M1 Region Research Articles

ATP1A1 de novo Mutation-Related Disorders: Clinical and Genetic Features.

Background: ATP1A1 encodes an α1 isoform of Na+/K+-ATPase, which is expressed abundantly in kidneys and central nervous system. ATP1A1 variants may cause Na+/K+-ATPase loss of function and lead to a wide spectrum of phenotypes. This study aims to summarize the clinical and genetic features of ATP1A1 de novo mutation-related disorders and explore the potential correlations between phenotypes and genotypes.Methods: We analyzed two new cases harboring novel de novo ATP1A1 variants and reviewed all reported cases.Results: Both our probands had developmental delay, patient 1 accompanied with sleep disorders, irritability, and patient 2 with refractory seizures. They each had a novel de novo heterozygous missense variant, c.2797G>A[p.Asp933Asn] (NM_000701) and c.2590G>A[p.Gly864Arg] (NM_000701) respectively. Four patients with de novo ATP1A1 variants have been reported in two previous papers. Among them, three patients had refractory seizures and one patient had complex hereditary spastic paraplegia (HSP). Therefore, all six patients had developmental delay, and four of them had epilepsy. All variants located in the transmembrane regions M3, M4, M7, and M8 of ATP1A1 protein. Four patients with mutations in M3 and M7 had more severe phenotypes, including developmental delay and epileptic encephalopathy, three of them with hypomagnesemia, whereas two patients with mutations in M4 and M8 had milder phenotypes, only with mild developmental delay, without seizures or hypomagnesemia. Correcting hypomagnesemia had not controlled those seizures.Conclusions: Two novel de novo ATP1A1 variants identified in two patients here enriched the genotypic and phenotypic spectrum of ATP1A1 mutation-related disorder. Our findings suggest that hypomagnesemia in this disorder might relate to more severe phenotype and indicate more severe Na+/K+-ATPase dysfunction. Variations in M3 and M7 transmembrane regions were related to more severe phenotype than those in M4 and M8, which suggested that variations in M3 and M7 might cause more severe ATP1A1 functional defect.

Analgesic Effect of Noninvasive Brain Stimulation for Neuropathic Pain Patients: A Systematic Review

IntroductionThe objective of this review is to systematically summarize the consensus on best practices for different NP conditions of the two most commonly utilized noninvasive brain stimulation (NIBS) technologies, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS).MethodsPubMed was searched according to the predetermined keywords and criteria. Only English language studies and studies published up to January 31, 2020 were taken into consideration. Meta-analyses, reviews, and systematic reviews were excluded first, and those related to animal studies or involving healthy volunteers were also excluded. Finally, 29 studies covering 826 NP patients were reviewed.ResultsThe results from the 24 enrolled studies and 736 NP patients indicate that rTMS successfully relieved the pain symptoms of 715 (97.1%) NP patients. Also, five studies involving 95 NP patients (81.4%) also showed that tDCS successfully relieved NP. In the included studied, the M1 region plays a key role in the analgesic treatment of NIBS. The motor evoked potentials (MEPs), the 10–20 electroencephalography system (EEG 10/20 system), and neuro-navigation methods are used in clinical practice to locate therapeutic targets. Based on the results of the review, the stimulation parameters of rTMS that best induce an analgesic effect are a stimulation frequency of 10–20 Hz, a stimulation intensity of 80–120% of RMT, 1000–2000 pulses, and 5–10 sessions, and the most effective parameters of tDCS are a current intensity of 2 mA, a session duration of 20–30 min, and 5–10 sessions.ConclusionsOur systematically reviewed the evidence for positive and negative responses to rTMS and tDCS for NP patient care and underscores the analgesic efficacy of NIBS in patients with NP. The treatment of NP should allow the design of optimal treatments for individual patients.

Abstract 25: Periinfarct Rewiring Supports Recovery After Primary Motor Cortex Stroke

Background and Purpose: After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with motor recovery involves the periinfarct or more remote brain regions. In humans, the challenge is to recruit patients with similar lesions in size and location. Methods: We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were studied at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of motor recovery were investigated at three spatial scales, i) ipsilesional non-infarcted M1, ii) core motor network (including M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Results: Hand dexterity was impaired only in the acute phase ( P =0.036). At a small spatial scale, improved dexterity was associated with increased FC involving mainly the ipsilesional non-infarcted M1 and contralesional motor regions (cM1: rho=0.732; P =0.004; cPMC: rho=0.837, P <0.001; cSMA: rho=0.736; P =0.004). At a larger scale, motor recovery correlated with the relative increase in total FC strength in the core motor network compared to the extended motor network (rho=0.71; P =0.006). Conclusions: FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. The ipsilesional non-infarcted M1 and core motor regions could hence be primary targets for future restorative therapies.

Parallel and Serial Sensory Processing in Developing Primary Somatosensory and Motor Cortex.

It is generally supposed that primary motor cortex (M1) receives somatosensory input predominantly via primary somatosensory cortex (S1). However, a growing body of evidence indicates that M1 also receives direct sensory input from the thalamus, independent of S1; such direct input is particularly evident at early ages before M1 contributes to motor control. Here, recording extracellularly from the forelimb regions of S1 and M1 in unanesthetized rats at postnatal day (P)8 and P12, we compared S1 and M1 responses to self-generated (i.e., reafferent) forelimb movements during active sleep and wake, and to other-generated (i.e., exafferent) forelimb movements. At both ages, reafferent responses were processed in parallel by S1 and M1; in contrast, exafferent responses were processed in parallel at P8 but serially, from S1 to M1, at P12. To further assess this developmental difference in processing, we compared exafferent responses to proprioceptive and tactile stimulation. At both P8 and P12, proprioceptive stimulation evoked parallel responses in S1 and M1, whereas tactile stimulation evoked parallel responses at P8 and serial responses at P12. Independent of the submodality of exafferent stimulation, pairs of S1-M1 units exhibited greater coactivation during active sleep than wake. These results indicate that S1 and M1 independently develop somatotopy before establishing the interactive relationship that typifies their functionality in adults.SIGNIFICANCE STATEMENT Learning any new motor task depends on the ability to use sensory information to update motor outflow. Thus, to understand motor learning, we must also understand how animals process sensory input. Primary somatosensory cortex (S1) and primary motor cortex (M1) are two interdependent structures that process sensory input throughout life. In adults, the functional relationship between S1 and M1 is well established; however, little is known about how S1 and M1 begin to transmit or process sensory information in early life. In this study, we investigate the early development of S1 and M1 as a sensory processing unit. Our findings provide new insights into the fundamental principles of sensory processing and the development of functional connectivity between these important sensorimotor structures.

ASPECTS Interobserver Agreement of 100 Investigators from the TENSION Study

PurposeEvaluating the extent of cerebral ischemic infarction is essential for treatment decisions and assessment of possible complications in patients with acute ischemic stroke. Patients are often triaged according to image-based early signs of infarction, defined by Alberta Stroke Program Early CT Score (ASPECTS). Our aim was to evaluate interrater reliability in a large group of readers.MethodsWe retrospectively analyzed 100 investigators who independently evaluated 20 non-contrast computed tomography (NCCT) scans as part of their qualification program for the TENSION study. Test cases were chosen by four neuroradiologists who had previously scored NCCT scans with ASPECTS between 0 and 8 and high interrater agreement. Percent and interrater agreements were calculated for total ASPECTS, as well as for each ASPECTS region.ResultsPercent agreements for ASPECTS ratings was 28%, with interrater agreement of 0.13 (95% confidence interval, CI 0.09–0.16), at zero tolerance allowance and 66%, with interrater agreement of 0.32 (95% CI: 0.21–0.44), at tolerance allowance set by TENSION inclusion criteria. ASPECTS region with highest level of agreement was the insular cortex (percent agreement = 96%, interrater agreement = 0.96 (95% CI: 0.94–0.97)) and with lowest level of agreement the M3 region (percent agreement = 68%, interrater agreement = 0.39 [95% CI: 0.17–0.61]).ConclusionInterrater agreement reliability for total ASPECTS and study enrollment was relatively low but seems sufficient for practical application. Individual region analysis suggests that some are particularly difficult to evaluate, with varying levels of reliability. Potential impairment of the supraganglionic region must be examined carefully, particularly with respect to the decision whether or not to perform mechanical thrombectomy.

Microscopic assessments of the effect of phoenix dactylifera L. in a rat model of mercury-triggered cerebral M1 changes

Context: Mercury is a widespread environmental and industrial pollutant that exerts toxic effects on vital organs. The cerebrum, composed of cortical areas such as the primary motor cortex (M1), is a vulnerable target of mercury toxicity within the central nervous system. Phoenix dactylifera is used in folk medicine to treat diverse disorders, such as loss of consciousness, memory disturbances, and nervous disorders. Aim: This study microscopically evaluated the neuroprotective effect of aqueous fruit pulp extract of P. dactylifera (AFPD) on mercury-triggered M1 changes in Wistar rats. Materials and Methods: Twenty-four Wistar rats were divided into six groups (I–VI; n = 4). Group I was administered distilled water (2 ml/kg); Group II administered mercuric chloride (MCL, 5 mg/kg); Group III administered Vitamin C (100 mg/kg) + MCL (5 mg/kg); Groups IV, V, and VI were administered AFPD (250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively) followed by MCL (5 mg/kg). Neuroprotective property was evaluated by microscopic assessment of M1 region applying histological techniques and analysis of histometric features of M1 neurons. Statistical Analysis Used: One-way ANOVA and paired sample t-test were used. Results: Microscopic examination of MCL-treated cerebral sections revealed M1 histoarchitectural distortion and neurodegenerative changes such as pyknosis, neuronal shrinkage, chromatolysis, loss of pyramidal neurites, and altered Nissl substance reactivity, relative to the control. Administration of AFPD remarkably ameliorated MCL-triggered M1 changes, especially at dose 500 mg/kg with neuroprotective property comparable to the reference drug, Vitamin C. Conclusion: AFPD is potentially efficacious in ameliorating mercury-triggered microscopic alterations in M1 region of Wistar rats. The neuroprotective property of AFPD could be attributed to antioxidant properties of constituent phytochemicals.

Mapping Large-Scale Networks Associated with Action, Behavioral Inhibition and Impulsivity.

A key aspect of behavioral inhibition is the ability to wait before acting. Failures in this form of inhibition result in impulsivity and are commonly observed in various neuropsychiatric disorders. Prior evidence has implicated medial frontal cortex, motor cortex, orbitofrontal cortex (OFC), and ventral striatum in various aspects of inhibition. Here, using distributed recordings of brain activity [with local-field potentials (LFPs)] in rodents, we identified oscillatory patterns of activity linked with action and inhibition. Low-frequency (δ) activity within motor and premotor circuits was observed in two distinct networks, the first involved in cued, sensory-based responses and the second more generally in both cued and delayed actions. By contrast, θ activity within prefrontal and premotor regions (medial frontal cortex, OFC, ventral striatum, and premotor cortex) was linked with inhibition. Connectivity at θ frequencies was observed within this network of brain regions. Interestingly, greater connectivity between primary motor cortex (M1) and other motor regions was linked with greater impulsivity, whereas greater connectivity between M1 and inhibitory brain regions (OFC, ventral striatum) was linked with improved inhibition and diminished impulsivity. We observed similar patterns of activity on a parallel task in humans: low-frequency activity in sensorimotor cortex linked with action, θ activity in OFC/ventral prefrontal cortex (PFC) linked with inhibition. Thus, we show that δ and θ oscillations form distinct large-scale networks associated with action and inhibition, respectively.

Distinct GluN1 and GluN2 Structural Determinants for Subunit-Selective Positive Allosteric Modulation of N-Methyl-d-aspartate Receptors.

N-Methyl-d-aspartate receptors (NMDARs) are ionotropic ligand-gated glutamate receptors that mediate fast excitatory synaptic transmission in the central nervous system (CNS). Several neurological disorders may involve NMDAR hypofunction, which has driven therapeutic interest in positive allosteric modulators (PAMs) of NMDAR function. Here we describe modest changes to the tetrahydroisoquinoline scaffold of GluN2C/GluN2D-selective PAMs that expands activity to include GluN2A- and GluN2B-containing recombinant and synaptic NMDARs. These new analogues are distinct from GluN2C/GluN2D-selective compounds like (+)-(3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone (CIQ) by virtue of their subunit selectivity, molecular determinants of action, and allosteric regulation of agonist potency. The (S)-enantiomers of two analogues (EU1180-55, EU1180-154) showed activity at NMDARs containing all subunits (GluN2A, GluN2B, GluN2C, GluN2D), whereas the (R)-enantiomers were primarily active at GluN2C- and GluN2D-containing NMDARs. Determination of the actions of enantiomers on triheteromeric receptors confirms their unique pharmacology, with greater activity of (S) enantiomers at GluN2A/GluN2D and GluN2B/GluN2D subunit combinations than (R) enantiomers. Evaluation of the (S)-EU1180-55 and EU1180-154 response of chimeric kainate/NMDA receptors revealed structural determinants of action within the pore-forming region and associated linkers. Scanning mutagenesis identified structural determinants within the GluN1 pre-M1 and M1 regions that alter the activity of (S)-EU1180-55 but not (R)-EU1180-55. By contrast, mutations in pre-M1 and M1 regions of GluN2D perturb the actions of only the (R)-EU1180-55 but not the (S) enantiomer. Molecular modeling supports the idea that the (S) and (R) enantiomers interact distinctly with GluN1 and GluN2 pre-M1 regions, suggesting that two distinct sites exist for these NMDAR PAMs, each of which has different functional effects.

Effects of Acupuncture Treatment on Functional Brain Networks of Parkinson’s Disease Patients during Treadmill Walking: An fNIRS Study

Acupuncture is increasingly being used as an alternative treatment for patients with Parkinson’s disease (PD). We aimed to evaluate the effects of acupuncture on gait-related brain function in patients with PD using functional near-infrared spectroscopy (fNIRS). Twenty-four patients with PD were randomly assigned to intervention (acupuncture twice a week for 4 weeks) or control (non-treatment) groups. fNIRS experiments applying a block design were performed at baseline (0 weeks) and 4- and 8-week follow-up and cortical activation and connectivity were evaluated. After acupuncture treatment, oxy-hemoglobin (HbO) levels in the intervention group were significantly increased in the primary motor cortex (M1), supplementary motor area (SMA), and prefrontal cortex (PFC). Furthermore, following acupuncture treatment in the intervention group, the connectivities in the M1 and PFC regions increased. The results show that acupuncture may be a useful complementary treatment for gait disturbances in patients with PD, and fNIRS can be applicable to evaluate neural plasticity directly. The evaluation method in this paper can be used to assess the neural plasticity related to various rehabilitation techniques.

Regional differences in beta amyloid plaque deposition and variable response to midlife environmental enrichment in the cortex of APP/PS1 mice

Environmentally enriched housing conditions can increase performance on cognitive tasks in APP/PS1 mice; however, the potential effects of environmental enrichment (EE) on disease modification in terms of pathological change are inconclusive. We hypothesized that previous contrasting findings may be attributable to regional differences in susceptibility to amyloid beta (Aβ) plaque deposition in cortical regions that are functionally associated with EE. We characterized fibrillar plaque deposition in 6, 12, and 18-22 months old APP/PS1 mice in the prefrontal (PFC), somatosensory (SS2), and primary motor cortex (M1). We found a significant increase in plaque load between 6 and 12 months in all regions. In animals over 12 months, only the PFC region continued to significantly accumulate plaques. Additionally, 12 months old animals subjected to 6 months of EE showed improved spatial navigation and had significantly fewer plaques in M1 and SS2, but not in the PFC. These findings suggest that the PFC region is selectively susceptible to Aβ deposition and less responsive to the attenuating effects of EE. In contrast, M1 and SS2 regions plateau with respect to Aβ deposition by 12 months of age and are susceptible to amyloid pathology modification by midlife EE.

P.417 The emotional disturbances in young patients with type 1 diabetes using various methods of insulin therapy by four-dimensional symptom questionnaire

The southern green stink bug, Nezara viridula is a polyphagous pest of commercially important crops during both nymph and adult stages. This insect has recently transitioned from a secondary agricultural pest to one of primary concern. Novel management solutions are needed due to the limited effectiveness of current control strategies. We performed biochemical and transcriptomic analyses to characterize digestive enzymes in the salivary glands and along midgut tissues of N. viridula nymphs and adults fed on sweet corn. The digestive profiles were more distinct between midgut regions (M1 to M3) than between life stages. Aminopeptidase and chymotrypsin activities declined from the M1 (anterior) toward the M3 midgut region. Cysteine protease activity was higher in the M2 and M3 regions than in M1. Differences in sensitivity to chymotrypsin inhibitors between midgut regions suggest that distinct genes or isoforms are expressed in different regions of the gut. In nymphs, DNA and RNA degradation was higher in M1 than in M3. Adult nuclease activity was low across all midgut regions, but high in salivary glands. The differences in protease activities are reflected by transcriptomic data and functional enrichment of GO terms. Together, our results show that different regions of the digestive tract of N. viridula have specific and distinct digestive properties, and increase our understanding of the physiology of this organism.

Association of location and diameter of alveolar antral artery to crest of alveolar bone in dentate and partially edentulous patients - A cone-beam computed tomography study.

Background:One of the most challenging anatomical conditions to manage during sinus augmentation using lateral window approach is the alveolar antral artery (AAA) when it is unusually wide in diameter and passes through the area of the osteotomy with a complete intraosseous course. The purpose of this study was to investigate the association of location and diameter of AAA to the crest of alveolar bone in dentate and partially edentulous patients using cone-beam computed tomography (CBCT).Materials and Methods:Totally 100 CBCT scans of patients (50 dentate and 50 edentulous) were selected and analyzed. The location and diameter of AAA in the lateral wall of the maxillary sinus were evaluated in association with alveolar bone height with respect to three posterior maxillary teeth: first premolar (P1), second premolar (P2), and first molar (M1).Results:The diameter of AAA in dentate patients was higher in M1 region (1.32 ± 0.34 mm) than P1 (0.91 ± 0.20 mm) and P2 (1.07 ± 0.24 mm) regions as compared to edentulous patients. It was found that the location of AAA for P1 in the dentate group (22.35 ± 4.17 mm) was significantly higher than that of the edentulous group (20.37 ± 2.48 mm). A negative relationship has been found between age and the distance between the AAA canal and crest of the alveolar ridge in both dentate (P = 0.001) and edentulous (P = 0.003).Conclusion:A significantly negative relationship existed between age, diameter, and location of AAA in both the dentate and edentulous groups.

ACTIVITY COMMAND ENCODING OF CEREBRAL CORTEX M1-EVOKED POTENTIALS OF THE SPRAGUE DAWLEY RAT USING TIME DELAY NEURAL NETWORKS

Understanding the neurons that transmit messages in the brain while we thinking, feeling, or acting is critical for research on the causes of neurological disease and treatment strategies. This research focuses on the primary motor cortex M1 region, which is involved in human motor function as an activity command center. Understanding this region can help us to determine the mechanism of movement control by the brain, with applicability to other activity mechanisms. A time delay neural network (TDNN) is a suitable model for studying brain signals. TDNN can analyze comprehensive information for a period of successive signals, which is similar to the transmission mechanism of the M1 region. Therefore, this study used a TDNN to build a three-stage encoding system corresponding to the signal type, type arrangement, and time sequence of the brainwave signal from the M1 region and the encoded results were defined as codes, symbols, and commands, respectively. This study aimed to understand the relationship between movement and the M1 region by decoding the signal when the rat undertakes an action. First, we recorded the M1 signal from three rat action types (walk, stand up, and shift head) and performed signal processing. This included using a nonlinear energy operator to find the response points of each action signal. The signals were separated into several sections according to the response time points and independent component analysis was then used to extract the features of the signal (the signal of interest). Finally, we found 16 representative sample signals through a dynamic dimension increasing algorithm to train a three-stage TDNN. We then input the remaining feature signals of interest into the three-stage TDNN for encoding and classification. The results showed an accuracy rate for the three actions of 51.4%, 80.0%, and 54.3%, which means that it is feasible to explain the brain signal of M1 from the free-moving animal using a three-stage TDNN encoding model.

Directed connectivity between primary and premotor areas underlying ankle force control in young and older adults

The control of ankle muscle force is an integral component of walking and postural control. Aging impairs the ability to produce force steadily and accurately, which can compromise functional capacity and quality of life. Here, we hypothesized that reduced force control in older adults would be associated with altered cortico-cortical communication within a network comprising the primary motor area (M1), the premotor cortex (PMC), parietal, and prefrontal regions. We examined electroencephalographic (EEG) responses from fifteen younger (20–26 ​yr) and fifteen older (65–73 ​yr) participants during a unilateral dorsiflexion force-tracing task. Dynamic Causal Modelling (DCM) and Parametric Empirical Bayes (PEB) were used to investigate how directed connectivity between contralateral M1, PMC, parietal, and prefrontal regions was related to age group and precision in force production. DCM and PEB analyses revealed that the strength of connections between PMC and M1 were related to ankle force precision and differed by age group. For young adults, bidirectional PMC-M1 coupling was negatively related to task performance: stronger backward M1-PMC and forward PMC-M1 coupling was associated with worse force precision. The older group exhibited deviations from this pattern. For the PMC to M1 coupling, there were no age-group differences in coupling strength; however, within the older group, stronger coupling was associated with better performance. For the M1 to PMC coupling, older adults followed the same pattern as young adults - with stronger coupling accompanied by worse performance - but coupling strength was lower than in the young group. Our results suggest that bidirectional M1-PMC communication is related to precision in ankle force production and that this relationship changes with aging. We argue that the observed differences reflect compensatory reorganization that counteracts age-related sensorimotor declines and contributes to maintaining performance.

Changes of the upper airway and bone in microimplant-assisted rapid palatal expansion: A cone-beam computed tomography (CBCT) study.

To evaluate the changes of maxillary expansion and upper airway structure after microimplant assisted rapid palatal expansion (MARPE) using cone-beam computed tomography (CBCT). This retrospective study included 19 subjects (15 females and 4 males) aged 15-29 years old (mean, 19.95±4.39 years) with maxillary transverse deficiency treated with MARPE. CBCT was performed at the initial diagnosis and 3 months after MARPE treatment. Measurements were taken to evaluate the amount of total expansion, skeletal expansion, and dental expansion at the maxillary first premolar (P1), second premolar (P2), first molar (M1), second molar (M2) regions and upper airway changes. After MARPE treatment, the maxillary skeletal base expansion, skeletal expansion, alveolar expansion and dental expansion were achieved at the P1, P2, M1, M2 region. The nasopharyngeal volume significantly increased 8.48% after MARPE treatment compared with that before the treatment (P < 0.05). The change of nasal lateral width (NLW) was also significantly different before and after MARPE (P < 0.05). However, there were no statistically significant change in the oropharyngeal, palatopharyngeal, glossopharyngeal and airway total volume (all P > 0.05). MARPE can produce more transverse bone expansion, relieve maxillary transverse deficiency and improve upper airway ventilation.

Spatially and Temporally Distinct Encoding of Muscle and Kinematic Information in Rostral and Caudal Primary Motor Cortex.

The organizing principle of human motor cortex does not follow an anatomical body map, but rather a distributed representational structure in which motor primitives are combined to produce motor outputs. Electrophysiological recordings in primates and human imaging data suggest that M1 encodes kinematic features of movements, such as joint position and velocity. However, M1 exhibits well-documented sensory responses to cutaneous and proprioceptive stimuli, raising questions regarding the origins of kinematic motor representations: are they relevant in top-down motor control, or are they an epiphenomenon of bottom-up sensory feedback during movement? Here we provide evidence for spatially and temporally distinct encoding of kinematic and muscle information in human M1 during the production of a wide variety of naturalistic hand movements. Using a powerful combination of high-field functional magnetic resonance imaging and magnetoencephalography, a spatial and temporal multivariate representational similarity analysis revealed encoding of kinematic information in more caudal regions of M1, over 200 ms before movement onset. In contrast, patterns of muscle activity were encoded in more rostral motor regions much later after movements began. We provide compelling evidence that top-down control of dexterous movement engages kinematic representations in caudal regions of M1 prior to movement production.

Phonatory and articulatory representations of speech production in cortical and subcortical fMRI responses

Speaking involves coordination of multiple neuromotor systems, including respiration, phonation and articulation. Developing non-invasive imaging methods to study how the brain controls these systems is critical for understanding the neurobiology of speech production. Recent models and animal research suggest that regions beyond the primary motor cortex (M1) help orchestrate the neuromotor control needed for speaking, including cortical and sub-cortical regions. Using contrasts between speech conditions with controlled respiratory behavior, this fMRI study investigates articulatory gestures involving the tongue, lips and velum (i.e., alveolars versus bilabials, and nasals versus orals), and phonatory gestures (i.e., voiced versus whispered speech). Multivariate pattern analysis (MVPA) was used to decode articulatory gestures in M1, cerebellum and basal ganglia. Furthermore, apart from confirming the role of a mid-M1 region for phonation, we found that a dorsal M1 region, linked to respiratory control, showed significant differences for voiced compared to whispered speech despite matched lung volume observations. This region was also functionally connected to tongue and lip M1 seed regions, underlying its importance in the coordination of speech. Our study confirms and extends current knowledge regarding the neural mechanisms underlying neuromotor speech control, which hold promise to study neural dysfunctions involved in motor-speech disorders non-invasively.

Preliminary findings on the role of high-frequency (5Hz) rTMS stimulation on M1 and pre-SMA regions in Parkinson's disease

It has been already shown that the motor symptoms of the Parkinson's Disease (PD) have been improved with high frequency rTMS although there is no consensus on the most suitable target brain localization for a maximal therapeutic efficacy. Here, we aimed to compare the therapeutic effect of high frequency (5Hz) rTMS stimulation on primary motor cortex (M1) and pre-supplementary (pre SMA) regions in patients with PD who were still on pharmacological treatment. The study included right-hand dominant16 patients with PD (5 females, 11 males) with demographically and clinically similar characteristics which were randomly assigned to group 1 (n=8) and group 2 (n=8) and received left M1 and the left pre-SMA rTMS procedure, respectively. Total and sequential motor scores of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) were applied to all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. Comparisons of the UPDRS-motor scores between two groups yielded significant improvements after the rTMS on pre-SMA compared to M1 (M1 p=0.14; pre-SMA p=0.01). which were especially significant for the bradykinesia (p=0.04) and axial score related items (p=0.01). This is the first study that shows the effect of rTMS on pre-SMA and it appears to be a promising option in the treatment of PD.

Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder

Several motor disabilities accompanied with autism spectrum disorder (ASD) are widely known despite limited reports of underlying neural mechanisms. Gamma-aminobutyric acid (GABA) levels in the motor-related cortical areas modulate several motor performances in healthy participants. We hypothesized that abnormal GABA concentrations in the primary motor area (M1) and supplementary motor area (SMA) associate with different motor difficulties for ASD adolescents/adults. We found that increased GABA concentrations in M1 measured using 1H-magnetic resonance spectroscopy exhibited lower motor performance in tasks requiring increased muscle strength while lower GABA concentrations in SMA were associated with lower scores in tests measuring body coordination. The degrees of neural inhibition in the M1 and SMA regions would contribute to different dimensions of motor disabilities in autism.

Do All ASPECT Score Regions have the Same Predictive Power for Functional Outcomes?

Background and PurposeASPECTS (Alberta Stroke Program Early CT Score) is a 10-point topographic CT scan score that has been shown to be a strong prognostic factor in acute ischemic stroke. We investigated whether all ASPECTS regions have the same prognostic value. MethodsClinical characteristics, ASPECTS, and 3-month modified Rankin Scale (mRS) data were retrospectively collected in 350 patients who were diagnosed with middle cerebral artery (MCA) territory stroke. To describe the 3-month mRS data, an ordered categorical approach was applied using a proportional odds model. Furthermore, external validation was performed using additional data from 30 patients. ResultsAs expected, ASPECTS was an independently important predictor. However, when 10 regions were analyzed separately, the M1, M2, and M3 regions, related to MCA cortex, were not found to predict 3-month mRS scores in the final model. The odds ratios for ischemic change in other regions (except M1, M2, and M3) ranged from 2.6 to 3.8. Moreover, among clinical characteristics, only age was identified as a significant predictor. The sensitivity and specificity of the final model in the external validation were 91% and 88%, respectively. ConclusionsAll ASPECTS regions did not have the same predictive power for functional outcomes, defined as the 3-month mRS. The implementation of a proportional odds model allowed a proper description of the ordered categorical nature of the mRS and the identification of relevant predictors.