Ipsilesional Primary Motor Area Research Articles

Use of cortical hemodynamic responses in digital therapeutics for upper limb rehabilitation in patients with stroke

BackgroundStroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics.MethodsThis cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl–Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment.ResultsThe participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1.ConclusionsThe results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.

Changes in Distributed Motor Network Connectivity Correlates With Functional Outcome After Surgical Resection of Brain Tumors

BACKGROUND: In patients with brain tumors around the motor cortices, deterioration of motor performance may be observed even if the integrity of the cortical output is maintained. Especially, resection of medial premotor area (PM) can cause postoperative deterioration called supplementary motor area syndrome. OBJECTIVE: To clarify the neuronal mechanisms underlying postsurgical deterioration with a case-control study. METHODS: Twelve patients with brain tumors underwent preoperative and postoperative sessions consisting of motor performance evaluation and 3T-magnetic resonance imaging data acquisition. Based on additional postsurgical motor deficits, 6 patients were classified into “deficit group,” and 6 others were into “no deficit group.” Using resting-state functional magnetic resonance imaging (fMRI), the integrity of functional connectivity was evaluated by placing a seed in the ipsilesional primary motor area (M1). With motor task fMRI, hand and foot representations were identified in the M1 and lateral and medial PMs. Probabilistic tractography assessed anatomic connectivity in the cortico-cortical and corticofugal networks. RESULTS: Functional connectivity among M1 and lateral and medial PMs during resting-state fMRI was reduced postoperatively in the deficit group (P < .05, corrected) and preserved in the no deficit group. The deficit was unlikely to be attributable to surgical resection of specific anatomic connectivity. The amplitude of motor-evoked potential was maintained in available cases. These intraoperative observations agree with imaging findings suggesting preserved anatomic connectivity of the estimated corticofugal pathway. CONCLUSION: The present findings suggest that supplementary motor area syndrome is caused by disorganization of functional connectivity among cortical motor networks rather than resection of anatomic connectivity of corticofugal pathway.

Pathway-Specific Mediation Effect Between Structure, Function, and Motor Impairment After Subcortical Stroke.

To investigate the pathway-specific correspondence between structural and functional changes resulting from focal subcortical stroke and their causal influence on clinical symptom. In this retrospective, cross-sectional study, we mainly focused on patients with unilateral subcortical chronic stroke with moderate-severe motor impairment assessed by Fugl-Meyer Assessment (upper extremity) and healthy controls. All participants underwent both resting-state fMRI and diffusion tensor imaging. To parse the pathway-specific structure-function covariation, we performed association analyses between the fine-grained corticospinal tracts (CSTs) originating from 6 subareas of the sensorimotor cortex and functional connectivity (FC) of the corresponding subarea, along with the refined corpus callosum (CC) sections and interhemispheric FC. A mediation analysis with FC as the mediator was used to further assess the pathway-specific effects of structural damage on motor impairment. Thirty-five patients (mean age 52.7 ± 10.2 years, 27 men) and 43 healthy controls (mean age 56.2 ± 9.3 years, 21 men) were enrolled. Among the 6 CSTs, we identified 9 structurally and functionally covaried pathways, originating from the ipsilesional primary motor area (M1), dorsal premotor area (PMd), and primary somatosensory cortex (p < 0.05, corrected). FC for the bilateral M1, PMd, and ventral premotor cortex covaried with secondary degeneration of the corresponding CC sections (p < 0.05, corrected). Moreover, these covarying structures and functions were significantly correlated with the Fugl-Meyer Assessment (upper extremity) scores (p < 0.05, uncorrected). In particular, FC between the ipsilesional PMd and contralesional cerebellum (β = -0.141, p < 0.05, CI = [-0.319 to -0.015]) and interhemispheric FC of the PMd (β = 0.169, p < 0.05, CI = [0.015-0.391]) showed significant mediation effects in the prediction of motor impairment with structural damage of the CST and CC. This study reveals causal influence of structural and functional pathways on motor impairment after subcortical stroke and provides a promising way to investigate pathway-specific structure-function coupling. Clinically, our findings may offer a circuit-based evidence for the PMd as a critical neuromodulation target in more impaired patients with stroke and also suggest the cerebellum as a potential target.

The modulatory effects of bilateral arm training (BAT) on the brain in stroke patients: a systematic review.

To systematically review the modulatory effects of bilateral arm training (BAT) on the brain of stroke patients in contrast to unilateral arm training (UAT) or regular motor training. We conducted a literature search using PubMed, EMBASE, MEDLINE, and Science Citation Index Expanded databases from the inception to March 2019 for identifying any relevant studies. Two authors independently screened the literature, extracted data, and qualitatively described the included studies. Eleven studies with a total of 225 stroke patients were included in this review. 156 out of those participants received neuroimaging or neurophysiological examinations. Six studies reported enhanced activation of the ipsilesional primary motor area (M1) induced by BAT, as measured by MEP and fMRI. Beyond the M1, three studies showed that supplementary motor area (SMA) was activated, and three studies found the primary sensory cortex area (S1) was activated by BAT in stroke patients, as measured by fMRI. One article showed that the inter-/intra-hemispheric functional connections of the sensorimotor network were more highly strengthened after BAT than regular motor training, in particular the functional connectivity between the SMA and the M1 in the bi-hemispheres. Three studies reported that BAT increased the inhibitory flow from the ipsilesional hemisphere to the contralesional hemisphere, as measured by interhemispheric transcallosal inhibition (IHI). However, the superiority of BAT in inducing a symmetric IHI than UAT was controversial. BAT is potentially more effective than UAT in improving upper limb recovery after stroke by activating the ipsilesional primary motor area (M1), supplementary motor area (SMA), and primary sensory cortex (S1) and enhancing the intra-hemispheric and interhemispheric connectivity within the sensorimotor network and the cortical motor system.

Evaluation of Changes in the Motor Network Following BCI Therapy Based on Graph Theory Analysis.

Despite the established effectiveness of the brain-computer interface (BCI) therapy during stroke rehabilitation (Song et al., 2014a, 2015; Young et al., 2014a,b,c, 2015; Remsik et al., 2016), little is understood about the connections between motor network reorganization and functional motor improvements. The aim of this study was to investigate changes in the network reorganization of the motor cortex during BCI therapy. Graph theoretical approaches are used on resting-state functional magnetic resonance imaging (fMRI) data acquired from stroke patients to evaluate these changes. Correlations between changes in graph measurements and behavioral measurements were also examined. Right hemisphere chronic stroke patients (average time from stroke onset = 38.23 months, standard deviation (SD) = 46.27 months, n = 13, 6 males, 10 right-handed) with upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device. Eyes-closed resting-state fMRI (rs-fMRI) scans, along with T-1 weighted anatomical scans on 3.0T MRI scanners were collected from these patients at four test points. Immediate therapeutic effects were investigated by comparing pre and post-therapy results. Results displayed that th average clustering coefficient of the motor network increased significantly from pre to post-therapy. Furthermore, increased regional centrality of ipsilesional primary motor area (p = 0.02) and decreases in regional centrality of contralesional thalamus (p = 0.05), basal ganglia (p = 0.05 in betweenness centrality analysis and p = 0.03 for degree centrality), and dentate nucleus (p = 0.03) were observed (uncorrected). These findings suggest an overall trend toward significance in terms of involvement of these regions. Increased centrality of primary motor area may indicate increased efficiency within its interactive network as an effect of BCI therapy. Notably, changes in centrality of the bilateral cerebellum regions have strong correlations with both clinical variables [the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT)]

Aberrances of Cortex Excitability and Connectivity Underlying Motor Deficit in Acute Stroke.

Purpose This study was aimed at evaluating the motor cortical excitability and connectivity underlying the neural mechanism of motor deficit in acute stroke by the combination of functional magnetic resonance imaging (fMRI) and electrophysiological measures. Methods Twenty-five patients with motor deficit after acute ischemic stroke were involved. General linear model and dynamic causal model analyses were applied to fMRI data for detecting motor-related activation and effective connectivity of the motor cortices. Motor cortical excitability was determined as a resting motor threshold (RMT) of motor evoked potential detected by transcranial magnetic stimulation (TMS). fMRI results were correlated with cortical excitability and upper extremity Fugl-Meyer assessment scores, respectively. Results Greater fMRI activation likelihood and motor cortical excitability in the ipsilesional primary motor area (M1) region were associated with better motor performance. During hand movements, the inhibitory connectivity from the contralesional to the ipsilesional M1 was correlated with the degree of motor impairment. Furthermore, ipsilesional motor cortex excitability was correlated with an enhancement of promoting connectivity in ipsilesional M1 or a reduction of interhemispheric inhibition in contralesional M1. Conclusions The study suggested that a dysfunction of the ipsilesional M1 and abnormal interhemispheric interactions might underlie the motor disability in acute ischemic stroke. Modifying the excitability of the motor cortex and correcting the abnormal motor network connectivity associated with the motor deficit might be the therapeutic target in early neurorehabilitation for stroke patients.

Excitatory Repetitive Transcranial Magnetic Stimulation Induces Contralesional Cortico-Cerebellar Pathways After Acute Ischemic Stroke: A Preliminary DTI Study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is proved to be effective in facilitating stroke recovery. However, its therapeutic mechanism remains unclear. The present study aimed to investigate changes in white matter fractional anisotropy (FA) after excitatory rTMS to better understand its role in motor rehabilitation.Materials and Methods: Acute stroke patients with unilateral subcortical infarction in the middle cerebral artery territory were recruited. The patients were randomly divided into an rTMS treatment group and a sham group. The treatment group received a 10-day 5 HZ rTMS applied over the ipsilesional primary motor area beginning at about 4 days after stroke onset. The sham group received sham rTMS. Diffusion tensor imaging (DTI) data were collected in every patient before and after the rTMS or sham rTMS. Voxel-based analysis was used to study the difference in FA between the two groups. The trial of this article has been registered on the ClinicalTrials.gov and the identifier is NCT03163758.Results: Before the rTMS, there is no significant difference in FA between the two groups. Differently, after the treatment, the rTMS group showed increased FA in the contralesional corticospinal tract, the pontine crossing tract, the middle cerebellar peduncle, the contralesional superior cerebellar peduncle, the contralesional medial lemniscus, and the ipsilesional inferior cerebellar peduncle. These fasciculi comprise the cortex-pontine-cerebellum-cortex loop. Increased FA was also found in the body of corpus callosum and the contralesional cingulum of the treatment group compared with the sham.Conclusion: The greater connectivity of contralesional cortico-cerebellar loop and the strengthening of interhemispheric connection may reflect contralesional compensation facilitated by the excitatory rTMS, which gives us a clue to understand the therapeutic mechanism of rTMS.

Axial diffusivity changes in the motor pathway above stroke foci and functional recovery after subcortical infarction.

Secondary degeneration of the fiber tract of the motor pathway below infarct foci and functional recovery after stroke have been well demonstrated, but the role of the fiber tract above stroke foci remains unclear. This study aimed to investigate diffusion changes in motor fibers above the lesion and identify predictors of motor improvement within 12 weeks after subcortical infarction. Diffusion tensor imaging and the Fugl-Meyer (FM) scale were conducted 1, 4, and 12 weeks (W) after a subcortical infarct. Proportional recovery model residuals were used to assign patients to proportional recovery and poor recovery groups. Region of interest analysis was used to assess diffusion changes in the motor pathway above and below a stroke lesion. Multivariable linear regression was employed to identify predictors of motor improvement within 12 weeks after stroke. Axial diffusivity (AD) in the underlying white matter of the ipsilesional primary motor area (PMA) and cerebral peduncle (CP) in both proportional and poor recovery groups was lower at W1 compared to the controls and values in the contralesional PMA and CP (all P < 0.05). Subsequently, AD in the ipsilesional CP became relatively stable, while AD in the ipsilesional PMA significantly increased from W4 to W12 after stroke (P < 0.05). In all of the patients, changes in the FM scores were greater in those with higher changes in AD of the ipsilesional PMA. Only initial impairment or lesion volume was predictive of motor improvement within 12 weeks after stroke in patients with proportional or poor recovery. Increases of AD in the motor pathway above stroke foci may be associated with motor recovery after subcortical infarction. Early measurement of diffusion metrics in the ipsilesional non-ischemic motor pathway has limited value in predicting future motor improvement patterns (proportional or poor recovery).

Comparison of localizing motor area before the surgery based on resting-state functional MRI with independent component analysis and electric cortical stimulation

Objective To evaluate the accuracy of presurgically resting-state fMRI(rs-fMRI) with subject order-independent group independent component analysis(ICA), compared to electric cortical stimulations. Methods Twenty-three patients with the lesion in motor area, which were recorded by our hospital from Jan, 2014 to Dec, 2015, were collected as the study sample. The data of 9 patients were excluded because of excessive head motion. As a result, 14 patients were included in this study. Rs-fMRI data before the surgery and the results of electric cortical stimulations were collected. Results All of this 14 patients were preoperatively located by rs-fMRI with SOI-GICA, including all the SMA and the ipsilesional primary motor area. On the side with lesion, the number of functional location of motor area was decreased compared with healthy side. Evaluate the accuracy of ICA by comparing the coincidence rate of these two techniques, based on the standardized electrical cortical stimulation in operation. The completely concordance between rs-fMRI with the SOI-GICA and electrical cortical stimulation in operation was 11 (11/14). Meanwhile the basically concordance of corresponded case was 3(3/14). Conclusions Rs-fMRI with the ICA has a relatively high accuracy rate in localizing motor area. Rs-fMRI has a remarkably referential contribution to the presurgically function assessment and surgical planning in implementation. Key words: Magnetic resonance imaging; Cerebral cortex; Electric stimulation; Comparative study

Serial treatments of primed low-frequency rTMS in stroke: Characteristics of responders vs. nonresponders

This study analyzed the characteristics of responders vs. nonresponders in people with stroke receiving a novel form of repetitive transcranial magnetic stimulation (rTMS) to improve hand function. Twelve people with stroke received five treatments of 6-Hz primed low-frequency rTMS to the contralesional primary motor area. We compared demographic factors, clinical features, and the ipsilesional/contralesional volume ratio of selected brain regions in those who improved hand performance (N = 7) on the single-hand component of the Test Évaluant la performance des Membres supérieurs des Personnes Âgées (TEMPA) and those who showed no improvement (N = 5). Responders showed significantly greater baseline paretic hand function on the TEMPA, greater preservation volume of the ipsilesional posterior limb of the internal capsule (PLIC), and lower scores (i.e., less depression) on the Beck Depression Inventory than nonresponders. There were no differences in age, sex, stroke duration, paretic side, stroke hemisphere, baseline resting motor threshold for ipsilesional primary motor area (M1), NIH Stroke Scale, Upper Extremity Fugl-Meyer, Mini-Mental State Examination, or preservation volume of M1, primary somatosensory area, premotor cortex, or supplementary motor area. Our results support that preserved PLIC volume is an important influential factor affecting responsiveness to rTMS.

Dynamic functional reorganization of the motor execution network after stroke

Numerous studies argue that cortical reorganization may contribute to the restoration of motor function following stroke. However, the evolution of changes during the post-stroke reorganization has been little studied. This study sought to identify dynamic changes in the functional organization, particularly topological characteristics, of the motor execution network during the stroke recovery process. Ten patients (nine male and one female) with subcortical infarctions were assessed by neurological examination and scanned with resting-state functional magnetic resonance imaging across five consecutive time points in a single year. The motor execution network of each subject was constructed using a functional connectivity matrix between 21 brain regions and subsequently analysed using graph theoretical approaches. Dynamic changes in topological configuration of the network during the process of recovery were evaluated by a mixed model. We found that the motor execution network gradually shifted towards a random mode during the recovery process, which suggests that a less optimized reorganization is involved in regaining function in the affected limbs. Significantly increased regional centralities within the network were observed in the ipsilesional primary motor area and contralesional cerebellum, whereas the ipsilesional cerebellum showed decreased regional centrality. Functional connectivity to these brain regions demonstrated consistent alterations over time. Notably, these measures correlated with different clinical variables, which provided support that the findings may reflect the adaptive reorganization of the motor execution network in stroke patients. In conclusion, the study expands our understanding of the spectrum of changes occurring in the brain after stroke and provides a new avenue for investigating lesion-induced network plasticity.