Motor Function Research Articles

Getting oriented: Redefining attention deficits in Parkinson's disease.

Parkinson's disease (PD) may affect not only motor functions, but also cognitive processes such as attention. While past research has examined PD impact on spatial attention, it has not addressed how the key functions of attentional orienting and alerting in PD are mediated by cueing format, an ecologically relevant parameter. We assessed how exogenous and endogenous orienting cue modes affect PD patients' visuospatial attention expressed as dorsal attention network orienting benefits, ventral attention network reorienting costs, and alerting abilities. Ninety PD patients and 72 healthy comparison participants performed a spatial attention task in an engaging game format which required selection of a target location without prior cueing, or with temporal, valid spatial, or invalid spatial exogenous or endogenous cueing. PD patients differed from healthy participants only in response time benefits in orienting under endogenous probabilistically predictive cue processing. They did not exhibit greater reorienting costs, differences in inhibition of return, or alerting deficits, irrespective of modes of cueing. These results suggest that fundamental orienting and alerting functions might be intact in PD, with challenges emerging only if additional cognitive processes, including those related to motor preparation, are required to utilize cue information. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model

The approval of splice-switching oligonucleotides with phosphorodiamidate morpholino oligomers (PMOs) for treating Duchenne muscular dystrophy (DMD) has advanced the field of oligonucleotide therapy. Despite this progress, PMOs encounter challenges such as poor tissue uptake, particularly in the heart, diaphragm, and central nervous system (CNS), thereby affecting patient’s prognosis and quality of life. To address these limitations, we have developed a PMOs-based heteroduplex oligonucleotide (HDO) technology. This innovation involves a lipid-ligand-conjugated complementary strand hybridized with PMOs, significantly enhancing delivery to key tissues in mdx mice, normalizing motor functions, muscle pathology, and serum creatine kinase by restoring internal deleted dystrophin expression. Additionally, PMOs-based HDOs normalized cardiac and CNS abnormalities without adverse effects. Our technology increases serum albumin binding to PMOs and improves blood retention and cellular uptake. Here we show that PMOs-based HDOs address the limitations in oligonucleotide therapy for DMD and offer a promising approach for diseases amenable to exon-skipping therapy.

Utility of routine mid-trimester fetal ultrasound scan in detecting filar cysts and follow-up outcomes.

To assess the value of routine mid-trimester fetal ultrasound scans in detecting FCs, as well as the related ultrasound and clinical follow-up outcomes. A retrospective analysis was conducted on 1064 fetuses who underwent standardized ultrasound screening during the mid-trimester. During the examination, high-frequency ultrasound was used to examine the fetal spine. Different frequency ultrasound probes were used to compare and analyze the detection rates of FCs. We conducted follow-up ultrasound observations on all FCs and conducted long-term follow-up observations in terms of the motor function of the children after birth. Among 1064 fetuses detected by ultrasound, a total of 910 fetuses were completely evaluated using high-frequency and low-frequency ultrasound, and 24 FCs were found. In all 24 cases of FCs, 7 cases were detected using low-frequency ultrasound, while high-frequency ultrasound detected all cases. There was a significant difference in the detection rates between the two groups (χ2 = 26.323, P = 0.000). Of all the 24 FCs, 21 cysts disappeared spontaneously (87.5%); one fetus was induced for abortion due to a concurrent cleft lip; after multiple ultrasound examinations, it was found that the cyst persisted in one fetus; one case was not followed up by ultrasound. There was no statistically significant difference in the start of sitting and crawling time between the control group and the FCs group. Routine mid-trimester fetal ultrasound scan detect FCs, particularly when high-frequency ultrasound probes were routinely applied. Most FCs detected by prenatal ultrasound spontaneously disappear and have no impact on the motor function of the fetus after birth (with the conus medullaris located at or above the L3 level). The shortest time interval from the detection to the disappearance of the cyst was 11days.

Synovial fluid analysis in healthy green turtles Chelonia mydas in Taiwan.

Septic arthritis is a frustrating disease in sea turtle rehabilitation because of its unclear pathogenesis, delayed onset during rehabilitation, long-term treatment requirements, and potentially poor prognosis. Radiography, blood cultures, and arthrocentesis have been used as diagnostic tools for suspected cases. However, there is currently a lack of data on the characteristics of synovial fluid in healthy sea turtles. To establish reference data for synovial fluid in sea turtles, we enrolled 14 green turtles Chelonia mydas rescued between 2019 and 2022 from 3 facilities using the following inclusion criteria: normal attitude and appetite, normal motor functions of the 4 limbs, no joint swelling, and no ongoing use of antibiotics for at least 1 mo. Bacterial cultures of blood and synovial fluid from the shoulder joints of these turtles were obtained and a qualitative analysis of the synovial fluid was performed. The results revealed bacterial culture-negative blood and synovial fluids at 37°C. Most characteristics of normal synovial fluid in green turtles, such as being transparent, colorless, and able to create a strand of over 2.5 cm by being pulled with a needle in viscosity trials, as well as the cytology of the normal synovial fluids being dominated by histiocytes and synovial lining cells, lymphocytes, and occasionally a few heterophils or erythrocytes were similar to those in mammals. This study provides information on the normal synovial fluid characteristics of green turtles in Taiwan, which may be beneficial for the diagnosis of joint diseases in sea turtles.

Limited cerebellar gradient extension in temporal lobe epilepsy with dystonic posturing.

Dystonic posturing (DP) is a common semiology in temporal lobe epilepsy (TLE). We aimed to explore cerebellar gradient alterations in functional connectivity in TLE patients with and without DP. Resting-state functional MRI data were obtained in 60 TLE patients and 32 matched healthy controls. Patients were further divided into two groups: TLE with DP (TLE + DP, 31 patients) and TLE without DP (TLP-DP, 29 patients). We explored functional gradient alterations in the cerebellum based on cerebellar-cerebral functional connectivity and combined with independent component analysis to evaluate cerebellar-cerebral functional integration and reveal the contribution of the motor components to the gradient. There were no obvious differences in clinical features and postoperative seizure outcomes between TLE + DP and TLE-DP patients. Patients and controls all showed a clear unimodal-to-transmodal gradient transition in the cerebellum, while TLE patients demonstrated an extended principal gradient in functional connectivity compared to healthy controls, which was more limited in TLE + DP patients. Gradient alterations were more widespread in TLE-DP patients, involving bilateral cerebellum, while gradient alterations in TLE + DP patients were limited in the cerebellum ipsilateral to the seizure focus. In addition, more cerebellar motor components contributed to the gradient alterations in TLE + DP patients, mainly in ipsilateral cerebellum. Extended cerebellar principal gradients in functional connectivity revealed excessive functional segregation between unimodal and transmodal systems in TLE. The functional connectivity gradients were more limited in TLE + DP patients. Functional connectivity in TLE patients with dystonic posturing involved more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Dystonic posturing contralateral to epileptic focus is a common symptom in temporal lobe epilepsy, and the cerebellum may be involved in its generation. In this study, we found cerebellar gradients alterations in functional connectivity in temporal lobe epilepsy patients with and without contralateral dystonic posturing. In particular, we found that TLE patients with dystonic posturing may have more limited cerebellar gradient in functional connectivity, involving more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Our study suggests a close relationship between ipsilateral cerebellum and contralateral dystonic posturing.

Group-based progressive functional, high-intensity training in adolescents and young adults with unilateral cerebral palsy – a tool to improve gross motor function, endurance and gait? – a pilot study

ABSTRACT Purpose This pilot study assessed the safety and effects of progressive functional high-intensity training in a group setting for adolescents with unilateral cerebral palsy (CP) on daily function indicators. Methods Nine adolescents (mean age 16.9 years, GMFCS levels I–II) participated in 12 weeks of training (2x/week). Evaluations included 3D gait analysis, the 6-min walking test (6MWT), clinical exams, and the Gross Motor Function Measure-66 (GMFM-66). Results No adverse events occurred, and GMFM-66 scores significantly improved (p = .031, Δ = 2.19%). Although increases in 6MWT (p = .09, Δ = 29.8 m) performance and propulsion ratio (p = .067, Δ = 5.4%) for the affected leg were observed, they were not statistically significant. Discussion The study suggests that this training is safe and may enhance gross motor function, endurance, and gait asymmetry in unilateral CP. Future research should include upper limb evaluations and out-of-clinic motion analysis with wearable inertial measurement units (IMUs) to provide a more comprehensive assessment of functional movements.

Negative emotions reduce sensorimotor cortex activity during proprioceptive modulation of rolandic ∼20HZ beta rhythm in typically developing children and those with neurodevelopmental conditions

BackgroundThe Rolandic ∼20-Hz beta rhythm of the sensorimotor cortex is associated with motor function and perception. However, the modulation of this rhythm by different emotional stimuli is an innovative area of research. AimsThis study aims at investigating the impact of affective pictures (positive, negative, and neutral) on the proprioceptive modulation of the Rolandic ∼20 Hz beta rhythm in typically developing children and children with neurodevelopmental disorders (i.e. cerebral palsy and autism). Methods and proceduresEEG was recorded while participants experienced passive wrist movements during the simultaneous viewing of affective pictures. Time-frequency analysis of the sensorimotor oscillatory activity was performed. Outcomes and resultsOur findings revealed that pictures with negative emotional valence notably diminish event-related synchronization (ERS) amplitude during the perception of hand movement in all groups of children. Conclusions and implicationsThese findings suggest that emotional stimuli, particularly the negative ones, could significantly influence brain's processing of proprioception, adding knowledge to the interaction of common comorbidities, such as sensorimotor disorders and emotional dysregulation, in children with neurodevelopmental disabilities.

Knockdown of BMP7 induced oligodendrocyte apoptosis, demyelination and motor function loss

BackgroundDemyelinating diseases, including multiple sclerosis (MS) and spinal cord injury (SCI), lead to significant neurological deficits primarily due to the loss of oligodendrocytes (OLs). Bone Morphogenetic Protein 7 (BMP7) is expressed abundantly in the central nervous system and previous studies showed its protective effect in reducing OL loss. In this study, we aim to explore BMP7's potential as a biomarker and therapeutic target for demyelinating diseases by investigating its expression and effects on OLs and myelin sheath integrity. MethodWe analyzed multiple Gene Expression Omnibus datasets for BMP7 expression profiles in demyelinating conditions such as MS and SCI. Experimentally, we employed a BMP7 knockdown model in rat spinal cords using adeno-associated virus8 vectors to specifically reduce BMP7 expression. Western blotting, immunofluorescence, and Nissl staining were used to assess the effect on OL and other types of cells. The structure of myelin sheath and locomotor function were evaluated using transmission electron microscopy and BBB scores, and statistical analysis included ROC curves and ANOVA to evaluate BMP7's diagnostic and therapeutic potential. ResultsBMP7 expression consistently decreased across various demyelinating models, and BMP7 knockdown led to increased OL apoptosis through the Smad1/5/9 pathway, with no apparent effect on other cell types. This reduction in OLs was associated with myelin degeneration, axonal damage, and impaired motor function. ConclusionThe study confirms BMP7's significant involvement in the pathophysiology of demyelinating diseases and supports its potential as a therapeutic target or biomarker. Future research should focus on therapeutic strategies to enhance BMP7 function and further investigate the mechanisms by which BMP7 supports myelin integrity.

TMS-induced phase resets depend on TMS intensity and EEG phase.

The phase of the electroencephalographic (EEG) signal predicts performance in motor, somatosensory, and cognitive functions. Studies suggest that brain phase resets align neural oscillations with external stimuli, or couple oscillations across frequency bands and brain regions. Transcranial Magnetic Stimulation (TMS) can cause phase resets noninvasively in the cortex, thus providing the potential to control phase-sensitive cognitive functions. However, the relationship between TMS parameters and phase resetting is not fully understood. This is especially true of TMS intensity, which may be crucial to enabling precise control over the amount of phase resetting that is induced. Additionally, TMS phase resetting may interact with the instantaneous phase of the brain. Understanding these relationships is crucial to the development of more powerful and controllable stimulation protocols.
Approach: To test these relationships, we conducted a TMS-EEG study. We applied single-pulse TMS at varying degrees of stimulation intensity to the motor area in an open loop. Offline, we used an autoregressive algorithm to estimate the phase of the intrinsic µ-Alpha rhythm of the motor cortex at the moment each TMS pulse was delivered.
Main results: We identified post-stimulation epochs where µ-Alpha phase resetting and N100 amplitude depend parametrically on TMS intensity and are significant versus peripheral auditory sham stimulation. We observed µ-Alpha phase inversion after stimulations near peaks but not troughs in the endogenous µ-Alpha rhythm.
Significance: These data suggest that low-intensity TMS primarily resets existing oscillations, while at higher intensities TMS may activate previously silent neurons, but only when endogenous oscillations are near the peak phase. These data can guide future studies that seek to induce phase resetting, and point to a way to manipulate the phase resetting effect of TMS by varying only the timing of the pulse with respect to ongoing brain activity.

Brain Tumour Patient Perceptions towards Repetitive Transcranial Magnetic Stimulation for Rehabilitation after Surgery

Abstract Background Repetitive Transcranial Magnetic Stimulation (rTMS) is established for depression and rehabilitation after stroke and is emerging for cognitive rehabilitation. We sought to evaluate patient and carer perceptions towards rTMS for rehabilitation after neurosurgery. Methods Two surveys were undertaken. Group 1: patients who received seven days of rTMS for motor or language rehabilitation for severe post-operative deficits following lesional resection were prospectively surveyed on the last day of their rTMS treatment, as well as their next-of-kin. Group 2: patients who had previously been diagnosed with glioma but did not receive rTMS were retrospectively surveyed through two brain tumour charities, including next-of-kin. Results Group1: 21 responses. 11 patients, 10 next-of-kin. Commonest pathology was WHO Grade 4 Glioma (n=3). Group2: 24 responses. 16 patients, 8 next-of-kin. Commonest pathology was WHO Grade 2 Glioma (n=7). Most Group1 respondents reported a positive experience of rTMS (15/21). Patients experienced subjective improvements in gross motor functions of arm and leg weakness and purposeful movement (9/11). Lack of subjective motor improvement was associated with adverse symptoms (e.g. headaches) (p=0.01). Group2 respondents were supportive of rTMS. Key priorities included motor and cognitive rehabilitation. They were accepting of longer and more frequent rTMS sessions than Group1 (p=0.028 and p<0.001 respectively). Commonest concerns pertained to side effects (seizures, headaches). Conclusions rTMS for rehabilitation was well-tolerated by patients with side effects being commoner in those with no subjective motor improvements. Non-treated patients and their next-of-kin would find longer and more sessions acceptable but have concerns about potential side effects.

Neuroprotective Effect of Melatonin in a Neonatal Hypoxia-Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway.

Melatonin has been shown to be neuroprotective in different animal models of neonatal hypoxic-ischemic brain injury. However, its exact molecular mechanism of action remains unknown. Our aim was to prove melatonin's short- and long-term neuroprotection and investigate its role on the AMPK (AMP-activated protein kinase)/mTOR (mammalian target of rapamycin) pathway following neonatal hypoxic-ischemic brain injury. Seven-day-old Wistar rat pups were exposed to hypoxia-ischemia, followed by melatonin or vehicle treatment. Detailed analysis of the AMPK/mTOR/autophagy pathway, short- and long-term neuroprotection, myelination, and oligodendrogenesis was performed at different time points. At 7 days after hypoxia-ischemia, melatonin-treated animals showed a significant decrease in tissue loss, increased oligodendrogenesis, and myelination. Long-term neurobehavioral results showed significant motor improvement following melatonin treatment. Molecular pathway analysis showed a decrease in the AMPK expression, with a significant increase at mTOR's downstream substrates, and a significant decrease at the autophagy marker levels in the melatonin group compared with the vehicle group. Melatonin treatment reduced brain area loss and promoted oligodendrogenesis with a clear improvement of motor function. We found that melatonin associated neuroprotection is regulated via the AMPK/mTOR/autophagy pathway. Considering the beneficial effects of melatonin and the results of our study, melatonin seems to be an optimal candidate for the treatment of newborns with hypoxic-ischemic brain injury in high- as well as in low- and middle-income countries.

Neural effects of acupuncture on stroke patients with motor dysfunction: an activation likelihood estimation meta-analysis.

Functional magnetic resonance imaging has been used in many studies to explore the neural mechanism of acupuncture in patients with post-stroke motor dysfunction. Inconsistent results have been found in these studies, however. This activation likelihood estimation (ALE) meta-analysis was designed to quantitatively integrate changes in brain activity and the neurological effects of acupuncture on patients with motor dysfunction after stroke. We searched PubMed, Embase, Web of Science, the Cochrane Library, China Science and Technology Journal Database, the China Biology Medicine, the China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform for literature from the establishment of the database until March 21, 2024. Research papers were selected, data extracted, and quality assessment was done independently by two researchers. The GingerALE software was used for meta-analysis, and Jackknife sensitivity analysis was employed to assess result robustness. We ended up analyzing 14 studies that included 235 patients and 100 healthy people. ALE meta-analysis showed that Compared with healthy people, the enhanced brain region in poststroke patients with motor dysfunction was located in the left posterior lobe of the cerebellum, the left inferior frontal gyrus, and the left precuneus (p < 0.001). After acupuncture, the activated regions were mainly located in the left posterior lobe of the cerebellum, the right lentiform nucleus putamen, the right medial frontal gyrus, the right inferior frontal gyrus, the left precuneus, the right middle temporal gyrus, the left claustrum, the left cerebellar tonsil, the right superior marginal gyrus, the inactivated area is located in the right medial frontal gyrus the left precentral gyrus and the right precuneus (p < 0.001). Acupuncture can reestablish motor function by causing extensive changes in the brain function of patients with stroke, which may be the neurological effect of acupuncture therapy on stroke patients. https://www.crd.york.ac.uk/prospero/, identifier CRD42024526263.

Prevalence of autonomic dysreflexia during spinal cord stimulation after spinal cord injury

Over the last decade, clinical trials have shown that spinal cord stimulation can restore motor functions that were thought to be permanently impaired in persons with spinal cord injury. However, the off-target effects of delivering electrical impulses to intertwined spinal networks remain largely unknown. This generates safety concerns for this otherwise fast-progressing technology. Herein, we present the prevalence of autonomic dysreflexia that occurred during implanted spinal cord stimulation testing for motor activation of the lower extremities. Eleven participants with spinal cord injury underwent implantation of temporary percutaneous epidural and dorsal root ganglia stimulation leads. Participants completed two days of parameter testing at baseline, then six days of motor rehabilitation sessions, and two days of parameter testing at end of study. The goal of parameter testing was to determine electrode configuration(s), pulse amplitudes and frequencies that activated lumbosacral spinal sensorimotor networks that generate lower extremity functions. During all parameter testing sessions, continuous blood pressure and heart rate monitoring recordings were collected. Evidence of autonomic dysreflexia was found in 22% of all parameter tests with participants at rest. Most of these episodes (97%) were asymptomatic. These episodes occurred more frequently when using epidural stimulation, at or near amplitudes that elicited whole leg muscle activation and using a wide-field electrode configuration. While monitoring occurred during passive testing, motor rehabilitation sessions employ stimulation for longer periods, at higher frequencies and amplitudes. These sessions may carry additional risks of autonomic dysreflexia. Investigation of these concerns should continue as spinal cord stimulation progresses towards clinical translation.

Perceived social support on objective measured sedentary behavior of stroke patients: the mediating role of exercise self-efficacy.

As stroke patients may have impaired motor function, there may have increased sedentary behavior. Factors associated with sedentary behavior need to be explored to develop targeted interventions. Although studies explore the effects of exercise self-efficacy and perceived social support on sedentary behavior, the relationship is not clear. The aim of this study was to explore the mediating effect of exercise self-efficacy on perceived social support and objective measured sedentary behavior in stroke patients. The random sampling method was adopted to select 275 stroke patients from the neurology department of a third-grade hospital of Henan Province from June 2023 to March 2024 in a cross-sectional descriptive study. A general data questionnaire, exercise self-efficacy scale, perceived social support scale, and ActiGraph GT3X accelerometer were used to investigate. The structural equation model was used to analyze the mediating effect of exercise self-efficacy between perceived social support and sedentary behavior. The mean sedentary behavior time in stroke patients in this study was (479.65 ± 112.65) min, the mean score of perceived social support was (47.53 ± 17.16), and the mean score of exercise self-efficacy was (24.19 ± 6.25). The correlation analysis revealed that, the sedentary behavior of stroke patients was negatively correlated with exercise self-efficacy and perceived social support. The results of the mediation analysis showed that exercise self-efficacy played a partial mediating role between perceived social support and sedentary behavior. Perceived social support and exercise self-efficacy were influential factors in sedentary behavior. Moreover, the impact of perceived social support on sedentary behavior was partially mediated by exercise self-efficacy. Therefore, to decrease the sedentary behavior, it is crucial to improve the level of perceived social support in stroke patients. Patients with less perceived social support can improve their exercise self-efficacy and thus perceive more social support.

Berberine attenuates neuronal ferroptosis via the AMPK–NRF2–HO-1-signaling pathway in spinal cord-injured rats

Ferroptosis, characterized by iron-dependent accumulation of lipid peroxides, plays an important role in spinal cord injury (SCI). Berberine (BBR), as a lipid peroxide scavenger, has been widely used in treating other diseases; however, its role in ferroptosis has not been fully elucidated. Therefore, here, to test our hypothesis that BBR can reduce the severity of SCI and promote motor function recovery by inhibiting neuronal ferroptosis, we evaluated the changes in ferroptosis-related indicators after BBR administration by establishing a cellular ferroptosis model and an SCI contusion model. We found that BBR administration significantly reduces lipid peroxidation damage, maintains normal mitochondrial function, reduces excessive accumulation of iron ions, enhances antioxidant capacity, and activates the ferroptosis defense system in vivo and in vitro. Mechanistically, BBR alleviates neuronal ferroptosis by inducing adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and up-regulating nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) protein expression to promote glutathione production. BBR administration also significantly improves motor function recovery in SCI rats. Meanwhile, applying the AMPK inhibitor Compound C blocks the neuroprotective and all other effects of BBR. Collectively, our findings demonstrate that BBR can attenuate neuronal ferroptosis after SCI by activating the AMPK–NRF2–HO-1 pathway.

Pectin-stabilized nanoceria double coated with lactoferrin/chitosan for management of experimental autoimmune encephalomyelitis

Cerium oxide nanoparticles are a unique antioxidant mimicking the activity of natural antioxidant enzymes. Previous research showed its’ promising effect mitigating free radical damage in neurodegenerative disorders. However, there is still unmet therapeutic needs due to poor BBB penetration, a high accumulation in liver, kidney and spleen. This study aimed to synthesize and optimize nanoceria stabilized by natural bioactive polymers suitable for intranasal administration to manage multiple sclerosis. Among the different employed biopolymers, pectin-stabilized nanoceria exhibited the ideal properties with small particles size 87.20±3.43nm, high zeta potential -56.37±2.39mV and high free radical scavenging activity 85.27±0.07%. Then coating was achieved for the first time by two biopolymers: lactoferrin and chitosan producing a double coated cationic nanoceria. Biological assessment involved using experimental autoimmune encephalomyelitis animal model treated in a dose of 1mg/kg nanoceria for 15 days. Motor function testing in rats revealed 6- and 17-folds increase in latency time in rotating rod and hanging wire tests, respectively. Biochemical analysis revealed significant reduction in lipid peroxidation along with about 1-fold upgrading of the intrinsic antioxidant system. Moreover, histologic examination disclosed decreased degeneration of the brain and spinal cord of treated rats and much decreased liver toxicity.

Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease.

Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy. Balance self-efficacy refers to one's level of confidence in their ability to balance while completing activities of daily living like getting dressed, bathing, and walking. Lower self-efficacy, or greater FoF during these activities is a function of motor, cognitive, and emotional impairments and may impact quality of life in PD. Unlike known cholinergic reduction, especially in the right lateral geniculate and caudate nuclei, little is known about the role of cholinergic transporters in FoF or mobility self-efficacy in PD. [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) studies were conducted to assess vesicular acetylcholine transporter (VAChT) expression in 126 patients with PD (male (m) = 95, female (f) = 31). Participants had a mean age of 67.3 years (standard deviation (SD) = 7.1) and median Hoehn Yahr stage of 2.5. Patients also completed the Short Falls Efficacy Scale (sFES-I) as a survey measure of concerns about falling. [18F]FEOBV data were processed in Statistical Parametric Mapping (SPM) using a voxel-wise regression model with sFES-I scores as the outcome measure. Reduced [18F]FEOBV binding in tectum, metathalamic (lateral more than medial geniculate nuclei), thalamus proper, bilateral mesiotemporal (hippocampal, parahippocampal, fusiform gyri and fimbriae), and right cerebellar lobule VI significantly associated with higher sFES-I scores (p < 0.05, family-wise error (FWE) correction after Threshold-Free Cluster Enhancement (TFCE)). Unlike the more limited involvement of the brainstem-thalamic complex and caudate nuclei cholinergic topography associated with falls in PD, cholinergic reductions in the extended connectivity between the thalamic complex and the temporal limbic system via the fimbriae associates with FoF. Additional cholinergic changes were seen in the cerebellum. The temporal limbic system plays a role not only in episodic memory but also in spatial navigation, scene and contextual (e.g., emotional) processing. Findings may augur novel therapeutic approaches to treat poor mobility self-efficacy in PD. No: NCT02458430. Registered 18 March, 2015, https://www. gov/study/NCT02458430; No: NCT05459753. Registered 01 July, 2022, https://www. gov/study/NCT05459753.

Motor development trajectories of children with cerebral palsy in a community-based early intervention program in rural South India

BackgroundDevelopmental trajectories are crucial for evidence-based prognostication, planning interventions, and monitoring progress in children with cerebral palsy (CP). AimsTo describe gross motor development patterns of children with CP in rural South India for the five Gross Motor Function Classification System (GMFCS) levels. MethodsLongitudinal cohort study of 302 children (176 males, 126 females) with CP aged 0 to 10 years, followed by a community-based early intervention program. GMFCS levels were 5.4 % level 1, 16.5 % level II, 22.8 % level III, 26.8 % level IV, and 28.5 % level V. Assessments were undertaken using the Gross Motor Function Measure (GMFM-66) at 6-month intervals between April 2017 and August 2020. Longitudinal analyses were performed using mixed-effects linear regression models. Outcomes and resultsFive distinct motor development curves were created for ages 0 to 10 years by GMFCS levels as a function of age and GMFM-66 with a stable limit model, variation in estimated limits and rates of development. Conclusions and ImplicationsMotor development trajectories for CP in an LMIC differ from those reported in HICs. Consideration of how social determinants of health, environmental and personal factors impact motor development in low-resource contexts is crucial. Further work is needed to describe developmental trajectories of children for CP in LMICs.

Development and Testing of the Spinal Cord Injury Bladder and Bowel Control Questionnaire (SCI-BBC-Q).

Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient-reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI-BBC-Q) was developed. The SCI-BBC-Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI-BBC-Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. The final 6-item SCI-BBC-Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI-BBC-Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI-BBC-Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. The SCI-BBC-Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury.

In addition to the loss of motor function, ~60% of patients develop pain after spinal cord injury. The cellular-molecular mechanisms are not well understood, but the data suggests that plasticity within the rostral, epicenter, and caudal penumbra of the injury site initiates a cellular-molecular interplay that acts as a rewiring mechanism leading to central neuropathic pain. Sprouting can lead to the formation of new connections triggering abnormal sensory transmission. The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity. Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen. In this study, we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury. We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters, leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting. Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control (placebo). We used von Frey monofilaments and the "up-down method" to evaluate mechanical allodynia. Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sex-dependent effect. The expression profile of glutamatergic transporters (excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1) revealed a sexual dimorphism in the rostral, epicenter, and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes. Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents. Analyses of peptidergic (calcitonin gene-related peptide-α) and non-peptidergic (isolectin B4) fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/ isolectin B4 ratio in comparison with sham, suggesting increased receptive fields in the dorsal horn. Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats, this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury. Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord. The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain, an area with a critical need for treatment.