Motor Cortex Research Articles

Brain functional alteration and cognitive performance in cardiovascular diseases: a systematic review of fMRI studies.

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. 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. 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. 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.

Feasibility of submillimeter functional quantitative susceptibility mapping using 3D echo planar imaging at 7 T.

Quantitative susceptibility mapping (QSM) is a tool for mapping tissue susceptibility. Using QSM for functional brain mapping, it is possible to directly quantify blood-oxygen-level-dependent (BOLD) susceptibility changes. This study presents a submillimeter functional QSM (fQSM) approach compared to BOLD fMRI from data acquired with 3D gradient-echo echo planar imaging (EPI) at ultra-high field. Complex EPI data were acquired in nine healthy subjects with varying temporal and spatial resolutions and used for BOLD fMRI and for fQSM. Right-hand finger tapping experiments were performed as well as one measurement with intentional subject movement. Susceptibility maps were computed using 3D path-based unwrapping, the variable-kernel sophisticated harmonic artifact reduction for phase data, and the streaking artifact reduction for QSM algorithm. Functional data analysis included general linear modeling and computation of z-scores. Submillimeter data were denoised using NOise reduction with DIstribution Corrected (NORDIC), which improved z-scores in the motor cortex for fQSM and fMRI. An expected increase in BOLD fMRI signal and corresponding decrease in magnetic susceptibility was observed in sensorimotor areas during active periods. For all experiments, fQSM showed smaller activation regions compared with fMRI. The percentage of high negative t-values localized in the cortex was higher for fQSM (52%) than for positive or negative t-values for fMRI (45%). For the scans with intentional motion, movement exceeded the size of a voxel, but paradigm dependent signal evolution could be recovered using motion correction. In conclusion, this study demonstrates the feasibility of submillimeter whole-brain fQSM with voxel volume of 0.53 μL. In comparison to traditional BOLD fMRI, fQSM provided improved localization of brain activation within the cortex, especially in submillimeter 3D EPI sequences.

Cognitive Impact of β-Amyloid Load in the Rapid Eye Movement Sleep Behavior Disorder-Lewy Body Disease Continuum.

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.

Integration of distinct cortical inputs to primary and higher order inhibitory cells of the thalamus.

The necortex regulates its own sensory input in part through top-down inhibitory mechanisms. Descending corticothalamic projections drive GABAergic neurons of the thalamic reticular nucleus (TRN), which then control thalamocortical cells via inhibition. Neurons in sensory TRN are organized into primary and higher order (HO) subpopulations, with separate intrathalamic connections and distinct genetic and functional properties. Here, we investigated top-down neocortical control over primary and HO neurons of somatosensory TRN. Projections from layer 6 of somatosensory cortex evoked stronger and more state-dependent activity in primary than in HO TRN, driven by more robust synaptic inputs and potent T-type calcium currents. However, HO TRN received additional, physiologically distinct, inputs from layer 5 of S1 and motor cortex. Thus, in a departure from the canonical focused sensory layer 6 innervation characteristic of primary TRN, HO TRN integrates broadly from multiple corticothalamic systems, with unique state-dependence, extending the range of mechanisms for top-down control.

Cortical drive may facilitate enhanced use of the paretic leg induced by random constraint force to the non-paretic leg during walking in chronic stroke.

The goal of this study was to determine the effects of applying random vs. constant constraint force to the non-paretic leg during walking on enhanced use of the paretic leg in individuals post-stroke, and examine the underlying brain mechanisms. Twelve individuals with chronic stroke were tested under two conditions while walking on a treadmill: random vs. constant magnitude of constraint force applied to the non-paretic leg during swing phase of gait using a custom designed robotic system. Leg kinematics, muscle activity of the paretic leg, and electroencephalography (EEG) were recorded during treadmill walking. Paretic step length and muscle activity of the paretic ankle plantarflexors significantly increased after walking with random and constant constraint forces. Cortico-cortical connectivity between motor cortices and cortico-muscular connectivity from the lesioned motor cortex to the paretic ankle plantarflexors significantly increased for the random force condition but not for the constant force condition. In addition, individuals post-stroke with greater baseline gait variability showed greater improvements in the paretic step length after walking with random force condition but not with the constant force condition. In conclusion, application of random constraint force to the non-paretic leg may enhance the use of the paretic leg during walking by facilitating cortical drive from the lesioned motor cortex to the paretic ankle plantarflexors. Results from this study may be used for the development of constraint induced locomotor intervention approaches aimed at improving locomotor function in individuals after stroke.

Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices.

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.

Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices

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.

Disrupted gray matter connectome in vestibular migraine: a combined machine learning and individual-level morphological brain network analysis

BackgroundAlthough gray matter (GM) volume alterations have been extensively documented in previous voxel-based morphometry studies on vestibular migraine (VM), little is known about the impact of this disease on the topological organization of GM morphological networks. This study investigated the altered network patterns of the GM connectome in patients with VM.MethodsIn this study, 55 patients with VM and 57 healthy controls (HCs) underwent structural T1-weighted MRI. GM morphological networks were constructed by estimating interregional similarity in the distributions of regional GM volume based on the Kullback–Leibler divergence measure. Graph-theoretical metrics and interregional morphological connectivity were computed and compared between the two groups. Partial correlation analyses were performed between significant GM connectome features and clinical parameters. Logistic regression (LR), support vector machine (SVM), and random forest (RF) classifiers were used to examine the performance of significant GM connectome features in distinguishing patients with VM from HCs.ResultsCompared with HCs, patients with VM exhibited increased clustering coefficient and local efficiency, as well as reduced nodal degree and nodal efficiency in the left superior temporal gyrus (STG). Furthermore, we identified one connected component with decreased morphological connectivity strength, and the involved regions were mainly located in the STG, temporal pole, prefrontal cortex, supplementary motor area, cingulum, fusiform gyrus, and cerebellum. In the VM group, several connections in the identified connected component were correlated with clinical measures (i.e., symptoms and emotional scales); however, these correlations did not survive multiple comparison corrections. A combination of significant graph- and connectivity-based features allowed single-subject classification of VM versus HC with significant accuracy of 77.68%, 77.68%, and 72.32% for the LR, SVM, and RF models, respectively.ConclusionPatients with VM had aberrant GM connectomes in terms of topological properties and network connections, reflecting potential dizziness, pain, and emotional dysfunctions. The identified features could serve as individualized neuroimaging markers of VM.

Direct interrogation of cortical interneuron circuits in amyotrophic lateral sclerosis.

Cortical hyperexcitability is a key pathogenic feature of amyotrophic lateral sclerosis (ALS), believed to be mediated through complex interplay of cortical interneurons. To date, there has been no technological approach to facilitate the direct capture of cortical interneuron function. Through combination of transcranial magnetic stimulation (TMS) with advanced EEG, the present study examined GABA-ergic dysfunction in ALS, through recording focussed cortical output whilst applying TMS over the primary motor cortex contralateral to the site of symptom onset. Using both a single pulse and novel inhibitory paired-pulse paradigms, TMS-EEG studies were undertaken on 21 ALS patients and results compared to healthy controls. TMS responses captured by EEG form a discrete waveform known as the transcranial evoked potential (TEP), with positive (P) or upward deflections occurring at 30ms (P30), 60 ms (P60) and 190 ms (P190) after TMS stimulus. Negative (N) or downward deflections occur at 44 ms (N44), 100 ms (N100) and 280ms (N280) after T,MS stimulus. The single pulse TEPs recorded in ALS patients demonstrated novel differences suggestive of cortical GABA-ergic dysfunction. When compared to controls, the N100 component was significantly reduced (P<0.05) while the P190 component increased (P<0.05) in ALS patients. Additionally, the N44 component correlated with muscle weakness (r=-0.501, P<0.05). These finding were supported by reduced paired pulse inhibition of TEP components in ALS patients (P60, P<0.01; N100, P<0.005), consistent with dysfunction of cortical interneuronal GABAA-ergic circuits. Further, the reduction in SICI, as reflected by changes in paired-pulse inhibition of the N100 component, was associated with longer disease duration in ALS patients (r=-0.698, P<0.001). In conclusion, intensive and focussed interrogation of the motor cortex utilising novel TMS-EEG combined technologies has established localised dysfunction of GABA-ergic circuits, supporting the notion that cortical hyperexcitability is mediated by cortical disinhibition in ALS. Dysfunction of GABA-ergic circuits correlated with greater clinical disability and disease duration implying pathophysiological significance.

Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behavior are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that traveled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced traveling wave. A depression of calcium signals followed the wave, during which we observed atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioral measures. Neural and behavioral changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

Reduced auditory perception and brain response with quiet TMS coil

BackgroundElectromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC). ObjectiveTo compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil. MethodsNine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120 % RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal while stimulating the primary motor cortex. ResultsRMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100 % coil-specific RMT sounded like Cool-B65 at 34 % RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS- DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation. ConclusionsThe stimulation efficiency of qTMS-DCC matched Cool-B65 while having substantially lower perceived loudness and auditory-evoked potentials.

SpinalTRAQ: A novel volumetric cervical spinal cord atlas identifies the corticospinal tract synaptic projectome in healthy and post-stroke mice.

Descending corticospinal tract (CST) connections to the neurons of the cervical spinal cord are vital for performance of forelimb-specific fine motor skills. In rodents, CST axons are almost entirely crossed at the level of the medullary decussation. While specific contralateral axon projections have been well-characterized using anatomic and molecular approaches, the field currently lacks a cohesive imaging modality allowing rapid quantitative assessment of the entire, bilateral cervical cord projectome at the level of individual laminae and cervical levels. This is potentially important as the CST is known to undergo marked structural remodeling in development, injury, and disease. We developed SpinalTRAQ (Spinal cord Tomographic Registration and Automated Quantification), a novel volumetric cervical spinal cord atlas and machine learning-driven microscopy acquisition and analysis pipeline that uses serial two-photon tomography- images to generate unbiased, region-specific quantification of the fluorescent pixels of anterograde AAV-labeled CST pre-synaptic terminals. In adult mice, the CST synaptic projectome densely innervates the contralateral hemicord, particularly in laminae 5 and 7, with sparse, monosynaptic input to motoneurons in lamina 9. Motor pools supplying axial musculature in the upper cervical cord are bilaterally innervated. The remainder of the ipsilateral cord has sparse labeling in a distinct distribution compared to the contralateral side. Following a focal stroke of the motor cortex, there is a complete loss of descending corticospinal axons from the injured side. Consistent with prior reports of axon collateralization, the CST spinal projectome increases at four weeks post-stroke and continues to elevate by six weeks post stroke. At six weeks post-stroke, we observed striking synapse formation in the denervated hemicord from the uninjured CST in a homotopic distribution. Additionally, CST synaptic reinnervation increases in the denervated lamina 9 in nearly all motoneuron pools, exhibiting novel patterns of connectivity. Detailed level- and lamina-specific quantification of the bilateral cervical spinal cord synaptic projectome reveals previously undescribed patterns of CST connectivity in health and injury-related plasticity.

Oxytocin moderates fMRI connectivity and response to implicit threat processing in cocaine use disorder

Stressful social experiences play an important role in increasing vulnerability to substance use, including cocaine. Oxytocin (OXT), known for its anxiolytic properties and involvement in social functioning, has been suggested as a potential therapeutic for cocaine use disorder (CUD). However, limited research has explored OXT’s influence on social stress in CUD, and no study has examined its effects on neural response to subconscious (implicit) social threat cues in this population. To address this gap, the present study administered intranasal OXT (24 IU) or placebo (PBO) to participants with CUD (CUD+, N = 76) or without CUD (CUD-, N = 61) in a randomized parallel design. Participants then completed a functional magnetic resonance imaging (fMRI) task involving briefly presented facial fear and anger (i.e., threat) cues, followed by neutral face stimuli. Whole-brain activation and amygdala functional connectivity (using psychophysiological interaction modeling) were examined in response to the facial threat cues. OXT reduced activation in the thalamus and pontine reticular formation in response to fear cues, and in the supplementary motor area for both fear and anger cues, regardless of CUD status. Additionally, under PBO, amygdala-medial prefrontal cortex connectivity to fear stimuli was negative for the CUD+ group, but under OXT, this coupling was positive, similar to the positive coupling observed for the CUD- group under both PBO and OXT administration. The finding of OXT-mediated reversal of amygdala-prefrontal coupling was specific to CUD+ and suggests that OXT alters circuitry related to threat surveillance and implicit emotion regulation in CUD. However, additional research is needed to determine whether these alterations due to OXT have clinical significance in CUD.

Effect of Electrode Distance and Size on Electrocorticographic Recordings in Human Sensorimotor Cortex.

Subdural electrocorticography (ECoG) is a valuable technique for neuroscientific research and for emerging neurotechnological clinical applications. As ECoG grids accommodate increasing numbers of electrodes and higher densities with new manufacturing methods, the question arises at what point the benefit of higher density ECoG is outweighed by spatial oversampling. To clarify the optimal spacing between ECoG electrodes, in the current study we evaluate how ECoG grid density relates to the amount of non-shared neurophysiological information between electrode pairs, focusing on the sensorimotor cortex. We simultaneously recorded high-density (HD, 3mm pitch) and ultra-high-density (UHD, 0.9mm pitch) ECoG, obtained intraoperatively from six participants. We developed a new metric, the normalized differential root mean square (ndRMS), to quantify the information that is not shared between electrode pairs. The ndRMS increases with inter-electrode center-to-center distance up to 15mm, after which it plateaus. We observed differences in ndRMS between frequency bands, which we interpret in terms of oscillations in frequencies below 32Hz with phase differences between pairs, versus (un)correlated signal fluctuations in the frequency range above 64Hz. The finding that UHD recordings yield significantly higher ndRMS than HD recordings is attributed to the amount of tissue sampled by each electrode. These results suggest that ECoG densities with submillimeter electrode distances are likely justified.

Spike-based computational primitives to reproduce neural dynamics in the parietal cortex during motor preparation

Abstract Biologically plausible spiking neural network models of sensory cortices can be instrumental in understanding and validating their principles of computation.&amp;#xD; Models based on Cortical Computational Primitives (CCPs), such as Hebbian plasticity and Winner-Take-All (WTA) networks, have already been successful in this approach.&amp;#xD; However, the specific nature and roles of CCPs in sensorimotor cortices during cognitive tasks are yet to be fully deciphered.&amp;#xD; The evolution of motor intention in the Posterior Parietal Cortex (PPC) before arm-reaching movements is a well-suited cognitive process to assess the effectiveness of different CCPs.&amp;#xD; To this end, we propose a biologically plausible model composed of heterogeneous spiking neurons which implements and combines multiple CCPs, such as multi-timescale learning and soft WTA modules.&amp;#xD; By training the model to replicate the dynamics of in-vivo recordings from non-human primates, we show how it is effective in generating meaningful representations from unbalanced input data, and in faithfully reproducing the transition from motor planning to action selection.&amp;#xD; Our findings elucidate the importance of distributing spike-based plasticity across multi-timescales, and provide an explanation for the role of different CCPs in models of frontoparietal cortical networks for performing multisensory integration to efficiently inform action execution.&amp;#xD;

Neural effects of multisensory dance training in Parkinson's disease: evidence from a longitudinal neuroimaging single case study.

Dance is associated with beneficial outcomes in motor and non-motor domains in Parkinson's disease (PD) and regular participation may help delay symptom progression in mild PD. However, little is known about the neurobiological mechanisms of dance interventions for PD. The present case study explored potential neuroplastic changes in a 69-year-old male with mild PD participating in regular dance classes over 29 weeks. Functional MRI was performed at four timepoints (pre-training, 11 weeks, 18 weeks, 29 weeks), where the individual imagined a dance choreography while listening to the corresponding music. Neural activity was compared between dance-imagery and fixation blocks at each timepoint. Analysis of functionally defined regions revealed significant blood-oxygen-level-dependent (BOLD) signal activation in the supplementary motor area, right and left superior temporal gyri and left and right insula, with modulation of these regions observed over the training period except for the left insula. The results suggest the potential for dance to induce neuroplastic changes in people with PD in regions associated with motor planning and learning, auditory processing, rhythm, emotion, and multisensory integration. The findings are consistent with dance being a multimodal therapeutic activity that could provide long-term benefits for people with PD.

Involvement of muscarinic acetylcholine receptor-mediated cholinergic neurotransmission in TMS–EEG responses

The combination of transcranial magnetic stimulation and electroencephalography (TMS–EEG) is emerging as a valuable tool for investigating brain functions in health and disease. However, the detailed neural mechanisms underlying TMS–EEG responses, including TMS-evoked EEG potentials (TEPs) and TMS-induced EEG oscillations (TIOs), remain largely unknown. Combining TMS–EEG with pharmacological interventions provides a unique opportunity to elucidate the roles of specific receptor-mediated neurotransmissions in these responses. Here, we investigated the involvement of muscarinic acetylcholine receptor (mAChR)-mediated cholinergic neurotransmission in TMS–EEG responses by evaluating the effects of mAChR antagonists on TEPs and TIOs in twenty-four healthy participants using a randomized, placebo-controlled crossover design. TEPs and TIOs were measured before and after administering a single oral dose of scopolamine (a non-selective mAChR antagonist), biperiden (an M1 mAChR antagonist), or placebo, with TMS targeting the left medial prefrontal cortex (mPFC), angular gyrus (AG), and supplementary motor area (SMA). The results indicated that mAChR-mediated cholinergic neurotransmission played a role in TEPs, but not TIOs, in a target-specific manner. Specifically, scopolamine significantly increased the amplitude of a local TEP component between approximately 40 and 63 ms post-stimulus when TMS was applied to the SMA, but not the mPFC or AG. Biperiden produced a similar but less pronounced effect. Importantly, the effects of these mAChR antagonists on TEPs were independent of those on sensory-evoked EEG potentials caused by TMS-associated sensory stimulation. These findings expand our understanding of TMS–EEG physiology, providing insights for its application in physiological and clinical research.

Structural and functional whole brain changes in autism spectrum disorder at different age stages.

Autism spectrum disorder (ASD) is a developmental disorder involving regional changes and local neural disturbances. However, few studies have investigated the dysfunctional phenomenon across different age stages. This study explores the structural and functional brain changes across different developmental stages in individuals with ASD, focusing on childhood (6-12 years), adolescence (12-18 years), and adulthood (18 + years). Using a comprehensive set of neuroimaging metrics, including modulated and non-modulated voxel-based morphometry (VBM), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF), we identified significant stage-specific alterations in both VBM and functional measurements. Our results reveal that ASD is associated with progressive and stage-specific abnormalities in brain structure and function, with distinct patterns emerging at each developmental stage. Specifically, we observed significant modulated VBM reductions in the precuneus, lentiform nucleus, and inferior parietal lobule, accompanied by increases in the midbrain and sub-gyral regions. Moreover, we observed unmodulated VBM increment in regions including lentiform nucleus and thalamus. Functionally, ReHo analyses demonstrated disrupted local synchronization in the medial frontal gyrus, while ALFF and fALFF metrics highlighted altered spontaneous brain activity in the sub-gyral and sub-lobar. Finally, correlation analyses revealed that stage-specific findings are closely linked to clinical social- and behavior-related scores, with VBM in the inferior parietal lobule and putamen as well as ReHo in supplemental motor area being significantly associated with restrictive repetitive behaviors in childhood. These findings underscore the importance of considering age-specific brain changes when studying ASD and suggest that targeted interventions may be necessary at different developmental stages.

Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain.

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.

Functional Roles of Sensorimotor Alpha and Beta Oscillations in Overt Speech Production.

Power decreases, or desynchronization, of sensorimotor alpha and beta oscillations (i.e., alpha and beta ERD) have long been considered as indices of sensorimotor control in overt speech production. However, their specific functional roles are not well understood. Hence, we first conducted a systematic review to investigate how these two oscillations are modulated by speech motor tasks in typically fluent speakers (TFS) and in persons who stutter (PWS). Eleven EEG/MEG papers with source localization were included in our systematic review. The results revealed consistent alpha and beta ERD in the sensorimotor cortex of TFS and PWS. Furthermore, the results suggested that sensorimotor alpha and beta ERD may be functionally dissociable, with alpha related to (somato-)sensory feedback processing during articulation and beta related to motor processes throughout planning and articulation. To (partly) test this hypothesis of a potential functional dissociation between alpha and beta ERD, we then analyzed existing intracranial electroencephalography (iEEG) data from the primary somatosensory cortex (S1) of picture naming. We found moderate evidence for alpha, but not beta, ERD's sensitivity to speech movements in S1, lending supporting evidence for the functional dissociation hypothesis identified by the systematic review.