Express Visuomotor Responses Reflect Knowledge of Both Target Locations and Contextual Rules during Reaches of Different Amplitudes.

When humans reach to visual targets, extremely rapid (∼90 ms) target-directed responses can be observed in 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 prestimulus expectations. Here, we show that the express visuomotor system incorporates information about the physical hand-to-target distance and contextual rules during visuospatial tasks requiring different movement amplitudes. In one experiment, we recorded the activity from two shoulder muscles as 14 participants (6 females) reached toward targets that appeared at different distances from the reaching hand. Increasing the reaching distance facilitated the generation of frequent and large express visuomotor responses. This suggests that both the direction and amplitude 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 12 participants (4 females) 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 nonveridical targets as in the anti-reach task. 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 STATEMENT Express (∼90 ms) arm muscle responses that are consistently tuned toward the location of visual stimuli suggest a subcortical contribution to target-directed visuomotor behavior in humans, potentially via the tecto-reticulo-spinal pathway. Here, we show that express muscle responses are modulated appropriately to reach targets at different distances, but generally suppressed when the task required nonveridical responses to overshoot/undershoot the real target. This suggests 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.

T1 mapping from routine 3D T1-weighted inversion recovery sequences in clinical practice: comparison against reference inversion recovery fast field echo T1 scans and feasibility in multiple sclerosis.

BACKGROUND AND PURPOSE: Quantitative T1 mapping can be an essential tool for assessing tissue injury in multiple sclerosis (MS). We introduce T1-REQUIRE, a method that converts a single high-resolution anatomical 3D T1-weighted Turbo Field Echo (3DT1TFE) scan into a parametric T1 map that could be used for quantitative assessment of tissue damage. We present the accuracy and feasibility of this method in MS. METHODS: 14 subjects with relapsing-remitting MS and 10 healthy subjects were examined. T1 maps were generated from 3DT1TFE images using T1-REQUIRE, which estimates T1 values using MR signal equations and internal tissue reference T1 values. Estimated T1 of lesions, white, and gray matter regions were compared with reference Inversion-Recovery Fast Field Echo T1 values and analyzed via correlation and Bland-Altman (BA) statistics. RESULTS: 159 T1-weighted (T1W) hypointense MS lesions and 288 gray matter regions were examined. T1 values for MS lesions showed a Pearson's correlation of r = 0.81 (p < 0.000), R2 = 0.65, and Bias = 4.18%. BA statistics showed a mean difference of -53.95 ms and limits of agreement (LOA) of -344.20 and 236.30 ms. Non-lesional normal-appearing white matter had a correlation coefficient of r = 0.82 (p < 0.000), R2 = 0.67, Bias = 8.78%, mean difference of 73.87 ms, and LOA of -55.67 and 203.41 ms. CONCLUSIONS: We demonstrate the feasibility of retroactively derived high-resolution T1 maps from routinely acquired anatomical images, which could be used to quantify tissue pathology in MS. The results of this study will set the stage for testing this method in larger clinical studies for examining MS disease activity and progression.

The effects of crank power and cadence on muscle fascicle shortening velocity, muscle activation and joint-specific power during cycling.

Whilst people typically choose to locomote in the most economical fashion, during bicycling they will, unusually, chose cadences that are higher than metabolically optimal. Empirical measurements of the intrinsic contractile properties of the vastus lateralis (VL) muscle during submaximal cycling suggest that the cadences that people self-selected might allow for optimal muscle fascicle shortening velocity for the production of knee extensor muscle power. It remains unclear, however, whether this is consistent across different power outputs where the self-selected cadence (SSC) varies. We examined the effect of cadence and external power requirements on muscle neuromechanics and joint power during cycling. VL fascicle shortening velocity, muscle activation and joint-specific power were measured during cycling between 60 and 120 rpm (including SSC), while participants produced 10%, 30% and 50% of peak maximal power. VL shortening velocity increased as cadence increased but was similar across the different power outputs. Although no differences were found in the distribution of joint power across cadence conditions, the absolute knee joint power increased with increasing crank power output. Muscle fascicle shortening velocity increased in VL at the SSC as pedal power demands increased from submaximal towards maximal cycling. A secondary analysis of muscle activation patterns showed minimized activation of VL and other muscles near the SSC at the 10% and 30% power conditions. Minimization of activation with progressively increasing fascicle shortening velocities at the SSC may be consistent with the theory that the optimum shortening velocity for maximizing power increases with the intensity of exercise and recruitment of fast twitch fibers.

Increased muscle force does not induce greater stretch-induced damage to calf muscles during work-matched heel drop exercise.

PURPOSE: To investigate the effect of muscle force during active stretch on quantitative and qualitative indicators of exercise-induced muscle damage (EIMD) in the medial gastrocnemius (MG) muscle. METHODS: Twelve recreationally active volunteers performed two trials of an eccentric heel drop exercise. Participants performed a single bout of low-load (body weight) and high-load (body weight + 30% body weight) exercises on separate legs. The total mechanical work output for each condition was matched between legs. Before, two hours and 48 h after each bout of eccentric exercise, electrically stimulated triceps surae twitch torque, muscle soreness, MG active fascicle length at maximum twitch torque and muscle passive stiffness were collected. Triceps surae electromyographic (EMG) activity, MG fascicle stretch and MG muscle-tendon unit (MTU) length were measured during the eccentric tasks. RESULTS: The high-load condition increased triceps surae muscle activity by 6-9%, but reduced MG fascicle stretch (p < 0.001). MTU stretch was similar between conditions. The greater muscle force during stretch did not give rise to additional torque loss (5 vs 6%) or intensify muscle soreness. CONCLUSIONS: Adding 30% body weight during eccentric contractions has a modest impact on exercise-induced muscle damage in the medial gastrocnemius muscle. These results suggest that muscle load may not be an important determinant of stretch-induced muscle damage in the human MG muscle. The muscle investigated does exhibit large pennation angles and high series elastic compliance; architectural features that likely buffer muscle fibres against stretch and damage.

Symbolic cues enhance express visuomotor responses in human arm muscles at the motor planning rather than the visuospatial processing stage.

Humans can produce "express" (∼100 ms) arm muscle responses that are inflexibly locked in time and space to visual target presentations, 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 corticotectal and corticoreticular projections exist that are well-placed to modulate prestimulus motor preparation state in subcortical circuits. Our results could reflect a neural mechanism by which contextually relevant motor responses to compatible visual inputs are rapidly released via subcortical circuits that are sufficiently along the sensory-to-motor continuum.NEW & NOTEWORTHY Express 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.

Engagement of the contralateral limb can enhance the facilitation of motor output by loud acoustic stimuli.

When intense sound is presented during light muscle contraction, inhibition of the corticomotoneuronal pathway is observed. During action preparation, this effect is reversed, with sound resulting in excitation of the corticomotoneuronal pathway. We investigated how the combined maintenance of a muscle contraction during preparation for a ballistic action impacts the magnitude of the facilitation of motor output by a loud acoustic stimulus (LAS), a phenomenon known as the StartReact effect. Participants executed ballistic wrist flexion movements and a LAS was presented simultaneously with the imperative signal in a subset of trials. We examined whether the force level or muscle used to maintain a contraction during preparation for the ballistic response impacted reaction time and/or the force of movements triggered by the LAS. These contractions were sustained either ipsilaterally or contralaterally to the ballistic response. The magnitude of facilitation by the LAS was greatest when low-force flexion contractions were maintained in the limb contralateral to the ballistic response during preparation. There was little change in facilitation when contractions recruited the contralateral extensor muscle or when they were sustained in the same limb that executed the ballistic response. We conclude that a larger network of neurons that may be engaged by a contralateral sustained contraction prior to initiation may be recruited by the LAS, further contributing to the motor output of the response. These findings may be particularly applicable in stroke rehabilitation, where engagement of the contralesional side may increase the benefits of a LAS to the functional recovery of movement.NEW & NOTEWORTHY The facilitation of reaction time, force, and vigor of a ballistic action by loud acoustic stimuli can be enhanced by the maintenance of a sustained contraction during preparation. This enhanced facilitation is observed when the sustained contraction is maintained with low force contralaterally and congruently with the ballistic response. This increased facilitation may be particularly applicable to rehabilitative applications of loud acoustic stimuli in improving the functional recovery of movement after neurological conditions such as stroke.

Task Errors Drive Memories That Improve Sensorimotor Adaptation.

Traditional views of sensorimotor adaptation (i.e., adaptation of movements to perturbed sensory feedback) emphasize the role of automatic, implicit correction of sensory prediction errors. However, latent memories formed during sensorimotor adaptation, manifest as improved relearning (e.g., savings), have recently been attributed to strategic corrections of task errors (failures to achieve task goals). To dissociate contributions of task errors and sensory prediction errors to latent sensorimotor memories, we perturbed target locations to remove or enforce task errors during learning and/or test, with male/female human participants. Adaptation improved after learning in all conditions where participants were permitted to correct task errors, and did not improve whenever we prevented correction of task errors. Thus, previous correction of task errors was both necessary and sufficient to improve adaptation. In contrast, a history of sensory prediction errors was neither sufficient nor obligatory for improved adaptation. Limiting movement preparation time showed that the latent memories driven by learning to correct task errors take at least two forms: a time-consuming but flexible component, and a rapidly expressible, inflexible component. The results provide strong support for the idea that movement corrections driven by a failure to successfully achieve movement goals underpin motor memories that manifest as savings. Such persistent memories are not exclusively mediated by time-consuming strategic processes but also comprise a rapidly expressible but inflexible component. The distinct characteristics of these putative processes suggest dissociable underlying mechanisms, and imply that identification of the neural basis for adaptation and savings will require methods that allow such dissociations.SIGNIFICANCE STATEMENT Latent motor memories formed during sensorimotor adaptation manifest as improved adaptation when sensorimotor perturbations are reencountered. Conflicting theories suggest that this "savings" is underpinned by different mechanisms, including a memory of successful actions, a memory of errors, or an aiming strategy to correct task errors. Here we show that learning to correct task errors is sufficient to show improved subsequent adaptation with respect to naive performance, even when tested in the absence of task errors. In contrast, a history of sensory prediction errors is neither sufficient nor obligatory for improved adaptation. Finally, we show that latent sensorimotor memories driven by task errors comprise at least two distinct components: a time-consuming, flexible component, and a rapidly expressible, inflexible component.

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 in arm muscles that are inflexibly tuned to the target location and occur 80-120 ms from stimulus presentation [stimulus-locked responses (SLRs)]. This suggests a subcortical pathway for visuomotor transformations that might involve 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 electromyogram (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 interpreting a symbolic cue (75% validity). Valid symbolic cues led to earlier and larger SLRs than control conditions; invalid symbolic cues produced later 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 ∼24 ms 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 earlier SLRs than control with the valid low-contrast cues, whereas the invalid cues led to the opposite results. These findings may reflect bottom-up attentional mechanisms, 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 & NOTEWORTHY Express 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 by both 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 facilitation mechanisms of the tecto-reticulo-spinal pathway.

The influence of temporal predictability on express visuomotor responses.

Humans are able to generate target-directed visuomotor responses in less than 100 ms after stimulus onset. 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, 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 target moving at a constant velocity that emerged from behind a barrier. 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 electromyogram (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 SLR expression 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.NEW & NOTEWORTHY Express stimulus-driven responses in humans have been proposed to be originated subcortically via the superior colliculus. These short-latency responses are facilitated by the presentation of dynamic visual stimuli. Here, we show that this facilitation is related to the predictable target timing, regardless of its kinematic attributes. We propose that the superior colliculus can be primed to generate express stimulus-driven motor responses via cortical top-down projection.

QSM in canine model of acute cerebral ischemia: A pilot study.

PURPOSE: In the present study, we investigated the potential of QSM to assess the physiological state of cortical tissue in the middle cerebral artery occlusion canine model of a cerebral ischemia. METHODS: Experiments were performed in 8 anesthetized canines. Gradient echo, perfusion, and DWI data of brains at normal and ischemic states were acquired. In the postprocessed susceptibility and quantitative cerebral blood flow maps, changes in values within the middle cerebral artery-fed cortical territories were quantified both on the ischemic and normal contralateral hemisphere side. RESULTS: QSM values in critically ischemic tissue were significantly different from contralateral values-namely, susceptibility increase was observed in the cases in which cerebral perfusion was maintained above the threshold of neuronal death. Furthermore, the data indicates presence of a significant correlation between the changes in susceptibility values, cerebral perfusion, and the infarct volume and pial collateral scores. Additionally, our data suggests that difference in cortical susceptibility is prospectively indicative of the infarct growth rate. CONCLUSION: In an experimental permanent middle cerebral artery occlusion model, QSM was shown to correlate with the functional parameters characterizing viability of ischemic tissue, thus warranting further research on its ability to provide complementary information during acute stroke MRI examinations in humans.

Plantar flexor voluntary activation capacity, strength and function in cerebral palsy.

PURPOSE: Distal lower limb motor impairment impacts gait mechanics in individuals with cerebral palsy (CP), however, the contribution of impairments of muscle activation to reduced gross motor function (GMF) is not clear. This study aimed to investigate deficits in plantar flexion voluntary activation capacity in CP compared to typically developed (TD) peers, and evaluate relationships between voluntary activation capacity, strength and GMF. METHODS: Fifteen ambulant individuals with spastic CP (23 ± 6 years, GMFCS I-III) and 14 TD (22 ± 2 years) people participated. Plantar- and dorsiflexion strength were assessed with a dynamometer. Voluntary activation capacity was assessed using the interpolated twitch technique via single twitch supramaximal tibial nerve stimulation. GMF was assessed using the timed upstairs test, 10 m walk test, muscle power sprint test and six-minute walk test. RESULTS: Plantar- and dorsiflexion strength were 55.6% and 60.7% lower in CP than TD (p < 0.001). Although voluntary activation capacity was 17.9% lower on average for CP than TD (p = 0.039), 46.7% of individuals with CP achieved a sufficiently high activation to fall within one standard deviation of the TD mean. Plantar flexion voluntary activation capacity did not correlate with strength (R2 = 0.092, p = 0.314) or GMF measures in the high functioning CP group (GMFCS I-II). CONCLUSION: In contrast to previous research, plantar flexion activation capacity did not strongly predict weakness or reduced GMF. We propose that muscle size contributes more to weakness than voluntary activation capacity in high functioning individuals with CP and that relationships between muscle activation and functional capacity are complicated by effects at multiple joints.

Cyclic eccentric stretching induces more damage and improved subsequent protection than stretched isometric contractions in the lower limb.

PURPOSE: Controversy remains about whether exercise-induced muscle damage (EIMD) and the subsequent repeated bout effect (RBE) are caused by the stretching of an activated muscle, or the production of high force at long, but constant, muscle lengths. The aim of this study was to determine the influence of muscle fascicle stretch elicited during different muscle contraction types on the magnitude of EIMD and the RBE. METHODS: Fourteen participants performed an initial bout of lower limb exercise of the triceps surae. One leg performed sustained static contractions at a constant long muscle length (ISO), whereas the contralateral leg performed a bout of eccentric heel drop exercise (ECC). Time under tension was matched between the ECC and ISO conditions. Seven days later, both legs performed ECC. Plantar flexor twitch torque, medial gastrocnemius (MG) fascicle length and muscle soreness were assessed before, 2 h and 2 days after each exercise bout. MG fascicle length and triceps surae surface electromyography were examined across the bouts of exercise. RESULTS: We found that both ECC and ISO conditions elicited EIMD and a RBE. ISO caused less damage 2 h after the initial bout (14% less drop in twitch torque, P = 0.03) and less protection from soreness 2 days after the repeated bout (56% higher soreness, P = 0.01). No differences were found when comparing neuromechanical properties across exercise bouts. CONCLUSION: For MG, the action of stretching an active muscle seems to be more important for causing damage than a sustained contraction at a long length.

Rapid Visuomotor Responses Reflect Value-Based Decisions.

Cognitive decision-making is known to be sensitive to the values of potential options, which are the probability and size of rewards associated with different choices. Here, we examine whether rapid motor responses to perturbations of visual feedback about movement, which mediate low-level and involuntary feedback control loops, reflect computations associated with high-level value-based decision-making. In three experiments involving human participants, we varied the value associated with different potential targets for reaching movements by controlling the distributions of rewards across the targets (Experiment 1), the probability with which each target could be specified (Experiment 2), or both (Experiment 3). We found that the size of rapid and involuntary feedback responses to movement perturbations was strongly influenced by the relative value between targets. A statistical model of relative value that includes a term for risk sensitivity provided the best fit to the visuomotor response data, illustrating that feedback control policies are biased to favor more frequent task success at the expense of the overall extrinsic reward accumulated through movement. Importantly however, the regulation of rapid feedback responses was associated with successful pursuit of high-value task outcomes. This implies that when we move, the brain specifies a set of feedback control gains that enable low-level motor areas not only to generate efficient and accurate movement, but also to rapidly and adaptively respond to evolving sensory information in a manner consistent with value-based decision-making.SIGNIFICANCE STATEMENT Current theories of sensorimotor control suggest that, rather than selecting and planning the details of movements in advance, the role of the brain is to set time-varying feedback gains that continuously transform sensory information into motor commands by feedback control. Here, we examine whether the fastest motor responses to perturbations of movement, which mediate low-level and involuntary feedback control loops (i.e., reflexes), reflect computations associated with high-level, value-based decision-making. We find that rapid feedback responses during reaching reflect the relative probabilities and rewards associated with target options. This suggests that low-order components of the sensorimotor control hierarchy, which generate rapid and automatic responses, can continuously evaluate evolving sensory evidence and initiate responses according to the prospect of reward.

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

Recent history influences subsequent perception, decision-making and motor behaviours. In this article, we address a discrepancy in the effects of recent sensory history on the perceived timing of auditory and visual stimuli. In the synchrony judgement (SJ) task, similar timing relationships in consecutive trials seem more synchronous (i.e. less like the repeated temporal order). This effect is known as rapid recalibration and is consistent with a negative perceptual aftereffect. Interestingly, the opposite is found in the temporal order judgement (TOJ) task (positive rapid recalibration). We aimed to determine whether a simple bias to repeat judgements on consecutive trials (choice-repetition bias) could account for the discrepant results in these tasks. Preliminary simulations and analyses indicated that a choice-repetition bias could produce apparently positive rapid recalibration in the TOJ and not the SJ task. Our first experiment revealed no evidence of rapid recalibration of TOJs, but negative rapid recalibration of associated confidence. This suggests that timing perception was rapidly recalibrated, but that the negative recalibration effect was obfuscated by a positive bias effect. In our second experiment, we experimentally mitigated the choice-repetition bias effect and found negative rapid recalibration of TOJs. We therefore conclude that timing perception is negatively rapidly recalibrated, and this is observed consistently across timing tasks. These results contribute to a growing body of evidence that indicates multisensory perception is constantly undergoing recalibration, such that perceptual synchrony is maintained. This work also demonstrates that participants' task responses reflect judgements that are contaminated by independent biases of perception and decision-making.

Increased preparation time reduces, but does not abolish, action history bias of saccadic eye movements.

The characteristics of movements are strongly history-dependent. Marinovic et al. (Marinovic W, Poh E, de Rugy A, Carroll TJ. eLife 6: e26713, 2017) showed that past experience influences the execution of limb movements through a combination of temporally stable processes that are strictly use dependent and dynamically evolving and context-dependent processes that reflect prediction of future actions. Here we tested the basis of history-dependent biases for multiple spatiotemporal features of saccadic eye movements under two preparation time conditions (long and short). Twenty people performed saccades to visual targets. To prompt context-specific expectations of most likely target locations, 1 of 12 potential target locations was specified on ~85% of the trials and each remaining target was presented on ~1% trials. In long preparation trials participants were shown the location of the next target 1 s before its presentation onset, whereas in short preparation trials each target was first specified as the cue to move. Saccade reaction times and direction were biased by recent saccade history but according to distinct spatial tuning profiles. Biases were purely expectation related for saccadic reaction times, which increased linearly as the distance from the repeated target location increased when preparation time was short but were similar to all targets when preparation time was long. By contrast, the directions of saccades were biased toward the repeated target in both preparation time conditions, although to a lesser extent when the target location was precued (long preparation). The results suggest that saccade history affects saccade dynamics via both use- and expectation-dependent mechanisms and that movement history has dissociable effects on reaction time and saccadic direction. NEW & NOTEWORTHY The characteristics of our movements are influenced not only by concurrent sensory inputs but also by how we have moved in the past. For limb movements, history effects involve both use-dependent processes due strictly to movement repetition and processes that reflect prediction of future actions. Here we show that saccade history also affects saccade dynamics via use- and expectation-dependent mechanisms but that movement history has dissociable effects on saccade reaction time and direction.

Pushing attention to one side: Force field adaptation alters neural correlates of orienting and disengagement of spatial attention.

Sensorimotor adaptation to wedge prisms can alter the balance of attention between left and right space in healthy adults, and improve symptoms of spatial neglect after stroke. Here we asked whether the orienting of spatial attention to visual stimuli is affected by a different form of sensorimotor adaptation that involves physical perturbations of arm movement, rather than distortion of visual feedback. Healthy participants performed a cued discrimination task before and after they made reaching movements to a central target. A velocity-dependent force field pushed the hand aside during each reach, and required participants to apply compensatory forces toward the opposite side. We used event-related potentials (ERPs) to determine whether electroencephalography (EEG) responses reflecting orienting (cue-locked N1) and disengagement (target-locked P1) of spatial attention are affected by adaptation to force fields. After adaptation, the cue-locked N1 was relatively larger for stimuli presented in the hemispace corresponding to the direction of compensatory hand force. P1 amplitudes evoked by invalidly cued targets presented on the opposite side were reduced. This suggests that force field adaptation boosted attentional orienting responses toward the side of hand forces, and impeded attentional disengagement from that side, mimicking previously reported effects of prism adaptation. Thus, remapping between motor commands and intended movement direction is sufficient to bias ERPs, reflecting changes in the orienting of spatial attention in the absence of visuo-spatial distortion or visuo-proprioceptive mismatch. Findings are relevant to theories of how sensorimotor adaptation can modulate attention, and may open new avenues for treatment of spatial neglect.

Absolute quantitative MR perfusion and comparison against stable-isotope microspheres.

PURPOSE: This work sought to compare a quantitative T1 bookend dynamic susceptibility contrast MRI based perfusion protocol for absolute cerebral blood flow (qCBF) against CBF measured by the stable-isotope neutron capture microsphere method, a recognized reference standard for measuring tissue blood flow, at normocapnia, hypercapnia, and in acute stroke. METHODS: CBF was measured in anesthetized female canines by MRI and microspheres over 2 consecutive days for each case. On day 1, 5 canines were measured before and during a physiological challenge induced by carbogen inhalation; on day 2, 4 canines were measured following permanent occlusion of the middle cerebral artery. CBF and cerebrovascular reactivity measured by MRI and microsphere deposition were compared. RESULTS: MRI correlated strongly with microspheres at the hemispheric level for CBF during normo- and hypercapnic states (r2 = 0.96), for individual cerebrovascular reactivity (r2 = 0.84), and for postocclusion CBF (r2 = 0.82). Correction for the delay and dispersion of the contrast bolus resulted in a significant improvement in the correlation between MRI and microsphere deposition in the ischemic state (r2 = 0.96). In all comparisons, moderate correlations were found at the regional level. CONCLUSION: In an experimental canine model with and without permanent occlusion of the middle cerebral artery, MRI-based qCBF yielded moderate to strong correlations for absolute quantitative CBF and cerebrovascular reactivity measurements during normocapnia and hypercapnia. Correction for delay and dispersion greatly improved the quantitation during occlusion of the middle cerebral artery, underscoring the importance for this correction under focal ischemic condition.

Correlation of post-contrast T1-weighted MRI surface regularity, tumor bulk, and necrotic volume with Ki67 and p53 in glioblastomas.

PURPOSE: p53 and Ki67 status can be relevant to the management of glioblastoma. The goal of this study is to determine whether tumor morphology and bulk depicted on MRI correlate with p53 and Ki67 in glioblastoma. METHODS: A retrospective review of 223 patients with glioblastoma and corresponding p53 or Ki67 status, along with T1-weighted post-contrast MR images was performed. Enhancing tumors were outlined for determining surface regularity, tumor bulk, and necrotic volume. The median value of 0.1 was chosen for p53 and 0.2 for Ki67 to separate each data set into two classes. T tests and receiver operating characteristic analysis were performed to determine the separation of the classes and the predicting power of each feature. RESULTS: There were significant differences between tumor surface regularity (p = 0.01) and necrotic volume (p = 0.0429) according to Ki67 levels, although neither had statistically significant predictive power (AUC = 0.697, p = 0.0506 and AUC = 0.577, p = 0.164, respectively). There were also significant differences between tumor bulk (p = 0.0239) and necrotic volume (p = 0.0200) according to p53 levels, but again no significant predictive power was found using ROC analysis (AUC = 0.5882, p = 0.0894 and AUC = 0.567, p = 0.155, respectively). CONCLUSION: Quantitative morphological tumor characteristics on post-contrast T1-weighted MRI can to a certain degree provide insights regarding Ki67 and p53 status in patients with glioblastoma.

Unilateral movement preparation causes task-specific modulation of TMS responses in the passive, opposite limb.

KEY POINTS: Activity in the primary motor cortices of both hemispheres increases during unilateral movement preparation, but the functional role of ipsilateral motor cortex activity is unknown. Ipsilateral motor cortical activity could represent subliminal 'motor planning' for the passive limb. Alternatively, it could represent the state of the active limb, to support coordination between the limbs should a bimanual movement be required. Here we assessed how preparation of forces toward different directions, with the left wrist, alters evoked responses to transcranial magnetic stimulation of left motor cortex. Preparation of a unilateral movement caused excitability increases in ipsilateral motor cortex that reflected forces produced with the active limb in an intrinsic (body-centred), rather than an extrinsic (world-centred), coordinate system. These results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb. ABSTRACT: Corticospinal excitability is modulated for muscles on both sides of the body during unilateral movement preparation. For the effector, there is a progressive increase in excitability, and a shift in direction of muscle twitches evoked by transcranial magnetic stimulation (TMS) toward the impending movement. By contrast, the directional characteristics of excitability changes in the opposite (passive) limb have not been fully characterized. Here we assessed how preparation of voluntary forces towards four spatially distinct visual targets with the left wrist alters muscle twitches and motor-evoked potentials (MEPs) elicited by TMS of left motor cortex. MEPs were facilitated significantly more in muscles homologous to agonist rather than antagonist muscles in the active limb, from 120 ms prior to voluntary EMG onset. Thus, unilateral motor preparation has a directionally specific influence on pathways projecting to the opposite limb that corresponds to the active muscles rather than the direction of movement in space. The directions of TMS-evoked twitches also deviated toward the impending force direction of the active limb, according to muscle-based coordinates, following the onset of voluntary EMG. The data indicate that preparation of a unilateral movement increases task-dependent excitability in ipsilateral motor cortex, or its downstream projections, that reflects the forces applied by the active limb in an intrinsic (body-centred), rather than an extrinsic (world-centred), coordinate system. The results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb.

Use-dependent directional bias does not transfer to the untrained limb during bimanual contractions.

Skills learned through practice with one limb can often be transferred to the untrained limb. In the present report, we sought to determine whether movement direction biases, acquired through repeated movement with one limb, transfer to the untrained limb. In order to do so, we asked participants to perform synchronized bilateral contractions of muscles in both wrists, followed by the unilateral contraction of muscles in one wrist. In four experiments, we manipulated the position of the unilateral target to create use-dependent directional biases; changed the direction of the cursor in relation to the wrist movement to control for attentional biases; and sought to induce directional biases with both right and left unilateral movements. The results showed clear movement-related biases for the wrist that performed unilateral contractions, but no evidence that movement-related bias transferred to the opposite limb during bilateral action. Thus, motor preparation and execution of unilateral contractions does not affect the direction of movement made by the opposite limb during subsequent bilateral contractions.