Ipsilateral Primary Motor Cortex Research Articles

Dorsal dentate gyrus mediated enriched environment-induced anxiolytic and antidepressant effects in cortical infarcted mice

Anxiety and depression are the most common mental health disorders worldwide, each affecting around 30% stroke survivors. These complications not only affect the functional recovery and quality of life in stroke patients, but also are distressing for caregivers. However, effective treatments are still lacking. Enriched environment (EE), characterized with novel and multi-dimensional stimulation, has been reported to exert therapeutic effects on physical and cognitive function. In addition, EE also had potential positive effects on emotional disorders after ischemic stroke; however, the underling mechanisms have not been well elucidated. This study aimed to explore the effectiveness of EE on emotional disorders after cerebral ischemia and its underling mechanism. Sensorimotor cortical infarction was induced by photothrombosis with stable infarct location and volume, resulting in motor dysfunction, anxiety and depression-like behaviors in mice, with decreased ALFF and ReHo values and decreased c-fos expression in the infarction area and adjacent regions. Seven days' EE treatment significantly improved motor function of contralateral forelimb and exhibited anxiolytic and antidepressant effects in infarcted mice. Compared to the mice housing in a standard environment, those subjected to acute EE stimulation had significantly increased ALFF and ReHo values in the bilateral somatosensory cortex (S1, S2), dorsal dentate gyrus (dDG), dorsal CA1 of hippocampus (dCA1), lateral habenular nucleus (LHb), periaqueductal gray (PAG), ipsilateral primary motor cortex (M1), retrosplenial cortex (RSC), parietal association cortex (PtA), dorsal CA3 of hippocampus (dCA3), claustrum (Cl), ventral pallidum (VP), amygdala (Amy), and contralateral auditory cortex (Au). Some of, but not all, the ipsilateral brain regions mentioned above showed accompanying increases in c-fos expression with the most significant changes in the dDG. The number of FosB positive cells in the dDG, decreased in infarcted mice, was significantly increased after chronic EE treatment. Chemogenetic activation of dDG neurons reduced anxiety and depressive-like behaviors in infarcted mice, while neuronal inhibition resulted in void of the anxiolytic and antidepressant effects of EE. Altogether, these findings indicated that dDG neurons may mediate EE-triggered anxiolytic and antidepressant effects in cortical infarcted mice.

Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain

L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu2/3) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu2/3 activation, we performed autoradiographic binding with [3H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [3H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, P<0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (49 % vs sham-lesioned rats, P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, P<0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05), GP (34 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [3H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all P<0.05). These results suggest that alterations in mGlu2/3 receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.

Neural Plasticity Changes Induced by Motor Robotic Rehabilitation in Stroke Patients: The Contribution of Functional Neuroimaging.

Robotic rehabilitation is one of the most advanced treatments helping people with stroke to faster recovery from motor deficits. The clinical impact of this type of treatment has been widely defined and established using clinical scales. The neurofunctional indicators of motor recovery following conventional rehabilitation treatments have already been identified by previous meta-analytic investigations. However, a clear definition of the neural correlates associated with robotic neurorehabilitation treatment has never been performed. This systematic review assesses the neurofunctional correlates (fMRI, fNIRS) of cutting-edge robotic therapies in enhancing motor recovery of stroke populations in accordance with PRISMA standards. A total of 7, of the initial yield of 150 articles, have been included in this review. Lessons from these studies suggest that neural plasticity within the ipsilateral primary motor cortex, the contralateral sensorimotor cortex, and the premotor cortices are more sensitive to compensation strategies reflecting upper and lower limbs' motor recovery despite the high heterogeneity in robotic devices, clinical status, and neuroimaging procedures. Unfortunately, the paucity of RCT studies prevents us from understanding the neurobiological differences induced by robotic devices with respect to traditional rehabilitation approaches. Despite this technology dating to the early 1990s, there is a need to translate more functional neuroimaging markers in clinical settings since they provide a unique opportunity to examine, in-depth, the brain plasticity changes induced by robotic rehabilitation.

Task-residual effective connectivity of motor network in transient ischemic attack

Transient ischemic attack (TIA) is a temporary episode of neurological dysfunction that results from focal brain ischemia. Although TIA symptoms are quickly resolved, patients with TIA have a high risk of stroke and persistent impairments in multiple domains of cognitive and motor functions. In this study, using spectral dynamic causal modeling, we investigate the changes in task-residual effective connectivity of patients with TIA during fist-closing movements. 28 healthy participants and 15 age-matched patients with TIA undergo functional magnetic resonance imaging at 7T. Here we show that during visually cued motor movement, patients with TIA have significantly higher effective connectivity toward the ipsilateral primary motor cortex and lower connectivity to the supplementary motor area than healthy controls. Our results imply that TIA patients have aberrant connections among motor regions, and these changes may reflect the decreased efficiency of primary motor function and disrupted control of voluntary movement in patients with TIA.

Greater task difficulty during unilateral motor tasks changes intracortical inhibition and facilitation in the ipsilateral primary motor cortex in young men

This study aimed to clarify the changes in short-interval intracortical inhibition (SICI) and facilitation (ICF) in the ipsilateral primary motor cortex (iM1) when the task difficulty during unilateral force-matching tasks was manipulated. Twelve young male adults matched their left index finger abduction force to a displayed target force. Task difficulty was manipulated by varying the acceptable force range of the mean target force (5% MVC). Briefly, unilateral force-matching tasks with lesser and greater task difficulty (EASY and DIFF, respectively) were assigned acceptable force ranges of ± 7% and ± 0% of the target force, respectively. To evaluate SICI and ICF in iM1, paired-pulse transcranial magnetic stimulation with 2-ms and 10-ms interstimulus intervals was applied to correct motor-evoked potentials (MEPs) from the first dorsal interosseous muscle during each task. Test stimulus intensity to evoke the MEP with a peak-to-peak amplitude of approximately 0.5–1.5 mV for each task was lower in DIFF than in EASY (P = 0.001), indicating that DIFF increased corticospinal excitability of the ipsilateral hemisphere compared with EASY. The MEPs in SICI and ICF were significantly larger in DIFF than in EASY (P < 0.050). These results suggest that greater corticospinal excitability in the ipsilateral hemisphere during DIFF is associated with reduced SICI and increased ICF.

Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand.

Altered frontoparietal activity in acoustic startle priming tasks during reticulospinal tract facilitation: An fNIRS study.

Because it is one of the important pathways for promoting motor recovery after cortical injury, the function of the reticulospinal tract (RST) has received increasing attention in recent years. However, the central regulatory mechanism of RST facilitation and reduction of apparent response time is not well understood. To explore the potential role of RST facilitation in the acoustic startle priming (ASP) paradigm and observe the cortical changes induced by ASP reaching tasks. Twenty healthy participants were included in this study. The reaching tasks were performed with their left and right hands. Participants were instructed to get ready after the warning cue and complete the reach as soon as they heard the Go cue. Half of the testing trials were set as control trials with an 80-dB Go cue. The other half of the trials had the Go cue replaced with 114-dB white noise to evoke the StartleReact effect, inducing reticulospinal tract facilitation. The response of the bilateral sternocleidomastoid muscle (SCM) and the anterior deltoid was recorded via surface electromyography. Startle trials were labeled as exhibiting a positive or negative StartleReact effect, according to whether the SCM was activated early (30-130 ms after the Go cue) or late, respectively. Functional near-infrared spectroscopy was used to synchronously record the oxyhemoglobin and deoxyhemoglobin fluctuations in bilateral motor-related cortical regions. The β values representing cortical responses were estimated via the statistical parametric mapping technique and included in the final analyses. Separate analyses of data from movements of the left or right side revealed significant activation of the right dorsolateral prefrontal cortex during RST facilitation. Moreover, left frontopolar cortex activation was greater in positive startle trials than in control or negative startle trials during left-side movements. Furthermore, decreased activity of the ipsilateral primary motor cortex in positive startle trials during ASP reaching tasks was observed. The right dorsolateral prefrontal cortex and the frontoparietal network to which it belongs may be the regulatory center for the StartleReact effect and RST facilitation. In addition, the ascending reticular activating system may be involved. The decreased activity of the ipsilateral primary motor cortex suggests enhanced inhibition of the non-moving side during the ASP reaching task. These findings provide further insight into the SE and into RST facilitation.

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n=14; 61 ± 7yrs) or abnormally enlarged (hyperechogenic; n=9; 60 ± 6yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p=.005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Modeling the Hemodynamic Response Function Using EEG-fMRI Data During Eyes-Open Resting-State Conditions and Motor Task Execution

Being able to accurately quantify the hemodynamic response function (HRF) that links the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) signal to the underlying neural activity is important both for elucidating neurovascular coupling mechanisms and improving the accuracy of fMRI-based functional connectivity analyses. In particular, HRF estimation using BOLD-fMRI is challenging particularly in the case of resting-state data, due to the absence of information about the underlying neuronal dynamics. To this end, using simultaneously recorded electroencephalography (EEG) and fMRI data is a promising approach, as EEG provides a more direct measure of neural activations. In the present work, we employ simultaneous EEG-fMRI to investigate the regional characteristics of the HRF using measurements acquired during resting conditions. We propose a novel methodological approach based on combining distributed EEG source space reconstruction, which improves the spatial resolution of HRF estimation and using block-structured linear and nonlinear models, which enables us to simultaneously obtain HRF estimates and the contribution of different EEG frequency bands. Our results suggest that the dynamics of the resting-state BOLD signal can be sufficiently described using linear models and that the contribution of each band is region specific. Specifically, it was found that sensory-motor cortices exhibit positive HRF shapes, whereas the lateral occipital cortex and areas in the parietal cortex, such as the inferior and superior parietal lobule exhibit negative HRF shapes. To validate the proposed method, we repeated the analysis using simultaneous EEG-fMRI measurements acquired during execution of a unimanual hand-grip task. Our results reveal significant associations between BOLD signal variations and electrophysiological power fluctuations in the ipsilateral primary motor cortex, particularly for the EEG beta band, in agreement with previous studies in the literature.

A multisynaptic pathway from the ventral midbrain toward spinal motoneurons in monkeys.

Motivation boosts motor performance. Activity of the ventral midbrain (VM), consisting of the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) and the retrorubral field (RRF), plays an important role in processing motivation. However, little is known about the neural substrate bridging the VM and the spinal motor output. We hypothesized that the VM might exert a modulatory influence over the descending motor pathways. By retrograde transneuronal labelling with rabies virus, we demonstrated the existence of multisynaptic projections from the VM to the cervical enlargement in monkeys. The distribution pattern of spinal projection neurons in the VM exhibited a caudorostral gradient, in that the RRF and the caudal part of the SNc contained more retrogradely labelled neurons than the VTA and the rostral part of the SNc. Electrical stimulation of the VM induced muscle responses in the contralateral forelimb with a delay of a few milliseconds following the responses of the ipsilateral primary motor cortex (M1). The magnitude and number of evoked muscle responses were associated with the stimulus intensity and number of pulses. The muscle responses were diminished during M1 inactivation. Thus, the present study has identified a multisynaptic VM–spinal pathway that is mediated, at least in part, by the M1 and might play a pivotal role in modulatory control of the spinal motor output.Key points Motivation to obtain reward is thought to boost motor performance, and activity in the ventral midbrain is important to the motivational process.Little is known about a neural substrate bridging the ventral midbrain and the spinal motor output.Retrograde trans‐synaptic experiments revealed that the ventral midbrain projects multisynaptically to the spinal cord in macaque monkeys.Ventral midbrain activation by electrical stimulation generated cortical activity in the motor cortex and forelimb muscle activity.A multisynaptic ventral midbrain–spinal pathway most probably plays a pivotal role in modulatory control of the spinal motor output.

The effect of clinical application of transcranial direct current stimulation combined with non-immersive virtual reality rehabilitation in stroke patients.

The ability to manipulate the upper limbs and fingers of stroke patients is very important for independent daily life. Among the latest approaches for upper limb rehabilitation training, transcranial direct current stimulation (tDCS) is a non-invasive stimulation method that stimulates the cranial nerves by attaching electrodes to the scalp. In addition, virtual reality (VR) is an intervention method that provides an environment similar to reality and can help restore function by performing body movements as if playing a game. In addition, VR is an intervention method that provides an environment similar to reality and helps to recover functions by performing body movements as if playing a game. This study was conducted to investigate the effect of anodal tDCS applied to the ipsilateral primary motor cortex (M1) during VR training on the upper limb function, cognition, and executive function of stroke patients. After 20 patients were randomly assigned to the experimental group and the control group, the experimental group received tDCS and VR, and the control group received sham tDCS and VR for 20 minutes a day, 5 days a week, for a total of 4 weeks. Participants were evaluated for upper limb function using Box and Block Test (BBT) and Jebsen-Taylor Hand Function Test (JTHFT), and cognitive and executive function using the Stroop Test (ST) and Trail Making Test (TMT). In the experimental group, significant differences were found in the pre- and post-test for the all variance (p< 0.05). Control group is significant differences were found in the pre- and post-test for BBT, ST, TMT (p< 0.05). There were significant differences between the two groups in the post test of BBT and ST (p< 0.05). The results of this study suggest that anodal tDCS applied to the ipsilateral M1 during VR training is effective for upper limb function, cognitive function, and executive function in stroke patients.

Para-Sports can Promote Functional Reorganization in the Ipsilateral Primary Motor Cortex of Lower Limbs Amputee

Background. Drastic functional reorganization was observed in the ipsilateral primary motor cortex (M1) of a Paralympic long jumper with a unilateral below-knee amputation in our previous study. However, it remains unclear whether long-term para-sports are associated with ipsilateral M1 reorganization since only 1 athlete with amputation was investigated. Objective. This study aimed to investigate the relationship between the long-term para-sports and ipsilateral M1 reorganization after lower limb amputation. Methods. Lower limb rhythmic muscle contraction tasks with functional magnetic resonance imaging and T1-weighted structural imaging were performed in 30 lower limb amputees with different para-sports experiences in the chronic phase. Results. Brain activity in the ipsilateral primary motor and somatosensory areas (SM1) as well as the contralateral dorsolateral prefrontal cortex, SM1, and inferior temporal gyrus showed a positive correlation with the years of routine para-sports participation (sports years) during contraction of the amputated knee. Indeed, twelve of the 30 participants who exhibited significant ipsilateral M1 activation during amputated knee contraction had a relatively longer history of para-sports participation. No significant correlation was found in the structural analysis. Conclusions. Long-term para-sports could lead to extensive reorganization at the brain network level, not only bilateral M1 reorganization but also reorganization of the frontal lobe and visual pathways. These results suggest that the interaction of injury-induced and use-dependent cortical plasticity might bring about drastic reorganization in lower limb amputees.

A single session of submaximal grip strength training with or without high-definition anodal-TDCS produces no cross-education of maximal force

BACKGROUND: Previous studies suggest that cross-education of strength may be modulated by increased corticospinal excitability of the ipsilateral primary motor cortex (M1) due to cross-activation. However, no study has examined the influence of bilateral TDCS of both M1 and how it affects corticospinal excitability, cross-activation and cross-education of muscle strength. METHOD: Twelve participants underwent three conditions in a randomized crossover design: (1) submaximal grip training and single-site unilateral-high definition-TDCS (2) submaximal grip training and bilateral anodal-high definition-TDCS, and (3) submaximal grip training and sham-high definition-TDCS. Submaximal gripping task involved a single-session of unilateral training which was squeezing the transducer at 70% of maximum voluntary isometric contraction (MVIC) grip force and performing four sets of 10 isometric contractions. Anodal-high definition-TDCS was applied for 15 min at 1.5 mA over right M1 or left and right M1s, and in a sham condition. Participants were pseudorandomized to receive either single-site or bilateral M1 stimulation with each session separated by one-week. Before and after each session, MVIC force of ipsilateral and contralateral gripping, ipsilateral stimulus-response curve, short-interval intracortical inhibition, cortical silent period, intracortical facilitation, long-interval intracortical inhibition, and cross-activation were measured. RESULTS: MVIC of the trained arm decreased by 43% (P=0.04) after training. We observed no changes in MVIC of the untrained hand and in any of the TMS measures (all P&gt;0.05). CONCLUSION: A single session of submaximal grip training with or without anodal-high definition-TDCS produces no cross-education of maximal grip force nor does it affect the excitability of the ipsilateral M1.

Ageing and the Ipsilateral M1 BOLD Response: A Connectivity Study.

Young people exhibit a negative BOLD response in ipsilateral primary motor cortex (M1) when making unilateral movements, such as button presses. This negative BOLD response becomes more positive as people age. In this study, we investigated why this occurs, in terms of the underlying effective connectivity and haemodynamics. We applied dynamic causal modeling (DCM) to task fMRI data from 635 participants aged 18–88 from the Cam-CAN dataset, who performed a cued button pressing task with their right hand. We found that connectivity from contralateral supplementary motor area (SMA) and dorsal premotor cortex (PMd) to ipsilateral M1 became more positive with age, explaining 44% of the variability across people in ipsilateral M1 responses. In contrast, connectivity from contralateral M1 to ipsilateral M1 was weaker and did not correlate with individual differences in rM1 BOLD. Neurovascular and haemodynamic parameters in the model were not able to explain the age-related shift to positive BOLD. Our results add to a body of evidence implicating neural, rather than vascular factors as the predominant cause of negative BOLD—while emphasising the importance of inter-hemispheric connectivity. This study provides a foundation for investigating the clinical and lifestyle factors that determine the sign and amplitude of the M1 BOLD response in ageing, which could serve as a proxy for neural and vascular health, via the underlying neurovascular mechanisms.

Abstract MP58: Motor Cortex and Spinal Cord Transcriptome After Post-Stroke Optogenetic Neuronal Stimulation

Background: Post-stroke brain stimulation is a promising neurorestorative technique to promote recovery. However, the underlying molecular mechanisms driving recovery are still unclear. Here we investigate the molecular changes in both the primary motor cortex and the cervical spinal cord after large cortical stroke in mice receiving repeated optogenetic stimulations in the ipsilateral primary motor cortex (iM1). Methods: C57Bl6 male mice (8 weeks) underwent stereotaxic surgery to express Channelrhodopsin2 in excitatory neurons in iM1, with optical fiber implanted in the same location. After five weeks the mice underwent a transient middle cerebral artery occlusion to induce stroke. Optogenetic stimulations were given daily from post-stroke days (PD) 5-14. Non-stimulated mice were used as controls. Rotating beam test was used to evaluate functional recovery after stroke. At PD 7 and 15, ipsi- and contralesional primary motor cortex (iM1 and cM1) and cervical spinal cords (iSp and cSp) were dissected and processed for RNA sequencing. Results: Repeated iM1 stimulations resulted in a robust recovery on the rotating beam test at PD14, with significant improvement in distance traveled (p&lt;0.05). RNA sequencing analysis (stimulated vs non-stimulated mice) revealed differential transcriptome in both motor cortex and spinal cord. Higher number of differentially expressed genes (DEGs) were observed in the ipsilesional regions (iM1 and iSp). At PD 7, stimulated mice exhibited upregulation of activity-dependent and neuroplasticity-related genes in iM1. Interestingly, at PD15, cholesterol metabolism and neuroinflammatory related genes in iM1 were downregulated. The expressions of the genes were negatively correlated with behavioral recovery. Higher number of DEGs were altered in the spinal cord than motor cortex, suggesting more dynamic molecular changes occur in this area during the post-stroke reinnervation processes. Expressions of synaptogenesis related genes were altered in both iSp and cSp at both timepoints. Conclusions: These transcriptome data reveal important insights into the molecular signaling involved in post-stroke stimulation-induced recovery and provide potential drug targets for enhancing recovery in stroke patients.

Role of the Ipsilateral Primary Motor Cortex in the Visuo-Motor Network During Fine Contractions and Accurate Performance.

It is widely recognized that continuous sensory feedback plays a crucial role in accurate motor control in everyday life. Feedback information is used to adapt force output and to correct errors. While primary motor cortex contralateral to the movement (cM1) plays a dominant role in this control, converging evidence supports the idea that ipsilateral primary motor cortex (iM1) also directly contributes to hand and finger movements. Similarly, when visual feedback is available, primary visual cortex (V1) and its interactions with the motor network also become important for accurate motor performance. To elucidate this issue, we performed and integrated behavioral and electroencephalography (EEG) measurements during isometric compression of a compliant rubber bulb, at 10% and 30% of maximum voluntary contraction, both with and without visual feedback. We used a semi-blind approach (functional source separation (FSS)) to identify separate functional sources of mu-frequency (8-13[Formula: see text]Hz) EEG responses in cM1, iM1 and V1. Here for the first time, we have used orthogonal FSS to extract multiple sources, by using the same functional constraint, providing the ability to extract different sources that oscillate in the same frequency range but that have different topographic distributions. We analyzed the single-trial timecourses of mu power event-related desynchronization (ERD) in these sources and linked them with force measurements to understand which aspects are most important for good task performance. Whilst the amplitude of mu power was not related to contraction force in any of the sources, it was able to provide information on performance quality. We observed stronger ERDs in both contralateral and ipsilateral motor sources during trials where contraction force was most consistently maintained. This effect was most prominent in the ipsilateral source, suggesting the importance of iM1 to accurate performance. This ERD effect was sustained throughout the duration of visual feedback trials, but only present at the start of no feedback trials, consistent with more variable performance in the absence of feedback. Overall, we found that the behavior of the ERD in iM1 was the most informative aspect concerning the accuracy of the contraction performance, and the ability to maintain a steady level of contraction. This new approach of using FSS to extract multiple orthogonal sources provides the ability to investigate both contralateral and ipsilateral nodes of the motor network without the need for additional information (e.g. electromyography). The enhanced signal-to-noise ratio provided by FSS opens the possibility of extracting complex EEG features on an individual trial basis, which is crucial for a more nuanced understanding of fine motor performance, as well as for applications in brain-computer interfacing.

Excitability of the Ipsilateral Primary Motor Cortex During Unilateral Goal-Directed Movement.

IntroductionPrevious transcranial magnetic stimulation (TMS) studies have revealed that the activity of the primary motor cortex ipsilateral to an active hand (ipsi-M1) plays an important role in motor control. The aim of this study was to investigate whether the ipsi-M1 excitability would be influenced by goal-directed movement and laterality during unilateral finger movements.MethodTen healthy right-handed subjects performed four finger tapping tasks with the index finger: (1) simple tapping (Tap) task, (2) Real-word task, (3) Pseudoword task, and (4) Visually guided tapping (VT) task. In the Tap task, the subject performed self-paced simple tapping on a touch screen. In the real-word task, the subject tapped letters displayed on the screen one by one to create a Real-word (e.g., apple). Because the action had a specific purpose (i.e., creating a word), this task was considered to be goal-directed as compared to the Tap task. In the Pseudoword task, the subject tapped the letters to create a pseudoword (e.g., gdiok) in the same manner as in the Real-word task; however, the word was less meaningful. In the VT task, the subject was required to touch a series of illuminated buttons. This task was considered to be less goal-directed than the Pseudoword task. The tasks were performed with the right and left hand, and a rest condition was added as control. Single- and paired-pulse TMS were applied to the ipsi-M1 to measure corticospinal excitability and short- and long-interval intracortical inhibition (SICI and LICI) in the resting first dorsal interosseous (FDI) muscle.ResultsWe found the smaller SICI in the ipsi-M1 during the VT task compared with the resting condition. Further, both SICI and LICI were smaller in the right than in the left M1, regardless of the task conditions.DiscussionWe found that SICI in the ipsi-M1 is smaller during visual illumination-guided finger movement than during the resting condition. Our finding provides basic data for designing a rehabilitation program that modulates the M1 ipsilateral to the moving limb, for example, for post-stroke patients with severe hemiparesis.

Reduced Facilitation of Parietal-Motor Functional Connections in Older Adults.

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement.

Aberrant brain oscillatory coupling from the primary motor cortex in children with autism spectrum disorders

Autism spectrum disorder (ASD) often involves dysfunction in general motor control and motor coordination, in addition to core symptoms. However, the neural mechanisms underlying motor dysfunction in ASD are poorly understood. To elucidate this issue, we focused on brain oscillations and their coupling in the primary motor cortex (M1). We recorded magnetoencephalography in 18 children with ASD, aged 5 to 7 years, and 19 age- and IQ-matched typically-developing children while they pressed a button during a video-game-like motor task. The motor-related gamma (70 to 90 Hz) and pre-movement beta oscillations (15 to 25 Hz) were analyzed in the primary motor cortex using an inverse method. To determine the coupling between beta and gamma oscillations, we applied phase-amplitude coupling to calculate the statistical dependence between the amplitude of fast oscillations and the phase of slow oscillations. We observed a motor-related gamma increase and a pre-movement beta decrease in both groups. The ASD group exhibited a reduced motor-related gamma increase and enhanced pre-movement beta decrease in the ipsilateral primary motor cortex. We found phase-amplitude coupling, in which high-gamma activity was modulated by the beta rhythm in the primary motor cortex. Phase-amplitude coupling in the ipsilateral primary motor cortex was reduced in the ASD group compared with the control group. Using oscillatory changes and their couplings, linear discriminant analysis classified the ASD and control groups with high accuracy (area under the receiver operating characteristic curve: 97.1%). The current findings revealed alterations in oscillations and oscillatory coupling, reflecting the dysregulation of motor gating mechanisms in ASD. These results may be helpful for elucidating the neural mechanisms underlying motor dysfunction in ASD, suggesting the possibility of developing a biomarker for ASD diagnosis.

Cortical Activation During Shoulder and Finger Movements in Healthy Adults: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

Characterization of cortical activation patterns during movement of the upper extremity in healthy adults is helpful in understanding recovery mechanisms following neurological disorders. This study explores cortical activation patterns associated with movements of the shoulder and fingers in healthy adults using functional near-infrared spectroscopy (fNIRS). Twelve healthy right-handed participants were recruited. Two motor tasks (shoulder abduction and finger extension) with two different trial lengths (10 s and 20 s) were performed in a sitting position at a rate of 0.5 Hz. The hemodynamic response, as indicated by oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR), over both hemispheres was acquired using a 54-channel fNIRS system. We found a generalized bilateral cortical activation during both motor tasks with greater activation in the contralateral compared to the ipsilateral primary motor cortex. Particularly in the more medial part of the contralateral hemisphere, significant higher activation was found during the shoulder compared to finger movements. Furthermore, cortical activation patterns are affected not only by motor tasks but also by trial lengths. HbO is more sensitive to detect cortical activation during finger movements in longer trials, while HbR is a better surrogate to capture active areas during shoulder movement in shorter trials. Based on these findings, reporting both HbO and HbR is strongly recommended for future fNIRS studies, and trial lengths should be taken into account when designing experiments and explaining results. Our findings demonstrating distinct cortical activation patterns associated with shoulder and finger movements in healthy adults provide a foundation for future research to study recovery mechanisms following neurological disorders.