When faced with multiple potential movement options, individuals either reach directly to one of the options, or initiate a reach intermediate between the options. It remains unclear why people generate these two types of behaviors. Using the go-before-you-know task (commonly used to study behavior under choice uncertainty) in humans, we examined two key questions. First, do these two types of responses actually reflect distinct movement strategies? If so, the relative desirability (i.e., weighing the success likelihood vs the attainable reward) of the two target options would not need to be computed identically for direct and intermediate reaches. We showed that indeed, when reward and success likelihood differed between the two options, reach direction was preferentially biased toward different directions for direct versus intermediate reaches. Importantly, this suggests that the computation of subjective values depends on the choice of movement strategy. Second, what drives individual differences in how...

Target reward influences motor planning strategies through modulation of movement vigor. Considering current theories of sensorimotor control suggesting that movement planning consists in selecting a goal-directed control strategy, we sought to investigate the influence of reward on feedback control. Here, we explored this question in three human reaching experiments. First, we altered the explicit reward associated with the goal target and found an overall increase in feedback gains for higher target rewards, highlighted by larger velocities, feedback responses to external loads, and background muscle activity. Then, we investigated whether the differences in target rewards across multiple goals impacted rapid motor decisions during movement. We observed idiosyncratic switching strategies dependent on both target rewards and, surprisingly, the feedback gains at perturbation onset: the more vigorous movements were less likely to switch to a new goal following perturbations. To gain further insight into a c...

Humans can perform complex movements with speed and agility in the face of constantly changing task demands. To accomplish this, motor plans are adapted to account for errors in our movements because of changes in our body (e.g., growth or injury) or in the environment (e.g., walking on sand vs ice). It has been suggested that adaptation that occurs in response to changes in the state of our body will generalize across different movement contexts and environments, whereas adaptation that occurs with alterations in the external environment will be context-specific. Here, we asked whether the ability to form generalizable versus context-specific motor memories develops during childhood. We performed a cross-sectional study of context-specific locomotor adaptation in 35 children (3–18 years old) and 7 adults (19–31 years old). Subjects first adapted their gait and learned a new walking pattern on a split-belt treadmill, which has two belts that move each leg at a different speed. Then, subjects walked overgro...

Cortical spreading depression (CSD) is a wave of pronounced depolarization of brain tissue accompanied by substantial shifts in ionic concentrations and cellular swelling. Here, we validate a computational framework for modeling electrical potentials, ionic movement, and cellular swelling in brain tissue during CSD. We consider different model variations representing wild-type (WT) or knock-out/knock-down mice and systematically compare the numerical results with reports from a selection of experimental studies. We find that the data for several CSD hallmarks obtained computationally, including wave propagation speed, direct current shift duration, peak in extracellular K+ concentration as well as a pronounced shrinkage of extracellular space (ECS) are well in line with what has previously been observed experimentally. Further, we assess how key model parameters including cellular diffusivity, structural ratios, membrane water and/or K+ permeabilities affect the set of CSD characteristics.

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), are implicit in causing obesity. Mutations that reduce BDNF and TrkB expression are associated with obesity in humans and mice. Recently, it was reported that Bdnf gene deletion in the neurons of the paraventricular hypothalamus (PVH) caused positive energy balance and severe obesity in the form of hyperphagia, impaired adaptive thermogenesis, and decreased energy expenditure. Thus, we hypothesize that activation of these neurons will have the opposite effect and provide an opportunity for long-lasting obesity treatment. To specifically activate BDNF-expressing PVH (PVHBDNF) neurons, we injected Cre-dependent adeno-associated virus (AAV) expressing the excitatory DREADD hM3Dq bilaterally into the PVH of Bdnf2A-Cre/+ knock-in mice and then administered clozapine-N-oxide (CNO). Using this technique, we demonstrated that acute activation of these neurons rapidly decreased normal nocturnal feeding and fasting-induc...

It has been shown that P3b is not a signature of perceptual awareness per se but is instead more closely associated with postperceptual processing ([Cohen et al., 2020][1]). Here, we seek to investigate whether human participants’ attentional states are different in the report and the no-report conditions. This difference in attentional states, if exists, may lead to degraded consciousness of the stimuli in the no-report condition, and it therefore remains unknown whether the disappearance of P3b is because of a lack of reportability or degraded consciousness. Results of our experiment 1 showed that participants did experience degraded contents of consciousness in the no-report condition. However, results of experiment 2 showed that the degraded contents of consciousness did not influence the amplitude of P3b. These findings strengthen the claim that P3b is not a signature of perceptual awareness but is associated with postperceptual processing. [1]: #ref-14

Cisplatin-induced ototoxicity can be partially attributed to excessive reactive oxygen species (ROS) production, and agmatine is well-known for the activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway to inhibit ROS production. Whether agmatine could be used to alleviate cisplatin-induced ototoxicity is investigated. Cisplatin-exposed House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants showed increased ROS production detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and decreased cell viability detected by Cell Counting Kit-8 (CCK-8) or Myosin 7a staining, which could be reversed by the agmatine pretreatment. Cisplatin intraperitoneally injected C57BL/6 mice demonstrated damaged auditory function as indicated by distortion products otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) assays, and trans-tympanically administrated agmatine in the left ears could partly prevent the auditory function loss. Mechanisticall...

Humans deftly parse statistics from sequences. Some theories posit that humans learn these statistics by forming cognitive maps, or underlying representations of the latent space which links items in the sequence. Here, an item in the sequence is a node, and the probability of transitioning between two items is an edge. Sequences can then be generated from walks through the latent space, with different spaces giving rise to different sequence statistics. Individual or group differences in sequence learning can be modeled by changing the time scale over which estimates of transition probabilities are built, or in other words, by changing the amount of temporal discounting. Latent space models with temporal discounting bear a resemblance to models of navigation through Euclidean spaces. However, few explicit links have been made between predictions from Euclidean spatial navigation and neural activity during human sequence learning. Here, we use a combination of behavioral modeling and intracranial encephalo...

For adaptive goal-directed action, the brain needs to monitor action performance and detect errors. The corresponding information may be conveyed via different sensory modalities; for instance, visual and proprioceptive body position cues may inform about current manual action performance. Thereby, contextual factors such as the current task set may also determine the relative importance of each sensory modality for action guidance. Here, we analyzed human behavioral, functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) data from two virtual reality-based hand–target phase-matching studies to identify the neuronal correlates of performance monitoring and error processing under instructed visual or proprioceptive task sets. Our main result was a general, modality-independent response of the bilateral frontal operculum (FO) to poor phase-matching accuracy, as evident from increased BOLD signal and increased source-localized gamma power. Furthermore, functional connectivity of the bi...

The ability to separate background noise from relevant acoustic signals is essential for appropriate sound-driven behavior in natural environments. Examples of this separation are apparent in the auditory system, where neural responses to behaviorally relevant stimuli become increasingly noise invariant along the ascending auditory pathway. However, the mechanisms that underlie this reduction in responses to background noise are not well understood. To address this gap in knowledge, we first evaluated the effects of auditory cortical inactivation on mice of both sexes trained to perform a simple auditory signal-in-noise detection task and found that outputs from the auditory cortex are important for the detection of auditory stimuli in noisy environments. Next, we evaluated the contributions of the two most common cortical inhibitory cell types, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, to the perception of masked auditory stimuli. We found that inactivation of either PV...