Biology subjects

Wallis, G.

Publications and source records attributed to Wallis, G..

12 recordsLinked to original sources

bioRxiv2025

Subcortical control of reaching in humans

Accurate visually guided reaching requires transformation of target-related photoreceptor responses into precisely coordinated activation of trunk and arm muscles. The cerebral cortex is widely believed to compute the requisite kinematic and musculoskeletal dynamics strategies in humans 1-3, even though vertebrates lacking a cerebral cortex achieve sophisticated visuomotor control 4-6, and brainstem circuits executing coordinated eye and head gaze shifts perform analogous sensorimotor computations in non-human primates 7. Here we used a visuomotor reaching task that yields extremely rapid, "express", target-directed muscle activations 8-10 to test whether a putative subcortical sensorimotor network can compute musculoskeletal dynamics to initiate reaching in humans. We found coordinated express visuomotor responses (EVRs) in task-relevant shoulder, elbow, and bi-articular muscles that reflected both starting posture and target direction in similar patterns to longer latency, presumably cortically mediated, muscle responses. When the task goal was to reach away from the stimulus (i.e. an "anti-reach"; 11) the EVR involved coordinated muscle activation to initiate the hand toward the stimulus location, opposite to the subsequent goal-directed response. The results suggest a unified theory of visuomotor control for reaching and gaze shifts, in which subcortical systems compute musculoskeletal dynamics based on sensory target information and cortically derived context. The results imply that the transformation from motor goals in extrapersonal space into musculoskeletal dynamics can be performed by neural circuitry in humans that does not involve the sensorimotor cortex.

neuroscience↗

bioRxiv2022

A complex reach direction rule that delays reaction time causes alternating excitation and inhibition in express muscle responses and corticospinal excitability

The dynamics of muscle activation during fast visually guided reaching are suggestive of two neural control signals; an early signal that acts at "express" latencies in response to the visual stimulus, and a longer latency signal that executes a strategic reach plan. Here we developed a task designed to temporally isolate the express visuomotor response from the longer latency muscle response, and to characterize the time course of corticospinal excitability changes in the express response time window when the late voluntary response is delayed. We tested this by measuring electromyograms (EMG) and changes in Motor Evoked Potential (MEP) amplitudes following Transcranial Magnetic Stimulation (TMS) of the motor cortex, as participants reached either towards or away from visual targets. Crucially, the information about the task rule was provided by the luminance of the target itself, and so was unknown to the subject until the instant of target presentation. This feature delayed reaction times, likely because additional (presumably cortical) processing was required to interpret and apply the rule before formation of a goal directed reach plan. The earliest EMG responses to target presentation occurred with a 70-105 ms time window, and were oriented to bring the hand toward the location of the target. However, there was also a slightly later response that was also time-locked to target appearance in a 105-140 ms time window. This second response was "reciprocal" to the first, such that it was oriented to take the hand in the direction opposite from the target. In some participants, additional oscillating cycles were apparent after the first two target-related responses. These multiphasic express visuomotor responses were nearly identical in both pro- and anti-reach conditions. These muscle activity responses were generally reflected in the temporal pattern of corticospinal excitability modulations in experiment two. Indeed, the MEP and background EMG responses showed an alternating pattern similar to that in experiment one, although the effect was clearer in the anti-reach than the pro-reach condition. Overall, the data show that the express and voluntary responses are indeed distinct neural control signals, which supports the hypothesis that at least two separate neural pathways (one slow and one fast) contribute to the control of visually guided reaching. The properties of the fast pathway are consistent with a tecto-reticulospinal pathway, while those of the slow pathway are consistent with a transcortical loop.

neuroscience↗

bioRxiv2022

A subcortical origin for rapid, target-oriented corticospinal excitability changes during visually guided reaching

During visually guided reaching, proximal limb muscles can be activated within 80 ms of target appearance. Such "express" visuomotor responses are temporally aligned with target appearance rather than movement onset, and invariably tuned towards the direction of the visual target regardless of the instructed reach direction. These features prompt the hypothesis that express visuomotor responses are driven by a subcortical pathway. We tested this by measuring the changes in Motor Evoked Potential (MEP) size following Transcranial Magnetic Stimulation (TMS) or Transcranial Electrical Stimulation (TES) of the motor cortex, as participants reached either towards or away from visual targets. We found that 70-80 ms after target presentation, MEPs in a primary shoulder flexor muscle (pectoralis major) were oriented towards the target direction regardless of whether the participant subsequently reached towards or away from the target. Similar target-oriented MEP modulations occurred in posterior deltoid and biceps brachii muscles, whereas MEPs in a finger muscle were affected neither by target nor reach direction. Critically, there were no significant differences in modulation of responses to TMS versus TES across all reaching conditions, which suggests that the target-oriented modulation occurs downstream of the motor cortex output neurons. Combined, our results are consistent with a subcortical rather than cortical origin for the earliest changes in corticospinal excitability following visual target onset. A prime candidate for such subcortical modulation includes the superior colliculus and reticular formation.

neuroscience↗

bioRxiv2022

Express visuomotor responses reflect knowledge of both target location and conscious intent during reaches of different amplitudes

When humans reach to visual targets, extremely rapid (~90 ms) bursts of activity can be observed on task-relevant proximal muscles. Such express visuomotor responses are inflexibly locked in time and space to the target and have been proposed to reflect rapid visuomotor transformations conveyed subcortically via the tecto-reticulo-spinal pathway. Previously, we showed that express visuomotor responses are sensitive to explicit cue-driven information about the target, suggesting that the express pathway can be modulated by cortical signals affording contextual pre-stimulus expectations. Here, we show that the express visuomotor system incorporates information about the veridical target-directed reaching metrics and contextual instructions during visuospatial tasks requiring different movement amplitudes. In one experiment, we recorded the activity from two shoulder muscles as participants reached toward targets that appeared at different distances. Longer hand-to-target distances led to larger and more prevalent express visuomotor responses than short-reach targets. This suggests that both the direction and distance of veridical hand-to-target reaches are encoded along the putative subcortical express pathway. In a second experiment, we modulated the movement amplitude by asking the participants to deliberately undershoot, overshoot, or stop (control) at the target. The overshoot and undershoot tasks impaired the generation of large and frequent express visuomotor responses, consistent with the inability of the express pathway to generate responses directed toward non-veridical targets (e.g. anti-reach tasks). Our findings appear to reflect strategic, cortically-driven modulation of the express visuomotor circuit to facilitate rapid and effective response initiation during target-directed actions. SIGNIFICANCE STATEMENTExpress (~90 ms) arm muscle responses that are consistently tuned toward the location of visual stimuli suggest a subcortical contribution to target-directed visuomotor behaviour in humans, potentially via the tecto-reticulo-spinal pathway. This study shows that express muscle responses are modulated appropriately to reach targets at different distances, but generally suppressed when the task required non-veridical responses to overshoot/undershoot the real target. The data suggest that the tecto-reticulo-spinal pathway can be exploited strategically by the cerebral cortex to facilitate rapid initiation of effective responses during a visuospatial task.

neuroscience↗

bioRxiv2022

Decision-making strategies of a coral reef fish given changing visual signal reliability

Making informed decisions is fundamental to intelligent life and is crucial to survival. The problem many organisms face, is how to make optimal decisions in the face of incomplete, unreliable, or conflicting information. In many aquatic environments, fish use visual information to guide key behaviours, but the environment itself can alter or mask the very signals they rely on. Here, we asked how a highly visual species, Rhinecanthus aculeatus, responds to a learned discrimination task as signal reliability decreases, and whether probabilistic information gained during previous experience can be incorporated into their decision strategy. Fish were first trained to select a target (dark grey circle) from three distractors (light grey circles). In the first experiment, the target was more likely to appear in one of four possible stimulus positions. In the second experiment, the target appeared in all positions equally. In a series of trials, the difference in brightness between the target and distractors was reduced until all four stimuli were identical. We found that target selection accuracy decreased with decreasing target and distractor disparity. However, in Experiment 1 where the target was more likely to be in one position, fish increasingly selected stimuli in the biased position as target selection accuracy decreased, but not in Experiment 2. These results demonstrate 1) that fish learned more than a simple select/avoid rule based on stimulus brightness, but also integrated information (stimulus position) that could be considered ancillary to the primary task. 2) Fish can learn probability distributions and apply this knowledge as uncertainty increases, ultimately increasing the overall frequency of correct choices. Our results reveal that probabilistic decision rules can be used by fish when visual information is unreliable, indicating a possible mechanism for decision making given the inherent noise in incoming sensory information.

animal behavior and cognition↗

bioRxiv2022

Cue-driven motor planning facilitates express visuomotor responses in human arm muscles

Humans can produce "express" ([~]100ms) arm muscle responses that are inflexibly locked in time and space to the presentation of a visual target, consistent with subcortical visuomotor transformations via the tecto-reticulo-spinal pathway. These express visuomotor responses are sensitive to explicit cue-driven expectations, but it is unclear at what stage of sensory-to-motor transformation such modulation occurs. Here, we recorded electromyographic activity from shoulder muscles as participants reached toward one of four virtual targets whose physical location was partially predictable from a symbolic cue. In an experiment in which targets could be veridically reached, express responses were inclusive of the biomechanical requirements for reaching the cued locations and not systematically modulated by cue validity. In a second experiment, movements were restricted to the horizontal plane so that the participants could perform only rightward or leftward reaches, irrespective of target position on the vertical axis. Express muscle responses were almost identical for targets that were validly cued in the horizontal direction, regardless of cue validity in the vertical dimension. Together, these findings suggest that the cue-induced enhancements of express responses are dominated by effects at the level of motor plans and not solely via facilitation of early visuospatial target processing. Notably, direct cortico-tectal and cortico-reticular projections exist that are well-placed to modulate pre-stimulus motor preparation state in subcortical circuits. Our results appear to reflect a neural mechanism by which contextually relevant motor plans can be stored within subcortical visuomotor nodes and rapidly released in response to compatible visual inputs. NEW & NOTEWORTHYExpress arm muscle responses to suddenly appearing visual targets for reaching rapid have been attributed to the tecto-reticulo-spinal pathway in humans. We demonstrate that symbolic cues before target presentation can modulate such express arm muscle responses compatibly with the biomechanics of the cued reaching direction and the cue validity. This implies cortically mediated modulation of one or more sensorimotor transformation nodes of the subcortical express pathway.

neuroscience↗

bioRxiv2021

Trial-by-trial modulation of express visuomotor responses induced by symbolic or barely detectable cues

Human cerebral cortex can produce visuomotor responses that are modulated by contextual and task-specific constraints. However, the distributed cortical network for visuomotor transformations limits the minimal response time of that pathway. Notably, humans can generate express visuomotor responses that are inflexibly tuned to the target location and occur 80-120ms from stimulus presentation (stimulus-locked responses, SLRs). This suggests a subcortical pathway for visuomotor transformations involving the superior colliculus and its downstream reticulo-spinal projections. Here we investigated whether cognitive expectations can modulate the SLR. In one experiment, we recorded surface EMG from shoulder muscles as participants reached toward a visual target whose location was unpredictable in control conditions, and partially predictable in cue conditions by extrapolating a symbolic cue (75% validity). Valid symbolic cues led to faster and larger SLRs than control conditions; invalid symbolic cues produced slower and smaller SLRs than control conditions. This is consistent with a cortical top-down modulation of the putative subcortical SLR-network. In a second experiment, we presented high-contrast targets in isolation (control) or ~24ms after low-contrast stimuli, which could appear at the same (valid cue) or opposite (invalid cue) location as the target, and with equal probability (50% cue validity). We observed faster SLRs than control with the valid low-contrast cues, whereas the invalid cues led to the opposite results. These findings may reflect exogenous priming mechanisms of the SLR network, potentially evolving subcortically via the superior colliculus. Overall, our results support both top-down and bottom-up modulations of the putative subcortical SLR network in humans. NEW & NOTEWORTHYExpress visuomotor responses in humans appear to reflect subcortical sensorimotor transformation of visual inputs, potentially conveyed via the tecto-reticulo-spinal pathway. Here we show that the express responses are influenced both by symbolic and barely detectable spatial cues about stimulus location. The symbolic cue-induced effects suggest cortical top-down modulation of the putative subcortical visuomotor network. The effects of barely detectable cues may reflect exogenous priming mechanisms of the tecto-reticulo-spinal pathway.

neuroscience↗

bioRxiv2020

Single-cell transcriptomic analyses define distinct peripheral B cell subsets and discrete development pathways

Separation of B cells into different subsets has been useful to understand their different functions in various immune scenarios. In some instances, the subsets defined by phenotypic FACS separation are relatively homogeneous and so establishing the functions associated with them is straightforward. Other subsets, such as the "Double negative" (DN, CD19+CD27-IgD-) population, are more complex with reports of differing functionality which could indicate a heterogeneous population. Recent advances in single-cell techniques enable an alternative route to characterise cells based on their transcriptome. To maximise immunological insight, we need to match prior data from phenotype-based studies with the finer granularity of the single-cell transcriptomic signatures. We also need to be able to define meaningful B cell subsets from single cell analyses performed on PBMCs, where the relative paucity of a B cell signature means that defining B cell subsets within the whole is challenging. Here we provide a reference single-cell dataset based on phenotypically sorted B cells and an unbiased procedure to better classify functional B cell subsets in the peripheral blood, particularly useful in establishing a baseline cellular landscape and in extracting significant changes with respect to this baseline from single-cell datasets. We find 10 different clusters of B cells and applied a novel, geometry-inspired, method to RNA velocity estimates in order to evaluate the dynamical transitions between B cell clusters. This indicated the presence of two main developmental branches of memory B cells. One involves IgM memory cells and two DN subpopulations, culminating in a population thought to be associated with Age related B cells and the extrafollicular response. The other branch involves a third DN cluster which appears to be a precursor of classical memory cells. In addition, we identify a novel DN4 population, which is IgE rich and on its own developmental branch but with links to the classical memory branch.

immunology↗

bioRxiv2020

The influence of temporal predictability on express visuomotor responses

Volitional visuomotor responses in humans are generally thought to manifest 100ms or more after stimulus onset. Under appropriate conditions, however, much faster target-directed responses can be produced at upper limb and neck muscles. These "express" responses have been termed stimulus-locked responses (SLRs) and are proposed to be modulated by visuomotor transformations performed subcortically via the superior colliculus. Unfortunately, for those interested in studying SLRs, these responses have proven difficult to detect consistently across individuals. The recent report of an effective paradigm for generating SLRs in 100% of participants appears to change this. The task required the interception of a moving target that emerged from behind a barrier at a time consistent with the target velocity. Here we aimed to reproduce the efficacy of this paradigm for eliciting SLRs and to test the hypothesis that its effectiveness derives from the predictability of target onset time as opposed to target motion per se. In one experiment, we recorded surface EMG from shoulder muscles as participants made reaches to intercept temporally predictable or unpredictable targets. Consistent with our hypothesis, predictably timed targets produced more frequent and stronger SLRs than unpredictably timed targets. In a second experiment, we compared different temporally predictable stimuli and observed that transiently presented targets produced larger and earlier SLRs than sustained moving targets. Our results suggest that target motion is not critical for facilitating the expression of an SLR and that timing predictability does not rely on extrapolation of a physically plausible motion trajectory. These findings provide support for a mechanism whereby an internal timer, probably located in cerebral cortex, primes the processing of both visual input and motor output within the superior colliculus to produce SLRs.

neuroscience↗

bioRxiv2019

Lipid metabolism links nutrient-exercise timing to insulin sensitivity in men classified as overweight or obese.

ContextPre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. We hypothesised that in men with overweight/obesity, acute exercise before versus after nutrient ingestion would increase whole-body and intramuscular lipid utilization, translating into greater increases in oral glucose insulin sensitivity over 6-weeks of training.\n\nDesign and ParticipantsWe showed in men with overweight/obesity (mean{+/-}SD for BMI: 30.2{+/-}3.5 kgxm-2 for acute, crossover study, 30.9{+/-}4.5 kgxm-2 for randomized, controlled, training study) a single exercise bout before versus after nutrient provision increased lipid utilisation at the whole-body level, but also in both type I (p<0.01) and type II muscle fibres (p=0.02). We then used a 6-week training intervention to show sustained, 2-fold increases in lipid utilisation with exercise before versus after nutrient provision (p<0.01).\n\nMain Outcome MeasuresPostprandial glycemia was not differentially affected by exercise training before vs after nutrient provision (p>0.05), yet plasma was reduced with exercise training before, but not after nutrient provision (p=0.03), resulting in increased oral glucose insulin sensitivity when training was performed before versus after nutrient provision (25{+/-}38 vs -21{+/-}32 mLxmin-1xm-2; p=0.01) and this was associated with increased lipid utilisation during exercise (r=0.50, p=0.02). Regular exercise prior to nutrient provision augmented remodelling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (p<0.05).\n\nConclusionsExperiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (i.e., in the fasted state) may exert beneficial effects on lipid utilisation and reduce postprandial insulinemia.\n\nPrecisExercise in the fasted-versus fed-state increased intramuscular and whole-body lipid use, translating into increased muscle adaptation and insulin sensitivity when regularly performed over 6 weeks.

physiology↗

bioRxiv2019

Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial

NAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

clinical trials↗

bioRxiv2019

Rapid recalibration of temporal order judgements: Response bias accounts for contradictory results

Recent findings indicate that timing perception is systematically changed after only a single presentation of temporal asynchrony. This effect is known as rapid recalibration. In the synchrony judgement task, similar timing relationships in consecutive trials seem more synchronous (positive rapid recalibration; Van der Burg et al., 2013, 2015). Interestingly, the direction of this effect is reversed for temporal order judgements (negative rapid recalibration; Roseboom, 2019). We aimed to determine whether negative rapid recalibration of temporal order judgements (TOJs) reflects genuine rapid temporal recalibration, or a choice-repetition bias unrelated to timing perception. In our first experiment we found no evidence of rapid recalibration of TOJs, but positive rapid recalibration of associated confidence. This suggests that timing perception had rapidly recalibrated, but that this was undetectable in TOJs, plausibly because the positive recalibration effect was obfuscated by a large negative bias effect. In our second experiment, we dissociated participants previous TOJ from the most recently presented timing relationship, mitigating the choice-repetition bias effect, and found evidence of positive rapid recalibration of TOJs. We therefore conclude that timing perception is rapidly recalibrated positively for both synchrony and temporal order judgements. It remains unclear whether rapid recalibration occurs at the level of sensory processing, leading to similar effects in all subsequent judgements, or reflects a generalised decision-making strategy.

neuroscience↗