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Acetylcholine esterases (AChEs) are essential enzymes in cholinergic synapses, terminating neurotransmission by hydrolysing acetylcholine. While membrane bound AChEs at synaptic clefts efficiently perform this task, soluble AChEs are less stable and effective, but function over broader areas. In vertebrates, a single gene produces alternatively spliced forms of AChE, whereas invertebrates often have multiple genes, producing both enzyme types. Despite their significance as pesticide targets, the physiological roles of invertebrate AChEs remain unclear. Here, we characterized seven putative AChEs in the wandering spider, Cupiennius salei, a model species for neurophysiological studies. Sequence analyses and homology modeling predicted CsAChE7 as the sole stable, membrane‐bound enzyme functioning at synaptic clefts, while the others are likely soluble enzymes. In situ hybridization of sections from the spider's nervous system revealed CsAChE7 transcripts co‐localizing with choline acetyltransferase in cells that also exhibited AChE activity. CsAChE7 transcripts were also found in rapidly adapting mechanosensory neurons, suggesting a role in precise and transient activation of postsynaptic cells, contrasting with slowly adapting, also cholinergic, neurons expressing only soluble AChEs, which allow prolonged activation of postsynaptic cells. These findings suggest that cholinergic transmission is influenced not only by postsynaptic receptors but also by the enzymatic properties regulating acetylcholine clearance. We also show that acetylcholine is a crucial neurotransmitter in the spider's visual system and sensory and motor pathways, but absent in excitatory motor neurons at neuromuscular junctions, consistent with other arthropods. Our findings on sequence structures may have implications for the development of neurological drugs and pesticides. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsMagnetic seizure therapy (MST) is more benign than electroconvulsive therapy (ECT) in terms of cognitive impairment. However, whether these two ‘artificial seizures’ facilitate the central motor neural pathway and the motor cortical effects have not been investigated. The study aimed to compare the effects of ECT and MST on motor-evoked potential (MEP) in patients with mental disorders.Forty-nine patients with mental disorders (major depressive disorder, bipolar disorder type II and schizophrenia [SCZ]) received 6 treatment sessions of vertex MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on the duration of motor seizures were collected for each treatment. MEP latency and the resting motor threshold (rMT) were measured at baseline and after every two treatments. Comparisons were performed between or within the groups.Seizure durations were significantly longer in the ECT group compared to the MST group across multiple sessions. Both MST and ECT demonstrated a significant reduction in rMT in the left and right hemispheres after the fourth (T3) and sixth treatments (T4) compared to baseline (T1). However, there were no significant changes in MEP latency within or between the groups throughout the treatment sessions. The only difference was that the rMT in the left cerebral hemisphere was significantly lower after T4 than after the second treatment (T2). There was no difference in rMT between the ECT and MST groups.Both ECT and MST facilitate the central motor pathway, with a shared mechanism of increased motor cortex excitability. [ABSTRACT FROM AUTHOR]

Background: Opicapone is a third-generation catechol-O-methyl-transferase inhibitor currently used for the treatment of motor fluctuations in Parkinson's disease. Its benefit and safety have been established by clinical trials; however, data about its use in a real-life context, and particularly in an Italian population of patients with Parkinson's disease, are missing. Objectives: We aimed to gather data about the real-life tolerability/safety of opicapone when used for the treatment of Parkinson's disease-related motor fluctuations. Methods: We enrolled 152 consecutive patients with Parkinson's disease and followed them for 2 years after opicapone introduction. We obtained baseline clinical and demographical information, including disease duration, stage, phenotype, as well as axial and non-motor symptoms. We collected the reasons for any treatment interruption and adverse events emerging after opicapone introduction. Results: Eighty-nine (58%) patients reported adverse events and 46 (30%) patients discontinued the treatment. Adverse events occurred less frequently in "earlier" patients accordingly to the disease course and l-Dopa treatment pathway; a motor fluctuation duration ≥12 months and Hoehn and Yahr scale score ≥2.5 were the main predictors of therapy withdrawal. Conclusions: This study confirms the good tolerability/safety profile of opicapone in a real-life setting and provides country-specific data for Italian patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Parcellation of human cerebellar pathways is essential for advancing our understanding of the human brain. Existing diffusion magnetic resonance imaging tractography parcellation methods have been successful in defining major cerebellar fibre tracts, while relying solely on fibre tract structure. However, each fibre tract may relay information related to multiple cognitive and motor functions of the cerebellum. Hence, it may be beneficial for parcellation to consider the potential importance of the fibre tracts for individual motor and cognitive functional performance measures. In this work, we propose a multimodal data‐driven method for cerebellar pathway parcellation, which incorporates both measures of microstructure and connectivity, and measures of individual functional performance. Our method involves first training a multitask deep network to predict various cognitive and motor measures from a set of fibre tract structural features. The importance of each structural feature for predicting each functional measure is then computed, resulting in a set of structure–function saliency values that are clustered to parcellate cerebellar pathways. We refer to our method as Deep Multimodal Saliency Parcellation (DeepMSP), as it computes the saliency of structural measures for predicting cognitive and motor functional performance, with these saliencies being applied to the task of parcellation. Applying DeepMSP to a large‐scale dataset from the Human Connectome Project Young Adult study (n = 1065), we found that it was feasible to identify multiple cerebellar pathway parcels with unique structure–function saliency patterns that were stable across training folds. We thoroughly experimented with all stages of the DeepMSP pipeline, including network selection, structure–function saliency representation, clustering algorithm, and cluster count. We found that a 1D convolutional neural network architecture and a transformer network architecture both performed comparably for the multitask prediction of endurance, strength, reading decoding, and vocabulary comprehension, with both architectures outperforming a fully connected network architecture. Quantitative experiments demonstrated that a proposed low‐dimensional saliency representation with an explicit measure of motor versus cognitive category bias achieved the best parcellation results, while a parcel count of four was most successful according to standard cluster quality metrics. Our results suggested that motor and cognitive saliencies are distributed across the cerebellar white matter pathways. Inspection of the final k = 4 parcellation revealed that the highest‐saliency parcel was most salient for the prediction of both motor and cognitive performance scores and included parts of the middle and superior cerebellar peduncles. Our proposed saliency‐based parcellation framework, DeepMSP, enables multimodal, data‐driven tractography parcellation. Through utilising both structural features and functional performance measures, this parcellation strategy may have the potential to enhance the study of structure–function relationships of the cerebellar pathways. [ABSTRACT FROM AUTHOR]

Parkinson's Disease (PD) is a prevalent neurodegenerative disorder characterized by motor and non-motor symptoms. Emerging evidence suggests that gut microbiota alterations, specifically involving short-chain fatty acids (SCFAs) like butyrate, may influence PD pathogenesis and symptomatology. This Systematic Review aims to synthesize current research on the role of butyrate in modulating motor symptoms and its neuroprotective effects in PD, providing insights into potential therapeutic approaches. A systematic literature search was conducted in April 2024 across databases, including ScienceDirect, Scopus, Wiley, and Web of Science, for studies published between 2000 and 2024. Keywords used were "neuroprotective effects AND butyrate AND (Parkinson disease OR motor symptoms)". Four authors independently screened titles, abstracts, and full texts, applying inclusion criteria focused on studies investigating butyrate regulation and PD motor symptoms. A total of 1377 articles were identified, with 40 selected for full-text review and 14 studies meeting the inclusion criteria. Data extraction was performed on the study population, PD models, methodology, intervention details, and outcomes. Quality assessment using the SYRCLE RoB tool highlighted variability in study quality, with some biases noted in allocation concealment and blinding. Findings indicate that butyrate regulation has a significant impact on improving motor symptoms and offers neuroprotective benefits in PD models. The therapeutic modulation of gut microbiota to enhance butyrate levels presents a promising strategy for PD symptom management. [ABSTRACT FROM AUTHOR]

Mitotic centromere-associated kinesin (MCAK) motor protein is a typical member of the kinesin-13 family, which can depolymerize microtubules from both plus and minus ends. A critical issue for the MCAK motor is how it performs the depolymerase activity. To address the issue, the pathway of the MCAK motor moving on microtubules and depolymerizing the microtubules is presented here. On the basis of the pathway, the dynamics of both the wild-type and mutant MCAK motors is studied theoretically, which include the full-length MCAK, the full-length MCAK with mutations in the α4-helix of the motor domain, the mutant full-length MCAK with a neutralized neck, the monomeric MCAK and the mutant monomeric MCAK with a neutralized neck. The studies show that a single dimeric MCAK motor can depolymerize microtubules in a processive manner, with either one tubulin or two tubulins being removed per times. The theoretical results are in agreement with the available experimental data. Moreover, predicted results are provided. [ABSTRACT FROM AUTHOR]

Objective: The role of ipsilateral descending motor pathways in voluntary movement of humans is still a matter of debate, with partly contradictory results. The aim of our study therefore was to examine the excitability of ipsilateral motor evoked potentials (iMEPs) regarding site and the specificity for unilateral and bilateral elbow flexion extension tasks. Methods: MR-navigated transcranial magnetic stimulation mapping of the dominant hemisphere was performed in twenty healthy participants during tonic unilateral (iBB), bilateral homologous (bBB) or bilateral antagonistic elbow flexion-extension (iBB-cAE), the map center of gravity (CoG) and iMEP area from BB were obtained. Results: The map CoG of the ipsilateral BB was located more anterior-laterally than the hotspot of the contralateral BB within the primary motor cortex, with a significant difference in CoG in iBB and iBB-cAE, but not bBB compared to the hotspot for the contralateral BB (each p < 0.05). However, different tasks had no effect on the size of the iMEPs. Conclusion: Our data demonstrated that excitability of ipsilateral and contralateral MEP differ spatially in a task-specific manner suggesting the involvement of different motor networks within the motor cortex. [ABSTRACT FROM AUTHOR]

Emerging questions in neuromuscular physiology revolve around whether males and females share similar neural control in diverse tasks across a broad range of intensities. In order to explore these features, high‐density electromyography was used to record the myoelectrical activity of biceps brachii during trapezoidal isometric contractions at 35% and 70% of maximal voluntary force (MVF) on 11 male and 13 female participants. Identified motor units were then classified as lower‐threshold (recruited at ≤30%MVF) and higher‐threshold (recruited at >30%MVF). The discharge rate, interspike interval variability, recruitment and derecruitment thresholds, and estimates of neural drive to motor neurons were assessed. Female lower‐threshold motor units showed higher neural drive (P < 0.001), accompanied by higher discharge rate at recruitment (P = 0.006), plateau (P = 0.001) and derecruitment (P = 0.001). On the other hand, male higher‐threshold motor units showed greater neural drive (P = 0.04), accompanied by higher discharge rate at recruitment (P = 0.005), plateau (P = 0.04) and derecruitment (P = 0.01). Motor unit discharge rate normalised by the recruitment threshold was significantly higher in female lower‐threshold motor units (P < 0.001), while no differences were observed in higher‐threshold motor units. Recruitment and derecruitment thresholds are higher in males across all intensities (P < 0.01). However, males and females have similar activation and deactivation strategies, as evidenced by similar recruitment‐to‐derecruitment ratios (P > 0.05). This study encompasses a broad intensity range to analyse motor unit sex‐related differences, highlighting higher neural drive and discharge rates in female lower‐threshold motor units, elevated recruitment and derecruitment thresholds in males, and convergences in activation and deactivation strategies. Highlights: What is the central question of the study?Do male and female motor units behave similarly in low‐ and high‐intensity contractions?What is the main finding and its importance?Female motor units show higher discharge rates in low‐intensity tasks and lower discharge rates in high‐intensity tasks, with no differences in recruitment behaviour. A broader inter‐spike interval variability was also observed in females. These findings underline that there are sex‐specific differences concern the firing strategies based on task intensity. [ABSTRACT FROM AUTHOR]

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson's Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation The corticospinal tract (CST) is considered the most important motor output pathway comprising fibers from the primary motor cortex (M1) and various premotor areas. Damage to its descending fibers after stroke commonly leads to motor impairment. While premotor areas are thought to critically support motor recovery after stroke, the functional role of their corticospinal output for different aspects of post‐stroke motor control remains poorly understood.We assessed the differential role of CST fibers originating from premotor areas and M1 in the control of basal (single‐joint muscle synergies and strength) and complex motor control (involving inter‐joint coordination and visuomotor integration) using a novel diffusion imaging approach in chronic stroke patients.While M1 sub‐tract anisotropy was positively correlated with basal and complex motor skills, anisotropy of PMd, PMv, and SMA sub‐tracts was exclusively associated with complex motor tasks. Interestingly, patients featuring persistent motor deficits showed an additional positive association between premotor sub‐tract integrity and basal motor control.While descending M1 output seems to be a prerequisite for any form of upper limb movements, complex motor skills critically depend on output from premotor areas after stroke. The additional involvement of premotor tracts in basal motor control in patients with persistent deficits emphasizes their compensatory capacity in post‐stroke motor control. In summary, our findings highlight the pivotal role of descending corticospinal output from premotor areas for motor control after stroke, which thus serve as prime candidates for future interventions to amplify motor recovery. [ABSTRACT FROM AUTHOR]

The regulation of circadian rhythms and the sleep–wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep–wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN–HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non–rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN–HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep–wake states regulation. [ABSTRACT FROM AUTHOR]

(1) Background: Restoring arm and hand function is one of the priorities of people with cervical spinal cord injury (cSCI). Noninvasive electromagnetic neuromodulation is a current approach that aims to improve upper-limb function in individuals with SCI. The aim of this study is to review updated information on the different applications of noninvasive electromagnetic neuromodulation techniques that focus on restoring upper-limb functionality and motor function in people with cSCI. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to structure the search protocol. A systematic review of the literature was performed in three databases: the Cochrane Library, PubMed, and Physiotherapy Evidence Database (PEDro). (3) Results: Twenty-five studies were included: four were on transcranial magnetic stimulation (TMS), four on transcranial direct current stimulation (tDCS), two on transcutaneous spinal cord stimulation (tSCS), ten on functional electrical stimulation (FES), four on transcutaneous electrical nerve stimulation (TENS), and one on neuromuscular stimulation (NMS). The meta-analysis could not be completed due to a lack of common motor or functional evaluations. Finally, we realized a narrative review of the results, which reported that noninvasive electromagnetic neuromodulation combined with rehabilitation at the cerebral or spinal cord level significantly improved upper-limb functionality and motor function in cSCI subjects. Results were significant compared with the control group when tSCS, FES, TENS, and NMS was applied. (4) Conclusions: To perform a meta-analysis and contribute to more evidence, randomized controlled trials with standardized outcome measures for the upper extremities in cSCI are needed, even though significant improvement was reported in each non-invasive electromagnetic neuromodulation study. [ABSTRACT FROM AUTHOR]

This article presents the findings of three studies that have mapped the nerve cord of fruit flies, specifically focusing on the ventral nerve cord (VNC) in adult male flies. The researchers used volume electron microscopy to create a detailed wiring diagram of the VNC, which consists of over 23,000 neurons connected by millions of synapses. The studies provide insights into the organization of pathways and the classification of neurons based on cell type. This research offers a comprehensive understanding of the neural organization underlying behavior in fruit flies and serves as a foundation for future studies on neural circuits. Additionally, the studies pave the way for mapping the nerve cords of other organisms and investigating how differences in neuronal wiring contribute to variations in traits and behaviors. [Extracted from the article]

• DIZE reduces intestinal inflammation, modulating 5-HT levels. • DIZE modulates the gut microbiota to increase central 5-HT during endotoxemia. • Central 5-HT regulates TNF levels via the splanchnic sympathetic efferent pathway. The sympathetic arm of the inflammatory reflex is the efferent pathway through which the central nervous system (CNS) can control peripheral immune responses. Diminazene aceturate (DIZE) is an antiparasitic drug that has been reported to exert protective effects on various experimental models of inflammation. However, the pathways by which DIZE promotes a protective immunomodulatory effects still need to be well established, and no studies demonstrate the capacity of DIZE to modulate a neural reflex to control inflammation. C57BL/6 male mice received intraperitoneal administration of DIZE (2 mg/Kg) followed by lipopolysaccharide (LPS, 5 mg/Kg, i.p.). Endotoxemic animals showed hyperresponsiveness to inflammatory signals, while those treated with DIZE promoted the activation of the inflammatory reflex to attenuate the inflammatory response during endotoxemia. The unilateral cervical vagotomy did not affect the anti-inflammatory effect of DIZE in the spleen and serum. At the same time, splenic denervation attenuated tumor necrosis factor (TNF) synthesis in the spleen and serum. Using broad-spectrum antibiotics for two weeks showed that LPS modulated the microbiota to induce a pro-inflammatory profile in the intestine and reduced the serum concentration of tryptophan and serotonin (5-HT), while DIZE restored serum tryptophan and increased the hypothalamic 5-HT levels. Furthermore, the treatment with 4-Chloro-DL-phenylalanine (pcpa, an inhibitor of 5-HT synthesis) abolished the anti-inflammatory effects of the DIZE in the spleen. Our results indicate that DIZE promotes microbiota modulation to increase central 5-HT levels and activates the efferent sympathetic arm of the inflammatory reflex to control splenic TNF production in endotoxemic mice. [ABSTRACT FROM AUTHOR]

Objective: The dentato‐thalamo‐cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross‐sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex. [ABSTRACT FROM AUTHOR]

The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl–Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations. NEW & NOTEWORTHY: For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke. [ABSTRACT FROM AUTHOR]

BACKGROUND: Apolygus lucorum, a major cotton pest, has undergone a significant expansion of the FMRFaR gene within the GPCR superfamily, resulting in two classes of GPCR, namely FMRFaR (A54‐55) and newly duplicated FMRFaR‐like (A56‐62). Notably, FMRFaR‐like genes, particularly A62, show enhanced expression in the legs and wings of adults, indicating their potential role in locomotion. Employing A62 as a representative of FMRFaR‐like, our study investigates the influence of FMRFa, FMRFaR, and FMRFaR‐like on locomotion and development of A. lucorum. RESULTS: FMRFaR and FMRFa exhibit comparable temporal and tissue expression patterns, whereas the FMRFaR‐like genes within A. lucorum exhibit completely distinct evolutionary and expression patterns compared to classical FMRFaR. RNA interference (RNAi) experiments revealed that suppressing FMRFa expression results in complete lethality in A. lucorum, but neither FMRFaR nor A62 exhibit the same effect after RNAi. Suppressing the expression of FMRFa only decreases the expression of the A54 gene simultaneously, suggesting that A54 may function as a classical FMRFaR activated by FMRFa. RNAi of A62 leads to wing malformation and a significant reduction in spontaneous movement behavior in A. lucorum. Further transcriptomic analysis revealed that A62 affects the A. lucorum's movement behavior through energy metabolism pathways and motor protein pathways. CONCLUSION: Our study unveils the unique and complex roles of FMRFa and its receptor in A. lucorum. These findings provide valuable insights into potential targets for pest control strategies aimed at managing A. lucorum populations in cotton fields. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Each individual's movements are sculpted by constant interactions between sensorimotor and sociocultural factors. A theoretical framework grounded in motor control mechanisms articulating how sociocultural and biological signals converge to shape movement is currently missing. Here, we propose a framework for the emerging field of ethnokinesiology aiming to provide a conceptual space and vocabulary to help bring together researchers at this intersection. We offer a first-level schema for generating and testing hypotheses about cultural differences in movement to bridge gaps between the rich observations of cross-cultural movement variations and neurophysiological and biomechanical accounts of movement. We explicitly dissociate two interacting feedback loops that determine culturally relevant movement: one governing sensorimotor tasks regulated by neural signals internal to the body, the other governing ecological tasks generated through actions in the environment producing ecological consequences. A key idea is the emergence of individual-specific and culturally influenced motor concepts in the nervous system, low-dimensional functional mappings between sensorimotor and ecological task spaces. Motor accents arise from perceived differences in motor concept topologies across cultural contexts. We apply the framework to three examples: speech, gait and grasp. Finally, we discuss how ethnokinesiological studies may inform personalized motor skill training and rehabilitation, and challenges moving forward. This article is part of the theme issue 'Minds in movement: embodied cognition in the age of artificial intelligence'. [ABSTRACT FROM AUTHOR]

• A detailed neurophysiological and biomechanical characterization of age-related oropharyngeal dysphagia is reported. • To our knowledge, this is the first time that an impairment of the pharyngeal motor cortical pathway with age has been described. • Pharyngeal sensory/afferent impairment may be the critical pathophysiological element for oropharyngeal dysphagia in older patients. To characterize swallowing biomechanics and neurophysiology in older patients with oropharyngeal dysphagia (OD). Observational study in 12 young healthy volunteers (HV), 9 older HV (OHV) and 12 older patients with OD with no previous diseases causing OD (OOD). Swallowing biomechanics were measured by videofluoroscopy, neurophysiology with pharyngeal sensory (pSEP) and motor evoked-potentials (pMEP) to intrapharyngeal electrical and transcranial magnetic stimulation (TMS), respectively, and salivary neuropeptides with enzyme-linked immunosorbent assay (ELISA). 83.3% of OOD patients had unsafe swallows (Penetration-Aspiration scale = 4.3 ± 2.1; p < 0.0001) with delayed time to laryngeal vestibule closure (362.5 ± 73.3 ms; p < 0.0001) compared to both HV groups. OOD patients had: (a) higher pharyngeal sensory threshold (p = 0.009) and delayed pSEP P1 and N2 latencies (p < 0.05 vs HV) to electrical stimulus; and (b) higher pharyngeal motor thresholds to TMS in both hemispheres (p < 0.05) and delayed pMEPs latencies (right, p < 0.0001 HV vs OHV/OOD; left, p < 0.0001 HV vs OHV/OOD). OOD patients have unsafe swallow and delayed swallowing biomechanics, pharyngeal hypoesthesia with disrupted conduction of pharyngeal sensory inputs, and reduced excitability and delayed cortical motor response. These findings suggest new elements in the pathophysiology of aging-associated OD and herald new and more specific neurorehabilitation treatments for these patients. [ABSTRACT FROM AUTHOR]

Introduction Trigeminal schwannoma surgery has shown a remarkable improvement in functional recovery and tumor resection. In the era of radiosurgery, these outcomes need to be characterized for tumors which are outside the realm of being treated with radiosurgery. We present a series of trigeminal schwannomas larger than 3 cm, surgical approaches used, and outcomes with an emphasis on functional recovery in a high-volume center with radiosurgery facilities. Method All consecutive cases of trigeminal schwannoma from January 2012 to May 2021 which were more than 3 cm in size and underwent microsurgery were included in this series. The surgical approach, neurological outcomes, and extent of resection were defined objectively with pre/postoperative magnetic resonance imaging. Results A total of 83 such cases (>3 cm) were found, with cranial nerve symptoms (5th most common) being the commonest. Twenty three percent cases had blindness due to secondary optic atrophy and eighteen percent had long tract motor symptoms signifying the tumor burden in our series. Radiological gross total excision was achieved in 75.9% cases. Conclusion Large-volume schwannomas present with cranial nerve involvement and may need extensive skull base approaches. Functional outcomes need to be prioritized and can be achieved albeit with lesser gross resection rates. Hearing and facial preservation in addition to relief of trigeminal symptoms should be the goal of resection with minimal additional morbidity. [ABSTRACT FROM AUTHOR]

The central nervous system uses muscle co-activation for body coordination, effector movement control, and joint stabilization. However, co-activation increases compression and shear stresses on the joints. Lifting activity is one of the leading causes of work-related musculoskeletal problems worldwide, and it has been shown that when the risk level rises, lifting enhances trunk muscle co-activation at the L5/S1 level. This study aims to investigate the co-activation of lower limb muscles during liftings at various risk levels and lifting types (one-person and vs. two-person team lifting), to understand how the central nervous system governs lower limb rigidity during these tasks. The surface electromyographic signal of thirteen healthy volunteers (seven males and six females, age range: 29–48 years) was obtained over the trunk and right lower limb muscles while lifting in the sagittal plane. Then co-activation was computed according to different approaches: global, full leg, flexor, extensor, and rostro-caudal. The statistical analysis revealed a significant increase in the risk level and a decrease in the two-person on the mean and/or maximum of the co-activation in almost all the approaches. Overall, our findings imply that the central nervous system streamlines the motor regulation of lifting by increasing or reducing whole-limb rigidity within a distinct global, extensor, and rostro-caudal co-activation scheme, depending on the risk level/lifting type. [ABSTRACT FROM AUTHOR]

This review presents recent data on the restoration of motor functions after spinal injuries, on spontaneous neuroplasticity, on plasticity dependent on physical activity, on results from the use of epidural and transcutaneous electrical stimulation of the spinal cord to restore motor control, and on the neurophysiological changes and mechanisms initiated by spinal electrical stimulation which may contribute to functional recovery after spinal cord injury. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is an incurable neurological disorder that degenerates the cerebrospinal nervous system and hinders motor functions. Electroencephalography (EEG) signal analysis can provide reliable information regarding PD conditions. However, EEG is a complex, multichannel, and nonlinear signal with noise that problematizes identifying PD symptoms. A few studies have employed fractal dimension (FD) to extract distinguishing PD features from EEG signals. However, no exploratory study exists, as per our knowledge, on the efficiency of the different FD measures. We aim to conduct a comparative analysis of the various FDs that, as feature extraction measures, can discriminate PD patients who are ON and OFF medication from healthy controls using ML architecture. This study has implemented and analyzed several techniques for segmentation, feature extraction, and ML models. The results show that k-nearest neighbors (KNN) classifier with Higuchi FD and 90% overlap for segmented window delivers the highest accuracies, yielding a mean accuracy of 99.65 ± 0.15 % for PD patients ON medication and 99.45 ± 0.18 % for PD patients OFF medication, respectively. The model accurately identifies the signs of the disease in resting-state EEG with almost equivalent accuracy in both OFF and ON medication patients. To enhance the interpretability in our study, we leveraged XGB's feature importance to generate brain topographic plots. This integration of explainable AI (XAI) enhanced the transparency and comprehensibility of our model's classifications. Additionally, a comparison between the performance of FD and a few entropy measures has also been drawn to validate the significance of FD as a superior feature extraction measure. This study contributes to the body of knowledge with an architectural pipeline for detecting PD in resting-state EEG while emphasizing fractal dimension as an effective way of extracting salient features from EEG signals. [ABSTRACT FROM AUTHOR]

Introduction: Maximal grip strength, a measure of how much force a person's hand can generate when squeezing an object, may be an effective method for understanding potential neurobiological differences during motor tasks. Grip strength in autistic individuals may be of particular interest due to its unique developmental trajectory. While autism-specific differences in grip-brain relationships have been found in adult populations, it is possible that such differences in grip-brain relationships may be present at earlier ages when grip strength is behaviorally similar in autistic and non-autistic groups. Further, such neural differences may lead to the later emergence of diagnostic-group grip differences in adolescence. The present study sought to examine this possibility, while also examining if grip strength could elucidate the neuro-motor sources of phenotypic heterogeneity commonly observed within autism. Methods: Using high resolution, multi-shell diffusion, and quantitative R1 relaxometry imaging, this study examined how variations in key sensorimotorrelated white matter pathways of the proprioception input, lateral grasping, cortico-cerebellar, and corticospinal networks were associated with individual variations in grip strength in 68 autistic children and 70 non-autistic (neurotypical) children (6-11 years-old). Results: In both groups, results indicated that stronger grip strength was associated with higher proprioceptive input, lateral grasping, and corticospinal (but not cortico-cerebellar modification) fractional anisotropy and R1, indirect measures concordant with stronger microstructural coherence and increased myelination. Diagnostic group differences in these grip-brain relationships were not observed, but the autistic group exhibited more variability particularly in the cortico-cerebellar modification indices. An examination into the variability within the autistic group revealed that attention-deficit/hyperactivity disorder (ADHD) features moderated the relationships between grip strength and both fractional anisotropy and R1 relaxometry in the premotor-primary motor tract of the lateral grasping network and the cortico-cerebellar network tracts. Specifically, in autistic children with elevated ADHD features (60% of the autistic group) stronger grip strength was related to higher fractional anisotropy and R1 of the cerebellar modification network (stronger microstructural coherence and more myelin), whereas the opposite relationship was observed in autistic children with reduced ADHD features. Discussion: Together, this work suggests that while the foundational elements of grip strength are similar across school-aged autistic and non-autistic children, neural mechanisms of grip strength within autistic children may additionally depend on the presence of ADHD features. Specifically, stronger, more coherent connections of the cerebellar modification network, which is thought to play a role in refining and optimizing motor commands, may lead to stronger grip in children with more ADHD features, weaker grip in children with fewer ADHD features, and no difference in grip in non-autistic children. While future research is needed to understand if these findings extend to other motor tasks beyond grip strength, these results have implications for understanding the biological basis of neuromotor control in autistic children and emphasize the importance of assessing co-occurring conditions when evaluating brain-behavior relationships in autism. [ABSTRACT FROM AUTHOR]

Modular control of the muscle, which is called muscle synergy, simplifies control of the movement by the central nervous system. The purpose of this study was to explore the synergy in both the frequency and movement domains based on the non-negative Tucker decomposition (NTD) method. Surface electromyography (sEMG) data of 8 upper limb muscles in 10 healthy subjects under wrist flexion (WF) and wrist extension (WE) were recorded. NTD was selected for exploring the multi-domain muscle synergy from the sEMG data. The results showed two synergistic flexor pairs, Palmaris longus–Flexor Digitorum Superficialis (PL-FDS) and Extensor Carpi Radialis–Flexor Carpi Radialis (ECR-FCR), in the WF stage. Their spectral components are mainly in the respective bands 0–20 Hz and 25–50 Hz. And the spectral components of two extensor pairs, Extensor Digitorum–Extensor Carpi Ulnar (ED-ECU) and Extensor Carpi Radialis–Brachioradialis (ECR-B), are mainly in the respective bands 0–20 Hz and 7–45 Hz in the WE stage. Additionally, further analysis showed that the Biceps Brachii (BB) muscle was a shared muscle synergy module of the WE and WF stage, while the flexor muscles FCR, PL and FDS were the specific synergy modules of the WF stage, and the extensor muscles ED, ECU, ECR and B were the specific synergy modules of the WE stage. This study showed that NTD is a meaningful method to explore the multi-domain synergistic characteristics of multi-channel sEMG signals. The results can help us to better understand the frequency features of muscle synergy and shared and specific synergies, and expand the study perspective related to motor control in the nervous system. [ABSTRACT FROM AUTHOR]

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, η p 2 = 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. Listen to this article's corresponding podcast at https://jneurophysiol.podbean.com/e/jnp-micro-podcast-pontine-reticular-nuclei-scales-with-handgrip-force/. [ABSTRACT FROM AUTHOR]

• This article reviews the organization and function of the human corticospinal tract and its cortico-motoneuronal connections. • Accumulating evidence suggests the motor symptoms of ALS reflect pathology selectively targeting cortico-motoneuronal connections. • Dysfunction and degeneration of cortico-motoneuronal connections impacts not only muscle strength but also motor skill; effects on the latter may be the distinctive feature of ALS. Corticospinal neurons located in motor areas of the cerebral neocortex project corticospinal axons which synapse with the spinal network; a parallel corticobulbar system projects to the cranial motor network and to brainstem motor pathways. The primate corticospinal system has a widespread cortical origin and an extensive range of different fibre diameters, including thick, fast-conducting axons. Direct cortico-motoneuronal (CM) projections from the motor cortex to arm and hand alpha motoneurons are a recent evolutionary feature, that is well developed in dexterous primates and particularly in humans. Many of these projections originate from the caudal subdivision of area 4 ('new' M1: primary motor cortex). They arise from corticospinal neurons of varied soma size, including those with fast- and relatively slow-conducting axons. This CM system has been shown to be involved in the control of skilled movements, carried out with fractionation of the distal extremities and at low force levels. During movement, corticospinal neurons are activated quite differently from 'lower' motoneurons, and there is no simple or fixed functional relationship between a so-called 'upper' motoneuron and its target lower motoneuron. There are key differences in the organisation and function of the corticospinal and CM system in primates versus non-primates, such as rodents. These differences need to be recognized when making the choice of animal model for understanding disorders such as amyotrophic lateral sclerosis (ALS). In this neurodegenerative brain disease there is a selective loss of fast-conducting corticospinal axons, and their synaptic connections, and this is reflected in responses to non-invasive cortical stimuli and measures of cortico-muscular coherence. The loss of CM connections influencing distal limb muscles results in a differential loss of muscle strength or 'split-hand' phenotype. Importantly, there is also a unique impairment in the coordination of skilled hand tasks that require fractionation of digit movement. Scores on validated tests of skilled hand function could be used to assess disease progression. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a global health concern and central nervous system (CNS) TB leads to high mortality and morbidity. CNS TB can manifest as tubercular meningitis, tuberculoma, myelitis, and arachnoiditis. Neuro-ophthalmological involvement by TB can lead to permanent blindness, ocular nerve palsies and gaze restriction. Visual impairment is a dreaded complication of tubercular meningitis (TBM), which can result from visual pathway involvement at different levels with varying pathogenesis. Efferent pathway involvement includes cranial nerve palsies and disorders of gaze. The purpose of this review is to outline the various neuro-ophthalmological manifestations of TB along with a description of their unique pathogenesis and management. Optochiasmatic arachnoiditis and tuberculomas are the most common causes of vision loss followed by chronic papilloedema. Abducens nerve palsy is the most commonly seen ocular nerve palsy in TBM. Gaze palsies with deficits in saccades and pursuits can occur due to brainstem tuberculomas. Corticosteroids are the cornerstone in the management of paradoxical reactions, but other immunomodulators such as thalidomide and infliximab are being explored. Toxic optic neuropathy caused by ethambutol necessitates careful monitoring and immediate drug discontinuation. Cerebrospinal fluid diversion through ventriculo-peritoneal shunting may be required in patients with hydrocephalus in stage I and II of TBM to prevent visual impairment. Early diagnosis and prompt management are crucial to prevent permanent disability. Prevention strategies, public health initiatives, regular follow-up and timely intervention are essential in reducing the burden of CNS TB and its neuro-ophthalmological complications. [ABSTRACT FROM AUTHOR]

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target. [ABSTRACT FROM AUTHOR]

Introduction: Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital syndrome with complex skin, eye, and central nervous system (CNS) symptoms. Diagnosis and treatment are challenging due to its rarity and diverse manifestations. It often involves issues like porencephalic cysts, cortical atrophy, and low-grade gliomas in the CNS, resulting in developmental delays. The spinal cord is frequently affected, leading to problems like medullary compression and radiculopathy, causing back pain and sensory/motor deficits. Surgical interventions are reserved for symptomatic cases to address hydrocephalus or alleviate spinal lipomas. This article reviews a case series to assess surgical risks and neurological outcomes. Case series: We present a case series ECCL, focusing on the diffuse lipomatosis of the spinal cord and the intricate surgical procedures involved. A multi-stage surgical approach was adopted, with continuous neuromonitoring employed to safeguard motor pathways. We discuss clinical characteristics, imaging studies, and indications for neurosurgical interventions. Discussion: ECCL is a complex syndrome. Diagnosis is challenging and includes clinical evaluation, neuroimaging, and genetic testing. Treatment targets specific symptoms, often requiring surgery for issues like lipomas or cerebral cysts. Surgery involves laminectomies, spinal fusion, and motor pathway monitoring. Thorough follow-up is crucial due to potential CNS complications like low-grade gliomas. Hydrocephalus occurs in some cases, with endoscopic third ventriculostomy (ETV) preferred over ventriculoperitoneal shunt placement. Conclusion: Neurosurgery for ECCL is for symptomatic cases. ETV is preferred for hydrocephalus, while the treatment for lipoma is based on the presence of symptoms; the follow-up should assess growth and prevent deformities. [ABSTRACT FROM AUTHOR]

Background: Most of DYT genotypes follow an autosomal dominant inheritance pattern with reduced penetrance; the mechanisms underlying the disease development remain unclear. The objective of the study was to investigate cortical thickness, grey matter (GM) volumes and white matter (WM) alterations in asymptomatic (DYT-A) and symptomatic dystonia (DYT-S) mutation carriers. Methods: Eight DYT-A (four DYT-TOR1A and four DYT-THAP1), 14 DYT-S (seven DYT-TOR1A, and seven DYT-THAP1), and 37 matched healthy controls underwent 3D T1-weighted and diffusion tensor (DT) MRI to study cortical thickness, cerebellar and basal ganglia GM volumes and WM microstructural changes. Results: DYT-S showed thinning of the frontal and motor cortical regions related to sensorimotor and cognitive processing, together with putaminal atrophy and subcortical microstructural WM damage of both motor and extra-motor tracts such as cerebral peduncle, corona radiata, internal and external capsule, temporal and orbitofrontal WM, and corpus callosum. DYT-A had cortical thickening of middle frontal areas and WM damage of the corona radiata. Conclusions: DYT genes phenotypic expression is associated with alterations of both motor and extra-motor WM and GM regions. Asymptomatic genetic status is characterized by a very subtle affection of the WM motor pathway, together with an increased cortical thickness of higher-order frontal regions that might interfere with phenotypic presentation and disease manifestation. [ABSTRACT FROM AUTHOR]

The distribution of activation among muscles from the same anatomical group can be affected by the mechanical constraints of the task, such as limb orientation. For example, the distribution of activation between the gastrocnemius medialis (GM) and lateralis (GL) muscles during submaximal plantarflexion depends on the orientation of the foot in the horizontal plane. The neural mechanisms behind these modulations are not known. The overall aim of this study was to determine whether the excitability of the two gastrocnemius muscles is differentially affected by changes in foot orientation. Nineteen males performed isometric plantarflexions with their foot internally (toes-in) or externally (toes-out) rotated. GM and GL motor unit discharge characteristics were estimated from high-density surface electromyography to estimate neural drive. GM and GL corticospinal excitability and intracortical activity were assessed using transcranial magnetic stimulation through motor-evoked potentials. The efficacy of synaptic transmission between Ia-afferent fibers and α-motoneurons of the GM and GL was evaluated through the Hoffmann reflex. We observed a differential change in neural drive between GM (toes-out > toes-in) and GL (toes-out < toes-in). However, there was no foot orientation-related modulation in corticospinal excitability of the GM or GL, either at the cortical level or through modulation of the efficacy of Ia-α-motoneuron transmission. These results demonstrate that change in the motor pathway excitability is not the mechanism controlling the different distribution of neural drive between GM and GL with foot orientation. NEW & NOTEWORTHY: Horizontal foot orientation affects the distribution of neural drive between the gastrocnemii during plantarflexion. There is no foot orientation-related modulation in the corticospinal excitability of the gastrocnemii, either at the cortical level or through modulation of the efficacy of Ia-α-motoneuron transmission. Change in motor pathway excitability is not the mechanism controlling the different distribution of neural drive between gastrocnemius medialis and lateralis with foot orientation. [ABSTRACT FROM AUTHOR]

The hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4-7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8-11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground ('plant' times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory-motor circuits.

This letter reports a case of a 72-year-old female with an unusual clinical onset of Neuromyelitis optica spectrum disorder (NMOSD). The patient presented with area postrema syndrome (APS) and painful tonic spasms (PTS), which are not typical initial manifestations of NMOSD. The case highlights the importance of early diagnosis and comprehensive neurological examination in patients with persistent vomiting and nausea. The patient's symptoms were effectively managed with medication, and she is currently free from relapses and without neurological deficits. [Extracted from the article]

Advancements have been made in diagnostic methods for early-stage diabetic polyneuropathy (DPN), a common complication of diabetes mellitus. Early and accurate diagnosis of DPN is crucial for preventing complications and enabling timely intervention. Diagnostic methods include skin biopsy, corneal confocal microscopy, and assessment of autonomic neuropathy. Researchers are also investigating blood-based biomarkers for diagnosing DPN. These advancements enhance our ability to detect and manage DPN effectively. [Extracted from the article]

Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms. [ABSTRACT FROM AUTHOR]

The exact mechanisms of the development of autism, a multifactorial neurological disorder, are not clear. The pathophysiology of autism is complex, and investigations at the cellular and molecular levels are ongoing to provide clarity. Mutations in specific genes have been identified as risk factors for autism. The role of heavy metals in the pathogenesis of autism is subject to many studies and remains debatable. Although no exact neuronal phenotypes have been identified linked to autistic symptoms, overproduction and reduction of specific neurons have been implicated. A growing literature on generating genetic and non-genetic models of autism aims to help with understanding mechanistic studies that can explain the complexity of the disorder. Both genetic and non-genetic methods of zebrafish have been used to model autism. For several human autism risk genes, validated zebrafish mutant models have been generated. There is growing evidence indicating a potential link between autism and inorganic arsenic exposure. We have previously shown that inorganic arsenic induces supernumerary spinal motor neurons via Sonic hedgehog (Shh) signaling pathway, and Cdk5 knockdown causes an overproduction of cranial and spinal motor neurons in zebrafish. Here, in this review, we provide a perspective on what these findings of neurogenic phenotypes mean in terms of dysregulated pathways of motor neuron development and their applicability to understanding cellular and molecular underpinnings of autism. [ABSTRACT FROM AUTHOR]

Background: Balance and mobility impairments are prevalent post-stroke and a large number of survivors require walking assistance at 6 months post-stroke which diminishes their overall quality of life. Personalized interventions for gait and balance rehabilitation are crucial. Recent evidence indicates that stroke lesions in primary motor pathways, such as corticoreticular pathways (CRP) and corticospinal tract (CST), may lead to reliance on alternate motor pathways as compensation, but the current evidence lacks comprehensive knowledge about the underlying neural mechanisms. Methods: In this study, we investigate the functional connectivity (FC) changes within the motor network derived from an individualized cortical parcellation approach in 33 participants with chronic stroke compared to 17 healthy controls. The correlations between altered motor FC and gait deficits (i.e., walking speed and walking balance) were then estimated in the stroke population to understand the compensation mechanism of the motor network in motor function rehabilitation post-stroke. Results: Our results demonstrated significant FC increases between ipsilesional medial supplementary motor area (SMA) and premotor in stroke compared to healthy controls. Furthermore, we also revealed a negative correlation between ipsilesional SMA-premotor FC and self-selected walking speed, as well as the Functional Gait Assessment (FGA) scores. Conclusion: The increased FC between the ipsilesional SMA and premotor regions could be a compensatory mechanism within the motor network following a stroke when the individual can presumably no longer rely on the more precise CST modulation of movements to produce a healthy walking pattern. These findings enhance our understanding of individualized motor network FC changes and their connection to gait and walking balance impairments post-stroke, improving stroke rehabilitation interventions. [ABSTRACT FROM AUTHOR]

Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome when obesity occurs during adolescence, a maturational period for brain structures critical for cognition. In rodent models, we recently reported that memory impairments induced by obesogenic high-fat diet (HFD) intake during the periadolescent period can be reversed by chemogenetic manipulation of the ventral hippocampus (vHPC). Here, we used an intersectional viral approach in HFD-fed male mice to chemogenetically inactivate specific vHPC efferent pathways to nucleus accumbens (NAc) or medial prefrontal cortex (mPFC) during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normalizing this activation. Inactivation of the vHPC-NAc pathway rescued HFD-induced deficits in recognition but not location memory. Conversely, inactivation of the vHPC-mPFC pathway restored location but not recognition memory impairments produced by HFD. Either pathway manipulation did not affect exploration or anxiety-like behaviour. These findings suggest that HFD intake throughout adolescence impairs different types of memory through overactivation of specific hippocampal efferent pathways and that targeting these overactive pathways has therapeutic potential. [ABSTRACT FROM AUTHOR]

Postoperative hemiparesis following frontal lobe lesion resection is alarming, and predicting motor function recovery is challenging. Supplementary motor area (SMA) syndrome following resection of frontal lobe lesions is often indistinguishable from postoperative motor deficit due to surgical injury of motor tracts. We aimed to describe the use of intraoperative transcranial electrical stimulation (TES) with motor evoked potential monitoring data as a diagnostic tool to distinguish between SMA syndrome and permanent motor deficit (PMD). A retrospective analysis of 235 patients undergoing craniotomy and resection with TES-MEP monitoring for a frontal lobe lesion was performed. Patients who developed immediate postoperative motor deficit were included. Motor deficit and TES-MEP findings were categorized by muscle group as left upper extremity, left lower extremity, right upper extremity, or right lower extremity. Statistical analysis was performed to determine the predictive value of stable TES-MEP for SMA syndrome versus PMD. This study included 20 patients comprising 29 cases of immediate postoperative motor deficit by muscle group. Of these, 27 cases resolved and were diagnosed as SMA syndrome, and 2 cases progressed to PMD. TES-MEP stability was significantly associated with diagnosis of SMA syndrome (P = 0.015). TES-MEP showed excellent diagnostic utility with a sensitivity and positive predictive value of 100% and 92.6%, respectively. Negative predictive value was 100%. Temporary SMA syndrome is difficult to distinguish from PMD immediately postoperatively. TES-MEP may be a useful intraoperative adjunct that may aid in distinguishing SMA syndrome from PMD secondary to surgical injury. [ABSTRACT FROM AUTHOR]

Brain–computer interfaces (BCIs) can provide a non-muscular channel of control to stroke patients for motor rehabilitation. This can be achieved through the use of motor imagery (MI) training, involving the modulation of sensorimotor rhythms. The practice of MI has been shown to be able to strengthen key motor pathways when reinforced with rewarding feedback. Recently, there has been a growing evidence of the positive impact of embodied virtual reality (VR) and vibrotactile feedback in MI training. Nonetheless, it is not yet clear what the optimal MI-BCI setup is for evoking stronger sensorimotor rhythms in VR. In this study, we investigate the impact of head-mounted VR, and vibrotactile feedback during MI-BCI training in the induced sensorimotor rhythms. To achieve this, 19 healthy subjects performed MI training with embodied VR between four conditions: head-mounted vs. screen VR, with and without vibrotactile feedback; and two control conditions: abstract MI without embodied feedback, and motor execution. The event-related desynchronization (ERD) and the lateralization indices (LI) of the Alpha and Beta EEG rhythms were analyzed in a within-subject design. Results show that the combination of vibrotactile feedback and embodied VR can induce stronger and more lateralized Alpha ERD; nonetheless, LI was not significantly different across conditions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging. [ABSTRACT FROM AUTHOR]

(1) Background: Degenerative cervical myelopathy is one of the main causes of disability in the elderly. The treatment of choice in patients with clear symptomatology and radiological correlation is surgical decompression. The application of navigated transcranial magnetic stimulation (nTMS) techniques has the potential to provide additional insights into the cortical and corticospinal behavior of the myelopathic cord and to better characterize the possible extent of clinical recovery. The objective of our study was to use nTMS to evaluate the effect of surgical decompression on neurophysiological properties at the cortical and corticospinal level and to better characterize the extent of possible clinical recovery. (2) Methods: We conducted a longitudinal study in which we assessed and compared nTMS neurophysiological indexes and clinical parameters (modified Japanese Orthopedic Association score and nine-hole pegboard test) before surgery, at 6 months, and at 12 months' follow-up in a population of 15 patients. (3) Results: We found a significant reduction in resting motor threshold (RMT; average 7%), cortical silent period (CSP; average 15%), and motor area (average 25%) at both 6 months and 12 months. A statistically significant linear correlation emerged between recruitment curve (RC) values obtained at follow-up appointments and at baseline (r = 0.95 at 6 months, r = 0.98 at 12 months). A concomitant improvement in the mJOA score and in the nine-hole pegboard task was observed after surgery. (4) Conclusions: Our results suggest that surgical decompression of the myelopathic spinal cord improves the neurophysiological balance at the cortical and corticospinal level, resulting in clinically significant recovery. Such findings contribute to the existing evidence characterizing the brain and the spinal cord as a dynamic system capable of functional and reversible plasticity and provide useful clinical insights to be used for patient counseling. [ABSTRACT FROM AUTHOR]

Motor and somatosensory pathway dysfunction due to degeneration of long tracts in hereditary spastic paraplegias (HSP) indicates that postural abnormalities may be a relevant disease feature. However, balance assessments have been underutilized to study these conditions. How does the static balance of individuals with HSP with eyes open and closed differ from healthy controls, and how does it relate to disease severity? This cross-sectional case–control study assessed the static balance of 17 subjects with genetically confirmed HSP and 17 healthy individuals, evaluating the center of pressure (COP) variables captured by a force platform. The root-mean-square of velocities and mean of displacements amplitudes in mediolateral and anteroposterior axes were correlated with disease severity. All COP parameters' performances were significantly impaired in HSP subjects compared to controls (p < 0.001 for all comparisons). COP with eyes open and closed differed for all variables within the HSP group, whereas in the control group, differences were observed only for anteroposterior velocity and amplitude. Spastic Paraplegia Rating Scale presented moderate direct correlations with the most COP variables (Rho = − 0.520 to − 0.736). HSP individuals presented significant postural instability with eyes open and to a greater extent with eyes closed, corroborating the clinical findings of somatosensorial and proprioceptive pathways dysfunction. The degrees of proprioceptive and motor impairments are mutually correlated, suggesting that similar pathophysiological mechanisms operate for the degeneration of these long tracts. COP parameters can be seen as disease severity biomarkers of HSP, and they should be assessed in future clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: The present review aims to analyze the scientific evidence of the hypothalamic control of hypothermia and the central and peripheral changes that are triggered in domestic animals. After the perception of a core temperature decreases, several mechanisms aiming to prevent heat loss or produce heat are initiated. However, the type of mechanism and degree of activation depend on the species. Therefore, understanding the hypothalamic control of hypothermia could help us to understand the implications of the compensatory mechanisms in domestic animals. When an organism detects decreases in their core body temperature, the hypothalamus, the main thermoregulatory center, triggers compensatory responses. These responses include vasomotor changes to prevent heat loss and physiological mechanisms (e.g., shivering and non-shivering thermogenesis) for heat production. Both types of changes require the participation of peripheral thermoreceptors, afferent signaling to the spinal cord and hypothalamus, and efferent pathways to motor and/or sympathetic neurons. The present review aims to analyze the scientific evidence of the hypothalamic control of hypothermia and the central and peripheral changes that are triggered in domestic animals. [ABSTRACT FROM AUTHOR]

Background and Purpose: Little is known of how cranial autonomic symptoms (CAS) in cluster headache and migraine may contribute to their severe headache phenotype. This strong association suggests the involvement of the cranial parasympathetic efferent pathway. To investigate its contribution, we studied the role of pituitary adenylate cyclase activating polypeptide‐38 (PACAP‐38), a potent sensory and parasympathetic neuropeptide, in modulating pre‐ and post‐ganglionic cranial parasympathetic projection neurons, and their influence on headache‐related trigeminal‐autonomic responses. Experimental Approach: Using PACAP‐38 and PACAP‐38 responsive receptor antagonists, electrophysiological, behavioural and facial neurovascular‐blood flow was measured in rats to probe trigeminal‐ and parasympathetic‐neuronal, periorbital thresholds and cranial‐autonomic outcomes, as they relate to primary headaches. Key Results: Sumatriptan attenuated the development of PACAP‐38 mediated activation and sensitization of trigeminocervical neurons and related periorbital allodynia. PACAP‐38 also caused activation and enhanced responses of dural‐responsive pre‐ganglionic pontine‐superior salivatory parasympathetic neurons. Further, the PACAP‐38 responsive receptor antagonists dissected a role of VPAC1 and PAC1 receptors in attenuating cranial‐autonomic and trigeminal‐neuronal responses to activation of the cranial parasympathetic projection, which requires post‐ganglionic parasympathetic neurotransmission. Conclusion and Implications: Given the prevailing view that sumatriptan acts to some degree via a peripheral mechanism, our data support that PACAP‐38 mediated receptor activation modulates headache‐related cranial‐autonomic and trigeminovascular responses via peripheral and central components of the cranial parasympathetic projection. This provides a mechanistic rationale for the association of CAS with more severe headache phenotypes in cluster headache and migraine, and supports the cranial parasympathetic projection as a potential novel locus for treatment by selectively targeting PACAP‐38 or PACAP‐38 responsive VPAC1/PAC1 receptors. [ABSTRACT FROM AUTHOR]

The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer. [ABSTRACT FROM AUTHOR]

Objective: A motor complete spinal cord injury (SCI) results in the loss of voluntary motor control below the point of injury. Some of these patients can regain partial motor function through inpatient rehabilitation; however, there is currently no biomarker to easily identify which patients have this potential. Evidence indicates that spasticity could be that marker. Patients with motor complete SCI who exhibit spasticity show preservation of descending motor pathways, the pathways necessary for motor signals to be carried from the brain to the target muscle. We hypothesized that the presence of spasticity predicts motor recovery after subacute motor complete SCI. Methods: Spasticity (Modified Ashworth Scale and pendulum test) and descending connectivity (motor evoked potentials) were tested in the rectus femoris muscle in patients with subacute motor complete (n = 36) and motor incomplete (n = 30) SCI. Motor recovery was assessed by using the International Standards for Neurological Classification of Spinal Cord Injury and the American Spinal Injury Association Impairment Scale (AIS). All measurements were taken at admission and discharge from inpatient rehabilitation. Results: We found that motor complete SCI patients with spasticity improved in motor scores and showed AIS conversion to either motor or sensory incomplete. Conversely, patients without spasticity showed no changes in motor scores and AIS conversion. In incomplete SCI patients, motor scores improved and AIS conversion occurred regardless of spasticity. Interpretation: These findings suggest that spasticity represents an easy‐to‐use clinical outcome that might help to predict motor recovery after severe SCI. This knowledge can improve inpatient rehabilitation effectiveness for motor complete SCI patients. ANN NEUROL 2024;95:71–86 [ABSTRACT FROM AUTHOR]