Sensitivity analyses of probabilistic and deterministic DTI tractography methodologies for studying arm muscle architecture.

PURPOSE: To determine the sensitivity profiles of probabilistic and deterministic DTI tractography methods in estimating geometric properties in arm muscle anatomy. METHODS: Spin-echo diffusion-weighted MR images were acquired in the dominant arm of 10 participants. Both deterministic and probabilistic tractography were performed in two different muscle architectures of the parallel-structured biceps brachii (and the pennate-structured flexor carpi ulnaris. Muscle fascicle geometry estimates and number of fascicles were evaluated with respect to tractography turning angle, polynomial fitting order, and SNR. The DTI tractography estimated fascicle lengths were compared with measurements obtained from conventional cadaveric dissection and ultrasound modalities. RESULTS: The probabilistic method generally estimated fascicle lengths closer to ranges reported by conventional methods than the deterministic method, most evident in the biceps brachii (p > 0.05), consisting of longer, arc-like fascicles. For both methods, a wide turning angle (50º-90°) generated fascicle lengths that were in close agreement with conventional methods, most evident in the flexor carpi ulnaris (p > 0.05), consisting of shorter, feather-like fascicles. The probabilistic approach produced at least two times more fascicles than the deterministic approach. For both approaches, second-order fitting yielded about double the complete tracts as third-order fitting. In both muscles, as SNR decreased, deterministic tractography produced less fascicles but consistent geometry (p > 0.05), whereas probabilistic tractography produced a consistent number but altered geometry of fascicles (p < 0.001). CONCLUSION: Findings from this study provide best practice recommendations for implementing DTI tractography in skeletal muscle and will inform future in vivo studies of healthy and pathological muscle structure.

Serial sarcomere number is substantially decreased within the paretic biceps brachii in individuals with chronic hemiparetic stroke.

A muscle's structure, or architecture, is indicative of its function and is plastic; changes in input to or use of the muscle alter its architecture. Stroke-induced neural deficits substantially alter both input to and usage of individual muscles. We combined in vivo imaging methods (second-harmonic generation microendoscopy, extended field-of-view ultrasound, and fat-suppression MRI) to quantify functionally meaningful architecture parameters in the biceps brachii of both limbs of individuals with chronic hemiparetic stroke and in age-matched, unimpaired controls. Specifically, serial sarcomere number (SSN) and physiological cross-sectional area (PCSA) were calculated from data collected at three anatomical scales: sarcomere length, fascicle length, and muscle volume. The interlimb differences in SSN and PCSA were significantly larger for stroke participants than for participants without stroke (P = 0.0126 and P = 0.0042, respectively), suggesting we observed muscle adaptations associated with stroke rather than natural interlimb variability. The paretic biceps brachii had ∼8,200 fewer serial sarcomeres and ∼2 cm2 smaller PCSA on average than the contralateral limb (both P < 0.0001). This was manifested by substantially smaller muscle volumes (112 versus 163 cm3), significantly shorter fascicles (11.0 versus 14.0 cm; P < 0.0001), and comparable sarcomere lengths (3.55 versus 3.59 µm; P = 0.6151) between limbs. Most notably, this study provides direct evidence of the loss of serial sarcomeres in human muscle observed in a population with neural impairments that lead to disuse and chronically place the affected muscle at a shortened position. This adaptation is consistent with functional consequences (increased passive resistance to elbow extension) that would amplify already problematic, neurally driven motor impairments.

Estimates of persistent inward currents are reduced in upper limb motor units of older adults.

Ageing is a natural process causing alterations in the neuromuscular system, which contributes to reduced quality of life. Motor unit (MU) contributes to weakness, but the mechanisms underlying reduced firing rates are unclear. Persistent inward currents (PICs) are crucial for initiation, gain control and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since concentrations of monoamines (i.e. serotonin and noradrenaline) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (ΔFrequency; or simply ΔF) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ∼1.6 pulses per second (pps) (P = 0.0292), and ΔF was reduced by ∼1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ∼1 pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in the upper limbs of older adults during submaximal isometric contractions. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and function in older individuals, but further work is required to understand the implications in other muscles and during a variety of motor tasks. KEY POINTS: Persistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. During ageing, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. Here we show that estimates of persistent inward currents (ΔF) of both elbow flexor and extensor motor units are reduced in older adults. Estimates of persistent inward currents have a negative relationship with age in the older adults, but not in the young. This novel mechanism may play a role in the alteration of motor firing rates that occurs with ageing, which may have consequences for motor control.

Limited capacity for ipsilateral secondary motor areas to support hand function post-stroke.

KEY POINTS: Ipsilateral-projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke-induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. ABSTRACT: Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post-stroke, although with no apparent capacity to support hand function.

Biomechanical parameters of the elbow stretch reflex in chronic hemiparetic stroke.

We sought to determine the relative velocity sensitivity of stretch reflex threshold angle and reflex stiffness during stretches of the paretic elbow joint in individuals with chronic hemiparetic stroke, and to provide guidelines to streamline spasticity assessments. We applied ramp-and-hold elbow extension perturbations ranging from 15 to 150°/s over the full range of motion in 13 individuals with hemiparesis. After accounting for the effects of passive mechanical resistance, we modeled velocity-dependent reflex threshold angle and torque-angle slope to determine their correlation with overall resistance to movement. Reflex stiffness exhibited substantially greater velocity sensitivity than threshold angle, accounting for ~ 74% (vs. ~ 15%) of the overall velocity-dependent increases in movement resistance. Reflex stiffness is a sensitive descriptor of the overall velocity-dependence of movement resistance in spasticity. Clinical spasticity assessments can be streamlined using torque-angle slope, a measure of reflex stiffness, as their primary outcome measure, particularly at stretch velocities greater than 100°/s.

The Biomechanical Basis of the Claw Finger Deformity: A Computational Simulation Study.

PURPOSE: Claw finger deformity occurs during attempted finger extension in patients whose intrinsic finger muscles are weakened or paralyzed by neural impairments. The deformity is generally not acutely present after intrinsic muscle palsy. The delayed onset, with severity progressing over time, suggests soft tissue changes that affect the passive biomechanics of the hand exacerbate and advance the deformity. Clinical interventions may be more effective if such secondary biomechanical changes are effectively addressed. Using a computational model, we simulated these altered soft tissue biomechanical properties to quantify their effects on coordinated finger extension. METHODS: To evaluate the effects of maladaptive changes in soft tissue biomechanical properties on the development and progression of the claw finger deformity after intrinsic muscle palsy, we completed 45 biomechanical simulations of cyclic index finger flexion and extension, varying the muscle excitation level, clinically relevant biomechanical factors, and wrist position. We evaluated to what extent (1) increased joint laxity, (2) decreased mechanical advantage of the extensors about the proximal interphalangeal joint, and (3) shortening of the flexor muscles contributed to the development of claw finger deformity in an intrinsic-minus hand model. RESULTS: Of the mechanisms studied, shortening (or contracture) of the extrinsic finger flexors was the factor most associated with the development of claw finger deformity in simulation. CONCLUSIONS: These simulations suggest that adaptive shortening of the extrinsic finger flexors is required for the development of claw finger deformity. Increased joint laxity and decreased extensor mechanical advantage only contributed to the severity of the deformity in simulations when shortening of the flexor muscles was present. CLINICAL RELEVANCE: In both the acute and chronic stages of intrinsic finger paralysis, maintaining extrinsic finger flexor length should be an area of focus in rehabilitation to prevent formation of the claw finger deformity and achieve optimal outcomes after surgical interventions.

Progressive recruitment of contralesional cortico-reticulospinal pathways drives motor impairment post stroke.

KEY POINTS: Activation of the shoulder abductor muscles in the arm opposite a unilateral brain injury causes involuntary increases in elbow, wrist and finger flexion in the same arm, a phenomenon referred to as the flexion synergy. It has been proposed that flexion synergy expression is related to reduced output from ipsilesional motor cortex and corticospinal pathways. In this human subjects study, we provide evidence that the magnitude of flexion synergy expression is instead related to a progressive, task-dependent recruitment of contralesional cortex. We also provide evidence that recruitment of contralesional cortex may induce excessive activation of ipsilateral reticulospinal descending motor pathways that cannot produce discrete movements, leading to flexion synergy expression. We interpret these findings as an adaptive strategy that preserves low-level motor control at the cost of fine motor control. ABSTRACT: A hallmark of hemiparetic stroke is the loss of fine motor control in the contralesional arm and hand and the constraint to a grouped movement pattern known as the flexion synergy. In the flexion synergy, increasing shoulder abductor activation drives progressive, involuntary increases in elbow, wrist and finger flexion. The neural mechanisms underlying this phenomenon remain unclear. Here, across 25 adults with moderate to severe hemiparesis following chronic stroke and 18 adults without neurological injury, we test the overall hypothesis that two inter-related mechanisms are necessary for flexion synergy expression: increased task-dependent activation of the intact, contralesional cortex and recruitment of contralesional motor pathways via ipsilateral reticulospinal projections. First, we imaged brain activation in real time during reaching motions progressively constrained by flexion synergy expression. Using this approach, we found that cortical activity indeed shifts towards the contralesional hemisphere in direct proportion to the degree of shoulder abduction loading in the contralesional arm. We then leveraged the post-stroke reemergence of a developmental brainstem reflex to show that anatomically diffuse reticulospinal motor pathways are active during synergy expression. We interpret this progressive recruitment of contralesional cortico-reticulospinal pathways as an adaptive strategy that preserves low-level motor control at the cost of fine motor control.

Unveiling neural coupling within the sensorimotor system: directionality and nonlinearity.

Neural coupling between the central nervous system and the periphery is essential for the neural control of movement. Corticomuscular coherence is a popular linear technique to assess synchronised oscillatory activity in the sensorimotor system. This oscillatory coupling originates from ascending somatosensory feedback and descending motor commands. However, corticomuscular coherence cannot separate this bidirectionality. Furthermore, the sensorimotor system is nonlinear, resulting in cross-frequency coupling. Cross-frequency oscillations cannot be assessed nor exploited by linear measures. Here, we emphasise the need of novel coupling measures, which provide directionality and acknowledge nonlinearity, to unveil neural coupling in the sensorimotor system. We highlight recent advances in the field and argue that assessing directionality and nonlinearity of neural coupling will break new ground in the study of the control of movement in healthy and neurologically impaired individuals.

Impact of motor task execution on an individual's ability to mirror forearm positions.

This work is motivated by our goal of determining why individuals with stroke are impaired when locating their arms in space. We assessed the ability of individuals without neurological impairments to mirror their forearms during various motor tasks so that we could identify baseline performance in an unimpaired population. Nine right-hand dominant participants without neurological impairments mirrored forearm positions bi-directionally (i.e., right forearm mirrors left forearm, vice versa) for three motor tasks (i.e., passive, passive/active, and active) and two position identification modes (i.e., mirroring to a position stored in working memory versus concurrently felt by the opposite arm). During each trial, the participant's reference forearm moved to a flexion ([Formula: see text]) or extension ([Formula: see text]) position, and then, their opposite forearm mirrored the position of their reference forearm. The main finding across all tested conditions is that participants mirrored forearm positions with an average magnitude of error [Formula: see text]. When controlling their forearms' movements (active motor task), participants mirrored forearm positions more accurately by up to, on average, [Formula: see text] at the flexion location than at the extension location. Moreover, participants mirrored forearm positions more accurately by up to, on average, [Formula: see text] when their forearms were moved for them rather than when they controlled their forearms' movements. Task directionality and position identification mode did not significantly affect participant arm mirroring accuracy. These findings are relevant for interpreting in future work the reason why impairments occur, on similar tasks, in individuals with altered motor commands, working memory, and arm impedance, e.g., post-stroke hemiparesis.

Quantification of task-dependent cortical activation evoked by robotic continuous wrist joint manipulation in chronic hemiparetic stroke.

BACKGROUND: Cortical damage after stroke can drastically impair sensory and motor function of the upper limb, affecting the execution of activities of daily living and quality of life. Motor impairment after stroke has been thoroughly studied, however sensory impairment and its relation to movement control has received less attention. Integrity of the somatosensory system is essential for feedback control of human movement, and compromised integrity due to stroke has been linked to sensory impairment. METHODS: The goal of this study is to assess the integrity of the somatosensory system in individuals with chronic hemiparetic stroke with different levels of sensory impairment, through a combination of robotic joint manipulation and high-density electroencephalogram (EEG). A robotic wrist manipulator applied continuous periodic disturbances to the affected limb, providing somatosensory (proprioceptive and tactile) stimulation while challenging task execution. The integrity of the somatosensory system was evaluated during passive and active tasks, defined as 'relaxed wrist' and 'maintaining 20% maximum wrist flexion', respectively. The evoked cortical responses in the EEG were quantified using the power in the averaged responses and their signal-to-noise ratio. RESULTS: Thirty individuals with chronic hemiparetic stroke and ten unimpaired individuals without stroke participated in this study. Participants with stroke were classified as having severe, mild, or no sensory impairment, based on the Erasmus modification of the Nottingham Sensory Assessment. Under passive conditions, wrist manipulation resulted in contralateral cortical responses in unimpaired and chronic stroke participants with mild and no sensory impairment. In participants with severe sensory impairment the cortical responses were strongly reduced in amplitude, which related to anatomical damage. Under active conditions, participants with mild sensory impairment showed reduced responses compared to the passive condition, whereas unimpaired and chronic stroke participants without sensory impairment did not show this reduction. CONCLUSIONS: Robotic continuous joint manipulation allows studying somatosensory cortical evoked responses during the execution of meaningful upper limb control tasks. Using such an approach it is possible to quantitatively assess the integrity of sensory pathways; in the context of movement control this provides additional information required to develop more effective neurorehabilitation therapies.

Robotic quantification of upper extremity loss of independent joint control or flexion synergy in individuals with hemiparetic stroke: a review of paradigms addressing the effects of shoulder abduction loading.

Unsupported or "against-gravity" reaching and hand opening movements are greatly impaired in individuals with hemiparetic stroke. The reduction in reaching excursion and hand opening is thought to be primarily limited by abnormal muscle co-activation of shoulder abductors with distal limb flexors, known as flexion synergy, that results in a loss of independent joint control or joint individuation. Our laboratory employs several methods for quantifying this movement impairment, however the most documented techniques are sophisticated and laboratory-based. Here a series of robotic methods that vary in complexity from comprehensive (laboratory-based) to focused (clinically relevant) are outlined in detail in order to facilitate translation and make recommendations for utilization across the translational spectrum as part of Journal of NeuroEngineering and Rehabilitation thematic series, "Technically-advanced assessments in sensory motor rehabilitation." While these methods focus on our published work utilizing the device, ACT3D, these methods can be duplicated using any mechatronic device with the appropriate characteristics. The common thread and most important aspect of the methods described is addressing the deleterious effects of abduction loading. Distal upper extremity joint performance is directly and monotonically modulated by proximal (shoulder abduction) joint demands. The employment of robotic metrics is the best tool for selectively manipulating shoulder abduction task requirements spanning the individual's full range of shoulder abduction strength. From the series of methods and the concluding recommendations, scientists and clinicians can determine the ideal robotic quantification method for the measurement of the impact of loss of independent joint control on reaching and hand function.

Mechanisms underlying chronic whiplash: contributions from an incomplete spinal cord injury?

OBJECTIVE: To explore the association between findings on advanced, but available, magnetic resonance imaging (MRI) sequences of the cervical spinal cord and muscular system, in tandem with biomechanical measures of maximum volitional plantar flexion torques as a proxy for a mild incomplete spinal cord injury. DESIGN: Observational case series. SETTING: University research laboratory. SUBJECTS: Three patients with chronic whiplash and one patient with history of whiplash injury but no current symptoms. METHODS: We measured lower extremity muscle fat, morphological changes in descending spinal cord pathways with advanced MRI applications and maximal activation of the plantar flexors. RESULTS: Larger magnitudes of lower extremity muscle fat corresponded to altered spinal cord anatomy and reductions in the ability to maximally activate plantar flexor torques in the three subjects with chronic whiplash. Such findings were not present in the recovered participant. CONCLUSIONS: The potential value of MRI to quantify neuromuscular degeneration in chronic whiplash is recognized. Larger scaled prospective studies are warranted before stronger conclusions can be drawn.

Peripheral nerve blocks of wrist and finger flexors can increase hand opening in chronic hemiparetic stroke.

Introduction: Hand opening is reduced by abnormal wrist and finger flexor activity in many individuals with stroke. This flexor activity also limits hand opening produced by functional electrical stimulation (FES) of finger and wrist extensor muscles. Recent advances in electrical nerve block technologies have the potential to mitigate this abnormal flexor behavior, but the actual impact of nerve block on hand opening in stroke has not yet been investigated. Methods: In this study, we applied the local anesthetic ropivacaine to the median and ulnar nerve to induce a complete motor block in 9 individuals with stroke and observed the impact of this block on hand opening as measured by hand pentagonal area. Volitional hand opening and FES-driven hand opening were measured, both while the arm was fully supported on a haptic table (Unloaded) and while lifting against gravity (Loaded). Linear mixed effect regression (LMER) modeling was used to determine the effect of Block. Results: The ropivacaine block allowed increased hand opening, both volitional and FES-driven, and for both unloaded and loaded conditions. Notably, only the FES-driven and Loaded condition's improvement in hand opening with the block was statistically significant. Hand opening in the FES and Loaded condition improved following nerve block by nearly 20%. Conclusion: Our results suggest that many individuals with stroke would see improved hand-opening with wrist and finger flexor activity curtailed by nerve block, especially when FES is used to drive the typically paretic finger and wrist extensor muscles. Such a nerve block (potentially produced by aforementioned emerging electrical nerve block technologies) could thus significantly address prior observed shortcomings of FES interventions for individuals with stroke.

Loss of independent limb control in childhood hemiparesis is related to time of brain injury onset.

This study investigated the presence of inter-limb activity at the elbow joint in individuals with childhood-onset hemiparesis, including spontaneous mirror movements during unilateral tasks and the ability to suppress them during bilateral tasks. Eighteen individuals with hemiparesis were divided into three categories of injury timing: before birth (PRE-natal), around the time of birth (PERI-natal), and after 6 months of age (POST-natal). Individuals with hemiparesis, as well as 12 typically developing peers, participated in unilateral and bilateral elbow flexion and extension tasks completed at maximal and submaximal effort while muscle activity was monitored and motor output was quantified by two multiple degrees-of-freedom load cells. Significantly, higher levels of paretic elbow flexion were found only in the PRE- and PERI-natal groups during the flexion of the non-paretic limb, which was modulated by effort level in both unilateral and bilateral tasks. The bilateral activation of elbow flexors in the PRE-/PERI-natal groups indicates potential use of a common cortical command source to drive both upper extremities, while the POST-natal/typically developing groups' flexors appear to receive input from different supraspinal structures.

Individuals with hemiparetic stroke abnormally perceive their elbow torques when abducting their paretic shoulder.

OBJECTIVE: Individuals with hemiparetic stroke exhibit an abnormal coupling between shoulder abduction and elbow flexion, or flexion synergy, due to an increased reliance on cortico-bulbospinal pathways. While this motor impairment is well documented, its impact on how movements are perceived remains unexplored. This study investigates whether individuals with hemiparetic stroke accurately perceive torques at their paretic elbow while abducting at their shoulder. METHODS: Ten individuals with hemiparetic stroke participated. We recorded the extent of their abnormal joint coupling as the torque at their elbow, with respect to the maximum voluntary torque in elbow flexion, when abducting at their shoulder. Next, we estimated the perception of their elbow torque by reporting their errors on our torque-matching task. RESULTS: When abducting at the shoulder, the participants with stroke generated a greater non-volitional torque at their paretic elbow (13.2 ± 8.7%) than their non-paretic elbow (1.2 ± 11.2%) (p = 0.003). Regarding the perception of our torque-matching task, participants overestimated their torques to a lesser extent at their paretic elbow (1.8 ± 6.6%) than at their non-paretic elbow (6.2 ± 5.4%) (p = 0.004). CONCLUSIONS: Torque perception at the paretic elbow differed from the non-paretic elbow when abducting at the shoulder. SIGNIFICANCE: This work advances our understanding of the i) somatosensory deficits occurring post hemiparetic stroke and ii) neural basis of torque perception.

A Method for Quantification of Stretch Reflex Excitability During Ballistic Reaching.

Stretch reflexes are crucial for performing accurate movements and providing rapid corrections for unpredictable perturbations. Stretch reflexes are modulated by supraspinal structures via corticofugal pathways. Neural activity in these structures is difficult to observe directly, but the characterization of reflex excitability during volitional movement can be used to study how these structures modulate reflexes and how neurological injuries impact this control, such as in spasticity after stroke. We have developed a novel protocol to quantify stretch reflex excitability during ballistic reaching. This novel method was implemented using a custom haptic device (NACT-3D) capable of applying high-velocity (270 °/s) joint perturbations in the plane of the arm while participants performed 3D reaching tasks in a large workspace. We assessed the protocol on four participants with chronic hemiparetic stroke and two control participants. Participants reached ballistically from a near to a far target, with elbow extension perturbations applied in random catch trials. Perturbations were applied before movement, during the early phase of movement, or near peak movement velocity. Preliminary results show that stretch reflexes were elicited in the stroke group in the biceps muscle during reaching, as measured by electromyographic (EMG) activity both before (pre-motion phase) and during (early motion phase) movement. Reflexive EMG was also seen in the anterior deltoid and pectoralis major in the pre-motion phase. In the control group, no reflexive EMG was seen, as expected. This newly developed methodology allows the study of stretch reflex modulation in new ways by combining multijoint movements with haptic environments and high-velocity perturbations.

Effect of Motor Task on Cortex Brainstem Modulation: Preliminary Results.

Reticulospinal Tracts (RSTs) have divergent connections to multiple spinal segments that innervate many upper extremity muscles. Therefore, increased RST engagement can often lead to muscle coactivation across multiple limb joints. The RST originates from the reticular formation (RF) and receives projections from the cortex. This provides the anatomical basis for cortex-brainstem modulation. Currently, we know little about how cortex modulates the RF to control RST engagement during motor preparation for various motor tasks, such as tasks involving proximal and distal upper limb joint coordination vs. a purely distal task. We hypothesize that since a simultaneous arm lifting and hand opening task (LIFTOPEN) requires more selective muscle recruitment than a hand opening task (OPEN), the cortex will suppress the RF to reduce the RST engagement at distal muscles during LIFTOPEN. To test this hypothesis, we investigated the startReact response in thirteen able-bodied participants performing the OPEN and LIFTOPEN tasks in response to a startling and non-startling acoustic stimulation. Our results showed that activation of distal muscles was significantly decreased, and the startle response was delayed in LIFTOPEN compared to OPEN. Both results suggest that the cortex suppressed RF and reduced the RST engagement in LIFTOPEN compared to OPEN.Clinical Relevance- Our results provide foundational knowledge of the task-specific nature of cortex-brainstem modulation. This scientific finding provides a base to compare how a unilateral brain injury may affect this cortex-brainstem modulation.

Characterization of Atypical Corticospinal Tract Microstructure and Hand Impairments in Early-Onset Hemiplegic Cerebral Palsy: Preliminary Findings.

Unilateral brain injuries occurring before at or shortly after full-term can result in hemiplegic cerebral palsy (HCP). HCP affects one side of the body and can be characterized in the hand with measures of weakness and a loss of independent hand control resulting in mirror movements. Hand impairment severity is extremely heterogeneous across individuals with HCP and the neural basis for this variability is unclear. We used diffusion MRI and tractography to investigate the relationship between structural morphology of the supraspinal corticospinal tract (CST) and the severity of two typical hand impairments experienced by individuals with HCP, grasp weakness and mirror movements. Results from nine children with HCP and eight children with typical development show that there is a significant hemispheric association between CST microstructure and hand impairment severity that may be explained by atypical development and fiber distribution of motor pathways. Further analysis in the non-lesioned (dominant) hemisphere shows significant differences for CST termination in the cortex between participants with HCP and those with typical development. These findings suggest that structural disparities at the cellular level in the seemingly unaffected hemisphere after early unilateral brain injury may be the cause of heterogeneous hand impairments seen in this population.Clinical Relevance- Quantitative measurement of the variability in hand function in individuals with HCP is necessary to represent the distinct impairments experienced by each person. Further understanding of the structural neural morphology underlying distal upper extremity motor deficits after early unilateral brain injury will help lead to the development of more specific targeted interventions that increase functional outcomes.

Motor unit firing rate modulation is more impaired during flexion synergy-driven contractions of the biceps brachii in chronic stroke.

Following a hemiparetic stroke, individuals exhibit altered motor unit firing patterns during voluntary muscle contractions, including impairments in firing rate modulation and recruitment. These individuals also exhibit abnormal muscle coactivation through multi-joint synergies (e.g., flexion synergy). Here, we investigate whether motor unit firing activity during flexion synergy-driven contractions of the paretic biceps brachii differs from that of voluntary contractions and use these differences to predict changes in descending motor commands. To accomplish this, we characterized motor unit firing patterns of the biceps brachii in individuals with chronic hemiparetic stroke during voluntary isometric elbow flexion contractions in the paretic and non-paretic limbs, as well as during contractions driven by voluntary effort and by flexion synergy expression in the paretic limb. We observed significant reductions in motor unit firing rate modulation from the non-paretic to paretic limb (non-paretic - paretic: 0.14 pps/%MVT, 95% CI: [0.09 0.19]) that were further reduced during synergy-driven contractions (voluntary paretic - synergy driven: 0.19 pps/%MVT, 95% CI: [0.14 0.25]). Moreover, using recently developed metrics, we evaluated how a stroke-induced reliance on indirect motor pathways alters the inputs that motor units receive and revealed progressive increases in neuromodulatory and inhibitory drive to the motor pool in the paretic limb, with the changes greatest during synergy-driven contractions. These findings suggest that an interplay between heightened neuromodulatory drive and alterations in inhibitory command structure may account for the observed motor unit impairments, further illuminating underlying neural mechanisms involved in the flexion synergy and its impact on motor unit firing patterns post-stroke.