Quantitative Predictions Orchestrate Visual Signaling in Drosophila.

Vision influences behavior, but ongoing behavior also modulates vision in animals ranging from insects to primates. The function and biophysical mechanisms of most such modulations remain unresolved. Here, we combine behavioral genetics, electrophysiology, and high-speed videography to advance a function for behavioral modulations of visual processing in Drosophila. We argue that a set of motion-sensitive visual neurons regulate gaze-stabilizing head movements. We describe how, during flight turns, Drosophila perform a set of head movements that require silencing their gaze-stability reflexes along the primary rotation axis of the turn. Consistent with this behavioral requirement, we find pervasive motor-related inputs to the visual neurons, which quantitatively silence their predicted visual responses to rotations around the relevant axis while preserving sensitivity around other axes. This work proposes a function for a behavioral modulation of visual processing and illustrates how the brain can remove one sensory signal from a circuit carrying multiple related signals.

Demographic models predict end-Pleistocene arrival and rapid expansion of pre-agropastoralist humans in Cyprus.

The antiquity of human dispersal into Mediterranean islands and ensuing coastal adaptation have remained largely unexplored due to the prevailing assumption that the sea was a barrier to movement and that islands were hostile environments to early hunter-gatherers [J. F. Cherry, T. P. Leppard, J. Isl. Coast. Archaeol. 13, 191-205 (2018), 10.1080/15564894.2016.1276489]. Using the latest archaeological data, hindcasted climate projections, and age-structured demographic models, we demonstrate evidence for early arrival (14,257 to 13,182 calendar years ago) to Cyprus and predicted that large groups of people (~1,000 to 1,375) arrived in 2 to 3 main events occurring within <100 y to ensure low extinction risk. These results indicate that the postglacial settlement of Cyprus involved only a few large-scale, organized events requiring advanced watercraft technology. Our spatially debiased and Signor-Lipps-corrected estimates indicate rapid settlement of the island within <200 y, and expansion to a median of 4,000 to 5,000 people (0.36 to 0.46 km-2) in <11 human generations (<300 y). Our results do not support the hypothesis of inaccessible and inhospitable islands in the Mediterranean for pre-agropastoralists, agreeing with analogous conclusions for other parts of the world [M. I. Bird et al., Sci. Rep. 9, 8220 (2019), 10.1038/s41598-019-42946-9]. Our results also highlight the need to revisit these questions in the Mediterranean and test their validity with new technologies, field methods, and data. By applying stochastic models to the Mediterranean region, we can place Cyprus and large islands in general as attractive and favorable destinations for paleolithic peoples.

Eye blinks as a visual processing stage.

Humans blink their eyes frequently during normal viewing, more often than it seems necessary for keeping the cornea well lubricated. Since the closure of the eyelid disrupts the image on the retina, eye blinks are commonly assumed to be detrimental to visual processing. However, blinks also provide luminance transients rich in spatial information to neural pathways highly sensitive to temporal changes. Here, we report that the luminance modulations from blinks enhance visual sensitivity. By coupling high-resolution eye tracking in human observers with modeling of blink transients and spectral analysis of visual input signals, we show that blinking increases the power of retinal stimulation and that this effect significantly enhances visibility despite the time lost in exposure to the external scene. We further show that, as predicted from the spectral content of input signals, this enhancement is selective for stimuli at low spatial frequencies and occurs irrespective of whether the luminance transients are actively generated or passively experienced. These findings indicate that, like eye movements, blinking acts as a computational component of a visual processing strategy that uses motor behavior to reformat spatial information into the temporal domain.

Spontaneous eye movements reflect the representational geometries of conceptual spaces.

Functional neuroimaging studies indicate that the human brain can represent concepts and their relational structure in memory using coding schemes typical of spatial navigation. However, whether we can read out the internal representational geometries of conceptual spaces solely from human behavior remains unclear. Here, we report that the relational structure between concepts in memory might be reflected in spontaneous eye movements during verbal fluency tasks: When we asked participants to randomly generate numbers, their eye movements correlated with distances along the left-to-right one-dimensional geometry of the number space (mental number line), while they scaled with distance along the ring-like two-dimensional geometry of the color space (color wheel) when they randomly generated color names. Moreover, when participants randomly produced animal names, eye movements correlated with low-dimensional similarity in word frequencies. These results suggest that the representational geometries used to internally organize conceptual spaces might be read out from gaze behavior.

January 6 arrests and media coverage do not remobilize conservatives on social media.

Social media's pivotal role in catalyzing social movements is widely acknowledged across scientific disciplines. Past research has predominantly explored social media's ability to instigate initial mobilization while leaving the question of its capacity to sustain these movements relatively uncharted. This study investigates the persistence of movement activity on Twitter and Gab following a substantial on-the-ground mobilization event catalyzed by social media-the StoptheSteal movement culminating in the January 6th Capitol attack. Our findings indicate that the online communities active in the January 6 mobilization did not display substantial remobilization in the subsequent year. These results highlight the fact that further exploration is needed to understand the factors shaping how and when movements are sustained by social media. In this regard, our study provides valuable insights for scientists across diverse disciplines, on how certain social media platforms may contribute to the evolving dynamics of collective action.

Microsaccades are directed toward the midpoint between targets in a variably cued attention task.

Reliable, noninvasive biomarkers that reveal the internal state of a subject are an invaluable tool for neurological diagnoses. Small fixational eye movements, called microsaccades, are a candidate biomarker thought to reflect a subject's focus of attention [Z. M. Hafed, J. J. Clark, VisionRes. 42, 2533-2545 (2002); R. Engbert, R. Kliegl, VisionRes. 43, 1035-1045 (2003)]. The linkage between the direction of microsaccades and attention has mainly been demonstrated using explicit and unambiguous attentional cues. However, the natural world is seldom predictable and rarely provides unambiguous information. Thus, a useful biomarker must be robust to such changes in environmental statistics. To determine how well microsaccades reveal visual-spatial attention across behavioral contexts, we analyzed these fixational eye movements in monkeys performing a conventional change detection task. The task included two stimulus locations and variable cue validities across blocks of trials. Subjects were adept at the task, showing precise and graded modulations of visual attention for subtle target changes and performing better and faster when the cue was more reliable [J. P. Mayo, J. H. R. Maunsell, J. Neurosci. 36, 5353 (2016)]. However, over tens of thousands of microsaccades, we found no difference in microsaccade direction between cued locations when cue variability was high nor between hit and miss trials. Instead, microsaccades were made toward the midpoint of the two target locations, not toward individual targets. Our results suggest that the direction of microsaccades should be interpreted with caution and may not be a reliable measure of covert spatial attention in more complex viewing conditions.

Perceptual learning across saccades: Feature but not location specific.

Perceptual learning is the ability to enhance perception through practice. The hallmark of perceptual learning is its specificity for the trained location and stimulus features, such as orientation. For example, training in discriminating a grating's orientation improves performance only at the trained location but not in other untrained locations. Perceptual learning has mostly been studied using stimuli presented briefly while observers maintained gaze at one location. However, in everyday life, stimuli are actively explored through eye movements, which results in successive projections of the same stimulus at different retinal locations. Here, we studied perceptual learning of orientation discrimination across saccades. Observers were trained to saccade to a peripheral grating and to discriminate its orientation change that occurred during the saccade. The results showed that training led to transsaccadic perceptual learning (TPL) and performance improvements which did not generalize to an untrained orientation. Remarkably, however, for the trained orientation, we found a complete transfer of TPL to the untrained location in the opposite hemifield suggesting high flexibility of reference frame encoding in TPL. Three control experiments in which participants were trained without saccades did not show such transfer, confirming that the location transfer was contingent upon eye movements. Moreover, performance at the trained location, but not at the untrained location, was also improved in an untrained fixation task. Our results suggest that TPL has both, a location-specific component that occurs before the eye movement and a saccade-related component that involves location generalization.

The temporal structure of REM sleep shows minute-scale fluctuations across brain and body in mice and humans.

Rapid eye movement sleep (REM) is believed to have a binary temporal structure with "phasic" and "tonic" microstates, characterized by motoric activity versus quiescence, respectively. However, we observed in mice that the frequency of theta activity (a marker of rodent REM) fluctuates in a nonbinary fashion, with the extremes of that fluctuation correlating with phasic-type and tonic-type facial motricity. Thus, phasic and tonic REM may instead represent ends of a continuum. These cycles of brain physiology and facial movement occurred at 0.01 to 0.06 Hz, or infraslow frequencies, and affected cross-frequency coupling and neuronal activity in the neocortex, suggesting network functional impact. We then analyzed human data and observed that humans also demonstrate nonbinary phasic/tonic microstates, with continuous 0.01 to 0.04-Hz respiratory rate cycles matching the incidence of eye movements. These fundamental properties of REM can yield insights into our understanding of sleep health.

Regional variability in intracerebral properties of NREM to REM sleep transitions in humans.

Transitions between wake and sleep states show a progressive pattern underpinned by local sleep regulation. In contrast, little evidence is available on non-rapid eye movement (NREM) to rapid eye movement (REM) sleep boundaries, considered as mainly reflecting subcortical regulation. Using polysomnography (PSG) combined with stereoelectroencephalography (SEEG) in humans undergoing epilepsy presurgical evaluation, we explored the dynamics of NREM-to-REM transitions. PSG was used to visually score transitions and identify REM sleep features. SEEG-based local transitions were determined automatically with a machine learning algorithm using features validated for automatic intra-cranial sleep scoring (10.5281/zenodo.7410501). We analyzed 2988 channel-transitions from 29 patients. The average transition time from all intracerebral channels to the first visually marked REM sleep epoch was 8 s ± 1 min 58 s, with a great heterogeneity between brain areas. Transitions were observed first in the lateral occipital cortex, preceding scalp transition by 1 min 57 s ± 2 min 14 s (d = -0.83), and close to the first sawtooth wave marker. Regions with late transitions were the inferior frontal and orbital gyri (1 min 1 s ± 2 min 1 s, d = 0.43, and 1 min 1 s ± 2 min 5 s, d = 0.43, after scalp transition). Intracranial transitions were earlier than scalp transitions as the night advanced (last sleep cycle, d = -0.81). We show a reproducible gradual pattern of REM sleep initiation, suggesting the involvement of cortical mechanisms of regulation. This provides clues for understanding oneiric experiences occurring at the NREM/REM boundary.

Motor System-Dependent Effects of Amygdala and Ventral Striatum Lesions on Explore-Exploit Behaviors.

Deciding whether to forego immediate rewards or explore new opportunities is a key component of flexible behavior and is critical for the survival of the species. Although previous studies have shown that different cortical and subcortical areas, including the amygdala and ventral striatum (VS), are implicated in representing the immediate (exploitative) and future (explorative) value of choices, the effect of the motor system used to make choices has not been examined. Here, we tested male rhesus macaques with amygdala or VS lesions on two versions of a three-arm bandit task where choices were registered with either a saccade or an arm movement. In both tasks we presented the monkeys with explore-exploit tradeoffs by periodically replacing familiar options with novel options that had unknown reward probabilities. We found that monkeys explored more with saccades but showed better learning with arm movements. VS lesions caused the monkeys to be more explorative with arm movements and less explorative with saccades, although this may have been due to an overall decrease in performance. VS lesions affected the monkeys' ability to learn novel stimulus-reward associations in both tasks, while after amygdala lesions this effect was stronger when choices were made with saccades. Further, on average, VS and amygdala lesions reduced the monkeys' ability to choose better options only when choices were made with a saccade. These results show that learning reward value associations to manage explore-exploit behaviors is motor system dependent and they further define the contributions of amygdala and VS to reinforcement learning.

Decoding Remapped Spatial Information in the Peri-Saccadic Period.

It has been suggested that, prior to a saccade, visual neurons predictively respond to stimuli that will fall in their receptive fields after completion of the saccade. This saccadic remapping process is thought to compensate for the shift of the visual world across the retina caused by eye movements. To map the timing of this predictive process in the brain, we recorded neural activity using electroencephalography during a saccade task. Human participants (male and female) made saccades between two fixation points while covertly attending to oriented gratings briefly presented at various locations on the screen. Data recorded during trials in which participants maintained fixation were used to train classifiers on stimuli in different positions. Subsequently, data collected during saccade trials were used to test for the presence of remapped stimulus information at the post-saccadic retinotopic location in the peri-saccadic period, providing unique insight into when remapped information becomes available. We found that the stimulus could be decoded at the remapped location ∼180 ms post-stimulus onset, but only when the stimulus was presented 100-200 ms before saccade onset. Within this range, we found that the timing of remapping was dictated by stimulus onset rather than saccade onset. We conclude that presenting the stimulus immediately before the saccade allows for optimal integration of the corollary discharge signal with the incoming peripheral visual information, resulting in a remapping of activation to the relevant post-saccadic retinotopic neurons.

Slowing of Movements in Healthy Aging as a Rational Economic Response to an Elevated Effort Landscape.

Why do we move slower as we grow older? The reward circuits of the brain, which tend to invigorate movements, decline with aging, raising the possibility that reduced vigor is due to the diminishing value that our brain assigns to movements. However, as we grow older, it also becomes more effortful to make movements. Is age-related slowing principally a consequence of increased effort costs from the muscles, or reduced valuation of reward by the brain? Here, we first quantified the cost of reaching via metabolic energy expenditure in human participants (male and female), and found that older adults consumed more energy than the young at a given speed. Thus, movements are objectively more costly for older adults. Next, we observed that when reward increased, older adults, like the young, responded by initiating their movements earlier. Yet, unlike the young, they were unwilling to increase their movement speed. Was their reluctance to reach quicker for rewards due to the increased effort costs, or because they ascribed less value to the movement? Motivated by a mathematical model, we next made the young experience a component of aging by making their movements more effortful. Now the young responded to reward by reacting faster but chose not to increase their movement speed. This suggests that slower movements in older adults are partly driven by an adaptive response to an elevated effort landscape. Moving slower may be a rational economic response the brain is making to mitigate the elevated effort costs that accompany aging.

Visual Feature Tuning Properties of Short-Latency Stimulus-Driven Ocular Position Drift Responses during Gaze Fixation.

Ocular position drifts during gaze fixation are significantly less well understood than microsaccades. We recently identified a short-latency ocular position drift response, of ∼1 min arc amplitude, that is triggered within <100 ms by visual onsets. This systematic eye movement response is feature-tuned and seems to be coordinated with a simultaneous resetting of the saccadic system by visual stimuli. However, much remains to be learned about the drift response, especially for designing better-informed neurophysiological experiments unraveling its mechanistic substrates. Here we systematically tested multiple new feature tuning properties of drift responses. Using highly precise eye tracking in three male rhesus macaque monkeys, we found that drift responses still occur for tiny foveal visual stimuli. Moreover, the responses exhibit size tuning, scaling their amplitude (both up and down) as a function of stimulus size, and they also possess a monotonically increasing contrast sensitivity curve. Importantly, short-latency drift responses still occur for small peripheral visual targets, which additionally introduce spatially directed modulations in drift trajectories toward the appearing peripheral stimuli. Drift responses also remain predominantly upward even for stimuli exclusively located in the lower visual field and even when starting gaze position is upward. When we checked the timing of drift responses, we found it was better synchronized to stimulus-induced saccadic inhibition than to stimulus onset. These results, along with a suppression of drift response amplitudes by peristimulus saccades, suggest that drift responses reflect the rapid impacts of short-latency and feature-tuned visual neural activity on final oculomotor control circuitry in the brain.

PP2B-Dependent Cerebellar Plasticity Sets the Amplitude of the Vestibulo-ocular Reflex during Juvenile Development.

Throughout life, the cerebellum plays a central role in the coordination and optimization of movements, using cellular plasticity to adapt a range of behaviors. Whether these plasticity processes establish a fixed setpoint during development, or continuously adjust behaviors throughout life, is currently unclear. Here, by spatiotemporally manipulating the activity of protein phosphatase 2B (PP2B), an enzyme critical for cerebellar plasticity in male and female mice, we examined the consequences of disrupted plasticity on the performance and adaptation of the vestibulo-ocular reflex (VOR). We find that, in contrast to Purkinje cell (PC)-specific deletion starting early postnatally, acute pharmacological as well as adult-onset genetic deletion of PP2B affects all forms of VOR adaptation but not the level of VOR itself. Next, we show that PC-specific genetic deletion of PP2B in juvenile mice leads to a progressive loss of the protein PP2B and a concurrent change in the VOR, in addition to the loss of adaptive abilities. Finally, re-expressing PP2B in adult mice that lack PP2B expression from early development rescues VOR adaptation but does not affect the performance of the reflex. Together, our results indicate that chronic or acute, genetic, or pharmacological block of PP2B disrupts the adaptation of the VOR. In contrast, only the absence of plasticity during cerebellar development affects the setpoint of VOR, an effect that cannot be corrected after maturation of the cerebellum. These findings suggest that PP2B-dependent cerebellar plasticity is required during a specific period to achieve the correct setpoint of the VOR.

Neural Correlates of Online Action Preparation.

When performing movements in rapid succession, the brain needs to coordinate ongoing execution with the preparation of an upcoming action. Here we identify the processes and brain areas involved in this ability of online preparation. Human participants (both male and female) performed pairs of single-finger presses or three-finger chords in rapid succession, while 7T fMRI was recorded. In the overlap condition, they could prepare the second movement during the first response and in the nonoverlap condition only after the first response was completed. Despite matched perceptual and movement requirements, fMRI revealed increased brain activity in the overlap condition in regions along the intraparietal sulcus and ventral visual stream. Multivariate analyses suggested that these areas are involved in stimulus identification and action selection. In contrast, the dorsal premotor cortex, known to be involved in planning upcoming movements, showed no discernible signs of heightened activity. This observation suggests that the bottleneck during simultaneous action execution and preparation arises at the level of stimulus identification and action selection, whereas movement planning in the premotor cortex can unfold concurrently with the execution of a current action without requiring additional neural activity.

Identifying Distinct Neural Features between the Initial and Corrective Phases of Precise Reaching Using AutoLFADS.

Many initial movements require subsequent corrective movements, but how the motor cortex transitions to make corrections and how similar the encoding is to initial movements is unclear. In our study, we explored how the brain's motor cortex signals both initial and corrective movements during a precision reaching task. We recorded a large population of neurons from two male rhesus macaques across multiple sessions to examine the neural firing rates during not only initial movements but also subsequent corrective movements. AutoLFADS, an autoencoder-based deep-learning model, was applied to provide a clearer picture of neurons' activity on individual corrective movements across sessions. Decoding of reach velocity generalized poorly from initial to corrective submovements. Unlike initial movements, it was challenging to predict the velocity of corrective movements using traditional linear methods in a single, global neural space. We identified several locations in the neural space where corrective submovements originated after the initial reaches, signifying firing rates different than the baseline before initial movements. To improve corrective movement decoding, we demonstrate that a state-dependent decoder incorporating the population firing rates at the initiation of correction improved performance, highlighting the diverse neural features of corrective movements. In summary, we show neural differences between initial and corrective submovements and how the neural activity encodes specific combinations of velocity and position. These findings are inconsistent with assumptions that neural correlations with kinematic features are global and independent, emphasizing that traditional methods often fall short in describing these diverse neural processes for online corrective movements.

Presaccadic Attention Depends on Eye Movement Direction and Is Related to V1 Cortical Magnification.

With every saccadic eye movement, humans bring new information into their fovea to be processed with high visual acuity. Notably, perception is enhanced already before a relevant item is foveated: During saccade preparation, presaccadic attention shifts to the upcoming fixation location, which can be measured via behavioral correlates such as enhanced visual performance or modulations of sensory feature tuning. The coupling between saccadic eye movements and attention is assumed to be robust and mandatory and considered a mechanism facilitating the integration of pre- and postsaccadic information. However, until recently it had not been investigated as a function of saccade direction. Here, we measured contrast response functions during fixation and saccade preparation in male and female observers and found that the pronounced response gain benefit typically elicited by presaccadic attention is selectively lacking before upward saccades at the group level-some observers even showed a cost. Individual observer's sensitivity before upward saccades was negatively related to their amount of surface area in primary visual cortex representing the saccade target, suggesting a potential compensatory mechanism that optimizes the use of the limited neural resources processing the upper vertical meridian. Our results raise the question of how perceptual continuity is achieved and how upward saccades can be accurately targeted despite the lack of-theoretically required-presaccadic attention.

Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, ß-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is ß-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.

Infants' reorienting efficiency depends on parental autistic traits and predicts future socio-communicative behaviors.

Attentional reorienting is dysfunctional not only in children with autism spectrum disorder (ASD), but also in infants who will develop ASD, thus constituting a potential causal factor of future social interaction and communication abilities. Following the research domain criteria framework, we hypothesized that the presence of subclinical autistic traits in parents should lead to atypical infants' attentional reorienting, which in turn should impact on their future socio-communication behavior in toddlerhood. During an attentional cueing task, we measured the saccadic latencies in a large sample (total enrolled n = 89; final sample n = 71) of 8-month-old infants from the general population as a proxy for their stimulus-driven attention. Infants were grouped in a high parental traits (HPT; n = 23) or in a low parental traits (LPT; n = 48) group, according to the degree of autistic traits self-reported by their parents. Infants (n = 33) were then longitudinally followed to test their socio-communicative behaviors at 21 months. Results show a sluggish reorienting system, which was a longitudinal predictor of future socio-communicative skills at 21 months. Our combined transgenerational and longitudinal findings suggest that the early functionality of the stimulus-driven attentional network-redirecting attention from one event to another-could be directly connected to future social and communication development.

Multiple representations of the body schema for the same body part.

Purposeful motor actions depend on the brain's representation of the body, called the body schema, and disorders of the body schema have been reported to show motor deficits. The body schema has been assumed for almost a century to be a common body representation supporting all types of motor actions, and previous studies have considered only a single motor action. Although we often execute multiple motor actions, how the body schema operates during such actions is unknown. To address this issue, I developed a technique to measure the body schema during multiple motor actions. Participants made simultaneous eye and reach movements to the same location of 10 landmarks on their hand. By analyzing the internal configuration of the locations of these points for each of the eye and reach movements, I produced maps of the mental representation of hand shape. Despite these two movements being simultaneously directed to the same bodily location, the resulting hand map (i.e., a part of the body schema) was much more distorted for reach movements than for eye movements. Furthermore, the weighting of visual and proprioceptive bodily cues to build up this part of the body schema differed for each effector. These results demonstrate that the body schema is organized as multiple effector-specific body representations. I propose that the choice of effector toward one's body can determine which body representation in the brain is observed and that this visualization approach may offer a new way to understand patients' body schema.