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Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Neural conditioning to scenarios of muscle disuse is undoubtedly a cause of functional decrements that typically exceed losses of muscle size. Yet establishing the relative contribution of neural adaptation and the specific location in the motor pathway remains technically challenging. Several studies of healthy humans have targeted this system and have established that motor unit firing rate is suppressed following disuse, with a number of critical caveats. It is suppressed in the immobilized limb only, at relative and absolute force levels, and preferentially targets lower‐threshold motor units. Concomitantly, electrophysiological investigation of neuromuscular junction transmission (NMJ) stability of lower‐threshold motor units reveals minimal change following disuse. These findings contrast with numerous other methods, which show clear involvement of the NMJ but are unable to characterize the motor unit to which they belong. It is physiologically plausible that decrements observed following disuse are a result of suppressed firing rate of lower‐threshold motor units and impairment of transmission of the NMJ of higher‐threshold motor units. As such, motor units within the pool should be viewed in light of their varying susceptibility to disuse. [ABSTRACT FROM AUTHOR]

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

Introduction: Schizophrenia patients have cognitive issues, such as attention deficits. Cognitive activity controls the micromechanics of cochlear outer hair cells (OHC). We integrated alternate auditory attention (ALAUDIN) tasks and contralateral suppression of otoacoustic emissions (CSOAE) to measure OHC micromechanics. Materials and methods: The ALAUDIN tasks' reliability has been evaluated in ten normal-hearing ears. Then, 36 healthy controls and 8 schizophrenia patients with normal auditory function has been included. The OAE amplitude was initially measured with 60 dB peak SPL clicks in the test ear without contralateral suppressors (CS) and re-measured with four types of CS, namely White Noise (CS1), White Noise + Attention Task I (CS2), White Noise + Attention Task II (CS3) and White Noise + Attention Task III (CS4), delivered randomly to non-test ears at 75 dB SPL. Suppression is a positive difference in OAE amplitudes with and without CS. Statistical analysis included Bayesian independent sample t-tests to compare suppression between groups and ears, as well as Bayesian repeated measures ANOVA to assess differences in suppression among various stimuli for all groups. Results: Interclass correlation showed moderate to high reliability across all CS. In the schizophrenia group, CS4 had the highest TEOAE suppression value. Suppression in schizophrenia is larger than healthy control in all stimuli with CS1 and CS4 showing significantly greater suppression. Stimuli did not affect CSOAE across groups. Conclusion: Cognitive deficits in schizophrenia patients may be objectively identified using the integrated ALAUDIN tasks-CSOAE. Their large suppression suggests dysconnectivity among brain regions, resulting in hyperactivity of the efferent pathway. [ABSTRACT FROM AUTHOR]

Adaptation of reactive saccades (RS), made toward the sudden appearance of stimuli in our environment, is a plastic mechanism thought to occur at the motor level of saccade generation. As saccadic oculomotor commands integrate multisensory information in the parietal cortex and superior colliculus, adaptation of RS should occur not only toward visual but also tactile targets. In addition, saccadic adaptation in one modality (vision or touch) should transfer cross-modally. To test these predictions, we used the double-step target paradigm to adapt rightward saccades made at two different eccentricities toward the participants' index and middle fingers, identified either visually (experiment 1) or tactually (experiment 2). In each experiment, the rate of adaptation induced for the adapted modality and the rate of adaptation transfer to the nonadapted modality were compared with that measured in a control (no adaptation) session. Results revealed that touch-triggered RS can be adapted as well as visually triggered ones. Moreover, the transfer pattern was asymmetric: visual saccadic adaptation transferred fully to tactile saccades, whereas tactile saccadic adaptation, despite full generalization to nonadapted fingers, transferred only partially to visual saccades. These findings disclose that in the case of tactile saccades, adaptation can be elicited in the absence of postsaccadic visual feedback. In addition, the asymmetric adaptation transfer across sensory modalities suggests that the adaptation locus for tactile saccades may occur in part upstream of the final motor pathway common to all saccades. These findings bring new insights both on the functional loci(us) and on the error signals of RS adaptation. NEW & NOTEWORTHY: The present study revealed that, as predicted from a large literature, adaptation of visual reactive saccades transfers to tactile saccades of the same as well as neighboring amplitudes. Furthermore, in a modified double-step target paradigm, tactile saccades exposed to repeated errors adapt with a similar rate and spatial generalization as visual saccades, but this adaptation only slightly transfers to visual saccades. These findings bring new information on saccadic adaptation processes. [ABSTRACT FROM AUTHOR]

This study investigated the influence of stimulation parameters on torque production when combining a brief muscle lengthening with electrical stimulation. Fifteen volunteers participated in one experimental session where two distinct stimulation modalities were compared: wide-pulse high-frequency (WPHF; pulse duration: 1 ms, frequency: 100 Hz), favoring afferent pathway activation, and narrow-pulse low-frequency (NPLF; pulse duration: 0.05 ms, frequency: 20 Hz), favoring activation of the efferent pathway. Both stimulation modalities were applied to evoke 5–10% of maximal voluntary contraction either in isometric conditions (WPHF and NPLF) or in combination with a muscle lengthening (lengthening condition: WPHF + LEN and NPLF + LEN). The torque-time integral (TTI) during the stimulation trains and the muscle activity after the cessation of the stimulation trains [sustained electromyographic (EMG) activity, normalized to the maximal EMG activity] were assessed and compared between the stimulation modalities and the conditions (2-way ANOVA). An interaction effect was obtained, revealing significant differences in TTI and sustained EMG activity between WPHF + LEN and the other tested conditions (P = 0.048 and P = 0.044, respectively). TTI and sustained EMG activity were higher for WPHF + LEN (228.4 ± 105.3 Nm·s and 0.085 ± 0.070, respectively) compared to WPHF (168.4 ± 72.9 Nm·s; 0.052 ± 0.026), NPLF + LEN (136.4 ± 38.9 Nm·s; 0.031 ± 0.016), and NPLF (125.2 ± 36.1 Nm·s; 0.028 ± 0.015). The increased TTI during the WPHF + LEN condition suggests that the contribution of afferent pathways to the evoked torque can be enhanced with the muscle lengthening superimposition. They highlight the importance of using WPHF stimulation that already solicits Ia afferents, to benefit from the cumulative afferent activation induced by the muscle lengthening to further increase torque production. NEW & NOTEWORTHY: The results of the present study highlight the importance of using electrical stimulation modalities that preferentially activate Ia afferents to take advantage of the superimposition of muscle lengthening to further enhance afferent pathways' contribution to evoked torque and, in turn, increase torque production. These results offer the opportunity to improve the efficacy of the wide-pulse high-frequency stimulation modality. [ABSTRACT FROM AUTHOR]

Evidence from clinical and preclinical studies has shown that the cerebellum contributes to cognitive functions, including social behaviors. Now that the cerebellum's role in a wider range of behaviors has been confirmed, the question arises whether the cerebellum contributes to social behaviors via the same mechanisms with which it modulates movements. This review seeks to answer whether the cerebellum guides motor and social behaviors through identical pathways. It focuses on studies in which cerebellar cells, synapses, or genes are manipulated in a cell-type specific manner followed by testing of the effects on social and motor behaviors. These studies show that both anatomically restricted and cerebellar cortex-wide manipulations can lead to social impairments without abnormal motor control, and vice versa. These studies suggest that the cerebellum employs different cellular, synaptic, and molecular pathways for social and motor behaviors. Future studies warrant a focus on the diverging mechanisms by which the cerebellum contributes to a wide range of neural functions. [ABSTRACT FROM AUTHOR]

Helicobacter pylori encodes homologues of PilM, PilN and PilO from bacteria with Type IV pili, where these proteins form a pilus alignment complex. Inactivation of pilO changes H. pylori motility in semi‐solid media, suggesting a link to the chemosensory pathways or flagellar motor. Here, we showed that mutation of the pilO or pilN gene in H. pylori strain SS1 reduced the mean linear swimming speed in liquid media, implicating PilO and PilN in the function, or regulation of, the flagellar motor. We also demonstrated that the soluble variants of H. pylori PilN and PilO share common biochemical properties with their Type IV pili counterparts which suggests their adapted function in the bacterial flagellar motor may be similar to that in the Type IV pili. [ABSTRACT FROM AUTHOR]

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]

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar cortical excitability in a polarity-dependent manner and affects inhibitory pathways from the cerebellum. The cerebellum modulates spinal reflex excitability via the vestibulospinal tract and other pathways projecting to the spinal motor neurons; however, the effects of ctDCS on the excitability of spinal motor neurons and vestibulospinal tract remain unclear. The experiment involved 13 healthy individuals. ctDCS (sham-ctDCS, anodal-ctDCS, and cathodal-ctDCS) was applied to the cerebellar vermis at 2 mA with an interval of at least 3 days between each condition. We measured the maximal M-wave (Mmax) and maximal H-reflex (Hmax) in the right soleus muscle to assess the excitability of spinal motor neurons. We applied galvanic vestibular stimulation (GVS) for 200 ms at 100 ms before tibial nerve stimulation to measure Hmax conditioned by GVS (GVS-Hmax) and calculated the change rate of Hmax by GVS as the excitability of vestibulospinal tract. We measured the Mmax, Hmax, and GVS-Hmax before, during, and after ctDCS in the sitting posture. No main effects of tDCS condition, main effects of time, or interaction effects were observed in Hmax/Mmax or the change rate of Hmax by GVS. It has been suggested that ctDCS does not affect the excitability of spinal motor neurons and vestibulospinal tract, as measured by neurophysiological methods, such as the H-reflex, in healthy individuals in a sitting posture. Effect of ctDCS on other descending pathways to spinal motor neurons, the neurological mechanism of tDCS and the cerebellar activity during the experiment may have contributed to these results. Therefore, we need to investigate the involvement of the cerebellum in Hmax/Mmax and the change rate of Hmax by GVS under different neuromodulation techniques and postural conditions. [ABSTRACT FROM AUTHOR]

• First meta -analysis characterized diagnostic accuracy of facial motor evoked potentials for cerebellopontine angle tumor surgeries. • Facial motor evoked potentials were a useful indicator for postoperative facial outcomes in both immediate and follow-up periods. • Amplitude cutoff criteria and a dichotomous facial strength assessment improved facial motor evoked potentials accuracy. Our aim is to explore the value of intraoperative facial motor evoked potentials (FMEP) for facial outcomes in cerebellopontine angle (CPA) tumor surgery to provide an evidence-based consensus standard for future clinical practice and prospective studies. Electronic databases were searched from inception to June 2023. Study quality was assessed with the QUADAS-2 tool. Bivariate and random-effects models for meta -analysis and meta -regression generated summary receiver operating characteristic curves (ROC) and forest plots for estimates of sensitivity and specificity. We included 17 studies (1,206 participants). Sensitivity was lower in the immediate (IM) post-operative (0.76, 95% CI 0.65–0.84) compared to follow-up (FU) period (0.82, 95% CI 0.74–0.88) while specificity was similar in both groups (IM, 0.94, 95% CI 0.89–0.97; FU, 0.93, 95% CI 0.87–0.96). Data driven estimates improved FMEP performance but require confirmation from future studies. Amplitude cutoff criteria and studies that scored new deficits as worse than House-Brackmann (HB) grade 2 yielded best sensitivities. FMEP demonstrated statistically significant accuracy for facial function monitoring. Implementation of FMEPs varied widely across studies. Our study is the first systematic review with meta -analysis to demonstrate that intraoperative FMEP is valuable in CPA tumor surgery for facial outcomes. Meta-regression identified the methods that were most useful in the application of FMEPs. [ABSTRACT FROM AUTHOR]

Adult central nervous system (CNS) neurons down-regulate growth programs after injury, leading to persistent regeneration failure. Coordinated lipids metabolism is required to synthesize membrane components during axon regeneration. However, lipids also function as cell signaling molecules. Whether lipid signaling contributes to axon regeneration remains unclear. In this study, we showed that lipin1 orchestrates mechanistic target of rapamycin (mTOR) and STAT3 signaling pathways to determine axon regeneration. We established an mTOR-lipin1-phosphatidic acid/lysophosphatidic acid-mTOR loop that acts as a positive feedback inhibitory signaling, contributing to the persistent suppression of CNS axon regeneration following injury. In addition, lipin1 knockdown (KD) enhances corticospinal tract (CST) sprouting after unilateral pyramidotomy and promotes CST regeneration following complete spinal cord injury (SCI). Furthermore, lipin1 KD enhances sensory axon regeneration after SCI. Overall, our research reveals that lipin1 functions as a central regulator to coordinate mTOR and STAT3 signaling pathways in the CNS neurons and highlights the potential of lipin1 as a promising therapeutic target for promoting the regeneration of motor and sensory axons after SCI. [ABSTRACT FROM AUTHOR]

Biological motions of native muscle tissues rely on the nervous system to interface movement with the surrounding environment. The neural innervation of muscles, crucial for regulating movement, is the fundamental infrastructure for swiftly responding to changes in body tissue requirements. This study introduces a bioelectronic neuromuscular robot integrated with the motor nervous system through electrical synapses to evoke cardiac muscle activities and steer robotic motion. Serving as an artificial brain and wirelessly regulating selective neural activation to initiate robot fin motion, a wireless frequency multiplexing bioelectronic device is used to control the robot. Frequency multiplexing bioelectronics enables the control of the robot locomotion speed and direction by modulating the flapping of the robot fins through the wireless motor innervation of cardiac muscles. The robots demonstrated an average locomotion speed of ~0.52 ± 0.22 millimeters per second, fin-flapping frequency up to 2.0 hertz, and turning locomotion path curvature of ~0.11 ± 0.04 radians per millimeter. These systems will contribute to the expansion of biohybrid machines into the brain-to-motor frontier for developing autonomous biohybrid systems capable of advanced adaptive motor control and learning. Editor's summary: Typically, biohybrid machines built from cardiac muscle cells have relied on the involuntary, contractile actuation of the cells to continuously propel the robot. However, without the nervous system, this rhythmic pumping action could not be adjusted or controlled. To imbue control, Tetsuka et al. developed a biohybrid swimmer with a neurocardiac muscle junction. Acting as an artificial brain, a frequency multiplexing wireless system was used to stimulate the motor neurons, which in turn activated the cardiac muscle cells. The robot's speed could be controlled by modulating the frequency and pulse duration of the electrical signal, and direction was altered by transmitting signals to the left and right fins independently. —Melisa Yashinski [ABSTRACT FROM AUTHOR]

AbstractUsing diffusion tensor imaging (DTI), we assessed the extent to which fractional anisotropy values in the dorsal (i.e., arcuate fasciculus; AF) versus ventral (i.e., inferior fronto-occipital fasciculus; IFOF) distinction of structural white matter pathways associated with selected reading processes, could be replicated in skilled adult readers (N = 17) and extended to adults with reading impairments (N = 13). In addition to the AF and IFOF, motor-based tracts (i.e., posterior limb of the internal capsule (PLIC) and the frontal aslant tract (FAT)) were isolated to explore their role in reading performance. Several interesting relationships with reading performance emerged. First, orthographic awareness was related to the left IFOF in skilled readers, whereas orthographic awareness was related to left PLIC for impaired readers. Morphological awareness was related to left FAT for skilled readers, whereas morphological awareness was related to right AF, right IFOF and left PLIC for impaired readers. Overall, these findings support the notion that adult reading performance (both skilled and impaired) is related to the structural properties of the ventral white matter pathways. More consideration should be paid to motor pathways, particularly the PLIC, and their role in compensatory reading strategies in individuals with reading impairments. [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]

Objective: 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. Methods: 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. Results: 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. Interpretation: 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]

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output. NEW & NOTEWORTHY: Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways. [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]

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]

Background: The motor function defects in stroke patients are mainly caused by damage to brain neurons and network disconnection, as viewed through neuroimaging. Structural and functional magnetic resonance imaging (sMRI and fMRI) are the most commonly used techniques in studying central nervous system diseases. This article reviews recent technological research to provide evidence for acupuncture research and development. Materials and Methods: Relevant articles were obtained from PubMed and China national knowledge infrastructure (CNKI) databases, as well as from CNKI database from 2014 to 2023. The data were then reviewed and the citations were examined. Results: The non-invasive technique of magnetic resonance imaging (MRI) is highly effective in accurately identifying abnormal brain activities, making it a top choice. As MRI technology rapidly evolves, additional techniques such as diffusion kurtosis imaging (DKI), diffusion spectrum imaging (DSI), and neurite orientation dispersion and density imaging (NODDI) can be used to observe post-IS motor neural injuries and related neural reshaping. Conclusions: These techniques about MRI could help doctors better understand the biological mechanisms underlying neural pathways and motor deficits in IS, aiding in the development of targeted therapies. [ABSTRACT FROM AUTHOR]

• 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]

Thermoregulation is critical for survival across species. In animals, the nervous system detects external and internal temperatures, integrates this information with internal states, and ultimately forms a decision on appropriate thermoregulatory actions. Recent work has identified critical molecules and sensory and motor pathways controlling thermoregulation. However, especially with regard to behavioral thermoregulation, many open questions remain. Here, we aim to both summarize the current state of research, the "knowledge," as well as what in our mind is still largely missing, the "future directions." Given the host of circuit entry points that have been discovered, we specifically see that the time is ripe for a neuro-computational perspective on thermoregulation. Such a perspective is largely lacking but is increasingly fueled and made possible by the development of advanced tools and modeling strategies. [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]

• 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]

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]

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]

The article "Neurons & Control of Movement" from Frontiers in Education focuses on a lesson for middle school students about the brain's role in voluntary movement and the communication between neurons. The lesson addresses Next Generation Science Standards and aims to help students recognize how neurons use electrical signaling to communicate. It includes teacher preparation tips, scientific vocabulary, and resources for instructors, as well as a detailed timeline for the lesson, which involves hands-on activities like using human-to-human interfaces and claw interfaces to understand brain control of movement. [Extracted from the article]

The article "Neurons & Control of Movement" from Frontiers in Education discusses a lesson plan for middle school students to learn about the brain's role in voluntary movement and the communication between neurons. The lesson aims to help students recognize how neurons use electrical signaling to communicate and understand how signals from the brain control movement. The lesson includes hands-on activities using human-to-human interfaces and claw interfaces to demonstrate these concepts. The article provides resources for instructors and outlines the timeline for the lesson, emphasizing the importance of safety and careful handling of equipment. [Extracted from the article]

This article discusses the phenomenon known as the "insertional effect" that occurs following the implantation of electrodes for deep brain stimulation (DBS). The insertional effect refers to the molecular, neurochemical, and electrophysiological changes that occur after electrode implantation, before the delivery of electrical stimulation. These changes can lead to clinical improvements in motor symptoms for movement disorders such as tremor, dystonia, and Parkinson's disease. The insertional effect has also been observed in patients with epilepsy, pain, and psychiatric disorders, although the clinical improvements in these conditions are largely subjective. The article highlights the importance of considering the insertional effect in both clinical and research settings, but notes that it is largely a transient effect and does not mitigate disease pathology or symptoms in the long term. The variability in the incidence and duration of the insertional effect among patients is not well understood and requires further investigation. [Extracted from the article]

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.

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]