Sensorimotor Dysfunction Research Articles

Exploring temporal congruence in motor imagery and movement execution in non-specific chronic low back pain

Chronic non-specific low back pain (NSCLBP) is linked to sensorimotor dysfunctions and altered motor planning, likely due to neuroplastic changes. Motor imagery (MI) and movement execution share neural pathways, but the relationship between imagined and executed movements in NSCLBP patients remains underexplored. This study aimed to assess the temporal congruence between imagined and executed movements in NSCLBP sufferers, with secondary goals of investigating group differences in movement chronometry, psychological well-being, and disability, as well as possible correlations among these factors. Fifty-six participants, including 28 NSCLBP patients and 28 asymptomatic subjects (AS), performed lumbar flexion and Timed Up and Go (TUG) tasks. NSCLBP patients showed significant temporal incongruence in both tasks, executing movements more slowly than imagined, whereas AS displayed incongruence only in the TUG task. NSCLBP patients also took longer to imagine and execute lumbar flexion movements compared to AS, with correlations observed between execution delays, higher disability, and greater fear of movement. The findings highlight a lack of temporal congruence in NSCLBP patients, especially in lumbar flexion, emphasizing the complex relationship between chronic pain, motor ability, and psychological factors. These results suggest that integrated treatment approaches addressing cognitive and emotional aspects are crucial for managing NSCLBP.

Known-Group Validity and Sensitivity to Change in the Sensory-Motor Dysfunction Questionnaire in Individuals with Neck Pain: A Pilot Study

Background/Objectives: Sensorimotor dysfunction is often reported in individuals experiencing neck pain, irrespective of severity and chronicity. The treatment of neck dysfunction has been found to positively impact sensorimotor integration (SMI), thereby improving sensorimotor function. However, no patient-reported outcome measure has been validated for discrimination between healthy individuals and neck pain patients with disordered SMI, nor has there been documentation of positive change in SMI following neck pain treatment.The purpose of this study was to administer the Sensory-Motor Dysfunction Questionnaire (SMD-Q), for the purposes of: (1) known-group validity between individuals without and with chronic neck pain (CNP) or subclinical neck pain (SCNP); (2) assess the questionnaire’s capacity to quantify changes in altered SMI following a tailored treatment plan. Methods: Part 1—Known Group Validity: The SMD-Q was administered to 30 neck pain (13 with CNP, and 17 with SCNP), and 30 healthy participants. Part 2—Sensitivity to Change: The SMD-Q was re-administered to neck pain participants following their tailored treatment plans (SCNP—8-weeks and CNP—12 weeks). Results: The SMD-Q can discriminate between healthy and neck pain participants (p ≤ 0.001), and may be sensitive to showing treatment effects (ηp2 = 0.162; large effect size (ES)), but the sample size was too small to determine if it can discriminate treatment effects between groups (ηp2 = 0.070; medium ES). Conclusions: Differing degrees of disordered SMI can be discriminated by the SMD-Q, but further research is needed to determine its sensitivity to treatment.

Cross-Cultural Adaptation, Reliability, and Validity of the Greek Version of the Fremantle Neck Awareness Questionnaire (FreNAQ-GR) in Patients with Chronic Neck Pain

Background: Neck self-awareness, related to sensorimotor dysfunction, can be monitored with the Fremantle Neck Awareness Questionnaire (FreNAQ). The cross-cultural adaptation of the FreNAQ in Greek (FreNAQ-GR) and an assessment of its psychometric properties were conducted. Methods: This study included 104 participants (65 female) with non-specific chronic neck pain (NSCNP). Once the cross-cultural adaptation process of the FreNAQ-GR was complete, the testing of its construct validity was conducted via an exploratory factor analysis (EFA). The construct validity examination also included a correlational analysis with a Pain Intensity Visual Analogue Scale (PI-VAS), the Neck Disability Index (NDI), the Tampa Scale of Kinesiophobia (TSK), the Pain Catastrophizing Scale (PCS), and demographics. The internal consistency of the FreNAQ-GR was also examined. A sub-sample of participants (n = 30) completed the FreNAQ-GR again after 5–7 days. Results: The dataset was appropriate for EFA (measure of sampling adequacy KMO = 0.763 and Bartlett’s test of sphericity p < 0.001). The FreNAQ-GR demonstrated a single-factor 6-item structure (items 7–9 removed), explaining 53.69% of the common variance. Statistically significant correlations (Spearman’s) were registered between the FreNAQ-GR (both versions) and the NDI (r = 0.33/0.29, p < 0.001), the TSK (r = 0.46/0.41, p < 0.001), and the PCS (r = 0.37/0.33, p < 0.001). For the 9-item and the 6-item FreNAQ-GR, the internal consistency (Chronbach’s a/McDonald’s ω) was 0.80/0.79 and 0.826/0.816, respectively. The test–retest reliability was excellent for both versions ICC2,1 (95% CI) = 0.98/0.98 (0.97–0.99/0.95–0.99), with low error values SEM = 0.90/0.74 and MDC95% = 2.49/2.05 points. Conclusions: The FreNAQ-GR is suitable for assessing neck self-awareness in Greek-speaking patients with NSCNP.

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

Dynamic Functional Network Connectivity in Acute Incomplete Cervical Cord Injury Patients and Its Associations With Sensorimotor Dysfunction Measures

BackgroundDynamic functional network connectivity (dFNC) captures temporal variations in functional connectivity during MRI acquisition. However, the neural mechanisms driving dFNC alterations in the brain networks of patients with Acute incomplete cervical cord injury (AICCI) remain unclear. MethodsThis study included 16 AICCI patients and 16 healthy controls (HC). Initially, Independent Component Analysis (ICA) was employed to extract whole-brain independent components (ICs) from resting-state functional MRI (rs-fMRI) data. Subsequently, a sliding time window approach, combined with k-means clustering, was used to estimate dFNC states for each participant. Finally, a correlation analysis was conducted to examine the association between sensorimotor dysfunction scores in AICCI patients and the temporal characteristics of dFNC. ResultICA was employed to extract 26 whole-brain ICs. Subsequent dynamic analysis identified four distinct connectivity states across the entire cohort. Notably, AICCI patients demonstrated a significant preference for State 3 compared to HC, as evidenced by a higher frequency and longer duration spent in this state. Conversely, State 4 exhibited a reduced frequency and shorter dwell time in AICCI patients. Moreover, correlation analysis revealed a positive association between sensorimotor dysfunction and both the mean dwell time and the fractional of time spent in State 3. ConclusionsPatients with AICCI demonstrate abnormal connectivity within dFNC states, and the temporal characteristics of dFNC are associated with sensorimotor dysfunction scores. These findings highlight the potential of dFNC as a sensitive biomarker for detecting network functional changes in AICCI patients, providing valuable insights into the dynamic alterations in brain connectivity related to sensorimotor dysfunction in this population.

Verifying the Efficacy of a Tactile Perceptual Discrimination Stimulation Approach for Individuals with Finger Sensorimotor Dysfunction: A Case Report and Literature Review

Verifying the Efficacy of a Tactile Perceptual Discrimination Stimulation Approach for Individuals with Finger Sensorimotor Dysfunction: A Case Report and Literature Review

Exploration of the complex origins of primary constipation

Constipation is a common gastrointestinal disorder characterized by infrequent bowel movements and difficulty in passing stools. It can significantly affect an individual's quality of life and overall well-being. Understanding the causes of constipation is important for its effective management and treatment. In this paper, we have reviewed the primary causes of constipation or functional constipation. Primary constipation is a bowel disorder associated with colonic or anorectal sensorimotor or neuromuscular dysfunction. As per the literature, it is multifactorial and involves factors such as decreased interstitial cells of Cajal, altered colonic motility, enteric nervous system dysfunction, intestinal flora disturbances, and psychological influences. Clinical symptoms include difficulty in defecation, decreased frequency of defecation, or a feeling of incomplete evacuation. A comprehensive evaluation and management of constipation require an interdisciplinary approach incorporating dietary modifications, lifestyle changes, pharmacotherapy, and psychological interventions. Further research is imperative to explain the intricate mechanisms underlying constipation and develop targeted therapies for improved patient outcomes.

Differential efficacy of modified enriched environment on motor, emotion, and cognition in cortical ischemic mice.

A modified enriched environment (mEE) with 12 h per night was recently proposed and exhibited cognitive improvement. The present study aimed to evaluate the effects of different courses of mEE on different deficits in ischemic mice. Mice were subjected to photothrombotic stroke at the left sensorimotor cortex and then randomly assigned to standard environment or mEE for 7 d (St-PE) or 28d (Ct-PE) on the third day post-stroke. Neurological deficits and sensorimotor, emotional, and cognitive performances were assessed at the 10th, 17th, and 31st days post-stroke. Our results demonstrated that Ct-PE ameliorated neurological deficits, forelimb using asymmetry, and reduced slip rates of the affected limbs at all time points, while this effect of St-PE was observed only on the 10th day. Similarly, Ct-PE for 28d promoted spatial learning and working memory, but St-PE did not. Differently, ischemic mice in both St-PE and Ct-PE groups exhibited increased exploration behavior in the open field, light-dark box and elevated plus maze, and less immobile behavior during the tail suspension at all the time points. Our findings indicated that Ct-PE improved sensorimotor and cognitive dysfunctions after cortical ischemia in a time-dependent manner, but St-PE appeared to have greater therapeutic potential on anxiety and depression.

The role of spinal cord neuroanatomy in the variances of epidural spinal recordings

BackgroundSpinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone.MethodTwo electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs.ResultsReconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an ‘off-disc’ stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds.ConclusionThe results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Brain and cervical spinal cord MRI correlates of sensorimotor impairment in patients with multiple sclerosis.

Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration. To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS. One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment. Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879-0.900), VDT (R2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT. cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS.

Development of the Sensory-Motor Dysfunction Questionnaire and Pilot Reliability Testing.

Both chronic and recurrent spinal pain alter sensorimotor integration (SMI), which is demonstrated using complex neurophysiological techniques. Currently, there is no patient-reported outcome measure that documents and/or assesses SMI in populations with spinal problems. The purpose of this study was to develop the Sensory-Motor Dysfunction Questionnaire (SMD-Q) and assess its test-retest reliability and internal consistency in individuals with recurrent spinal pain. The SMD-Q was developed based on the existing literature on motor control disturbances associated with disordered SMI. The initial SMD-Q drafts underwent review by two separate panels of subject matter experts and a focus group with subclinical spine pain. Their suggestions were incorporated into the questionnaire prior to reliability testing. The questionnaire was administered twice at a seven-day interval using QualtricsTM. A total of 20 participants (14 females and 6 males; 20.95 ± 2.46 years of age) completed the study. Quadratic weighted kappa (Kw) was used to assess test-retest reliability and Cronbach's alpha (α) was used to assess internal consistency. Four items had a Kw < 0.40, seven had a 0.40 < Kw < 0.75, and one had a Kw > 0.75 (excellent agreement), with excellent internal consistency (α > 0.90). The pilot SMD-Q appears to reliably measure altered SMI, suggesting that revisions and testing with a larger sample are worth pursuing.

Evidence from comprehensive independent validation studies for smooth pursuit dysfunction as a sensorimotor biomarker for psychosis

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis. Balanced accuracies of 64% for the prediction of psychosis status are in line with recent results from other large heterogenous psychiatric samples. They are confirmed by external validation in independent large samples including probands with (1) psychosis (N = 727) versus healthy controls (N = 292), (2) psychotic (N = 49) and non-psychotic bipolar disorder (N = 36), and (3) non-psychotic affective disorders (N = 119) and psychosis (N = 51) yielding accuracies of 65%, 66% and 58%, respectively, albeit slightly different psychosis syndromes. Our findings make a significant contribution to the identification of biologically defined profiles of heterogeneous psychosis syndromes on an individual level underlining the impact of sensorimotor dysfunction in psychosis.

Alterations in cortical thickness and volumes of subcortical structures in pediatric patients with complete spinal cord injury.

To study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of dysfunction beyond sensory motor dysfunction after CSCI, and provide a possible neural basis for corresponding functional intervention training. Thirty-seven pediatric CSCI patients and 34 age-, gender-matched healthy children as healthy controls (HCs) were recruited. The 3D high-resolution T1-weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Statistical differences between pediatric CSCI patients and HCs in cortical thickness and volumes of subcortical gray matter structures were evaluated. Then, correlation analyses were performed to analyze the correlation between the imaging indicators and clinical characteristics. Compared with HCs, pediatric CSCI patients showed decreased cortical thickness in the right precentral gyrus, superior temporal gyrus, and posterior segment of the lateral sulcus, while increased cortical thickness in the right lingual gyrus and inferior occipital gyrus. The volume of the right thalamus in pediatric CSCI patients was significantly smaller than that in HCs. No significant correlation was found between the imaging indicators and the injury duration, sensory scores, and motor scores of pediatric CSCI patients. These findings demonstrated that the brain structural reorganizations of pediatric CSCI occurred not only in sensory motor areas but also in cognitive and visual related brain regions, which may suggest that the visual processing, cognitive abnormalities, and related early intervention therapy also deserve greater attention beyond sensory motor rehabilitation training in pediatric CSCI patients.

Meal effects on gastric bioelectrical activity utilizing body surface gastric mapping in healthy subjects.

Gastric sensorimotor disorders are prevalent. While gastric emptying measurements are commonly used, they may not fully capture the underlying pathophysiology. Body surface gastric mapping (BSGM) recently emerged to assess gastric sensorimotor dysfunction. This study assessed varying meal size on BSGM responses to inform test use in a wider variety of contexts. Data from multiple healthy cohorts receiving BSGM were pooled, using four different test meals. A standard BSGM protocol was employed: 30-min fasting, 4-h post-prandial, using Gastric Alimetry® (Alimetry, New Zealand). Meals comprised: (i) nutrient drink + oatmeal bar (482 kcal; 'standard meal'); (ii) oatmeal bar alone; egg and toast meal, and pancake (all ~250 kcal). Gastric Alimetry metrics included BMI-adjusted Amplitude, Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI) and Fed:Fasted Amplitude Ratio (ff-AR). 238 participants (59.2% female) were included. All meals significantly increased amplitude and frequency during the first postprandial hour (p < 0.05). There were no differences in postprandial frequency across meals (p > 0.05). The amplitude and GA-RI of the standard meal (n = 110) were significantly higher than the energy bar alone (n = 45) and egg meal (n = 65) (all p < 0.05). All BSGM metrics were comparable across the three smaller meals (p > 0.05). A higher symptom burden was found in the oatmeal bar group versus the standard meal and pancake meal (p = 0.01, 0.003, respectively). The consumption of lower calorie meals elicited different postprandial responses, when compared to the standard Gastric Alimetry meal. These data will guide interpretations of BSGM when applied with lower calorie meals.

Musculoskeletal mimics of lumbosacral radiculopathy.

Electrodiagnostic evaluations are commonly requested for patients with suspected radiculopathy. Understanding lower extremity musculoskeletal conditions is essential for electrodiagnostic medicine specialists, as musculoskeletal disorders often mimic or coexist with radiculopathy. This review delineates radicular pain from other types originating from the lumbosacral spine and describes musculoskeletal conditions frequently mimicking radiculopathy, such as those that cause radiating pain and sensorimotor dysfunction. In clinical evaluation, a history of pain radiating along a specific dermatomal territory with associated sensory disturbance suggests radiculopathy. Physical examination findings consistent with radiculopathy include myotomal weakness, depressed or absent muscle stretch reflexes, focal atrophy along a discrete nerve root territory, and potentially positive dural tension maneuvers like the straight leg raise. However, electrodiagnostic medicine specialists must be knowledgeable of musculoskeletal mimics, which may manifest as incomplete radiation within or beyond a dermatomal territory, non-radiating pain, tenderness, and give-way weakness, in the context of a normal neurological examination. A systematic approach to musculoskeletal examination is vital, and this review focuses on high-yield physical examination maneuvers and diagnostic investigations to differentiate between musculoskeletal conditions and radiculopathy. This approach ensures accurate diagnoses, promotes resource stewardship, enhances patient satisfaction, and optimizes care delivery. Musculoskeletal conditions resembling L1 to S4 radiculopathy are reviewed, emphasizing their distinctive features in history, physical examination, and diagnostic investigation. Among the more than 30 musculoskeletal disorders reviewed are hip and knee osteoarthritis, lumbar facet syndrome, myofascial pain syndrome, greater trochanteric pain syndrome, and plantar fasciitis.

A Developmental Perspective on Early and Current Motor Abnormalities and Psychotic-Like Symptoms.

Psychotic-like experiences (PLEs) are prevalent in the general population and, because they represent a lower end of the psychosis vulnerability spectrum, may be useful in informing mechanistic understanding. Although it is well-understood that motor signs characterize formal psychotic disorders, the developmental trajectory of these features and their relationships with PLEs are less well-understood. Data from 7559 adolescents and young adults (age 11-21) in the Philadelphia Neurodevelopmental Cohort were used to investigate whether early-life milestone-attainment delays relate to current adolescent sensorimotor functioning and positive and negative PLEs. Current sensorimotor functioning was assessed using the Computerized Finger Tapping task (assessing motor slowing) and Mouse Practice task (assessing sensorimotor planning). Early developmental abnormalities were related to current adolescent-aged motor slowing (t(7415.3) = -7.74, corrected-P < .001) and impaired sensorimotor planning (t(7502.5) = 5.57, corrected-P < .001). There was a significant interaction between developmental delays and current sensorimotor functioning on positive and negative PLEs (t = 1.67-4.51), such that individuals with early developmental delays had a stronger positive relationship between sensorimotor dysfunction and PLEs. Importantly, interaction models were significantly better at explaining current PLEs than those treating early and current sensorimotor dysfunction independently (χ2 = 4.89-20.34). These findings suggest a relationship between early developmental delays and current sensorimotor functioning in psychosis proneness and inform an understanding of heterotypic continuity as well as a neurodevelopmental perspective of motor circuits. Furthermore, results indicate that motor signs are a clear factor in the psychosis continuum, suggesting that they may represent a core feature of psychosis vulnerability.

Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice. ICH was induced by intrastriatal injection of collagenase type VII, where hematoma invaded into IC. Neuron-specific overexpression of Nurr1 was induced by microinjection of synapsin I promoter-driven adeno-associated virus (AAV) vector into the primary motor cortex. Nurr1 overexpression significantly alleviated motor dysfunction but showed only modest effect on sensorimotor dysfunction after ICH. Nurr1 overexpression also preserved axonal structures in IC, while having no effect on hematoma-associated inflammatory events, oxidative stress, and neuronal death in the striatum after ICH. Immunostaining revealed that Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Moreover, administration of Nurr1 ligands 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane or amodiaquine increased phosphorylation levels of Akt and ERK1/2 as well as expression of glial cell line-derived neurotrophic factor and Ret genes in the cerebral cortex. These results suggest that the therapeutic effect of Nurr1 on striatal ICH is attributable to the preservation of CST by acting on cortical neurons.

Comparisons of Evoked Skin Vasomotor and Sudomotor Responses to Single Pulse Median Nerve Stimulation

The sensorimotor dysfunction caused by cervical and thoracic spinal cord injury (SCI) is concomitant with sympathetic nervous system dysfunction, evidenced by the high prevalence of orthostatic hypotension and autonomic dysreflexia. Although the International Standards for Neurological Classification of SCI evaluate sensorimotor function both above and below the injury level, there are limited quantitative measures for gauging sympathetic outflow and the extent of dysautonomia resulting from neurological damage. Despite studies on the effects of SCI on electrodermal activity (EDA) and blood pressure (BP), there is a lack of detailed feature comparisons involving EDA, skin vasomotor activity, and BP. Therefore, we investigated the relationship between EDA, skin vasomotor, and BP responses to sympathetic activation via median nerve stimulation in persons with and without SCI. Adults with and without SCI (cohort demographics presented in poster) participated in this study. Lead II electrocardiogram (ECG), pneumogram (P), photoplethysmogram (PPG), and EDA were recorded from either the trunk (ECG, P) or both limbs (PPG, EDA). Beat-by-beat BP was recorded from the middle finger of the left hand (VitalStream, CareTaker Medical). Evoked responses in the above signals were measured surrounding a cathodal electrical pulse (30 mA, 200 μs) delivered to the distal right median nerve 1-2 cm proximal and medial to the radial styloid process either during systole or diastole of the cardiac cycle. There were notable differences between baseline signals before and after the experimental session, along with a consistent reduction of limb temperature (&gt; 2° Celsius). Increases in EDA (greater than two standard deviations from baseline) were found across non-SCI participants following stimulation both during systole and diastole, along with skin vasoconstriction following the onset of EDA modulation (&gt; 50% of trials). Individual differences were noted in evoked responses to stimulation at systole vs. diastole. Furthermore, attenuated responses were observed in individuals with SCI. Stimulation caused no evoked signal response habituation across trials within participants. Additionally, evoked BP changes were not consistent across all individuals with respect to stimulation. Our results show a fixed relationship between evoked skin vasomotor and sudomotor responses to single pulse stimuli across participants and had consistent waveform features. Potential individual effects of stimulation delivered at systole vs. diastole warrant an in-depth analysis of reflex gating of sudomotor and skin vasomotor responses. This would present insight into the population with SCI, where dysfunction could greatly exaggerate reflex gating. 1R01NS131493-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

BackgroundIntracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated.MethodsC57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism.ResultsMas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3–5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH.ConclusionsMas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Modular organization of functional brain networks in patients with degenerative cervical myelopathy

Previous studies have indicated that brain functional plasticity and reorganization in patients with degenerative cervical myelopathy (DCM). However, the effects of cervical cord compression on the functional integration and separation between and/or within modules remain unclear. This study aimed to address these questions using graph theory. Functional MRI was conducted on 46 DCM patients and 35 healthy controls (HCs). The intra- and inter-modular connectivity properties of the whole-brain functional network and nodal topological properties were then calculated using theoretical graph analysis. The difference in categorical variables between groups was compared using a chi-squared test, while that between continuous variables was evaluated using a two-sample t-test. Correlation analysis was conducted between modular connectivity properties and clinical parameters. Modules interaction analyses showed that the DCM group had significantly greater inter-module connections than the HCs group (DMN-FPN: t = 2.38, p = 0.02); inversely, the DCM group had significantly lower intra-module connections than the HCs group (SMN: t = − 2.13, p = 0.036). Compared to HCs, DCM patients exhibited higher nodal topological properties in the default-mode network and frontal–parietal network. In contrast, DCM patients exhibited lower nodal topological properties in the sensorimotor network. The Japanese Orthopedic Association (JOA) score was positively correlated with inter-module connections (r = 0.330, FDR p = 0.029) but not correlated with intra-module connections. This study reported alterations in modular connections and nodal centralities in DCM patients. Decreased nodal topological properties and intra-modular connection in the sensory-motor regions may indicate sensory-motor dysfunction. Additionally, increased nodal topological properties and inter-modular connection in the default mode network and frontal-parietal network may serve as a compensatory mechanism for sensory-motor dysfunction in DCM patients. This could provide an implicative neural basis to better understand alterations in brain networks and the patterns of changes in brain plasticity in DCM patients.