Reticulospinal Tract Research Articles

An ANN models cortical-subcortical interaction during post-stroke recovery of finger dexterity.

Finger dexterity, and finger individuation in particular, is crucial for human movement, and disruptions due to brain injury can significantly impact quality of life. Understanding the neurological mechanisms responsible for recovery is vital for effective neurorehabilitation. This study explores the role of two key pathways in finger individuation: the corticospinal tract (CST) from the primary motor cortex and premotor areas, and the subcortical reticulospinal tract (RST) from the brainstem. We aimed to investigate how the cortical-reticular network reorganizes to aid recovery of finger dexterity following lesions in these areas. To provide a potential biologically plausible answer to this question, we developed an artificial neural network (ANN) to model the interaction between a premotor planning layer, a cortical layer with excitatory and inhibitory corticospinal outputs, and reticulospinal outputs controlling finger movements. The ANN was trained to simulate normal finger individuation and strength. A simulated stroke was then applied to the corticospinal (CS) area, reticulospinal (RS) area, or both, and the recovery of finger dexterity was analyzed. In the intact model, the ANN demonstrated a near-linear relationship between the forces of instructed and uninstructed fingers, resembling human individuation patterns. Post-stroke simulations revealed that lesions in both CS and RS regions led to increased unintended force in uninstructed fingers, immediate weakening of instructed fingers, improved control during early recovery, and increased neural plasticity. Lesions in the CS region alone significantly impaired individuation, while RS lesions affected strength and to a lesser extent, individuation. The model also predicted the impact of stroke severity on finger individuation, highlighting the combined effects of CS and RS lesions. This model provides insights into the interactive role of cortical and subcortical regions in finger individuation. It suggests that recovery mechanisms involve reorganization of these networks, which may inform neurorehabilitation strategies.

Heightened Reticulospinal Excitability after Severe Corticospinal Damage in Chronic Stroke.

After severe corticospinal tract damage poststroke in humans, some recovery of strength and movement proximally is evident. It is possible that alternate motor pathways, such as the reticulospinal tract, may be upregulated to compensate for the loss of corticospinal tract input. We investigated the extent of reticulospinal tract excitability modulation and its inter-dependence on the severity of corticospinal tract damage after stroke in humans. We used a novel startle conditioned transcranial magnetic stimulation paradigm to elicit ipsilateral motor evoked potentials, an index of reticulospinal tract excitability, in 22 chronic stroke participants with mild to severe corticospinal tract damage and 14 neurotypical age-matched controls. We found that ipsilateral motor evoked potential presence was higher in the paretic arm of people with severe corticospinal tract damage compared to their non-paretic arm, people with mild corticospinal tract damage, and age-matched controls. Interestingly, ipsilateral motor evoked potential presence was correlated with motor impairment across the entire stroke cohort, whereby individuals with worse impairment exhibited more frequent ipsilateral motor evoked potentials (ie, higher reticulospinal tract excitability). Following severe corticospinal tract damage, upregulated reticulospinal tract activity may compensate for a loss of corticospinal tract input, providing some proximal recovery of isolated and within-synergy movements, but deficits in performing out of synergy movements and finger fractionation remain. Interventions aimed at modulating the reticulospinal tract could be beneficial or detrimental to ameliorating motor impairment depending on the degree of reliance on this pathway for residual motor output. ANN NEUROL 2024.

Inducing ipsilateral motor-evoked potentials in the biceps brachii muscle in healthy humans.

To assess reticulospinal tract excitability, high-intensity transcranial magnetic stimulation (TMS) has been used to elicit ipsilateral motor-evoked potentials (iMEPs). However, there is no consensus on robust and valid methods for use in human studies. The present study proposes a standardized method for eliciting and analysing iMEPs in the biceps brachii. Twenty-four healthy young adults participated in this study. Electromyography (EMG) electrodes recorded contralateral MEPs (cMEPs) from the right and iMEPs from the left biceps brachii. A dynamic preacher curl task was used with ~15% of the subject's one-repetition maximum load. The protocol included maximal compound action potential (M-max) determination of the right biceps brachii muscle, TMS hotspot determination, and four sets of five repetitions where 100% stimulator output was delivered at an elbow angle of 110° of flexion. We normalized cMEP amplitude by M-max (% M-max) and iMEP by cMEP amplitude ratio (ICAR). Clear iMEPs above background EMG were observed in 21 subjects (88%, ICAR = .31 ± .19). Good-to-excellent agreement (intraclass correlation coefficient [ICC] = .795-1.000) and low bias (.01-.08 mV and .60-1.11 ms) were demonstrated when comparing two different analysis methods (i.e. fixed time-window vs. manual onset detection) to determine the cMEP and iMEP amplitude and latency, respectively. Most subjects demonstrated clear iMEPs above background EMG triggered at a pre-determined joint angle during a light-load dynamic preacher curl exercise. Similar results were obtained when comparing a single-trial manual identification of iMEP and a semi-automated time-window data analysis approach.

Tract-specific magnetization transfer ratio provides insights into the severity of degenerative cervical myelopathy.

Cross-sectional study. This study's goal is to report whether Magnetization Transfer Ratio (MTR) can evaluate the severity of white matter (WM) injury in degenerative cervical myelopathy (DCM). Laureate Institute of Brain Research, USA; Department of Neurosurgery, University of Oklahoma Health Sciences Center, USA. 27 DCM patients were aged-matched with 20 healthy controls (HC) and categorized into treatment groups based on modified Japanese Orthopedic Association (mJOA) severity (11 mild and 16 moderate/severe). Regional and tract MTRs were extracted from the two vertebral levels containing maximum compression within magnetization transfer images. MTR differences between groups were assessed using a one-way ANOVA or Kruskal-Wallis test. The association between MTR and mJOA measures was evaluated using Spearman's correlation. Significant decreases in MTR were found between HC and moderate/severe groups in the overall (p = 0.0065) and ventral (p = 0.0009) WM regions; and ventral corticospinal (p = 0.0101), ventral reticulospinal (p = 0.0084), spinal lemniscus (p = 0.0079), and fasciculus cuneatus (p = 0.0219) tracts. The spinal lemniscus MTR also significantly decreased between HC and mild groups (p = 0.038). Ventral reticulospinal tract MTR correlated with upper (r = 0.439; p = 0.022) and lower (r = 0.386; p = 0.047) limb motor mJOA scores. Significant tract-based MTR changes and correlations align with known DCM symptoms, are demonstrated to be lost at the regional level, and display the inhomogeneous compressive damage occurring within DCM spinal cords.

The Effects of the StartReact on Reaction Time, Rate of Force Development, and Muscle Activity in Biceps Brachii

ABSTRACTThe StartReact test, increasingly popular for assessing cortico‐reticular functioning, is a valid method to influence the firing of reticulospinal tract neurons noninvasively. However, there remains limited evidence on how different stimuli employed in the StartReact test impact motor output in humans. The present study tested elbow flexor responses of 33 adults (aged 26–48 years) to visual stimuli only (LED light), audio‐visual (80 dB) stimuli, and startle‐inducing audio‐visual (120 dB) stimuli sitting with the arm supinated in an electromechanical dynamometer. Surface electromyogram (EMG) recorded muscle activity from the right biceps brachii muscle. Participants were presented with 20 stimuli for each of the three conditions in pseudorandom order with interstimulus intervals of ~8 s. Reaction times were calculated from the stimulus trigger to the initial rise in the EMG signal above 7 × SD from baseline. Rate of torque development (RTD) and EMG signals were recorded throughout and analyzed over their initial 50 ms and 100 ms time‐windows. Reaction times were reduced from visual (169 ± 23) to audio‐visual (140 ± 23) and further reduced to startle‐inducing audio‐visual stimuli (108 ± 19, p < 0.001). While RTD and EMG were consistently greatest following startle‐inducing stimuli (p < 0.001), they were also enhanced following all audio‐visual stimuli over 100 ms (p < 0.05). It appears that startle‐inducing audio‐visual stimuli result in shorter reaction times, increased RTD, and enhanced muscle activity within the initial 50 ms, likely from subcortical upregulation. However, the 100 ms time‐window suggests cortical upregulation following all audio‐visual stimuli considering the longer transmission times.

Evidence of the existence of multiple modules for the stroke-caused flexion synergy from Fugl-Meyer assessment scores.

Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.NEW & NOTEWORTHY We demonstrate that abnormal synergies are still selectively excited depending on the context.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis–nucleus accumbens deep brain stimulation for treatment-resistant depression

BackgroundStructural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of...

Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Contribution of changes in the spinal cord and brain to the onset and progression of hand clumsiness symptoms in cervical spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) stands as the most prevalent form of spinal cord injury, frequently prompting various changes in both the brain and spinal cord. However, the precise nature of these changes within the brains and spinal cords of CSM patients experiencing hand clumsiness (HCL) symptoms has remained elusive. The authors aimed to scrutinize these alterations and explore potential links between these changes and the onset of HCL symptoms. Using the modified Japanese Orthopaedic Association (mJOA) scale, the authors classified CSM patients into two groups: those without HCL and those with HCL. The authors performed voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (FC) evaluations in the brain. Additionally, they used the Spinal Cord Toolbox to calculate the fractional anisotropy (FA) of spinal cord tracts. The analysis also encompassed an examination of the correlation of these measures with improvements in mJOA scores. Significant disparities in zALFF values surfaced in the right calcarine, right cuneus, right precuneus, right middle occipital gyrus (MOG), right superior occipital gyrus (SOG), and right superior parietal gyrus (SPG) between healthy controls (HC), patients without HCL, and patients with HCL, primarily within the visual cortex. In the patient group, patients with HCL displayed reduced FC between the right calcarine, right MOG, right SOG, right SPG, right SFG, bilateral MFG, and left median cingulate and paracingulate gyri when compared with patients without HCL. Moreover, significant differences in FA values of the corticospinal tract (CST) and reticulospinal tract (REST) at the C2 level emerged among HC, patients without HCL, and patients with HCL. Notably, zALFF, FC, and FA values in specific brain regions and spinal cord tracts exhibited correlations with mJOA upper-extremity scores. Additionally, FA values of the CST and REST correlated with zALFF values in the right calcarine, right MOG, right SOG, and right SPG. Alterations within brain regions associated with the visual cortex, the fronto-parietal-occipital attention network, and spinal cord pathways appear to play a substantial role in the emergence and progression of HCL symptoms. Furthermore, the existence of a potential connection between the spinal cord and the brain suggests that this link might be related to the clinical symptoms of CSM.

Age-related changes in reticulospinal contributions to anticipatory postural adjustments between back extensors and abdominal muscles.

Anticipatory postural adjustments (APAs) give feedforward postural control of the trunk, but they are delayed with ageing, affecting balance and mobility in older individuals. The reticulospinal tract contributes to postural control of the trunk; however, the extent to which age-related changes affect the reticulospinal contributions to APAs of the trunk remains unknown in humans. Here, we tested the hypothesis that a startling acoustic sound, which activates the reticulospinal tract, improves delayed APAs in older individuals. Twenty-two old (75±6years) and 20 healthy young adults (21±4years) performed a self-initiated fast bilateral shoulder flexion or shoulder extension task in response to visual, visual and auditory (80dB), or visual and startling (115dB) cues. Electromyography (EMG) was recorded from bilateral anterior deltoid (AD) and erector spinae (ES) during shoulder flexion and from bilateral posterior deltoid (PD) and rectus abdominis (RA) during shoulder extension. EMG onset of all muscles shortened during the startling cue in both age groups, suggesting a non-specific modulation of the reticulospinal tract on prime movers (AD or PD) and non-prime movers (ES or RA). Interestingly, APAs of the ES were accelerated in older participants to a similar degree as in younger participants during the startling cue. Conversely, APAs of the RA were not influenced by the startling cue in older participants. Our results suggest differential effects of ageing on functional contributions of the reticulospinal tract to APAs between back extensors and abdominal muscles.

245 Linking Cervical Spinal Cord White Matter Magnetization Transfer Ratio to NIH Toolbox Based Analyses of Motor Function in Degenerative Cervical Myelopathy

INTRODUCTION: Traditional spine imaging technique present disparity between degenerative cervical myelopathy (DCM) disease severity and prognosis. Advancement in spine neuroimaging has unveiled key changes that enhance our understanding of DCM pathogenesis. We investigated region- and tract-specific SC white matter (WM) damage and their relationship to motor deficit in DCM. METHODS: A cohort of 20 DCM and 23 age-matched HC participants were recruited in a cross-sectional study. We utilized a consensus MT-imaging protocol, Spinal cord Toolbox, and objective motor assessment tool battery to assess the extent of WM injury and functional deficits in DCM. The SC WM region- and tract-based MTR were calculated in three different ROIs: maximum compressed level (MCL), caudal uncompressed level (C7), and central region of compression. RESULTS: DCM patients demonstrated significant functional deficits compared to HC in motor assessments. DCM exhibited reduced MTR measures denoting WM injury in the anterior region of the SC and within selected motor tracts in the ROIs. MTR values in reticulospinal, vestibulospinal, and lateral corticospinal tracts were significantly associated with dexterity and grip strength measures. CONCLUSIONS: Our methodology enables precise mapping of ROIs within the SC allowing us to demonstrate an association between tract-specific WM damage and functional motor deficits in DCM patients. Additionally, the observation of decreased MTR measures in seemingly uncompressed SC regions indicates the pathophysiology of DCM that may provide insight into the varying presentations of DCM. Identification of specific WM injury may help better understand DCM deficits that can be targeted for effective interventions to improve patient outcomes

Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

Evaluation of the structural integrity of different spinal cord tracts with magnetization transfer ratio in degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM. Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients' clinical disability rate were also evaluated. A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord (R = 0.38, adjusted p < 0.05) and the ventral spinocerebellar tract (R = 0.41, adjusted p < 0.05) were revealed. The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition.

Strength-trained adults demonstrate greater corticoreticular activation versus untrained controls.

The rapid increase in strength following strength-training involves neural adaptations, however, their specific localisation remains elusive. Prior focus on corticospinal responses prompts this study to explore the understudied cortical/subcortical adaptations, particularly cortico-reticulospinal tract responses, comparing healthy strength-trained adults to untrained peers. Fifteen chronically strength-trained individuals (≥2 years of training, mean age: 24 ± 7 years) were compared with 11 age-matched untrained participants (mean age: 26 ± 8 years). Assessments included maximal voluntary force (MVF), corticospinal excitability using transcranial magnetic stimulation (TMS), spinal excitability (cervicomedullary stimulation), voluntary activation (VA) and reticulospinal tract (RST) excitability, utilizing StartReact responses and ipsilateral motor-evoked potentials (iMEPs) for the flexor carpi radialis muscle. Trained participants had higher normalized MVF (6.4 ± 1.1 N/kg) than the untrained participants (4.8 ± 1.3 N/kg) (p = .003). Intracortical facilitation was higher in the strength-trained group (156 ± 49%) (p = .02), along with greater VA (98 ± 3.2%) (p = .002). The strength-trained group displayed reduced short-interval-intracortical inhibition (88 ± 8.0%) compared with the untrained group (69 ± 17.5%) (p < .001). Strength-trained individuals exhibited a greater normalized rate of force development (38.8 ± 10.1 N·s-1/kg) (p < .009), greater reticulospinal gain (2.5 ± 1.4) (p = .02) and higher ipsilateral-to-contralateral MEP ratios compared with the untrained group (p = .03). Strength-trained individuals displayed greater excitability within the intrinsic connections of the primary motor cortex and the RST. These results suggest greater synaptic input from the descending cortico-reticulospinal tract to α-motoneurons in strength-trained individuals, thereby contributing to the observed increase in VA and MVF.

Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Moving toward elucidating alternative motor pathway structures post-stroke: the value of spinal cord neuroimaging.

Stroke results in varying levels of motor and sensory disability that have been linked to the neurodegeneration and neuroinflammation that occur in the infarct and peri-infarct regions within the brain. Specifically, previous research has identified a key role of the corticospinal tract in motor dysfunction and motor recovery post-stroke. Of note, neuroimaging studies have utilized magnetic resonance imaging (MRI) of the brain to describe the timeline of neurodegeneration of the corticospinal tract in tandem with motor function following a stroke. However, research has suggested that alternate motor pathways may also underlie disease progression and the degree of functional recovery post-stroke. Here, we assert that expanding neuroimaging techniques beyond the brain could expand our knowledge of alternate motor pathway structure post-stroke. In the present work, we will highlight findings that suggest that alternate motor pathways contribute to post-stroke motor dysfunction and recovery, such as the reticulospinal and rubrospinal tract. Then we review imaging and electrophysiological techniques that evaluate alternate motor pathways in populations of stroke and other neurodegenerative disorders. We will then outline and describe spinal cord neuroimaging techniques being used in other neurodegenerative disorders that may provide insight into alternate motor pathways post-stroke.

Identifying spinal tracts transmitting distant effects of trans-spinal magnetic stimulation.

Estimating the state of tract-specific inputs to spinal motoneurons is critical to understand movement deficits induced by neurological injury and potential pathways to recovery, but remains challenging in humans. In this study we explored the capability of trans-spinal magnetic stimulation (TSMS) to modulate distal reflex circuits in young adults. TSMS was applied over thoracic spine to condition soleus H-reflexes involving sacral-level motoneurons. Three TSMS intensities below motor threshold were applied at inter-stimulus intervals (ISIs) between 2-20 ms relative to peripheral nerve stimulation (PNS). While low intensity TSMS yielded no changes in H-reflexes across ISIs, the two higher stimulus intensities yielded two phases of H-reflex inhibition: a relatively long-lasting period at 2-9 ms ISIs, and a short phase at 11-12 ms ISIs. H-reflex inhibition at 2 ms ISI was uniquely dependent on TSMS intensity. To identify the candidate neural pathways contributing to H-reflex suppression, we constructed a tract-specific conduction time estimation model. Based upon our model, H-reflex inhibition at 11-12 ms ISIs is likely a manifestation of orthodromic transmission along the lateral reticulospinal tract. In contrast, the inhibition at 2 ms ISI likely reflects orthodromic transmission along sensory fibers with activation reaching brain, before descending along motor tracts. Multiple pathways may contribute to H-reflex modulation between 4-9 ms ISIs, orthodromic transmission along sensorimotor tracts and antidromic transmission of multiple motor tracts. Our findings suggest that non-invasive TSMS can influence motoneuron excitability at distal segments and that the contribution of specific tracts to motoneuron excitability may be distinguishable based upon conduction velocities.

Mapping subcortical motor pathways in humans with startle-conditioned TMS

Subcortical motor pathways, such as the reticulospinal tract, are critical for producing and modulating voluntary movements and have been implicated in neurological conditions. Previous research has described the presence of ipsilateral motor evoked potentials (iMEPs) in the arm to transcranial magentic stimulation (TMS), and suggested they could be mediated by the uncrossed corticospinal tract or by ipsilateral cortico-reticulospinal connections. Here, we sought to elucidate the role of the reticulospinal tract in mediating iMEPs by assessing their modulation by a startling acoustic stimulus and mapping these responses across multiple upper limb effectors. In a first experiment, we delivered TMS at various intervals (1, 5, 10 and 15 ms) after a startling acoustic stimulus, known to excite the reticular formation, to elicit iMEPs in the arm. We observed robust facilitation of iMEP area when startle conditioning preceded TMS at the 10 ms interval. In a second experiment, we replicated our findings showing that both the area and number of iMEPs in the arm increases with startle conditioning. Using this technique, we observed that iMEPs are more prominent in the arm compared with the hand. In a third experiment, we also observed greater presence of iMEPs in flexor compared with extensor muscles. Together, these findings are consistent with properties of the reticulospinal tract observed in animals, suggesting that iMEPs primarily reflect reticulospinal activity. Our findings imply that we can use this approach to track modulation of cortico-reticulospinal excitability following interventions or neurological conditions where the reticulospinal tract may be involved in motor recovery.

Identifying the role of the reticulospinal tract for strength and motor recovery: A scoping review of nonhuman and human studies.

In addition to the established postural control role of the reticulospinal tract (RST), there has been an increasing interest on its involvement in strength, motor recovery, and other gross motor functions. However, there are no reviews that have systematically assessed the overall motor function of the RST. Therefore, we aimed to determine the role of the RST underpinning motor function and recovery. We performed a literature search using Ovid Medline, Embase, CINAHL Plus, and Scopus to retrieve papers using key words for RST, strength, and motor recovery. Human and animal studies which assessed the role of RST were included. Studies were screened and 32 eligible studies were included for the final analysis. Of these, 21 of them were human studies while the remaining were on monkeys and rats. Seven experimental animal studies and four human studies provided evidence for the involvement of the RST in motor recovery, while two experimental animal studies and eight human studies provided evidence for strength gain. The RST influenced gross motor function in two experimental animal studies and five human studies. Overall, the RST has an important role for motor recovery, gross motor function and at least in part, underpins strength gain. The role of RST for strength gain in healthy people and its involvement in spasticity in a clinical population has been limitedly described. Further studies are required to ascertain the role of the RST's role in enhancing strength and its contribution to the development of spasticity.

Neural Substrates of Mobility and Postural Impairments in People with Multiple Sclerosis

Background & Purpose Damage to the central nervous system is a primary corollary of multiple sclerosis (MS) and commonly results in mobility and balance impairments, placing people with MS at greater risk for experiencing a fall, thereby decreasing independence and quality of life. To date, research has largely focused on the role of the corticospinal tract in mobility and balance impairments seen in people with MS. However, evidence from lesion studies in animals suggests that the reticulospinal tract (RST), a bilateral motor neuron pathway originating in the brainstem, is critical for gross motor movements such as posture and locomotion. Methods We collected behavioral data in the form of the Mini-Balance Evaluation Systems Test from 25 MS and 25 neurotypical participants to assess gait and mobility. We then used transcranial magnetic stimulation and electromyography recordings from the tibialis anterior on both legs to assess neural communication via the RST. Lastly, we used diffusion tensor imaging as an anatomic measure of neural structure to determine if there are white matter differences in the RST. Results To date our analysis has only been performed on the behavioral data, showing that people with MS score lower on all sections of the Mini-Balance Evaluation Systems Test. By the time of this conference, we will have preliminary evidence from both of our other measures to share. Discussion Recent literature suggests that acute neural adaptations to resistance training may be mediated by the RST. Several studies have found that resistance training in people with MS increases muscle strength and functional capacity. However, the underlying neural adaptions have yet to be fully determined. Our results will highlight the RST as a key contributor to mobility deficits in people with MS and suggest that stimulation of the RST such as with resistance training could promote better balance and mobility. Damage to the central nervous system is a primary corollary of multiple sclerosis (MS) and commonly results in mobility and balance impairments, placing people with MS at greater risk for experiencing a fall, thereby decreasing independence and quality of life. To date, research has largely focused on the role of the corticospinal tract in mobility and balance impairments seen in people with MS. However, evidence from lesion studies in animals suggests that the reticulospinal tract (RST), a bilateral motor neuron pathway originating in the brainstem, is critical for gross motor movements such as posture and locomotion. We collected behavioral data in the form of the Mini-Balance Evaluation Systems Test from 25 MS and 25 neurotypical participants to assess gait and mobility. We then used transcranial magnetic stimulation and electromyography recordings from the tibialis anterior on both legs to assess neural communication via the RST. Lastly, we used diffusion tensor imaging as an anatomic measure of neural structure to determine if there are white matter differences in the RST. To date our analysis has only been performed on the behavioral data, showing that people with MS score lower on all sections of the Mini-Balance Evaluation Systems Test. By the time of this conference, we will have preliminary evidence from both of our other measures to share. Recent literature suggests that acute neural adaptations to resistance training may be mediated by the RST. Several studies have found that resistance training in people with MS increases muscle strength and functional capacity. However, the underlying neural adaptions have yet to be fully determined. Our results will highlight the RST as a key contributor to mobility deficits in people with MS and suggest that stimulation of the RST such as with resistance training could promote better balance and mobility.