The acquisition of a motor skill involves adaptations of spinal and supraspinal pathways to alpha motoneurons. In this study, we estimated the shared synaptic contributions of these pathways to understand the neural mechanisms underlying the short-term acquisition of a new force-matching task. High-density surface electromyography (HDsEMG) was acquired from the first dorsal interosseous (FDI; 7 males and 6 females) and tibialis anterior (TA; 7 males and 4 females) during 15 trials of an isometric force-matching task. For two selected trials (pre- and post-skill acquisition), we decomposed the HDsEMG into motor unit spike trains, tracked motor units between trials, and calculated the mean discharge rate and the coefficient of variation of interspike interval (COVISI). We also quantified the post/pre ratio of motor units’ coherence within delta, alpha, and beta bands. Force-matching improvements were accompanied by increased mean discharge rate and decreased COVISI for both muscles. Moreover, the area under ...

Early-life stressors can affect reproductive development and change responses to adult stress. We tested if resource scarcity in the form of limited bedding and nesting (LBN) from postnatal days (PND) 4 to 11 delayed sexual maturation in male and female mice and/or altered the response to an acute, layered, psychosocial stress (ALPS) in adulthood. Contrary to the hypotheses, age and mass at puberty were unaffected by the present application of LBN. Under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, and proestrous females reared in standard (STD) or LBN environments were similar. ALPS disrupts the luteinizing hormone (LH) surge in most mice when applied on the morning of proestrus; this effect was not changed by resource scarcity. In this study, the paucity of effects in the offspring may relate to a milder response of CBA dams to the paradigm. While LBN dams exited the nest more often and their offspring were smaller than STD-reared offspring on PND11, dam cor...

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. ...

Reading depends on a brain region known as the “visual word form area” (VWFA) in the left ventral occipitotemporal cortex. This region's function is debated because its stimulus selectivity is not absolute, it is modulated by a variety of task demands, and it is inconsistently localized. We used fMRI to characterize the combination of sensory and cognitive factors that activate word-responsive regions that we precisely localized in 16 adult humans (4 male). We then presented three types of character strings: English words, pseudowords, and unfamiliar characters with matched visual features. Participants performed three different tasks while viewing those stimuli: detecting real words, detecting color in the characters, and detecting color in the fixation mark. There were three primary findings about the VWFA's response: (1) It preferred letter strings over unfamiliar characters even when the stimuli were ignored during the fixation task. (2) Compared with those baseline responses, engaging in the word read...

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 ...

Generation of human induced pluripotent stem cell (hiPSC)-derived motor neurons (MNs) offers an unprecedented approach to modeling movement disorders such as dystonia and amyotrophic lateral sclerosis. However, achieving survival poses a significant challenge when culturing induced MNs, especially when aiming to reach late maturation stages. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we assembled two types of coculture systems: direct coculturing of neurons with astrocytes and indirect coculture using culture inserts that physically separate neurons and astrocytes. Both systems significantly enhance neuron survival. Compared with these two systems, no significant differences in neurodevelopment, maturation, and survival within 3 weeks, allowing to prepare neurons at maturation stages. Using the indirect coculture system, we obtained highly pure MNs at the late mature stage from hiPSCs. Transcriptomic studies of hiPSC-derived MNs showed a typical neurodevelopmental switch in gene ex...

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 ...

Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine (VM) than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and VM, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel ( r  = 1.5 cm) versus rat dowel ( r  = 3.5 cm). EPM results indicate that CGRP alone or OVAR alone did not increase anxiety indices. However, the combination of CGRP and OVAR did elicit anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. These res...