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Working memory, the process through which information is transiently maintained and manipulated over a brief period, is essential for most cognitive functions1-4. However, the mechanisms underlying the generation and evolution of working-memory neuronal representations at the population level over long timescales remain unclear. Here, to identify these mechanisms, we trained head-fixed mice to perform an olfactory delayed-association task in which the mice made decisions depending on the sequential identity of two odours separated by a 5 s delay. Optogenetic inhibition of secondary motor neurons during the late-delay and choice epochs strongly impaired the task performance of the mice. Mesoscopic calcium imaging of large neuronal populations of the secondary motor cortex (M2), retrosplenial cortex (RSA) and primary motor cortex (M1) showed that many late-delay-epoch-selective neurons emerged in M2 as the mice learned the task. Working-memory late-delay decoding accuracy substantially improved in the M2, but not in the M1 or RSA, as the mice became experts. During the early expert phase, working-memory representations during the late-delay epoch drifted across days, while the stimulus and choice representations stabilized. In contrast to single-plane layer 2/3 (L2/3) imaging, simultaneous volumetric calcium imaging of up to 73,307 M2 neurons, which included superficial L5 neurons, also revealed stabilization of late-delay working-memory representations with continued practice. Thus, delay- and choice-related activities that are essential for working-memory performance drift during learning and stabilize only after several days of expert performance.

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourettes syndrome, the supplementary motor area in Parkinsons disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

Background: Transcranial direct current stimulation (tDCS) has been demonstrated to facilitate motor performance in healthy individuals; however, results are variable. The neuromodulatory effects of tDCS during visuomotor tasks may be influenced by extrinsic visual feedback, However, this interaction between tDCS and visual feedback has not been explored for the lower limb. Hence, our objective was to explore if tDCS over the primary lower limb motor cortex differentially facilitates motor performance based on the availability of visual feedback. Methods: Twenty -two neurotypical adults performed ankle plantarflexion and dorsiflexion movements while tracking a sinusoidal target. Spatiotemporal, spatial. and temporal error were calculated between the ankle position and target. Participants attended two sessions, a week apart. with (Stim) and without (No-Stim) anodal tDCS. Sessions were divided into two blocks containing randomized visual feedback conditions: full, no, and blindfold. During Stim sessions. the first block included the application of tDCS to the lower limb M1. Results: Spatiotemporal and spatial error increased as feedback faded (p < .001). A two-way repeated-measures analysis of variance showed a significant interaction between tDCS and visual feedback (p < .05) on spatiotemporal error. Post hoc analyses revealed a significant improvement in spatiotemporal error when visual feedback was absent (p < .01). Spatial and temporal errors were not significantly affected by stimulation or visual feedback. Discussion: Our results suggest that tDCS enhances spatiotemporal ankle motor performance only when visual feedback is not available. These findings indicate that visual feedback may play an important role in demonstrating the effectiveness of tDCS. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lifelong PE patients show altered resting-state brain network in the left precuneus. • Right supplementary motor area (SMA) also exhibits significant network changes. • DC values correlated with IELT and CIPE in left precuneus, right SMA regions. The aim of this study was to investigate alterations in the resting-state brain functional network characteristics of lifelong premature ejaculation (PE) patients using surface-based degree centrality (DC), and to analyze the correlation between these alterations and clinical symptoms in PE patients. The study included individuals with lifelong PE (patient group, n = 36) and a control group matched by age and education level (control group, n = 22). Resting-state functional magnetic resonance imaging (fMRI) scans were performed on all participants. Surface-based degree centrality analysis was conducted and the differences between the two groups were compared using t-tests. Further, the DC values of brain regions showing significant differences were correlated with clinical symptoms. Compared to the control group, the patient group exhibited significantly reduced degree centrality (DC) values in the left precuneus and significantly increased DC values in the right supplementary motor area (SMA). Furthermore, intravaginal ejaculatory latency time (IELT) and Chinese Index of Premature Ejaculation (CIPE) values were positively correlated with left precuneus DC values and negatively correlated with right SMA DC values. Patients with primary lifelong ejaculation demonstrate abnormalities in key brain network nodes and their connections with relevant brain regions, which are strongly associate with clinical symptoms. These findings enhance our understanding of the neuronal pathological changes in PE patients. [ABSTRACT FROM AUTHOR]

Background: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. Methods: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance -- LTD) were measured. Results: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p<0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). Conclusions: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas. [ABSTRACT FROM AUTHOR]

Background: Small artery occlusion (SAO) is a common ischemic stroke subtype. However, its clinical outcome can be more severe than commonly understood. The severity of SAO can vary, ranging from mild to moderate. Iron deposition has been associated with the development and progression of stroke. However, its specific distribution and relationship with stroke severity in SAO remain unclear. The study's purpose is to investigate the differences in iron deposition between mild stroke with SAO (SAO-MiS) and moderate stroke with SAO (SAO-MoS) through quantitative susceptibility mapping (QSM) and its association with neurological deficits. Methods: Sixty-eight SAO participants within 24 hours of first onset were enrolled and separated into SAO-MiS and SAO-MoS according to the National Institutes of Health Stroke Scale (NIHSS) scores. QSM helped calculate the susceptibility maps, reflecting the iron content within the brain. The susceptibility maps were analyzed using voxel-wise statistical analysis to compare the iron deposition between SAO-MiS and SAO-MoS. Then, differentially distributed iron deposition helped differentiate between mild and moderate stroke using support vector machine (SVM) methods. Results: Compared with SAO-MiS, SAO-MoS depicted elevated iron deposition in the left pallidum, parahippocampal gyrus, and superior frontal gyrus medial region, and is lower in the right superior/middle frontal gyrus and bilateral supplementary motor area. Based on iron deposition, the SVM classifier's analysis revealed a high power to discriminate SAO-MoS from SAO-MiS. In addition, fibrinogen, triglyceride (TG), and total cholesterol (TC) were linked with QSM values in specific brain regions. Conclusions: Our study first revealed the brain iron distribution after SAO and differently distributed iron deposition in SAO-MiS and SAO-MoS. The results indicate that iron deposition could play a role in the pathophysiology of SAO and its correlation with stroke severity. [ABSTRACT FROM AUTHOR]

• We assessed posture-dependent changes in cortical motor maps in awake marmosets. • The results demonstrated rapid modulation in forelimb motor maps. • Hindlimb posture was particularly effective in inducing these modulations. • Posture is a crucial variable to be controlled in future studies of motor control. Recent neuroimaging and electrophysiological studies have suggested substantial short-term plasticity in the topographic maps of the primary motor cortex (M1). However, previous methods lack the temporal resolution to detect rapid modulation of these maps, particularly in naturalistic conditions. To address this limitation, we previously developed a rapid stimulation mapping procedure with implanted cortical surface electrodes. In this study, employing our previously established procedure, we examined rapid topographical changes in forelimb M1 motor maps in three awake male marmoset monkeys. The results revealed that although the hotspot (the location in M1 that elicited a forelimb muscle twitch with the lowest stimulus intensity) remained constant across postures, the stimulus intensity required to elicit the forelimb muscle twitch in the perihotspot region and the size of motor representations were posture-dependent. Hindlimb posture was particularly effective in inducing these modulations. The angle of the body axis relative to the gravitational vertical line did not alter the motor maps. These results provide a proof of concept that a rapid stimulation mapping system with chronically implanted cortical electrodes can capture the dynamic regulation of forelimb motor maps in natural conditions. Moreover, they suggest that posture is a crucial variable to be controlled in future studies of motor control and cortical plasticity. Further exploration is warranted into the neural mechanisms regulating forelimb muscle representations in M1 by the hindlimb sensorimotor state. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Selective serotonin reuptake inhibitors are thought to exert a clinical effect through various mechanisms, including through alteration in synaptic plasticity. Repetitive transcranial magnetic stimulation can induce temporary changes in synaptic excitability in cerebral cortex that resemble long‐term potentiation and long‐term depression that serve as a measure of synaptic plasticity in vivo. A version of repetitive transcranial magnetic stimulation called continuous theta burst stimulation can induce inhibition of cortical excitability that can be measured through a motor evoked potential. Previous work has suggested that this response can be modulated by administration of selective serotonin reuptake inhibitors.Thirty‐one healthy volunteers received both fluoxetine 20 mg and placebo in randomly ordered sessions, followed by spaced continuous theta burst stimulation to motor cortex. Changes in Motor Evoked Potentials were then recorded over 60 min.The response to spaced continuous theta burst stimulation did not differ significantly between fluoxetine and placebo sessions. Spaced continuous theta burst stimulation produced a paradoxical excitatory response in an unexpected number of participants.A single dose of fluoxetine 20 mg does not influence the response to continuous theta burst stimulation. Previous results suggesting an effect of selective serotonin reuptake inhibitors on inhibitory non‐invasive brain stimulation protocols may be due to insufficiently large sample sizes. [ABSTRACT FROM AUTHOR]

Introduction: Inadequate exposure to real-life operating can impede timely acquisition of technical competence among surgical residents, and is a major challenge faced in the current training climate. Mental rehearsal (MR)--the cognitive rehearsal of a motor task without overt physical movement--has been shown to accelerate surgical skills learning. However, the neuroplastic effect of MR of a complex bimanual surgical task is unknown. The aim of this study is to use functional near-infrared spectroscopy (fNIRS) to assess the impact of MR on prefrontal and motor cortical activation during a laparoscopic knot tying task. Methods: Twelve surgical residents performed a laparoscopic knot tying task before and after either mental rehearsal (MR, intervention group) or textbook reading (TR, control group). In both groups, fNIRS was used to measure changes in oxygenated hemoglobin concentration (HbO2) in the prefrontal (24 channels) and motor cortices (22 channels). Technical performance was measured using leak volume, objective performance score and task progression score. Results: MR led to a decrease in HbO2 (reduced activation) in the bilateral prefrontal cortex (PFC), and an increase in HbO2 (increased activation) in the left middle frontal gyrus, left precentral gyrus, and left postcentral gyrus. No discernible changes in activation were observed after TR in either the PFC or motor cortex. Moreover, smaller ΔHbO2 responses in the right PFC and greater ΔHbO2 responses in the left motor cortex were observed in the MR group compared with the TR group. Leak volume was significantly less following MR (p = 0.019), but not after TR (p = 0.347). Mean objective performance score was significantly higher following MR compared with TR (p = 0.043). Conclusion: Mental rehearsal may enhance surgical skill acquisition and technical proficiency by reducing utilization of attentional resources in the prefrontal cortex and improving neural efficiency in motor areas during a laparoscopic surgical task. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Methods: Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. Results: The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA – ipsilateral cerebellum) changes and BBS changes in SMA group. Discussion: In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. Clinical trial registration: Registration number: ChiCTR2200060955, https://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

Background: People who regularly use cannabis exhibit altered brain dynamics during cognitive control tasks, though the impact of regular cannabis use on the neural dynamics serving motor control remains less understood. Aims: We sought to investigate how regular cannabis use modulates the neural dynamics serving motor control. Methods: Thirty-four people who regularly use cannabis (cannabis+) and 33 nonusers (cannabis−) underwent structured interviews about their substance use history and performed the Eriksen flanker task to map the neural dynamics serving motor control during high-density magnetoencephalography (MEG). The resulting neural data were transformed into the time–frequency domain to examine oscillatory activity and were imaged using a beamforming approach. Results: MEG sensor-level analyses revealed robust beta (16–24 Hz) and gamma oscillations (66–74 Hz) during motor planning and execution, which were imaged using a beamformer. Both responses peaked in the left primary motor cortex and voxel time series were extracted to evaluate the spontaneous and oscillatory dynamics. Our key findings indicated that the cannabis+ group exhibited weaker spontaneous gamma activity in the left primary motor cortex relative to the cannabis− group, which scaled with cannabis use and behavioral metrics. Interestingly, regular cannabis use was not associated with differences in oscillatory beta and gamma activity, and there were no group differences in spontaneous beta activity. Conclusions: Our findings suggest that regular cannabis use is associated with suppressed spontaneous gamma activity in the left primary motor cortex, which scales with the degree of cannabis use disorder symptomatology and is coupled to behavioral task performance. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the cerebellum contributes to contraction-induced facilitation (CIF) of contralateral corticospinal excitability. To this end, repetitive cerebellar transcranial magnetic stimulation (TMS) was used to test whether it modulates CIF. Overall, 20 healthy young individuals participated in the study. Single-pulse TMS was applied to the left primary motor cortex to induce motor-evoked potentials (MEP) on electromyography of the right first dorsal interosseous (FDI) muscle to test corticospinal excitability. This measurement was conducted during contraction (10% maximum voluntary contraction [MVC]) and rest (0% MVC) of the FDI muscle. CIF, cerebellar brain inhibition (CBI), cortical silent period (cSP), and resting motor threshold (rMT) were measured before and after low-frequency repetitive TMS (crTMS) of the right cerebellum to downregulate cerebellar output. The CIF (contraction/rest of the MEP), CBI (conditioned/unconditioned MEP) during contraction, cSP, and rMT were not affected by crTMS. At rest, CBI was decreased. These findings indicated that the primary motor cortex function for the increase in corticospinal excitability was not affected by crTMS. This study contributes to our understanding of the role of the cerebellum in motor control. Additionally, it may inform decision-making for the site of cerebellar ataxia treatment using non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

The Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone "deep" TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD). Sixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted. Subjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups. SMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA‐DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA‐DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA‐DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA‐DRB*15‐positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation. These findings informed a neuropathological characterisation of these proteins in a large autopsy cohort of 41 MS cases (18 HLA‐DRB1*15‐positive and 23 HLA‐DRB1*15‐negative), and seven non‐neurological controls on motor cortical, cervical and lumbar spinal cord tissue. Biglycan and decorin demonstrate a striking perivascular expression pattern in controls that is reduced in MS (−36.5%, p = 0.036 and − 24.7%, p = 0.039; respectively) in lesional and non‐lesional areas. A concomitant increase in diffuse parenchymal accumulation of biglycan and decorin is seen in MS (p = 0.015 and p = 0.001, respectively), particularly in HLA‐DRB1*15‐positive cases (p = 0.007 and p = 0.046, respectively). Prolargin shows a faint parenchymal pattern in controls that is markedly increased in MS cases where a perivascular deposition pattern is observed (motor cortex +97.5%, p = 0.001; cervical cord +49.1%, p = 0.016). Our findings point to ECM proteins and the vascular interface playing a central role in MS pathology within and outside the plaque area. As ECM proteins are known potent pro‐inflammatory molecules, their parenchymal accumulation may contribute to disease severity. This study brings to light novel factors that may contribute to the heterogeneity of the topographical variation of MS pathology. [ABSTRACT FROM AUTHOR]

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V–VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acquisition of motor skills in the rotor rod task varies among individual animals. • Specific properties of M1 layer V neurons correlate with individual performance. • Individual motor performance correlates synaptic plasticity of M1 layer V neurons. • Rapid spine plasticity of M1 layer V neurons correlates with individual performance. • Training-induced ACh increases in M1 correlate with individual motor performance. Layer V neurons in primary motor cortex (M1) are required for motor skill learning. We analyzed training-induced plasticity using a whole-cell slice patch-clamp technique with a rotor rod task, and found that training induces diverse changes in intrinsic properties and synaptic plasticity in M1 layer V neurons. Although the causal relationship between specific cellular changes and motor performance is unclear, by linking individual motor performance to cellular/synaptic functions, we identified several cellular and synaptic parameters that represent acquired motor skills. With respect to cellular properties, motor performance was positively correlated with resting membrane potential and fast afterhyperpolarization, but not with the membrane resistance, capacitance, or threshold. With respect to synaptic function, the performance was positively correlated with AMPA receptor-mediated postsynaptic currents, but not with GABA A receptor-mediated postsynaptic currents. With respect to live imaging analysis in Thy1-YFP mice, we further demonstrated a cross-correlation between motor performance, spine head volume, and self-entropy per spine. In the present study, we identified several changes in M1 layer V pyramidal neurons after motor training that represent acquired motor skills. Furthermore, training increased extracellular acetylcholine levels known to promote synaptic plasticity, which is correlated with individual motor performance. These results suggest that systematic control of specific intracellular parameters and enhancement of synaptic plasticity in M1 layer V neurons may be useful for improving motor skills. [ABSTRACT FROM AUTHOR]

Background: The neuropathophysiological mechanisms of brain damage underlying hypothyroidism remain unclear. Fractional amplitude of low-frequency fluctuations (fALFF) has been established as a reliable indicator for investigation of abnormal spontaneous brain activity that occurs at specific frequencies in different types of mental disorder. However, the changes of fALFF in specific frequency bands in hypothyroidism have not yet been investigated. Methods: Fifty-three hypothyroid patients and 39 healthy controls (HCs) underwent thyroid-related hormone levels tests, neuropsychological assessment, and magnetic resonance imaging (MRI) scans. The fALFF in the standard band (0.01-0.1 Hz), slow-4 (0.027-0.073 Hz), and slow-5 bands (0.01-0.027 Hz) were analyzed. An analysis of Pearson correlation was conducted between fALFF, thyroid-related hormone levels, and neuropsychological scores in hypothyroid patients. Results: Compared to HCs, within the routine band, hypothyroidism group showed significantly decreased fALFF in left lingual gyrus, middle temporal gyrus (MTG), precentral gyrus, calcarine cortex, and right inferior occipital gyrus; within the slow-5 band, the hypothyroidism group exhibited decreased fALFF in left lingual gyrus, MTG, superior temporal gyrus, postcentral gyrus, and paracentral lobule, and increased fALFF in supplementary motor area (SMA) and right middle frontal gyrus; additionally, fALFF in the left lingual gyrus within the routine and slow-5 bands were negatively correlated with the level of thyroid stimulating hormone. Conclusions: In this study, the slow-5 frequency band exhibits better sensitivity than the standard band in detecting fALFF values. A decrease of fALFF values in the lingual gyrus and MTG was observed in both the standard and slow-5 bands and might present potential neuroimaging biomarkers for hypothyroidism. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. Methods: This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10- Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results: Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. Conclusion: This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat various neurological disorders. However, the molecular mechanism underlying the therapeutic effect of rTMS on Parkinson's disease (PD) has not been fully elucidated. Neuroinflammation like regulatory T-cells (Tregs) appears to be a key modulator of disease progression in PD. If rTMS affects the peripheral Tregs in PD remains unknown. Methods: Here, we conducted a prospective clinical study (Chinese ClinicalTrials. gov: ChiCTR 2100051140) involving 54 PD patients who received 10-day rTMS (10 Hz) stimulation on the primary motor cortex (M1) region or sham treatment. Clinical and function assessment as well as flow cytology study were undertaken in 54 PD patients who were consecutively recruited from the department of neurology at Zhujiang hospital between September 2021 and January 2022. Subsequently, we implemented flow cytometry analysis to examine the Tregs population in spleen of MPTP-induced PD mice that received rTMS or sham treatment, along with quantitative proteomic approach reveal novel molecular targets for Parkinson's disease, and finally, the RNA interference method verifies the role of these new molecular targets in the treatment of PD. Results: We demonstrated that a 10-day rTMS treatment on the M1 motor cortex significantly improved motor dysfunction in PD patients. The beneficial effects persisted for up to 40 days, and were associated with an increase in peripheral Tregs. There was a positive correlation between Tregs and motor improvements in PD cases. Similarly, a 10-day rTMS treatment on the brains of MPTP-induced PD mice significantly ameliorated motor symptoms. rTMS reversed the downregulation of circulating Tregs and tyrosine hydroxylase neurons in these mice. It also increased anti-inflammatory mediators, deactivated microglia, and decreased inflammatory cytokines. These effects were blocked by administration of a Treg inhibitor anti-CD25 antibody in MPTP-induced PD mice. Quantitative proteomic analysis identified TLR4, TH, Slc6a3 and especially Syt6 as the hub node proteins related to Tregs and rTMS therapy. Lastly, we validated the role of Treg and rTMS-related protein syt6 in MPTP mice using the virus interference method. Conclusions: Our clinical and experimental studies suggest that rTMS improves motor function by modulating the function of Tregs and suppressing toxic neuroinflammation. Hub node proteins (especially Syt6) may be potential therapeutic targets. Trial registration: Chinese ClinicalTrials, ChiCTR2100051140. Registered 15 December 2021, https://www.chictr.org.cn/bin/project/edit?pid=133691 rTMS is a safe and non-invasive method for Parkinson's disease. In this study, we showed the proportion of CD4+CD25+CD127- regulatory T-cells (Tregs) in the peripheral blood was significantly increased after rTMS treatment. Similar effects of rTMS treatment were verified in MPTP-induced PD mice. Proteomic analysis and RNA interference analyses identified TLR4, TH, Slc6a3 and especially Syt6 as hub node proteins that can be modulated by rTMS therapy in PD. [ABSTRACT FROM AUTHOR]

We present a quantitative strategy to identify all projection neuron types from a given region with statistically different patterns of anatomical targeting. We first validate the technique with mouse primary motor cortex layer 6 data, yielding two clusters consistent with cortico-thalamic and intra-telencephalic neurons. We next analyze the presubiculum, a less-explored region, identifying five classes of projecting neurons with unique patterns of divergence, convergence, and specificity. We report several findings: individual classes target multiple subregions along defined functions; all hypothalamic regions are exclusively targeted by the same class also invading midbrain and agranular retrosplenial cortex; Cornu Ammonis receives input from a single class of presubicular axons also projecting to granular retrosplenial cortex; path distances from the presubiculum to the same targets differ significantly between classes, as do the path distances to distinct targets within most classes; the identified classes have highly non-uniform abundances; and presubicular somata are topographically segregated among classes. This study thus demonstrates that statistically distinct projections shed light on the functional organization of their circuit. The classification of different types of neurons has been a long-standing challenge in neuroscience. Here, the authors present a strategy to quantify all statistically distinct axonal patterns from a brain region based on their anatomical targeting, with this projection-driven neuron classification informing the functional architecture of the circuit. [ABSTRACT FROM AUTHOR]

Background: In China's coal mines, employees work in environments reaching depths of 650 m, with temperatures around 40°C and humidity levels as high as 90%, adversely affecting their health, safety capabilities, and cognitive functions, especially working memory. This study aims to explore different temperature and humidity conditions' impact on neurocognitive mechanisms to enhance occupational health and safety. Methods: This study, conducted between June and August 2023, with 100 coalmine workers from the Hongliulin Mining Group, utilized functional near infrared spectroscopy (fNIRS) and short-term visual memory tasks to evaluate the effects of high temperatures and humidity on working memory by monitoring activity in the cerebral cortex. Behavioral data, and neurophysiological data were analyzed using Tukey's HSD for significant differences and multiple regression to explore the impact of temperature and humidity. The β-values of Oxy-Hb for different regions of interest were calculated using General liner model (GLM), and the activation maps were plotted by NIRS_;KIT. Results: High temperature and humidity (Condition IV) significantly depressed reaction times and working memory compared to other conditions, with temperature having a more pronounced impact than humidity on these cognitive measures (p < 0.05). Oxy-Hb concentration increased notably under Condition IV, emphasizing temperature's influence on brain oxygen levels. ROI analysis revealed varied brain activation patterns. The activation of ROI A and B (prefrontal cortex) increased with the increase of temperature and humidity, while ROI C (supplementary motor area) was less sensitive to temperature, indicating the complex influence of environmental factors on brain function. Conclusion: This study highlights the important effects of temperature and humidity on cognitive performance and brain function, highlighting the need to optimize the environment of miners' sites to improve productivity and safety. [ABSTRACT FROM AUTHOR]

Background: Functional magnetic resonance imaging (fMRI) is a useful tool to evaluate brain inefficiencies secondary to cardiovascular diseases (CVDs); nevertheless, limited fMRI studies have been conducted to investigate the effect of CVDs on brain functional changes and cognitive function. This systematic review aims to explore, synthesise, and report fMRI outcomes (resting state and task-based) and cognitive performance in patients with CVDs. Methods: Two reviewers independently searched published literature until April 2024 on ScienceDirect, PubMed, Web of Science, and ClinicalTrials.gov adhering to the PRISMA protocol. A total of 26 eligible studies were considered for full-text screening, of which 10 were included in this review. The methodological quality was assessed by mixed methods appraisal tool and was reported as empirically fair. Results: Among 336 subjects with CVDs, aged between 49.90  ±  6.10 to 72.20  ±  5.70  years, the majority had coronary artery diseases (n = 177, 52.68%) and hypertension (n = 200, 59.52%), and approximately half of them were females (n = 169, 50.30%). Based on the qualitative synthesis, subjects with CVDs demonstrated an increased cognitive decline (reduced Mini-Mental State Examination/Montreal Cognitive Assessment mean values) and attenuated task performance (lower mean 2-back task scores and slower reaction time). Results also indicated impaired brain activity at the supplementary motor area associated with poor ejection fraction; reduced default mode network suppression linked to high low-density lipoprotein cholesterol; lower regional homogeneity and amplitude of low-frequency fluctuation values; and reduced functional connectivity. In summary, alterations in brain networks connectivity may have contributed to an impaired cognitive performance in patients with cardiovascular diseases. Conclusion: It can be extrapolated that CVDs tend to alter the brain network connectivity and result in cognitive impairment and poorer task performance. However, for future imaging studies, more stringent and homogenous demographic data are highly recommended. [ABSTRACT FROM AUTHOR]

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep. [ABSTRACT FROM AUTHOR]

Incentives tend to drive improvements in performance. But when incentives get too high, we can "choke under pressure" and underperform right when it matters most. What neural processes might lead to choking under pressure? We studied rhesus monkeys performing a challenging reaching task in which they underperformed when an unusually large "jackpot" reward was at stake, and we sought a neural mechanism that might result in that underperformance. We found that increases in reward drive neural activity during movement preparation into, and then past, a zone of optimal performance. We conclude that neural signals of reward and motor preparation interact in the motor cortex (MC) in a manner that can explain why we choke under pressure. [Display omitted] • Rhesus monkeys "choke under pressure" in a difficult reaching task • Neural activity in the motor cortex scales monotonically with reward magnitude • These reward signals adversely interact with movement preparation • This adverse interaction constitutes a neural basis of choking under pressure Why do we "choke under pressure," underperforming when we want to succeed the most? Smoulder et al. identify a neural basis of this paradoxical phenomenon in the motor cortex, where greater rewards influence movement preparatory neural states to be closer to, then farther from, an optimal zone for upcoming movements. [ABSTRACT FROM AUTHOR]

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8–10 days, striatal projection and interneuronal dynamics did not—eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics. [Display omitted] • Motor, but not parietal, cortex is necessary for performing goal-directed actions • Movement-related dynamics in the striatum are absent following lesions of M1 • Behavior and striatal activity partly recover but are not comparable to pre-lesion • M1 lesions cause freezing of gait, suggesting its role in motor-state regulation Nicholas and Yttri find that in the absence of motor cortex, the stratum alone is not capable of producing goal-directed behavior. Lesions of motor cortex also produce a freezing of gait-like behavior, implicating motor cortex in the setting and updating of motor state. [ABSTRACT FROM AUTHOR]

Introduction: Mental rotation (MR) tasks of body parts involve anatomically interconnected brain systems. The systems are implicated in sensorimotor information integration and activate cortical motor-related areas, corresponding to the execution of similar motor tasks. In this study, we aimed to investigate the effect of varying the angle in the hand MR task on cerebral activation of the motor-related areas. Methods: Twenty healthy right-handed participants were recruited. We investigated cerebral activation while each participant decided whether a hand-palm image, rotated by 0°, 90°, 180°, and 270°, was a right or left hand. Results and discussion: A significant negative correlation between the angle and brain activity was observed in the right and left supplementary motor area (SMA) and right posterior anterior cingulate gyrus. The SMA was inactivated with 180°- or 270°-rotated images in the regions of interest analysis. 180°- and 270°-rotated palms would be biomechanically difficult to position; thus, SMA deactivation may be closely associated with biomechanical constraints. This study provided novel findings regarding the neurophysiological mechanisms of motor imagery and may be useful in developing treatment plans using MR tasks during patient rehabilitation. [ABSTRACT FROM AUTHOR]

Astrocytes are crucial for the functioning of the nervous system as they maintain the ion homeostasis via volume regulation. Pathological states, such as amyotrophic lateral sclerosis (ALS), affect astrocytes and might even cause a loss of such functions. In this study, we examined astrocytic swelling/volume recovery in both the brain and spinal cord of the SOD1 animal model to determine the level of their impairment caused by the ALS-like pathology. Astrocyte volume changes were measured in acute brain or spinal cord slices during and after exposure to hyperkalemia. We then compared the results with alterations of extracellular space (ECS) diffusion parameters, morphological changes, expression of the Kir4.1 channel and the potassium concentration measured in the cerebrospinal fluid, to further disclose the link between potassium and astrocytes in the ALS-like pathology. Morphological analysis revealed astrogliosis in both the motor cortex and the ventral horns of the SOD1 spinal cord. The activated morphology of SOD1 spinal astrocytes was associated with the results from volume measurements, which showed decreased swelling of these cells during hyperkalemia. Furthermore, we observed lower shrinkage of ECS in the SOD1 spinal ventral horns. Immunohistochemical analysis then confirmed decreased expression of the Kir4.1 channel in the SOD1 spinal cord, which corresponded with the diminished volume regulation. Despite astrogliosis, cortical astrocytes in SOD1 mice did not show alterations in swelling nor changes in Kir4.1 expression, and we did not identify significant changes in ECS parameters. Moreover, the potassium level in the cerebrospinal fluid did not deviate from the physiological concentration. The results we obtained thus suggest that ALS-like pathology causes impaired potassium uptake associated with Kir4.1 downregulation in the spinal astrocytes, but based on our data from the cortex, the functional impairment seems to be independent of the morphological state. [ABSTRACT FROM AUTHOR]

Numerous studies have reported that long-term sports training can affect inhibitory control and induce brain functional alterations. However, the influence of environmental dynamics in sports training on inter-cortical connectivity has not been well studied. In the current study, we used twin-coil transcranial magnetic stimulation to investigate the functional connectivity between dorsolateral prefrontal cortex (DLPFC) and ipsilateral primary motor cortex (M1) during proactive and reactive inhibition in participants with sports skills in dynamic environment (open-skill experts), stable environment (closed-skill experts), and no sports skills (controls). Using a modified stop signal task, proactive inhibition was measured by the response delay effect (RDE), and reactive inhibition was measured by the stop-signal reaction time (SSRT). Intra-hemispheric DLPFC-M1 interactions and single pulse motor-evoked potentials (MEPs) were measured during the task. A stronger inhibitory effect of the DLPFC over M1 was observed during early reactive control stages compared to baseline levels. In addition, this inhibitory effect was pronounced when comparing open-skill experts to non-athlete controls, a relationship that was significantly correlated with superior reactive control performance. Furthermore, DLPFC to M1 influencing direction shifted from late proactive control to reactive control. Behavioral results also demonstrated enhanced proactive control abilities in open-skill experts relative to controls. Such enhancement may be due to the combination of environmental complexity and physical fitness in long-term skill training. [ABSTRACT FROM AUTHOR]

Impairments in postural responses to perturbation are common in people with Parkinson's disease (PwPD) and lack effective treatment. We recently showed that a single session of transcranial direct current stimulation (tDCS) promotes acute improvement of postural response to perturbation in PwPD. However, the effects of multiple tDCS sessions remain unclear. What is the efficacy of eight sessions of anodal tDCS on postural responses to external perturbation in PwPD? Twenty-two PwPD participated in this randomized, double-blind, parallel-arm, and sham-controlled study. Participants were randomly distributed into active (a-tDCS; n=11) or sham stimulation (s-tDCS; n=11). Eight tDCS sessions were applied over the primary motor cortex (M1), with the a-tDCS group receiving 2 mA for 20 minutes. Postural responses to external perturbations were assessed before, 48 hours after, and one month after (follow-up) the completion of tDCS sessions. Primary outcome measures included the onset latency of medial gastrocnemius (MG) muscle and range of center of pressure. Secondary outcomes included electromyography and CoP parameters, and prefrontal cortex (PFC) activity. ANOVA revealed a trend for Group*Moment interaction for MG onset latency (p=0.058). a-tDCS tended to have shorter MG onset latency at post-test (p=0.040; SRM = −0.63) compared to pre-test. For the secondary outcomes, only a-tDCS decreased the time taken to recover balance after the perturbation at post-test and follow-up compared to pre-test (both p<0.001; SRM=-1.42 and −1.53, respectively). Also, only a-tDCS demonstrated lower PFC activity at post-test compared to pre-test (p=0.017; SRM = −0.82) and follow-up (p=0.001). Eight sessions of tDCS over M1 improved postural response to perturbation in PwPD. Some benefits lasted for at least a month. Neuromuscular and behavioral changes observed after the intervention were accompanied by decreased PFC activity (executive-attentional control), suggesting that tDCS applied over M1 can improve movement automaticity. • A tendency to decreased MG onset latency was evidenced in a-tDCS at post vs. pre-test. • tDCS over M1 decreased the recovery time after perturbation in PwPD. • tDCS over M1 decreased the PFC activity after perturbation in PwPD. • Effects of tDCS on postural response were sustained for at least a month in PwPD. [ABSTRACT FROM AUTHOR]

Neural activity cannot be directly observed using fMRI; rather it must be inferred from the hemodynamic responses that neural activity causes. Solving this inverse problem is made possible through the use of forward models, which generate predicted hemodynamic responses given hypothesised underlying neural activity. Commonly‐used hemodynamic models were developed to explain data from healthy young participants; however, studies of ageing and dementia are increasingly shifting the focus toward elderly populations. We evaluated the validity of a range of hemodynamic models across the healthy adult lifespan: from basis sets for the linear convolution models commonly used to analyse fMRI studies, to more advanced models including nonlinear fitting of a parameterised hemodynamic response function (HRF) and nonlinear fitting of a biophysical generative model (hemodynamic modelling, HDM). Using an exceptionally large sample of participants, and a sensorimotor task optimized for detecting the shape of the BOLD response to brief stimulation, we first characterised the effects of age on descriptive features of the response (e.g., peak amplitude and latency). We then compared these to features from more complex nonlinear models, fit to four regions of interest engaged by the task, namely left auditory cortex, bilateral visual cortex, left (contralateral) motor cortex and right (ipsilateral) motor cortex. Finally, we validated the extent to which parameter estimates from these models have predictive validity, in terms of how well they predict age in cross‐validated multiple regression. We conclude that age‐related differences in the BOLD response can be captured effectively by models with three free parameters. Furthermore, we show that biophysical models like the HDM have predictive validity comparable to more common models, while additionally providing insights into underlying mechanisms, which go beyond descriptive features like peak amplitude or latency, and include estimation of nonlinear effects. Here, the HDM revealed that most of the effects of age on the BOLD response could be explained by an increased rate of vasoactive signal decay and decreased transit rate of blood, rather than changes in neural activity per se. However, in the absence of other types of neural/hemodynamic data, unique interpretation of HDM parameters is difficult from fMRI data alone, and some brain regions in some tasks (e.g., ipsilateral motor cortex) can show responses that are more difficult to capture using current models. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) triggers time‐locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. Here, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared specific TEP peaks and components between studies using distinct methods. Reporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and preprocessing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the "prototypical" TEP waveform following stimulation of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long‐latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP magnitudes. In summary, some aspects of reporting practices could be improved in future TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted. [ABSTRACT FROM AUTHOR]

Although significant progress has been made in understanding the cortical correlates underlying balance control, these studies focused on a single task, limiting the ability to generalize the findings. Different balance tasks may elicit cortical activations in the same regions but show different levels of activation because of distinct underlying mechanisms. In this study, twenty young, neurotypical adults were instructed to maintain standing balance while the standing support surface was either translated or rotated. The differences in cortical activations in the frontocentral region between these two widely used tasks were examined using electroencephalography (EEG). Additionally, the study investigated whether transcranial magnetic stimulation could modulate these cortical activations during the platform translation task. Higher delta and lower alpha relative power were found over the frontocentral region during the platform translation task when compared to the platform rotation task, suggesting greater engagement of attentional and sensory integration resources for the former. Continuous theta burst stimulation over the supplementary motor area significantly reduced delta activity in the frontocentral region but did not alter alpha activity during the platform translation task. The results provide a direct comparison of neural activations between two commonly used balance tasks and are expected to lay a strong foundation for designing neurointerventions for balance improvements with effects generalizable across multiple balance scenarios. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Rapid eye movement sleep behavior disorder (RBD) is linked to the diffuse‐malignant subtype and higher cognitive burden in Lewy body disease (LBD).This study explores brain β‐amyloid deposition and its association with cognitive decline across the RBD–LBD continuum.Patients with isolated RBD (iRBD), Parkinson's disease with probable RBD (PDRBD), and dementia with Lewy bodies with probable RBD (DLBRBD) underwent 18F‐florbetaben positron emission tomography, 3T magnetic resonance imaging scans, and comprehensive neuropsychological assessments. Subjects were categorized as cognitively normal (NC), mild cognitive impairment (MCI), or dementia. Global and regional standardized uptake value ratios (SUVR) were estimated in predefined cognitive volumes of interest (VOI) derived from voxel‐wise comparison analysis among the cognitive groups, namely the prefrontal, parietal, precentral cortices, lingual gyrus, and supplementary motor area. Generalized linear models assessed the relationship between 18F‐florbetaben SUVRs and neuropsychological testing, adjusting for age and sex. Subgroup analysis focused on the polysomnography‐confirmed iRBD‐continuum subset (n = 41) encompassing phenoconverters and nonconverters in our prospective iRBD cohort.Eighty‐six subjects were classified as follows: 14 NC, 54 MCI, and 18 dementia. The proportion of positive β‐amyloid scans increased with advanced cognitive stages (P = 0.038). β‐Amyloid signals in cognitive VOIs were elevated in subgroups showing impairment in Trail‐Making Test B (TMT‐B). A linear association between TMT‐B z score and global cortical β‐amyloid levels was observed in the iRBD‐continuum subset (P = 0.013).Cortical β‐amyloid accumulates with declines in executive function within the RBD–LBD continuum. TMT‐B performance may be a useful marker associating with β‐amyloid load, particularly in the iRBD population. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

[Display omitted] Magnetic resonance-guided focused ultrasound surgery (MRgFUS) thalamotomy is an emerging technique for medication-refractory essential tremor (ET), but with variable outcomes. This study used pattern regression analysis to identify brain signatures predictive of tremor improvements. Fifty-four ET patients (mean age = 63.06 years, standard deviation (SD) = 10.55 years, 38 males) underwent unilateral MRgFUS thalamotomy and were scanned for resting-state functional magnetic resonance imaging (rs-fMRI). Seventy-four healthy controls (mean age = 58.09 years, SD = 10.30 years, 38 males) were recruited for comparison. Tremor responses at 12 months posttreatment were evaluated by the Clinical Rating Scale for Tremor. The fractional amplitude of low-frequency fluctuations (fALFF) was calculated from rs-fMRI data. Two-sample t -test was used to generate a disease-specific mask, within which Multivariate Kernel Ridge Regression analyses were conducted. Predicted and actual clinical scores were compared using Pearson's correlation coefficient (r) and normalized mean squared error (Norm. MSE). Permutation test and leave-one-out strategy were applied for results validation. KRR identified fALFF patterns that significantly predicted the hand tremor improvement (r = 0.23, P = 0.025; Norm. MSE = 0.05, P = 0.026) and the postural tremor improvement (r = 0.28, P = 0.025; Norm. MSE = 0.06, P = 0.023), but not action tremor improvement. Lobule VI of right cerebellum (Cerebelum_6_R), right superior occipital gyrus (Occipital_Sup_R) and lobule X of vermis (Vermis_10) contributed most for hand tremor prediction (normalized weights (NW): 2.77%, 2.40%, 2.34%) while Vermis_10, left supplementary motor area (Supp_Motor_Area_L) and right hippocampus (Hippocampus_R) for postural tremor prediction (NW: 2.69%, 2.12%, 2.05%). The low contributing NW of the individual brain regions suggested that the fALFF pattern as a whole is an overall predicting feature. Preoperative fALFF pattern predicts tremor benefits induced by MRgFUS thalamotomy. ClinicalTrials.gov number: NCT04570046. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD) is a disabling disorder in which the temporal variability of regional brain connectivity is not well understood. The aim of this study was to investigate alterations in static and dynamic intrinsic neural activity (INA) in first-episode OCD and whether these changes have the potential to reflect neurotransmitters. A total of 95 first-episode OCD patients and 106 matched healthy controls (HCs) were included in this study. Based on resting-state functional magnetic resonance imaging (rs-fMRI), the static and dynamic local connectivity coherence (calculated by static and dynamic regional homogeneity, sReHo and dReHo) were compared between the two groups. Furthermore, correlations between abnormal INA and PET- and SPECT-derived maps were performed to examine specific neurotransmitter system changes underlying INA abnormalities in OCD. Compared with HCs, OCD showed decreased sReHo and dReHo values in left superior, middle temporal gyrus (STG/MTG), left Heschl gyrus (HES), left putamen, left insula, bilateral paracentral lobular (PCL), right postcentral gyrus (PoCG), right precentral gyrus (PreCG), left precuneus and right supplementary motor area (SMA). Decreased dReHo values were also found in left PoCG, left PreCG, left SMA and left middle cingulate cortex (MCC). Meanwhile, alterations in INA present in brain regions were correlated with dopamine system (D2, FDOPA), norepinephrine transporter (NAT) and the vesicular acetylcholine transporter (VAChT) maps. Static and dynamic INA abnormalities exist in first-episode OCD, having the potential to reveal the molecular characteristics. The results help to further understand the pathophysiological mechanism and provide alternative therapeutic targets of OCD. • Static and dynamic ReHo were used to investigate the alterations in intrinsic neural activity in first-episode OCD. • PET - and SPECT derived maps were used to analyze the association between changes in INA and neurotransmitters in OCD. • Different window sizes were used to verify the robustness of dReHo results. • The INA abnormalities present in the first-episode OCD have the potential to reveal molecular characteristics, which may provide new ideas for revealing pathological mechanisms and therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Methods: Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl- Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. Results: The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA – ipsilateral cerebellum) changes and BBS changes in SMA group. Discussion: In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Long-range axonal projections of diverse classes of neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging of fluorescently labeled axons from genetically defined neurons located in posterior primary somatosensory barrel cortex and supplemental somatosensory cortex. We used convolutional networks to segment axon-containing voxels and quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different classes of glutamatergic neurons using transgenic mouse lines selectively expressing Cre recombinase in layer 2/3 intratelencephalic projection neurons (Rasgrf2-dCre), layer 4 intratelencephalic projection neurons (Scnn1a-Cre), layer 5 intratelencephalic projection neurons (Tlx3-Cre), layer 5 pyramidal tract projection neurons (Sim1-Cre), layer 5 projection neurons (Rbp4-Cre), and layer 6 corticothalamic neurons (Ntsr1-Cre). We found distinct axonal projections from the different neuronal classes to many downstream brain areas, which were largely similar for primary and supplementary somatosensory cortices. Functional connectivity maps obtained from optogenetic activation of sensory cortex and wide-field imaging revealed topographically organized evoked activity in frontal cortex with neurons located more laterally in somatosensory cortex signaling to more anteriorly located regions in motor cortex, consistent with the anatomical projections. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain. We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity. LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex. The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10. In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsIdentify relations of gross motor function and primary motor cortex (M1) functional activity pre and post gross motor interventions for children with unilateral cerebral palsy (UCP).Thirteen children with UCP completed a gross motor intervention. Pre/post-intervention functional MRI outcomes included the laterality index (LI), activation volume, and spatial overlap of M1 activation during active ankle dorsiflexion. Advanced gross motor function (Challenge) was assessed pre/post-intervention, and 2–6 months later. Bivariate correlations and linear regression assessed relations between neuroimaging and motor function.Mean pre-intervention M1 activity was contralateral during dominant (LI =  +0.85, SD 0.21) but variable during the affected (LI =  +0.43, SD 0.57) ankle dorsiflexion. Changes in motor function and neuroimaging outcomes were not significantly associated. However, smaller affected ankle activation and less spatial overlap between ankle activations pre-intervention predicted Challenge improvements post-intervention (adjusted R2 = 0.74, p = .001.)This exploratory study identified pre-intervention neuroimaging predictors of post-intervention improvements in advanced gross motor function. [ABSTRACT FROM AUTHOR]

Handwriting is an outstanding case of a highly complex and efficient fine motor skill. However, little is known about its neural underpinnings during continuous handwriting production. In the present study, we examined the effects of orthographic character complexity (i.e. the stroke number of a Chinese character) on both neural and behavioural activities during an EEG‐based naturalistic fluent sentence‐handwriting task from 102 adult Chinese native speakers. For each written character, the interval between finishing the preceding character and its onset (inter‐character interval) as well as the amplitudes of the onset‐synchronized event‐related potential (ERP) in pre‐ and post‐onset time windows was defined as dependent variables. The effects of character complexity and other confounding factors were analysed with linear mixed models. Character complexity increased the inter‐character interval and significantly affected ERP amplitudes in both pre‐ and post‐onset time windows. The ERP pattern in the pre‐event time window exhibited a dipole‐like activation in the left motor cortex, and its amplitude increased with character complexity in line with the documented relationship between the lateralized readiness potential and motor complexity. This study demonstrates the feasibility of studying neurocognitive processes in complex naturalistic motor tasks and extends our knowledge about the dynamic pattern of handwriting‐related neural activities. [ABSTRACT FROM AUTHOR]

• Females treated with AMNS and LPS displayed deficits in neuromuscular strength. • Males treated with only LPS displayed increased anxiety-like behaviours. • Males treated with only AMNS displayed decreased S1R in the CA1 and DG. • Females treated with AMNS and LPS displayed decreased S1R in the CA1 and DG. • Males treated with either LPS or AMNS displayed less GFRA1 than females in the M1. Puberty is a sensitive developmental period during which stressors can cause lasting brain and behavioural deficits. While the acute effects of pubertal lipopolysaccharide (LPS) and antimicrobial (AMNS) treatments are known, their enduring impacts on neurodegeneration-related mechanisms and behaviours remain unclear. This study examined these effects in male and female mice. At five weeks old, mice received 200ul of either broad-spectrum antimicrobials or water through oral gavage twice daily for seven days. At six weeks of age, they received an intraperitoneal injection of either saline or LPS. Four weeks later, adult mice underwent neurodegeneration-related behavioural tests, including the rotarod, forepaw stride length, reversed grid hang, open field, and buried pellet tests. Two days after the final test, brain and ileal samples were collected. Results showed that female mice treated with both AMNS and LPS exhibited deficits in neuromuscular strength, while males treated with LPS alone showed increased anxiety-like behaviours. Males treated with AMNS alone had decreased sigma-1 receptor (S1R) expression in the cornu ammonis 1 (CA1) and dentate gyrus (DG), while females treated with both AMNS and LPS had decreased S1R expression. Additionally, males treated with either LPS or AMNS had lower glial-derived neurotrophic factor receptor alpha-1 (GFRA1) expression in the primary motor cortex (M1) than females. Mice treated with LPS alone had decreased GFRA1 expression in the DG and decreased S1R expression in the secondary motor cortex (M2). These findings suggest that pubertal AMNS and LPS treatments may lead to enduring changes in biomarkers and behaviours related to neurodegeneration. [ABSTRACT FROM AUTHOR]

The ability to perform intricate movements is crucial for human motor function. The neural mechanisms underlying precision and power grips are incompletely understood. Corticospinal output from M1 is thought to be modulated by GABAA-ergic intracortical networks within M1. The objective of our study was to investigate the contribution of M1 intracortical inhibition to fine motor control using adaptive threshold hunting (ATH) with paired-pulse TMS during pinch and grasp. We hypothesized that short-interval intracortical inhibition (SICI) could be assessed during voluntary activation and that corticomotor excitability and SICI modulation would be greater during pinch than grasp, reflecting corticospinal control. Seventeen healthy participants performed gradual pinch and grasp tasks. Using ATH, paired-pulse TMS was applied in the anterior-posterior current direction to measure MEP latencies, corticomotor excitability, and SICI. MEP latencies indicated that the procedure preferentially targeted late I-waves. In terms of corticomotor excitability, there was no difference in the TMS intensity required to reach the MEP target during pinch and grasp. Greater inhibition was found during pinch than during grasp. ATH with paired-pulse TMS permits investigation of intracortical inhibitory networks and their modulation during the performance of dexterous motor tasks revealing a greater modulation of GABAA-ergic inhibition contributing to SICI during pinch compared with grasp. NEW & NOTEWORTHY: Primary motor cortex intracortical inhibition was investigated during dexterous manual task performance using adaptive threshold hunting. Motor cortex intracortical inhibition was uniquely modulated during pinching versus grasping tasks. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study investigates the relationship between movement-related beta synchrony and primary motor cortex (M1) excitability, focusing on the time-dependent inhibition of movement. Voluntary movement induces beta frequency (13–30 Hz) event-related desynchronisation (B-ERD) in M1, followed by post-movement beta rebound (PMBR). Although PMBR is linked to cortical inhibition, its temporal relationship with motor cortical excitability is unclear. This study aims to determine whether PMBR acts as a marker for post-movement inhibition by assessing motor-evoked potentials (MEPs) during distinct phases of the beta synchrony profile. Methods: Twenty-five right-handed participants (mean age: 24 years) were recruited. EMG data were recorded from the first dorsal interosseous muscle, and TMS was applied to the M1 motor hotspot to evoke MEPs. A reaction time task was used to elicit beta oscillations, with TMS delivered at participant-specific time points based on EEG-derived beta power envelopes. MEP amplitudes were compared across four phases: B-ERD, early PMBR, peak PMBR, and late PMBR. Results: Our findings demonstrate that MEP amplitude significantly increased during B-ERD compared to rest, indicating heightened cortical excitability. In contrast, MEPs recorded during peak PMBR were significantly reduced, suggesting cortical inhibition. While all three PMBR phases exhibited reduced cortical excitability, a trend toward amplitude-dependent inhibition was observed. Conclusions: This study confirms that PMBR is linked to reduced cortical excitability, validating its role as a marker of motor cortical inhibition. These results enhance the understanding of beta oscillations in motor control and suggest that further research on altered PMBR could be crucial for understanding neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

The older population often experiences a gradual age-related decline in the primary motor cortex, leading to muscle weakness that can harm their physical performances. Exercise could improve physical performance and prevent falling in older adults. However, the decrease in motor function and motor skills in older adults reduces the efficiency of fall prevention. Transcranial Direct Current Stimulation (tDCS) is a non-invasive intervention aimed at improving muscle strength in various conditions by utilizing transcranial direct current stimulation applied to the primary motor cortex (M1). Pre- and post-studies were conducted to demonstrate the effects of a single 20-minute session of tDCS alone, as well as to assess any potential side effects. Sixteen older individuals, both male and female, aged 65 years or older, with or without underlying diseases, were assessed for leg and hand grip strength, followed by physical performance tests. Subsequently, they underwent stimulation of the primary motor cortex through the placement of anodal tDCS (a-tDCS) over the left M1 for 20 min. Immediate effects were evaluated within 24 h, and side effects were recorded for up to 2 weeks after the stimulation. The results demonstrated that a single session of tDCS led to a significant increase in leg strength by 13 kg (5.9 to 20.1 kg, p < 0.01). There was also a significant correlation observed with hand grip strength (r = 0.68, p < 0.01). All physical performance tests, except the fastest speed in the 10-meter walk test, showed statistically significant improvements (p < 0.01). Participants reported no serious side effects, and the intervention will now be incorporated into prospective clinical studies involving older populations to compare its effectiveness with other treatments. [ABSTRACT FROM AUTHOR]

Objective: Locomotion is an automated voluntary movement sustained by coordinated neural synchronization across a distributed brain network. The cerebral cortex is central for adapting the locomotion pattern to the environment and alterations of cortical network dynamics can lead to gait impairments. Gait problems are a common symptom with a still unclear pathophysiology and represent an unmet therapeutical need in Parkinson's disease. Little is known about the cortical network dynamics of locomotor control in these patients. Methods: We studied the cortical basis of parkinsonian gait by combining metabolic brain imaging with high‐density EEG recordings and kinematic measurements performed at rest and during unperturbed overground walking. Results: We found significant changes in functional connectivity between frontal, sensorimotor, and visuomotor cortical areas during walking as compared to resting. Specifically, hypokinetic gait was associated with poor information flow from the supplementary motor area (SMA) to precuneus and from calcarine to lingual gyrus, as well as high information flow from calcarine to cuneus. Interpretation: Our findings support a role for visuomotor integration processes in PD‐related hypokinetic gait and suggest that reinforcing visual information may act as a compensatory strategy to allow SMA‐mediated feedforward locomotor control in PD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the features of resting‐state functional magnetic resonance imaging (rs‐fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. Methods: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low‐frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed‐based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. Results: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed‐based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. Conclusion: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness. [ABSTRACT FROM AUTHOR]