γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain which mediates its rapid effects on neuronal excitability via ionotropic GABAA receptors. GABA levels in the brain are critically dependent upon GABA-aminotransferase (GABA-AT) which promotes its degradation. Vigabatrin, a low-affinity GABA-AT inhibitor, exhibits anticonvulsant efficacy, but its use is limited due to cumulative ocular toxicity. OV329 is a rationally designed, next-generation GABA-AT inhibitor with enhanced potency. We demonstrate that sustained exposure to OV329 in mice reduces GABA-AT activity and subsequently elevates GABA levels in the brain. Parallel increases in the efficacy of GABAergic inhibition were evident, together with elevations in electroencephalographic delta power. Consistent with this, OV329 exposure reduced the severity of status epilepticus and the development of benzodiazepine refractory seizures. Thus, OV329 may be of utility in treating seizure disorders and associated pathologi...

The gaze-following patch (GFP) is located in the posterior temporal cortex and has been described as a cortical module dedicated to processing other people's gaze-direction in a domain-specific manner. Thus, it appears to be the neural correlate of Baron-Cohen's eye direction detector (EDD) which is one of the core modules in his mindreading system—a neurocognitive model for the theory of mind concept. Inspired by Jerry Fodor's ideas on the modularity of the mind, Baron-Cohen proposed that, among other things, the individual modules are domain specific. In the case of the EDD, this means that it exclusively processes eye-like stimuli to extract gaze-direction and that other stimuli, which may carry directional information as well, are processed elsewhere. If the GFP is indeed EDD's neural correlate, it must meet this expectation. To test this, we compared the GFP's BOLD activity during gaze-direction following with the activity during arrow-direction following in the present human fMRI study. Contrary to t...

Psychotic symptoms and delusional beliefs have been linked to dopamine transmission in both healthy and clinical samples and are assumed to result at least in part from perceiving illusory patterns in noise. However, the existing literature on the role of dopamine in detecting patterns in noise is inconclusive. To address this issue, we assessed the effect of manipulating dopaminergic neurotransmission on illusory pattern perception in healthy individuals ( n  = 48, n  = 19 female) in a double-blind placebo-controlled within-subjects design (see preregistration at <https://osf.io/a4k9j/>). We predicted individuals on versus off ʟ-DOPA to be more likely to perceive illusory patterns, specifically objects in images containing only noise. Using a signal detection model, however, we found no credible evidence that ʟ-DOPA compared with placebo increased false alarm rates. Further, ʟ-DOPA did not reliably modulate measures of accuracy, discrimination sensitivity, and response bias. In all cases, Bayesian statist...

Impaired inhibition—and the resulting disruption of the brain's excitatory–inhibitory (E–I) balance—has historically been theorized to play a critical role in epileptogenesis and seizures (Treiman, 2001). This concept is supported by numerous studies showing impaired function of gamma-aminobutyric acid (GABA)-ergic function in both genetic and acquired animal models of epilepsy and in human epileptic brain tissue. Furthermore, medications that enhance GABAergic signaling have an anticonvulsant effect whereas GABA antagonists are proconvulsant. Yet, despite a large body of evidence implicating GABA in epileptogenesis and epilepsy, the direct causal role of inhibitory interneuron loss (or impairment) has remained incompletely understood. In the case of acquired models of epilepsy, such as temporal lobe epilepsy, interneuron loss is central to signature pathophysiology but occurs alongside multiple other pathological and neuroplastic changes that are also likely to influence disease progression. In the case ...

We investigated the neural signatures of expert decision-making in the context of police training in a virtual reality–based shoot/don’t shoot scenario. Police officers can use stopping force against a perpetrator, which may require using a firearm and each decision made by an officer to discharge their firearm or not has substantial implications. Therefore, it is important to understand the cognitive and underlying neurophysiological processes that lead to such a decision. We used virtual reality–based simulations to elicit ecologically valid behavior from authorized firearms officers (AFOs) in the UK and matched novices in a shoot/don't shoot task and recorded electroencephalography concurrently. We found that AFOs had consistently faster response times than novices, suggesting our task was sensitive to their expertise. To investigate differences in decision-making processes under varying levels of threat and expertise, we analyzed electrophysiological signals originating from the anterior cingulate cort...

The adult turtle spinal cord can generate multiple kinds of limb movements, including swimming, three forms of scratching, and limb withdrawal (flexion reflex), even without brain input and sensory feedback. There are many multifunctional spinal neurons, activated during multiple motor patterns, and some behaviorally specialized neurons, activated during only one. How do multifunctional and behaviorally specialized neurons each contribute to motor output? We analyzed in vivo intracellular recordings of multifunctional and specialized neurons. Neurons tended to spike in the same phase of the hip-flexor (HF) activity cycle during swimming and scratching, though one preferred opposite phases. During both swimming and scratching, a larger fraction of multifunctional neurons than specialized neurons were highly rhythmic. One group of multifunctional neurons was active during the HF-on phase and another during the HF-off phase. Thus, HF–extensor alternation may be generated by a subset of multifunctional spinal ...

Perceptual decisions are often accompanied by a feeling of decision confidence. Where the parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on the (pre)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electroencephalography was measured. ...

As rapid responders to their environments, microglia engage in functions that are mirrored by their cellular morphology. Microglia are classically thought to exhibit a ramified morphology under homeostatic conditions which switches to an ameboid form during inflammatory conditions. However, microglia display a wide spectrum of morphologies outside of this dichotomy, including rod-like, ramified, ameboid, and hypertrophic states, which have been observed across brain regions, neurodevelopmental timepoints, and various pathological contexts. We applied dimensionality reduction and clustering to consider contributions of multiple morphology measures together to define a spectrum of microglial morphological states in a mouse dataset that we used to demonstrate the utility of our toolset. Using ImageJ, we first developed a semiautomated approach to characterize 27 morphology features from hundreds to thousands of individual microglial cells in a brain region-specific manner. Within this pool of features, we def...

We are fortunate to belong to a large undergraduate R1 research institution [at the time of writing, over 57,000 undergraduate students are enrolled at Texas A&M University (TAMU)]. Research is a major part of the undergraduate experience, and in fact many of our degree plans require undergraduate students to participate in at least one semester of laboratory research. As the principal investigator (PI) of a neuroscience laboratory (J.N.D.), former Associate Director for Undergraduate Research (S.M.M.), and current undergraduate researchers (P.G. and A.S.), we each have unique perspectives on the benefits of undergraduate research experiences (UREs). According to a 2007 report based on self-reported outcomes among undergraduates and their URE mentors, UREs increase interest in science, technology, engineering, and math (STEM) careers for over two-thirds of students who participate, and the large majority (88%) of students improve their understanding of how to conduct research (Russell et al., 2007). In an...

In the article “Apolipoprotein A1 Enhances Endothelial Cell Survival in an In Vitro Model of ALS,” by Svitlana Garbuzova-Davis, Alison E. Willing, and Cesario V. Borlongan, …