2025) recorded two individuals’ functional connectivity patterns over 30 consecutive days to find a marker of the passage of time in the human brain. The authors measured the similarity of brain connectivity patterns over days, focusing on key regions involved in spatial navigation and declarative memory that have been previously shown to exhibit slow changes in activity patterns over time: the entorhinal cortex (EC) and the hippocampus (HPC). The authors show that connectivity pattern similarity decreased over time—more temporally distant resting-states had more distinct functional connectivity profiles. This result is consistent with the idea that brain activity intrinsically drifts over time (Driscoll et al., 2022). Additionally, the authors observed an anatomical gradient such that the anterior HPC showed stronger temporal drift than the posterior HPC, and the anterolateral EC showed stronger temporal drift than...

Alcohol use disorder (AUD) is one of the top behavioral causes of global disease burden in the United States. Repeated cycles of alcohol intoxication and abstinence induce neuroplastic alterations which induce excessive drinking and cognitive impairments. A system deeply dysregulated by chronic drinking is norepinephrine (NE). At moderate levels, NE has beneficial effects on cognition and behavior, mediated by the α2 adrenergic receptor (AR) subtype. Whether α2 AR activation blunts alcohol consumption in models of heavy drinking has not been determined, and whether α2 AR activation improves cognitive performance following chronic alcohol consumption is unknown. Here, we show that the α2 AR agonist clonidine worsens ethanol-induced hypothermia and sedation in male mice, while the more selective α2 AR agonist guanfacine is devoid of these effects. We also observed that, in male and female mice, while both clonidine and guanfacine reduce heavy alcohol drinking, guanfacine does so with higher potency. Furtherm...

Speech in everyday life is often masked by background noise, making comprehension effortful. Characterizing brain activity patterns when individuals listen to masked speech can help clarify the mechanisms underlying such effort. In the current study, we used functional magnetic resonance imaging (fMRI) in humans of either sex to investigate how neural signatures of story listening change in the presence of masking noise. We show that, as speech masking increases, spatial and temporal activation patterns in auditory regions become more idiosyncratic to each listener. In contrast, spatial activity patterns in brain networks linked to effort (e.g., cingulo-opercular network) are more similar across listeners when speech is highly masked and less intelligible, suggesting shared neural processes. Moreover, at times during stories when one meaningful event ended and another began, neural activation increased in frontal, parietal, and medial cortices. This event-boundary response appeared little affected by backg...

Daughterless (Da), the Drosophila melanogaster homolog of mammalian E-protein transcription factor 4 (TCF4), is well studied in fruit fly embryonic development but its functions in adult nervous system are poorly understood. Mutations in human TCF4 gene lead to intellectual disabilities such as Pitt–Hopkins syndrome and TCF4 has also been linked to schizophrenia. Here, to explore the roles of Da in the Drosophila mature brain, we map Da DNA binding sites and study the transcriptomics of the brains where Da function is inhibited by pan-neuronal Extramacrohaete (Emc) overexpression, in both male and female Drosophila . Our transcriptome analyses reveal that in the adult brain Da regulates the expression of genes involved in behavior, memory, synaptic signaling, protein translation, and metabolic processes. Moreover, combining the RNA sequencing data with Da ChIP sequencing results indicates that genes associated with neuronal projection guidance, metabolism, and translation are direct targets of Da. In addit...

The chemokine CXCL12 plays critical roles in the development of the hippocampus dentate gyrus during both embryogenesis and adulthood. While multiple cell types in the hippocampus express Cxcl12 , their individual contributions to the dentate gyrus development and function remain unclear. Here, using Cxcl12 reporter mice of both sexes, we characterize Cxcl12 expression in Cajal–Retzius (CR) cells—neurons that guide dentate gyrus morphogenesis and influence hippocampal circuitry. We show that CR cells prominently express Cxcl12 during early postnatal development, although both the number and proportion of Cxcl12 -expressing CR cells decline significantly in adulthood. Notably, partial deletion of Cxcl12 from hippocampal CR cells in male and female mice does not result in detectable changes in dentate gyrus architecture, adult neurogenesis, or specific behaviors. These findings suggest that CR cell-derived CXCL12 may be less critical for dentate gyrus development than previously assumed and underscore the co...

An exciting aspect of neuroscience is developing and testing hypotheses via experimentation. However, due to logistical and financial hurdles, the experiment and discovery component of neuroscience is generally lacking in classroom and outreach settings. To address this issue, here we introduce RetINaBox: a low-cost open–source electronic visual system simulator that provides users with a hands-on tool to discover how the visual system builds feature detectors. RetINaBox includes an LED array for generating visual stimuli and photodiodes that act as an array of model photoreceptors. Custom software on a Raspberry Pi computer reads out responses from model photoreceptors and allows users to control the polarity and delay of the signal transfer from model photoreceptors to model retinal ganglion cells. Interactive lesson plans are provided, guiding users to discover different types of visual feature detectors—including ON/OFF, center-surround, orientation-selective, and direction-selective receptive fields—a...

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.

Picture a man in a deckchair, umbrella overhead, relaxing with a drink in hand—while surrounded by industrial wasteland and decay. This was the iconic 1975 album cover for Supertramp's Crisis? What Crisis? The image perfectly captured the cognitive dissonance of denying catastrophe while sitting in its midst. Rick Davies conceived the artwork to satirize how some responded to England's economic crisis of the mid-1970s: “Crisis? What crisis?” Fifty years later, I find myself in my own version of that deckchair—though instead of industrial ruins, I am surrounded by what may be “arguably the largest science crisis of all time.” And just like that man with his parasol, I am tempted to pretend everything is fine (Figure 1). But it is not fine. Not even close. We are facing an uncomfortable truth: the scientific literature is being flooded with fraudulent papers on an industrial scale. This crisis threatens to erode public trust in research at the very moment we need that trust most. Paper mills are commercia...