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.

Quantification of Collateral Supply with Local-AIF Dynamic Susceptibility Contrast MRI Predicts Infarct Growth.

In ischemic stroke, leptomeningeal collaterals can provide compensatory blood flow to tissue at risk despite an occlusion, and impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that local perfusion with an appropriate Local Arterial Input Function (AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion. Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Magnetic resonance dynamic susceptibility contrast (DSC) was imaged and post-processed as cerebral blood flow maps with both a traditionally chosen single arterial input function (AIF) applied globally to the whole brain (i.e. "Global-AIF") and a novel automatic delay and dispersion corrected AIF (i.e. "Local AIF") that is sensitive to retrograde flow. Pial collateral recruitment was assessed from x-ray angiograms and infarct growth via serially acquired diffusion weighted MRI scans both blinded to DSC. The degree of collateralization at x-ray correlated strongly with quantitative perfusion determined using the Local AIF in the ischemic penumbra (R2=0.81) compared to a traditionally chosen Global-AIF (R2=0.05). Quantitative perfusion calculated using a Local-AIF was negatively correlated (less infarct progression as local perfusion increased) with infarct growth (R2 = 0.79) compared to Global-AIF (R2=0.02). Local DSC perfusion with a Local-AIF is more accurate for assessing tissue status and degree of leptomeningeal collateralization than traditionally chosen AIFs. These findings support use of a Local-AIF in determining quantitative tissue perfusion with collateral supply in occlusive disease.

Efficacy Assessment of Cerebral Perfusion Augmentation Through Functional Connectivity in an Acute Canine Stroke Model.

BACKGROUND AND PURPOSE: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of NEH (Norepinephrine and Hydralazine), a cerebral perfusion augmentation therapy, on RSN integrity in a hyper-acute canine stroke model. MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Post-occlusion, the treatment group received intra-arterial Norepinephrine (0.1-1.52 µg/kg/min, adjusted for 25-45 mmHg above baseline mean arterial pressure) and Hydralazine (20mg). Resting-state fMRI data were acquired with a 3.0 T scanner using a BOLD-sensitive EPI sequence (TR/TE=1400 ms/20ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm FWHM), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis (ICA) and weighted whole-brain ROI-to-ROI connectome, pre-and post-MCAO. RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the Higher-order Visual and Parietal RSNs, as evidenced by thresholded statistical mapping (TFCE p-corr > 0.95). However, this preservation was network-dependent, with no significant changes in the Primary Visual and Sensorimotor networks. CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity following ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable endpoint for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation. ABBREVIATIONS: NEH＝ Norepinephrine and Hydralazine; RSN＝ Resting-State Network; ICA = Independent Component Analysis; rsfMRI = resting-state Functional Magnetic Resonance Imaging; MCAO = Middle Cerebral Artery Occlusion; TFCE = Threshold-Free Cluster Enhancement.

Dopamine Increases Accuracy and Lengthens Deliberation Time in Explicit Motor Skill Learning.

Although animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females; 11 males; aged 18-29 years) first consumed either 100 mg of levodopa (n = 19), a dopamine precursor that increases dopamine availability, or placebo (n = 19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets jumped mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy and not speed. The effect of the dopamine manipulations on skill learning was assessed during training and after an overnight follow-up. Increasing dopamine availability at training improved aiming accuracy and lengthened reaction times, particularly for larger, more difficult aiming angles, both at training and, importantly, at follow-up, despite prominent session-by-session performance improvements in both accuracy and speed. Exogenous dopamine thus seems to result in a learnt, persistent propensity to better adhere to task goals. Results support the proposal that dopamine is important in engagement of instrumental motivation to optimize adherence to task goals, particularly when learning to execute goal-directed strategies in motor skill learning.

Transient susceptibility imaging as a measure of hemodynamic compromise: A pilot study.

BACKGROUND AND PURPOSE: The purpose of this study was to test the hypothesis that hemodynamically compromised brains exhibit transient changes in magnetic susceptibility throughout the cardiac cycle, and to model these changes using Linear System Theory to extract an index that reflects cerebrovascular reserve. MATERIALS AND METHODS: Eleven patients with angiographically-confirmed intracranial atherosclerotic disease with >50% stenosis were imaged with susceptibility weighted, cardiac-gated single shot images of cerebral Oxygen Extraction Fraction (OEF) at different timepoints of the cardiac cycle. Cardiac gating of the OEF acquisition allowed interrogation of oxygenated blood and the detection of changes throughout the cardiac cycle. Independent component analysis (ICA) of raw k-space data across the cardiac phase allowed MRI signal decomposition into dynamic and static components for image reconstruction. An asymmetry index score of the resultant parametric images were compared to test the hypothesis that variation in hemoglobin-induced susceptibility across the cardiac cycle indeed reflects pathophysiology of cerebrovascular disease. A mathematical model was derived to parameterize physiologic changes induced by the presence of a hemodynamically significant stenosis in the brain as a tissue impulse response parameter (ß). RESULTS: OEF was elevated in the affected hemisphere (50.34 ± 12.13% vs 46.93 ± 12.34%), but failed to reach statistical significance (p < .0796). Transient changes in the OEF signal showed significant distinction between healthy and compromised tissue (0.56 ± 0.067 vs 0.44 ± 0.067, p < .019)). The derived tissue impulse response function was found to be significant as well (10.72 ± 3.48 10-3 ms-1, 9.69 ± 3.51 10-3 ms-1; p < .037). CONCLUSION: In this pilot study, we found transient OEF and ß to be significant predictors of hemispheric compromise.

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.

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.

Effectiveness of ocrelizumab on clinical and MRI outcome measures in multiple sclerosis across black and white cohorts: A single-center retrospective study.

OBJECTIVE: To examine differences in the therapeutic response to ocrelizumab in multiple sclerosis (MS) patients who self-identified as either White or Black, assessed longitudinally by expanded disability status scale (EDSS) progression and MRI brain volume loss. METHODS: MS subjects treated with ocrelizumab were retrospectively identified. Clinical data were available for 229 subjects (White 146; Black 83) and MRI data from for 48 subjects (White 31; Black 17). Outcome measures were changes in the EDSS and brain volume over time. EDSS were analyzed as raw scores, ambulatory (EDSS <5.0) vs. ambulatory with assistance (5.5 ≤ EDSS ≤ 6.5) status, and EDSS severity (< 3.0, 3.0-5.0, and > 5.5 ≤ 6.5). General linear mixed model was used for statistical analysis. FreeSurfer was used for volumetric analysis. RESULTS: The Black cohort had overrepresentation of females (78% vs. 62%, p = 0.013), lower age (median, 45 (IQR 39-51) vs. 49 (38-58), p = 0.08), lower Vitamin D levels (33 (21-45) vs. 40 (29-52), p = 0.002), and higher EDSS (4 (2-6) vs. 2.5 (1-6), p = 0.019). There was no progression of EDSS scores over the 2-year observation period. The covariates with significant influence on the baseline EDSS scores were older age, race, longer disease duration, prior MS treatment, and lower vitamin D levels. No differences were observed between the racial groups over time in the cortical, thalamic, caudate, putamen, and brainstem gray matter volumes nor in the cortical thickness or total lesion volume. CONCLUSION: In this real-world clinical and radiological study, ocrelizumab treatment was highly effective in stabilizing clinical and MRI measures of disease progression in Blacks and Whites, despite higher baseline disability in the Black cohort.

Musculoskeletal simulations to examine the effects of accentuated eccentric loading (AEL) on jump height.

Background: During counter movement jumps, adding weight in the eccentric phase and then suddenly releasing this weight during the concentric phase, known as accentuated eccentric loading (AEL), has been suggested to immediately improve jumping performance. The level of evidence for the positive effects of AEL remains weak, with conflicting evidence over the effectiveness in enhancing performance. Therefore, we proposed to theoretically explore the influence of implementing AEL during constrained vertical jumping using computer modelling and simulation and examined whether the proposed mechanism of enhanced power, increased elastic energy storage and return, could enhance work and power. Methods: We used a simplified model, consisting of a ball-shaped body (head, arm, and trunk), two lower limb segments (thigh and shank), and four muscles, to simulate the mechanisms of AEL. We adjusted the key activation parameters of the muscles to influence the performance outcome of the model. Numerical optimization was applied to search the optimal solution for the model. We implemented AEL and non-AEL conditions in the model to compare the simulated data between conditions. Results: Our model predicted that the optimal jumping performance was achieved when the model utilized the whole joint range. However, there was no difference in jumping performance in AEL and non-AEL conditions because the model began its push-off at the similar state (posture, fiber length, fiber velocity, fiber force, tendon length, and the same activation level). Therefore, the optimal solution predicted by the model was primarily driven by intrinsic muscle dynamics (force-length-velocity relationship), and this coupled with the similar model state at the start of the push-off, resulting in similar push-off performance across all conditions. There was also no evidence of additional tendon-loading effect in AEL conditions compared to non-AEL condition. Discussion: Our simplified simulations did not show improved jump performance with AEL, contrasting with experimental studies. The reduced model demonstrates that increased energy storage from the additional mass alone is not sufficient to induce increased performance and that other factors like differences in activation strategies or movement paths are more likely to contribute to enhanced performance.

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.

Application of a novel T1 retrospective quantification using internal references (T1-REQUIRE) algorithm to derive quantitative T1 relaxation maps of the brain.

Most MRI sequences used clinically are qualitative or weighted. While such images provide useful information for clinicians to diagnose and monitor disease progression, they lack the ability to quantify tissue damage for more objective assessment. In this study, an algorithm referred to as the T1-REQUIRE is presented as a proof-of-concept which uses nonlinear transformations to retrospectively estimate T1 relaxation times in the brain using T1-weighted MRIs, the appropriate signal equation, and internal, healthy tissues as references. T1-REQUIRE was applied to two T1-weighted MR sequences, a spin-echo and a MPRAGE, and validated with a reference standard T1 mapping algorithm in vivo. In addition, a multiscanner study was run using MPRAGE images to determine the effectiveness of T1-REQUIRE in conforming the data from different scanners into a more uniform way of analyzing T1-relaxation maps. The T1-REQUIRE algorithm shows good agreement with the reference standard (Lin's concordance correlation coefficients of 0.884 for the spin-echo and 0.838 for the MPRAGE) and with each other (Lin's concordance correlation coefficient of 0.887). The interscanner studies showed improved alignment of cumulative distribution functions after T1-REQUIRE was performed. T1-REQUIRE was validated with a reference standard and shown to be an effective estimate of T1 over a clinically relevant range of T1 values. In addition, T1-REQUIRE showed excellent data conformity across different scanners, providing evidence that T1-REQUIRE could be a useful addition to big data pipelines.

Specificity and incremental predictive validity of implicit attitudes: studies of a race-based phenotype.

Four studies involving 2552 White American participants were conducted to investigate bias based on the race-based phenotype of hair texture. Specifically, we probed the existence and magnitude of bias in favor of Eurocentric (straight) over Afrocentric (curly) hair and its specificity in predicting responses to a legal decision involving the phenotype. Study 1 revealed an implicit preference, measured by an Implicit Association Test (IAT), favoring Eurocentric over Afrocentric hair texture among White Americans. This effect was not reducible to a Black/White implicit race attitude nor to mere perceptual preference favoring straight over curly hair. In Study 2, the phenotype (hair) IAT significantly and uniquely predicted expressions of support in response to an actual legal case that involved discrimination on the basis of Afrocentric hair texture. Beyond replicating this result, Studies 3 and 4 (the latter preregistered) provided further, and even more stringent, evidence for incremental predictive validity: in both studies, the phenotype IAT was associated with support for a Black plaintiff above and beyond the effects of two parallel explicit scales and, additionally, a race attitude IAT. Overall, these studies support the idea that race bias may be uniquely detected by examining implicit attitudes elicited by group-based phenotypicality, such as hair texture. Moreover, the present results inform theoretical investigations of the correspondence principle in the context of implicit social cognition: they suggest that tailoring IATs to index specific aspects of an attitude object (e.g., by decomposition of phenotypes) can improve prediction of intergroup behavior.

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.

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.

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.

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.