M1 Connectivity Research Articles

Test-retest reliability of intrahemispheric dorsal premotor and primary motor cortex dual-site TMS connectivity measures

ObjectiveInvestigating the optimal interstimulus interval (ISI) and the 24-hour test–retest reliability for intrahemispheric dorsal premotor cortex (PMd) – primary motor cortex (M1) connectivity using dual-site transcranial magnetic stimulation (dsTMS). MethodsIn 21 right-handed adults, left intrahemispheric PMd–M1 connectivity has been investigated with a stacked-coil dsTMS setup (conditioning stimulus: 75% of resting motor threshold; test stimulus: eliciting MEPs of 1–1.5 mV) at ISIs of 3, 5–8, and 10 ms. Additionally, M1–M1 short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were investigated to assess comparability to standard paired-pulse setups. ResultsConditioning PMd led to significant inhibition of M1 output at ISIs of 3 and 5 ms, whereas 10 ms resulted in facilitation (all, p < 0.001), with a fair test–retest reliability for 3 (ICC: 0.47) and 6 ms (ICC: 0.44) ISIs. Replication of SICI (p < 0.001) and ICF (p = 0.017) was successful, with excellent test–retest reliability for SICI (ICC: 0.81). ConclusionThis dsTMS setup can probe the inhibitory and facilitatory PMd–M1 connections, as well as reliably replicate SICI and ICF paradigms. SignificanceThe stacked-coil dsTMS setup for investigating intrahemispheric PMd–M1 connectivity offers promising possibilities to better understand motor control.

Synaptic correlates of the corticocortical circuit in motor learning.

Rodents actively learn new motor skills for survival in reaction to changing environments. Despite the classic view of the primary motor cortex (M1) as a simple muscle relay region, it is now known to play a significant role in motor skill acquisition. The secondary motor cortex (M2) is reported to be a crucial region for motor learning as well as for its role in motor execution and planning. Although these two regions are known for the part they play in motor learning, the role of direct connection and synaptic correlates between these two regions remains elusive. Here, we confirm M2 to M1 connectivity with a series of tracing experiments. We also show that the accelerating rotarod task successfully induces motor skill acquisition in mice. For mice that underwent rotarod training, learner mice showed increased synaptic density and spine head size for synapses between activated cell populations of M2 and M1. Non-learner mice did not show these synaptic changes. Collectively, these data suggest the potential importance of synaptic plasticity between activated cell populations as a potential mechanism of motor learning. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Real-time cortical dynamics during motor inhibition

The inhibition of action is a fundamental executive mechanism of human behaviour that involve a complex neural network. In spite of the progresses made so far, many questions regarding the brain dynamics occurring during action inhibition are still unsolved. Here, we used a novel approach optimized to investigate real-time effective brain dynamics, which combines transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recordings. 22 healthy volunteers performed a motor Go/NoGo task during TMS of the hand-hotspot of the primary motor cortex (M1) and whole-scalp EEG recordings. We reconstructed source-based real-time spatiotemporal dynamics of cortical activity and cortico-cortical connectivity throughout the task. Our results showed a task-dependent bi-directional change in theta/gamma supplementary motor cortex (SMA) and M1 connectivity that, when participants were instructed to inhibit their response, resulted in an increase of a specific TMS-evoked EEG potential (N100), likely due to a GABA-mediated inhibition. Interestingly, these changes were linearly related to reaction times, when participants were asked to produce a motor response. In addition, TMS perturbation revealed a task-dependent long-lasting modulation of SMA–M1 natural frequencies, i.e. alpha/beta activity. Some of these results are shared by animal models and shed new light on the physiological mechanisms of motor inhibition in humans.

Interhemispheric Structural Connectivity Underlies Motor Recovery after Stroke.

Although ample evidence highlights that the ipsilesional corticospinal tract (CST) plays a crucial role in motor recovery after stroke, studies on cortico-cortical motor connections remain scarce and provide inconclusive results. Given their unique potential to serve as structural reserve enabling motor network reorganization, the question arises whether cortico-cortical connections may facilitate motor control depending on CST damage. Diffusion spectrum imaging (DSI) and a novel compartment-wise analysis approach were used to quantify structural connectivity between bilateral cortical core motor regions in chronic stroke patients. Basal and complex motor control were differentially assessed. Both basal and complex motor performance were correlated with structural connectivity between bilateral premotor areas and ipsilesional primary motor cortex (M1) as well as interhemispheric M1 to M1 connectivity. Whereas complex motor skills depended on CST integrity, a strong association between M1 to M1 connectivity and basal motor control was observed independent of CST integrity especially in patients who underwent substantial motor recovery. Harnessing the informational wealth of cortico-cortical connectivity facilitated the explanation of both basal and complex motor control. We demonstrate for the first time that distinct aspects of cortical structural reserve enable basal and complex motor control after stroke. In particular, recovery of basal motor control may be supported via an alternative route through contralesional M1 and non-crossing fibers of the contralesional CST. Our findings help to explain previous conflicting interpretations regarding the functional role of the contralesional M1 and highlight the potential of cortico-cortical structural connectivity as a future biomarker for motor recovery post-stroke. ANN NEUROL 2023;94:785-797.

Brain network characteristics between subacute and chronic stroke survivors in active, imagery, passive movement task: a pilot study.

The activation patterns and functional network characteristics between stroke survivors and healthy individuals based on resting-or task-state neuroimaging and neurophysiological techniques have been extensively explored. However, the discrepancy between stroke patients at different recovery stages remains unclear. To investigate the changes in brain connectivity and network topology between subacute and chronic patients, and hope to provide a basis for rehabilitation strategies at different stages after stroke. Fifteen stroke survivors were assigned to the subacute group (SG, N = 9) and chronic group (CG, N = 6). They were asked to perform hand grasping under active, passive, and MI conditions when recording EEG. The Fugl-Meyer Assessment Upper Extremity subscale (FMA_UE), modified Ashworth Scale (MAS), Manual Muscle Test (MMT), grip and pinch strength, modified Barthel Index (MBI), and Berg Balance Scale (BBS) were measured. Functional connectivity analyses showed significant interactions on frontal, parietal and occipital lobes connections in each frequency band, particularly in the delta band. The coupling strength of premotor cortex, M1, S1 and several connections linked to frontal, parietal, and occipital lobes in subacute subjects were lower than in chronic subjects in low alpha, high alpha, low beta, and high beta bands. Nodal clustering coefficient (CC) analyses revealed that the CC in chronic subjects was higher than in subacute subjects in the ipsilesional S1 and occipital area, contralesional dorsolateral prefrontal cortex and parietal area. Characteristic path length (CPL) analyses showed that CPL in subacute subjects was lower than in chronic subjects in low beta, high beta, and gamma bands. There were no significant differences between subacute and chronic subjects for small-world property. Subacute stroke survivors were characterized by higher transfer efficiency of the entire brain network and weak local nodal effects. Transfer efficiency was reduced, the local nodal role was strengthened, and more neural resources needed to be mobilized to perform motor tasks for chronic survivors. Overall, these results may help to understand the remodeling pattern of the brain network for different post-stroke stages on task conditions and the mechanism of spontaneous recovery.

Neural bases of motor fatigue in multiple sclerosis: A multimodal approach using neuromuscular assessment and TMS-EEG

Motor fatigue is one of the most common symptoms in multiple sclerosis (MS) patients. Previous studies suggested that increased motor fatigue in MS may arise at the central nervous system level. However, the mechanisms underlying central motor fatigue in MS are still unclear.This paper investigated whether central motor fatigue in MS reflects impaired corticospinal transmission or suboptimal primary motor cortex (M1) output (supraspinal fatigue). Furthermore, we sought to identify whether central motor fatigue is associated with abnormal M1 excitability and connectivity within the sensorimotor network.Twenty-two patients affected by relapsing-remitting MS and 15 healthy controls (HCs) performed repeated blocks of contraction at different percentages of maximal voluntary contraction with the right first dorsal interosseus muscle until exhaustion. Peripheral, central, and supraspinal components of motor fatigue were quantified by a neuromuscular assessment based on the superimposed twitch evoked by peripheral nerve and transcranial magnetic stimulation (TMS). Corticospinal transmission, excitability and inhibition during the task were tested by measurement of motor evoked potential (MEP) latency, amplitude, and cortical silent period (CSP). M1 excitability and connectivity was measured by TMS-evoked electroencephalography (EEG) potentials (TEPs) elicited by M1 stimulation before and after the task.Patients completed fewer blocks of contraction and showed higher values of central and supraspinal fatigue than HCs. We found no MEP or CSP differences between MS patients and HCs. Patients showed a post-fatigue increase in TEPs propagation from M1 to the rest of the cortex and in source-reconstructed activity within the sensorimotor network, in contrast to the reduction observed in HCs. Post-fatigue increase in source-reconstructed TEPs correlated with supraspinal fatigue values.To conclude, MS-related motor fatigue is caused by central mechanisms related explicitly to suboptimal M1 output rather than impaired corticospinal transmission. Furthermore, by adopting a TMS-EEG approach, we proved that suboptimal M1 output in MS patients is associated with abnormal task-related modulation of M1 connectivity within the sensorimotor network. Our findings shed new light on the central mechanisms of motor fatigue in MS by highlighting a possible role of abnormal sensorimotor network dynamics. These novel results may point to new therapeutical targets for fatigue in MS.

Connectivity from ipsilateral and contralateral dorsolateral prefrontal cortex to the active primary motor cortex during approaching-avoiding behavior.

Automatic action tendency is reflected by a fast reaction to approach positive stimulus and to avoid negative stimulus (automatic behaviors), while a slow reaction to approach negative stimulus and avoid positive stimulus (controlled behaviors). The dorsolateral prefrontal cortex (DLPFC) is involved in the modulation of the automatic action tendency; however, it remains unclear whether DLPFC modulates the behavior through motor inhibition or excitation, as well as the exact timing of the modulation. We used paired-pulse, dual-site TMS protocols to investigate the connectivity between left/right DLPFC and the left primary motor cortex (M1) during the manikin task performed with the right hand. For the behavioral data, the results from reaction time (RT) and premotor time (PMT), which represents the beginning of finger movements, of the approaching-avoiding behavior in both experiments showed a shorter duration for automatic behavior compared to the controlled behavior. There was stronger facilitation of the left DLPFC-left M1 connectivity at interstimulus-interval of 25ms in controlled behavior compared to automatic behavior (positive-approaching vs. positive-avoiding: P=.002; negative-avoiding vs. negative-approaching: P=.017). The right DLPFC-left M1 connectivity did not change with the task. The present study confirmed the automatic action tendency from both reaction time and the premotor time. During the right-handed task, the DLPFC contralateral but not ipsilateral to the effector could facilitate the left M1 to speed up the execution of the controlled behavior through a polysynaptic pathway.

Exploring phase–amplitude coupling from primary motor cortex-basal ganglia–thalamus network model

The purpose of this study is to develop a primary motor cortex (M1)-basal ganglia–thalamus model capable of reproducing the physiological phenomenon of exaggerated phase–amplitude coupling (PAC) in Parkinson’s disease and exploring the potential sources of PAC anomalies in M1. The subthalamic nucleus (STN) phase-STN amplitude coupling, STN phase–M1 amplitude coupling, and M1 phase–M1 amplitude coupling are reproduced, where the phase frequencies are distributed in the beta band and the amplitude frequencies are distributed in the broad gamma band. We mainly study the impacts of thalamus →M1 connections and STN↔M1 bidirectional synaptic connections. Abnormal beta oscillations generated within the basal ganglia are found to be transmitted to M1 through the STN or thalamus and could be one of the potential sources of PAC-related beta oscillations in M1, thereby interfering with high-frequency signals in the motor cortex. Furthermore, the weakening of M1→STN leads to a shift of the oscillations of the STN from the high beta band to the low beta band, which is more consistent with pathological experiments, thus supporting the experimental results that the hyper-direct path from M1 to STN drives the beta oscillations of STN. Finally, the suppression effect of STN deep brain stimulation on PAC is investigated. As the stimulation frequency increases, the PAC modulation index within different regions gradually decreases, in general agreement with the trend of synchronization level and beta oscillation energy, indirectly indicating that PAC can be used as a feedback indicator of parkinsonian state.

Maladaptive motor cortical excitability and connectivity in polyneuropathy with neuropathic pain.

Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain. This cross-sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging. Thirty-three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short-latency afferent inhibition at an interstimulus interval of 20ms was associated with structural connectivity of left M1 with brain areas associated with pain perception. Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy.

Contralateral S1 function is involved in electroacupuncture treatment-mediated recovery after focal unilateral M1 infarction.

Acupuncture at acupoints Baihui (GV20) and Dazhui (GV14) has been shown to promote functional recovery after stroke. However, the contribution of the contralateral primary sensory cortex (S1) to recovery remains unclear. In this study, unilateral local ischemic infarction of the primary motor cortex (M1) was induced by photothrombosis in a mouse model. Electroacupuncture (EA) was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques. Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction. Intrinsic neuronal excitability and activity were also disturbed, which was rescued by EA. Furthermore, the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1. We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction. Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction. The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine (approval No. 20200407009) April 7, 2020.

Dual-task walking and automaticity after Stroke: Insights from a secondary analysis and imaging sub-study of a randomised controlled trial

Objective: To test the extent to which initial walking speed influences dual-task performance after walking intervention, hypothesising that slow walking speed affects automatic gait control, limiting executive resource availability. Design: A secondary analysis of a trial of dual-task (DT) and single-task (ST) walking interventions comparing those with good (walking speed ⩾0.8 m s−1, n = 21) and limited (walking speed <0.79 m s−1, n = 24) capacity at baseline. Setting: Community. Subjects: Adults six-months post stroke with walking impairment. Interventions: Twenty sessions of 30 minutes treadmill walking over 10 weeks with (DT) or without (ST) cognitive distraction. Good and limited groups were formed regardless of intervention received. Main measures: A two-minute walk with (DT) and without (ST) a cognitive distraction assessed walking. fNIRS measured prefrontal cortex activation during treadmill walking with (DT) and without (ST) Stroop and planning tasks and an fMRI sub-study used ankle-dorsiflexion to simulate walking. Results: ST walking improved in both groups (∆baseline: Good = 8.9 ± 13.4 m, limited = 5.3±8.9 m, Group × time = P < 0.151) but only the good walkers improved DT walking (∆baseline: Good = 10.4 ± 13.9 m, limited = 1.3 ± 7.7 m, Group × time = P < 0.025). fNIRS indicated increased ispilesional prefrontal cortex activation during DT walking following intervention (P = 0.021). fMRI revealed greater DT cost activation for limited walkers, and increased resting state connectivity of contralesional M1 with cortical areas associated with conscious gait control at baseline. After the intervention, resting state connectivity between ipsilesional M1 and bilateral superior parietal lobe, involved in integrating sensory and motor signals, increased in the good walkers compared with limited walkers. Conclusion: In individual who walk slowly it may be difficult to improve dual-task walking ability. Registration: ISRCTN50586966

Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1.

Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.

Brain Plasticity Mechanisms Underlying Motor Control Reorganization: Pilot Longitudinal Study on Post-Stroke Subjects.

Functional Electrical Stimulation (FES) has demonstrated to improve walking ability and to induce the carryover effect, long-lasting persisting improvement. Functional magnetic resonance imaging has been used to investigate effective connectivity differences and longitudinal changes in a group of chronic stroke patients that attended a FES-based rehabilitation program for foot-drop correction, distinguishing between carryover effect responders and non-responders, and in comparison with a healthy control group. Bayesian hierarchical procedures were employed, involving nonlinear models at within-subject level—dynamic causal models—and linear models at between-subjects level. Selected regions of interest were primary sensorimotor cortices (M1, S1), supplementary motor area (SMA), and angular gyrus. Our results suggest the following: (i) The ability to correctly plan the movement and integrate proprioception information might be the features to update the motor control loop, towards the carryover effect, as indicated by the reduced sensitivity to proprioception input to S1 of FES non-responders; (ii) FES-related neural plasticity supports the active inference account for motor control, as indicated by the modulation of SMA and M1 connections to S1 area; (iii) SMA has a dual role of higher order motor processing unit responsible for complex movements, and a superintendence role in suppressing standard motor plans as external conditions changes.

Effects of transcranial direct current stimulation on cortex modulation by stimulation of the primary motor cortex and parietal cortex in humans

Aim of the study Transcranial magnetic stimulation (TMS) is used to measure corticospinal excitability (CSE) from the primary motor cortex (M1) in humans through motor-evoked potentials (MEPs). The variability of CSE responses to transcranial direct current stimulation (tDCS) protocols is high and needs to be reproduced in the healthy population. The M1 and posterior parietal cortex (PPC) are anatomically and functionally connected and could play a role in understanding the variability in CSE responses. We tested the individual MEPs following a common cathodal (ctDCS) protocol over the M1 and PPC. Materials and methods Twenty-eight healthy subjects were randomized for a ctDCS stimulation over the left M1 and PPC for 20 min on a separate days. The first dorsal interosseous muscle (FDI) contralateral stimulation of the left M1 was used as the resting motor threshold (RMT), while 15 single pulses 4–8 s apart at an intensity of 120% RMT were used to determine the baseline MEP amplitude and at T0, 5, 10, 20, 30, 40, 50, and 60 min after ctDCS stimulation in both sessions. Results A 20 min duration of ctDCS stimulation significantly deceased the CSE only at T0 (p = 0.046 at M1, p = 0.010 at PPC). Conclusion Our results suggested that PPC stimulation can modulate M1 excitability and PPC–M1 connectivity, but a significant effect is only observed immediately post ctDCS. The tDCS showed variability in response to the tDCS protocol is consistent with other non-invasive brain stimulation studies.

Mapping mesoscale cortical connectivity in monkey sensorimotor cortex with optical imaging and microstimulation.

To map in vivo cortical circuitry at the mesoscale, we applied a novel approach to map interareal functional connectivity. Electrical intracortical microstimulation (ICMS) in conjunction with optical imaging of intrinsic signals (OIS) was used map functional connections in somatosensory cortical areas in anesthetized squirrel monkeys. ICMS produced activations that were focal and that displayed responses which were stimulation intensity dependent. ICMS in supragranular layers of Brodmann Areas 3b, 1, 2, 3a, and M1 evoked interareal activation patterns that were topographically appropriate and appeared consistent with known anatomical connectivity. Specifically, ICMS revealed Area 3b connections with Area 1; Area 1 connections with Areas 2 and 3a; Area 2 connections with Areas 1, 3a, and M1; Area 3a connections with Areas M1, 1, and 2; and M1 connections with Areas 3a, 1, and 2. These somatosensory connectivity patterns were reminiscent of feedforward patterns observed anatomically, although feedback contributions are also likely present. Further consistent with anatomical connectivity, intra-areal and intra-areal patterns of activation were patchy with patch sizes of 200-300 μm. In summary, ICMS with OIS is a novel approach for mapping interareal and intra-areal connections in vivo. Comparisons with feedforward and feedback anatomical connectivity are discussed.

Principles of Intrinsic Motor Cortex Connectivity in Primates.

The forelimb representation in motor cortex (M1) is an important model system in contemporary neuroscience. Efforts to understand the organization of the M1 forelimb representation in monkeys have focused on inputs and outputs. In contrast, intrinsic M1 connections remain mostly unexplored, which is surprising given that intra-areal connections universally outnumber extrinsic connections. To address this knowledge gap, we first mapped the M1 forelimb representation with intracortical microstimulation (ICMS) in male squirrel monkeys. Next, we determined the connectivity of individual M1 sites with ICMS + intrinsic signal optical imaging (ISOI). Every stimulation site activated a distinctive pattern of patches (∼0.25 to 1.0 mm radius) that we quantified in relation to the motor map. Arm sites activated patches that were mostly in arm zones. Hand sites followed the same principle, but to a lesser extent. The results collectively indicate that preferential connectivity between functionally matched patches is a prominent organizational principle in M1. Connectivity patterns for a given site were conserved across a range of current amplitudes, train durations, pulse frequencies, and microelectrode depths. In addition, we found close correspondence in somatosensory cortex between connectivity that we revealed with ICMS+ISOI and connections known from tracers. ICMS+ISOI is therefore an effective tool for mapping cortical connectivity and is particularly advantageous for sampling large numbers of sites. This feature was instrumental in revealing the spatial specificity of intrinsic M1 connections, which appear to be woven into the somatotopic organization of the forelimb representation. Such a framework invokes the modular organization well-established for sensory cortical areas.SIGNIFICANCE STATEMENT Intrinsic connections are fundamental to the operations of any cortical area. Surprisingly little is known about the organization of intrinsic connections in motor cortex (M1). We addressed this knowledge gap using intracortical microstimulation (ICMS) concurrently with intrinsic signal optical imaging (ISOI). Quantifying the activation patterns from dozens of M1 sites allowed us to uncover a fundamental principle of M1 organization: M1 patches are preferentially connected with functionally matched patches. Relationship between intrinsic connections and neurophysiological map is well-established for sensory cortical areas, but our study is the first to extend this framework to M1. Microstimulation+imaging opened a unique possibility for investigating the connectivity of dozens of tightly spaced M1 sites, which was the linchpin for uncovering organizational principles.

Effects of a 12-Week Aerobic Spin Intervention on Resting State Networks in Previously Sedentary Older Adults.

Objective: We have previously demonstrated that aerobic exercise improves upper extremity motor function concurrent with changes in motor cortical activity using task-based functional magnetic resonance imaging (fMRI). However, it is currently unknown how a 12-week aerobic exercise intervention affects resting-state functional connectivity (rsFC) in motor networks. Previous work has shown that over a 6-month or 1-year exercise intervention, older individuals show increased resting state connectivity of the default mode network and the sensorimotor network (Voss et al., 2010b; Flodin et al., 2017). However, the effects of shorter-term 12-week exercise interventions on functional connectivity have received less attention.Method: Thirty-seven sedentary right-handed older adults were randomized to either a 12-week aerobic, spin cycling exercise group or a 12-week balance-toning exercise group. Resting state functional magnetic resonance images were acquired in sessions PRE/POST interventions. We applied seed-based correlation analysis to left and right primary motor cortices (L-M1 and R-M1) and anterior default mode network (aDMN) to test changes in rsFC between groups after the intervention. In addition, we performed a regression analysis predicting connectivity changes PRE/POST intervention across all participants as a function of time spent in aerobic training zone regardless of group assignment.Results: Seeding from L-M1, we found that participants in the cycling group had a greater PRE/POST change in rsFC in aDMN as compared to the balance group. When accounting for time in aerobic HR zone, we found increased heart rate workload was positively associated with increased change of rsFC between motor networks and aDMN. Interestingly, L-M1 to aDMN connectivity changes were also related to motor behavior changes in both groups. Respective of M1 laterality, comparisons of all participants from PRE to POST showed a reduction in the extent of bilateral M1 connectivity after the interventions with increased connectivity in dominant M1.Conclusion: A 12-week physical activity intervention can change rsFC between primary motor regions and default mode network areas, which may be associated with improved motor performance. The decrease in connectivity between L-M1 and R-M1 post-intervention may represent a functional consolidation to the dominant M1.Topic Areas: Neuroimaging, Aging.

S143. Brain plasticity marker in response to paired-pulse transcranial magnetic stimulation

Introduction Intracortical inhibition (ICI) and facilitation (ICF) in the primary motor cortex (M1) can be measured using a paired-pulse transcranial magnetic stimulation (ppTMS) protocol. The aim of the present study is to characterize the M1 connectivity (inhibition and facilitation) by means of navigated-ppTMS and cognitive assessment using the attention switching task (AST) through the Cambridge Neuropsychological Test Automated Battery. Methods We examined the responses of the left and right M1 to sub-threshold and supra-threshold single and pp stimulation in healthy (n = 50; 46% men; age, 35.5 ± 14.9 years) right-handed individuals using ppTMS. The subjects were evaluated using a combination of physiological motor evoked potentials (MEPs), motor threshold (MT), 3 ms intracortical inhibition (SICI), 7 ms and 12 ms ICF, and long intracortical inhibition (LICI) (100 ms). The cognitive function was evaluated using the AST. Results We report significant SICI (3 ms), ICF (12 ms), and LICI (100 ms) in the left and right hemispheres. We found significant differences in the right hemispheric cortico-spinal excitability (12 ms) between men and women. A correlation analysis revealed no significant relationship between AST performance and MEPs in subjects prior to and following ppTMS. Conclusion ppTMS is a promising tool to better characterize the regulation of the balance between inhibition and facilitation within the M1.

Effectiveness and neural mechanisms of home-based telerehabilitation in patients with stroke based on fMRI and DTI: A study protocol for a randomized controlled trial.

Background:Stroke is one of leading diseases causing adult death and disability worldwide. Home-based telerehabilitation has become a novel approach for stroke patients as effective as conventional rehabilitation, and more convenient and economical than conventional rehabilitation. However, there is no study assessing the mechanism of home-based telerehabilitation in promoting motor recovery among stroke patients with hemiplegic.Aims:This study is designed to determine the efficacy and explore the mechanism of motor recovery after home-based telerehabilitation in stroke patients with motor deficits.Methods/Design:In a single-blinded randomized controlled pilot study, patients with acute subcortical stroke (n = 40) are assigned to receive home-based telerehabilitation or conventional rehabilitation. Task-based or resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), and Fugl–Meyer assessment (FMA) score will acquired before and after rehabilitation. Activation volume of bilateral primary motor (M1), supplementary motor area (SMA), premotor cortex (PMC); lateralization index (LI) of interhemispheric M1, SMA, and PMC; functional connectivity of bilateral M1, SMA, PMC; fractional anisotropy (FA) will be measured; correlation analyses will be performed between neuroimaging biomarkers and FMA score pre- and postrehabilitation.Discussion:We present a study design and rationale to explore the effectiveness and neural mechanism of home-based rehabilitation for stroke patients with motor deficits. The study limitations related to the small-amount sample. Moreover, home-based rehabilitation may provide an alternative means of recovery for stroke patients. Ultimately, results of this trial will help to understand the neural mechanism of home-based telerehabilitation among stroke patients with hand movement disorder.

High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of Cortical Input and Output in Human M1

Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases.