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...

Axon guidance receptors such as deleted in colorectal cancer (DCC) contribute to the normal formation of neural circuits, and their mutations can be associated with neural defects. In humans, heterozygous mutations in DCC have been linked to congenital mirror movements, which are involuntary movements on one side of the body that mirror voluntary movements of the opposite side. In mice, obvious hopping phenotypes have been reported for bi-allelic Dcc mutations, while heterozygous mutants have not been closely examined. We hypothesized that a detailed characterization of Dcc heterozygous mice may reveal impaired corticospinal and spinal functions. Anterograde tracing of the Dcc +/− motor cortex revealed a normally projecting corticospinal tract, intracortical microstimulation (ICMS) evoked normal contralateral motor responses, and behavioral tests showed normal skilled forelimb coordination. Gait analyses also showed a normal locomotor pattern and rhythm in adult Dcc +/− mice during treadmill locomotion, ex...

Electrical synapses couple inhibitory neurons across the brain, underlying a variety of functions that are modifiable by activity. Despite recent advances, many functions and contributions of electrical synapses within neural circuitry remain underappreciated. Among these are the sources and impacts of electrical synapse asymmetry. Using multi-compartmental models of neurons coupled through dendritic electrical synapses, we investigated intrinsic factors that contribute to effective synaptic asymmetry and that result in modulation of spike timing and synchrony between coupled cells. We show that electrical synapse location along a dendrite, input resistance, internal dendritic resistance, or directional conduction of the electrical synapse itself each alter asymmetry as measured by coupling between cell somas. Conversely, we note that asymmetrical gap junction (GJ) conductance can be masked by each of these properties. Furthermore, we show that asymmetry modulates spike timing and latency of coupled cells ...

The human sensorimotor system is sensitive to both limb-related prediction errors and task-related performance errors. Prediction error signals are believed to drive implicit refinements to motor plans. However, an understanding of the mechanisms that performance errors stimulate has remained unclear largely because their effects have not been probed in isolation from prediction errors. Diverging from past work, we induced performance errors independent of prediction errors by shifting the location of a reach target but keeping the intended and actual kinematic consequences of the motion matched. Our first two experiments revealed that rather than implicit learning, motor adjustments in response to performance errors reflect the use of deliberative, volitional strategies. Our third experiment revealed a potential dissociation of performance-error-driven strategies based on error size. Specifically, behavioral changes following large errors were consistent with goal-directed or model-based control, known to...

Overlap between events can lead to interference because of a trade-off between encoding the present event and retrieving the past event. Temporal context information, “when” something occurred, a defining feature of episodic memory, can cue retrieval of a past event. However, the influence of temporal overlap, or proximity in time, on the mechanisms of interference is unclear. Here, by identifying brain states using scalp eEEG from male and female human subjects, we show the extent to which temporal overlap promotes interference and induces retrieval. In this experiment, subjects were explicitly directed to either encode the present event or retrieve a past, overlapping event while perceptual input was held constant. We find that the degree of temporal overlap between events leads to selective interference. Specifically, greater temporal overlap between two events leads to impaired memory for the past event selectively when the top-down goal is to encode the present event. Using pattern classification anal...

To explore whether the thalamus participates in lexical status (word vs. nonword) processing during spoken word production, we recorded local field potentials from the ventral lateral thalamus in 11 essential tremor patients (three females) undergoing thalamic deep brain stimulation lead implantation during a visually cued word- and nonword-reading aloud task. We observed task-related beta (12-30 Hz) activity decreases that were preferentially time-locked to stimulus presentation, and broadband gamma (70-150 Hz) activity increases, which are thought to index increased multi-unit spiking activity, occurring shortly before and predominantly time-locked to speech onset. We further found that thalamic beta activity decreases bilaterally were greater when nonwords were read, demonstrating bilateral sensitivity to lexical status that likely reflects the tracking of task effort; in contrast, greater nonword-related increases in broadband gamma activity were observed only on the left, demonstrating lateralization ...

During visually guided behaviors, mere hundreds of milliseconds can elapse between a sensory input and its associated behavioral response. How spikes occurring at different times are integrated to drive perception and action remains poorly understood. We delivered random trains of optogenetic stimulation (white noise) to excite inhibitory interneurons in V1 of mice of both sexes while they performed a visual detection task. We then performed a reverse correlation analysis on the optogenetic stimuli to generate a neuronal-behavioral kernel: an unbiased, temporally-precise estimate of how suppression of V1 spiking at different moments around the onset of a visual stimulus affects detection of that stimulus. Electrophysiological recordings enabled us to capture the effects of optogenetic stimuli on V1 responsivity and revealed that the earliest stimulus-evoked spikes are preferentially weighted for guiding behavior. These data demonstrate that white noise optogenetic stimulation is a powerful tool for underst...

Habituated animals retain a latent capacity for robust engagement with familiar stimuli. In most instances, the ability to override habituation is best explained by postulating that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies and that habituation override occurs through disinhibition. Previous work has shown that inhibitory plasticity contributes to specific forms of olfactory and gustatory habituation in Drosophila . Here we analyze how exposure to a novel stimulus causes override of gustatory (proboscis-extension reflex or “PER”) habituation. While brief sucrose contact with tarsal hairs causes naïve Drosophila to extend their proboscis, persistent exposure reduces PER to subsequent sucrose stimuli. We show that in so habituated animals, either brief exposure of the proboscis to yeast or direct thermogenetic activation of sensory neurons restores PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief...

Understanding the human brain is a “Grand Challenge” for 21st century research. Computational approaches enable large and complex datasets to be addressed efficiently, supported by artificial neural networks, modeling and simulation. Dynamic generative multiscale models, which enable the investigation of causation across scales and are guided by principles and theories of brain function, are instrumental for linking brain structure and function. An example of a resource enabling such an integrated approach to neuroscientific discovery is the BigBrain, which spatially anchors tissue models and data across different scales and ensures that multiscale models are supported by the data, making the bridge to both basic neuroscience and medicine. Research at the intersection of neuroscience, computing and robotics has the potential to advance neuro-inspired technologies by taking advantage of a growing body of insights into perception, plasticity and learning. To render data, tools and methods, theories, basic pr...

Neurite degeneration is associated with early stages of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease (PD), and amyotrophic lateral sclerosis. One method that is commonly used to analyze neurite degeneration involves calculation of a Degeneration Index (DI) following utilization of the Analyze Particles tool of ImageJ to detect neurite fragments in micrographs of cultured cells. However, DI analyses are prone to several types of measurement error, can be time consuming to perform, and are limited in application. Here, we describe an improved method for performing DI analyses. Accuracy of measurements was enhanced through modification of selection criteria for detecting neurite fragments, removal of image artifacts and non-neurite materials from images, and optimization of image contrast. Such enhancements were implemented into an ImageJ macro that enables rapid and fully automated DI analysis of multiple images. The macro features operations for automated removal of cell bodi...