Voluntary movements are usually preceded by a slow, negative-going brain signal over motor areas, the so-called readiness potential (RP). To date, the exact nature and causal role of the RP in movement preparation have remained heavily debated. Although the RP is influenced by several motorical and cognitive factors, it has remained unclear whether people can learn to exert mental control over their RP, for example, by deliberately suppressing it. If people were able to initiate spontaneous movements without eliciting an RP, this would challenge the idea that the RP is a necessary stage of the causal chain leading up to a voluntary movement. We tested the ability of participants to control the magnitude of their RP in a neurofeedback experiment. Participants performed self-initiated movements, and after every movement, they were provided with immediate feedback about the magnitude of their RP. They were asked to find a strategy to perform voluntary movements such that the RPs were as small as possible. We ...

Female subjects have been widely excluded from past neuroscience work because of a number of biases, including the notion that cycling sex hormones increase variability. However, it is necessary to conduct behavioral research in mice that includes both sexes as mice are typically used for developing and evaluating future therapeutics. Understanding sex differences in learning is fundamental for the development of targeted therapies for numerous neurologic and neurodegenerative disorders, including Alzheimer’s disease, which is more prevalent in females than males. This study set out to confirm the role of sex and necessity of circulating ovarian hormones in the acquisition of the temporal associative memory task trace eyeblink conditioning (tEBC) in C57BL/6J mice. We present evidence that sex and ovarian hormones are important factors in learning. Specifically, intact female mice learn significantly faster than both male and ovariectomized (ovx) female mice. Data from pseudoconditioned control mice indicat...

Angelman syndrome (AS) is a neurodevelopmental disorder with unique behavioral phenotypes, seizures, and distinctive electroencephalographic (EEG) patterns. Recent studies identified motor, social communication, and learning and memory deficits in a CRISPR engineered rat model with a complete maternal deletion of the Ube3a gene. It is unknown whether this model recapitulates other aspects of the clinical disorder. We report here the effect of Ube3a maternal deletion in the rat on epileptiform activity, seizure threshold, and quantitative EEG. Using video-synchronized EEG (vEEG) monitoring, we assessed spectral power and epileptiform activity early postnatally through adulthood. While EEG power was similar to wild-type (WT) at 1.5 weeks postnatally, at all other ages analyzed, our findings were similar to the AS phenotype in mice and humans with significantly increased δ power. Analysis of epileptiform activity in juvenile and adult rats showed increased time spent in epileptiform activity in AS compared wi...

We can focus visuospatial attention by covertly attending to relevant locations, moving our eyes, or both simultaneously. How does shifting versus holding covert attention during fixation compare with maintaining covert attention across saccades? We acquired human fMRI data during a combined saccade and covert attention task. On Eyes-fixed trials, participants either held attention at the same initial location (“hold attention”) or shifted attention to another location midway through the trial (“shift attention”). On Eyes-move trials, participants made a saccade midway through the trial, while maintaining attention in one of two reference frames: the “retinotopic attention” condition involved holding attention at a fixation-relative location but shifting to a different screen-centered location, whereas the “spatiotopic attention” condition involved holding attention on the same screen-centered location but shifting relative to fixation. We localized the brain network sensitive to attention shifts (shift > ...

Motor adaptation is commonly thought to be a trial-and-error process in which the accuracy of movement improves with repetition of behavior. We challenged this view by testing whether erroneous movements are necessary for motor adaptation. In the eye movement system, the association between movements and errors can be disentangled, since errors in the predicted stimulus trajectory can be perceived even without movements. We modified a smooth pursuit eye movement adaptation paradigm in which monkeys learn to make an eye movement that predicts an upcoming change in target direction. We trained the monkeys to fixate on a target while covertly, an additional target initially moved in one direction and then changed direction after 250 ms. The monkeys showed a learned response to infrequent probe trials in which they were instructed to follow the moving target. Additional experiments confirmed that probing learning or residual eye movements during fixation did not drive learning. These results show that motor ad...

The lateral orbitofrontal cortex (LOFC) is thought to encode information associated with consumption of rewarding substances and is essential for flexible decision-making. Indeed, firing patterns of LOFC neurons are modulated following changes in reward value associated with an action outcome relationship. Damage to the LOFC impairs behavioral flexibility in humans and is associated with suboptimal performance in reward devaluation protocols in rodents. As chronic intermittent ethanol (CIE) exposure also impairs OFC-dependent behaviors, we hypothesized that CIE exposure would alter LOFC neuronal activity during alcohol drinking, especially under conditions when the reward value of ethanol was modulated by aversive or appetitive tastants. To test this hypothesis, we monitored LOFC activity using GCaMP6f fiber photometry in mice receiving acute injections of ethanol and in those trained in operant ethanol self-administration. In naive mice, an acute injection of ethanol caused a dose-dependent decrease in th...

When performing a long chain of actions in rapid sequence, future movements need to be planned concurrently with ongoing action. However, how far ahead we plan, and whether this ability improves with practice, is currently unknown. Here, we designed an experiment in which healthy volunteers produced sequences of 14 finger presses quickly and accurately on a keyboard in response to numerical stimuli. On every trial, participants were only shown a fixed number of stimuli ahead of the current keypress. The size of this viewing window varied between 1 (next digit revealed with the pressing of the current key) and 14 (full view of the sequence). Participants practiced the task for 5 days, and their performance was continuously assessed on random sequences. Our results indicate that participants used the available visual information to plan multiple actions into the future, but that the planning horizon was limited: receiving information about more than three movements ahead did not result in faster sequence pro...

Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicates that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression, may be key mediators of cognitive decline in AD. In this review, we discuss characteristics of neuronal network excitability in AD, and the role of Aβ and tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Aβ production suffer from seizures and epilepsy before the development of plaques. Similarly, pathologic accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Aβ on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.

Circuit compensation is often observed in patients with acute ischemic stroke, suggesting the importance of the interaction between brain regions. Also, contextual fear memory is an association between multisensory contexts and fearful stimuli, for which the interaction between the hippocampus and the amygdala is believed to be critical. To understand how focal ischemia in one region could influence the other region, we used a modified photo-thrombosis to induce focal ischemia in the hippocampus or the amygdala or both in freely-moving rats. We found that the learning curve and short-term memory (STM) were not affected in the rats although focal ischemia was induced 5 h before learning in either the hippocampus or the amygdala; these were impaired by the induction of ischemia in both the regions. Furthermore, the learning curve and STM were impaired when ischemia was induced 24 h before learning in either the hippocampus or the amygdala when the synaptic transmission was altered in one region because of is...

The recent trend toward an industrialization of brain exploration and the technological prowess of artificial intelligence algorithms and high-performance computing has caught the imagination of the public. These impressive advances are fueling an uncontrolled societal hype, the more amplified, the more “Blue Sky” the claim is. Will we ever be able to simulate a brain in silico ? Will “it” (the digital avatar) be conscious? The Blue Brain Project (BBP) and the European flagship the Human Brain Project (HBP) have surfed on this wave for the past 10 years. Their already significant lifetimes now offer new case studies for neuroscience sociology and epistemology, as the projects mature. Their distinctive “Blue Sky” flavor has been a key feature in securing unprecedented funding (more than one billion Euros) mostly through supranational institutions. The longitudinal analysis of these ventures provides clues to how the neuromyth they propagate sells science, in a scientific world based on an economy of promises.