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

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Michelle Y Cheng ◽  
Haruto Uchino ◽  
Terrance Chiang ◽  
Anika Kim ◽  
Zhijuan Cao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Rna Sequencing ◽  
Primary Motor Cortex ◽  
Cholesterol Metabolism ◽  
Sequencing Analysis ◽  
Beam Test ◽  
Rotating Beam ◽  
Molecular Changes ◽  
Post Stroke

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<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.

scholarly journals Effect of opposing needling on motor cortex excitability in healthy participants and in patients with post-stroke hemiplegia: study protocol for a single-blind, randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mindong Xu ◽  
Yinyu Zi ◽  
Jianlu Wu ◽  
Nenggui Xu ◽  
Liming Lu ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Motor Evoked Potentials ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Post Stroke ◽  
Motor Cortex Excitability ◽  
Opposing Needling ◽  
Single Blind ◽  
Healthy Participants

Abstract Background Opposing needling has an obvious curative effect in the treatment of post-stroke hemiplegia; however, the mechanism of the opposing needling in the treatment of post-stroke hemiplegia is still not clear. The purpose of this study is to investigate the effect of opposing needling on the excitability of primary motor cortex (M1) of healthy participants and patients with post-stroke hemiplegia, which may provide insight into the mechanisms of opposing needling in treating post-stroke hemiplegia. Methods This will be a single-blind, randomised, sham-controlled trial in which 80 healthy participants and 40 patients with post-stroke hemiplegia will be recruited. Healthy participants will be randomised 1:1:1:1 to the 2-Hz, 50-Hz, 100-Hz, and sham electroacupuncture groups. Patients with post-stroke hemiplegia will be randomised 1:1 to the opposing needling or conventional treatment groups. The M1 will be located in all groups by using neuroimaging-based navigation. The stimulator coil of transcranial magnetic stimulation (TMS) will be moved over the left and right M1 in order to identify the TMS hotspot, followed by a recording of resting motor thresholds (RMTs) and motor-evoked potentials (MEPs) of the thenar muscles induced by TMS before and after the intervention. The primary outcome measure will be the percent change in the RMTs of the thenar muscles at baseline and after the intervention. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the MEPs of the thenar muscles at baseline and after the intervention. Discussion The aim of this trial is to explore the effect of opposing needling on the excitability of M1 of healthy participants and patients with post-stroke hemiplegia. Trial registration Chinese Clinical Trial Registry ChiCTR1900028138. Registered on 13 December 2019.

The effect of transcranial magnetic stimulation on the excitability of the motor neuron pools of the muscles of the lower extremities

2021 ◽  
Author(s):  
S.S. Ananiev ◽  
D.A. Pavlov ◽  
R.N. Yakupov ◽  
V.A. Golodnova ◽  
M.V. Balykin
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Transcranial Magnetic Stimulation ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Lower Extremities ◽  
Transcutaneous Electrical Stimulation ◽  
Stimulation Of

The study was conducted on 22 healthy men aged 18-23 years. The primary motor cortex innervating the lower limb was stimulated with transcranial magnetic stimulation. Using transcutaneous electrical stimulation of the spinal cord, evoked motor responses of the muscles of the lower extremities were initiated when electrodes were applied cutaneous between the spinous processes in the Th11-Th12 projection. Research protocol: Determination of the thresholds of BMO of the muscles of the lower extremities during TESCS; determination of the BMO threshold of the TA muscle in TMS; determination of the thresholds of the BMO of the muscles of the lower extremities during TESCS against the background of 80% and 90% TMS. It was found that magnetic stimulation of the motor cortex of the brain leads to an increase in the excitability of the neural structures of the lumbar thickening of the spinal cord and an improvement in neuromuscular interactions. Key words: transcranial magnetic stimulation, transcutaneous electrical stimulation of the spinal cord, neural networks, excitability, neuromuscular interactions.

scholarly journals Brain stimulation for arm recovery after stroke (B-STARS): protocol for a randomised controlled trial in subacute stroke patients

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e016566
Author(s):  
Eline C C van Lieshout ◽  
Johanna M A Visser-Meily ◽  
Sebastiaan F W Neggers ◽  
H Bart van der Worp ◽  
Rick M Dijkhuizen
Keyword(s):  
Motor Cortex ◽  
Upper Limb ◽  
Brain Stimulation ◽  
Primary Outcome ◽  
Primary Motor Cortex ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Stroke Patients ◽  
Post Stroke ◽  
Subacute Stroke

IntroductionMany patients with stroke have moderate to severe long-term sensorimotor impairments, often including inability to execute movements of the affected arm or hand. Limited recovery from stroke may be partly caused by imbalanced interaction between the cerebral hemispheres, with reduced excitability of the ipsilesional motor cortex while excitability of the contralesional motor cortex is increased. Non-invasive brain stimulation with inhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional hemisphere may aid in relieving a post-stroke interhemispheric excitability imbalance, which could improve functional recovery. There are encouraging effects of theta burst stimulation (TBS), a form of TMS, in patients with chronic stroke, but evidence on efficacy and long-term effects on arm function of contralesional TBS in patients with subacute hemiparetic stroke is lacking.Methods and analysisIn a randomised clinical trial, we will assign 60 patients with a first-ever ischaemic stroke in the previous 7–14 days and a persistent paresis of one arm to 10 sessions of real stimulation with TBS of the contralesional primary motor cortex or to sham stimulation over a period of 2 weeks. Both types of stimulation will be followed by upper limb training. A subset of patients will undergo five MRI sessions to assess post-stroke brain reorganisation. The primary outcome measure will be the upper limb function score, assessed from grasp, grip, pinch and gross movements in the action research arm test, measured at 3 months after stroke. Patients will be blinded to treatment allocation. The primary outcome at 3 months will also be assessed in a blinded fashion.Ethics and disseminationThe study has been approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, The Netherlands. The results will be disseminated through (open access) peer-reviewed publications, networks of scientists, professionals and the public, and presented at conferences.Trial registration numberNTR6133

The effect of continuous theta burst stimulation over premotor cortex on circuits in primary motor cortex and spinal cord

2009 ◽  
Vol 120 (4) ◽  
pp. 796-801 ◽  
Author(s):  
Ying-Zu Huang ◽  
John C. Rothwell ◽  
Chin-Song Lu ◽  
JiunJie Wang ◽  
Yi-Hsin Weng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation

scholarly journals Trains of Epidural DC Stimulation of the Cerebellum Tune Corticomotor Excitability

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nordeyn Oulad Ben Taib ◽  
Mario Manto
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Spatial Representation ◽  
Primary Motor Cortex ◽  
Anterior Horn ◽  
Adult Rats ◽  
Afferent Inhibition ◽  
Antagonist Muscles ◽  
Conditioned Motor ◽  
Stimulation Of

We assessed the effects of anodal/cathodal direct current stimulation (DCS) applied epidurally over the cerebellum. We studied the excitability of both the motor cortex and the anterior horn of the spinal cord in adult rats under continuous anesthesia. We also investigated the effects on the spatial representation of a couple of agonist/antagonist muscles on primary motor cortex. Moreover, we evaluated the effects on the afferent inhibition in a paradigm of conditioned corticomotor responses. Anodal DCS of the cerebellum (1) decreased the excitability of the motor cortex, (2) reduced the excitability ofFwaves, as shown by the decrease of both meanF/meanMratios and persistence ofFwaves, (3) exerted a “smoothing effect” on corticomotor maps, reshaping the representation of muscles on the motor cortex, and (4) enhanced the afferent inhibition of conditioned motor evoked responses. Cathodal DCS of the cerebellum exerted partially reverse effects. DCS of the cerebellum modulates the excitability of both motor cortex and spinal cord at the level of the anterior horn. This is the first demonstration that cerebellar DCS tunes the shape of corticomotor maps. Our findings provide a novel mechanism by which DCS of the cerebellum exerts a remote neuromodulatory effect upon motor cortex.

scholarly journals Primary motor cortex activity traces distinct trajectories of population dynamics during spontaneous facial motor sequences in mice

2021 ◽  
Author(s):  
Juan Carlos Boffi ◽  
Tristan Wiessalla ◽  
Robert Prevedel
Keyword(s):  
Population Dynamics ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Neuronal Population ◽  
Future Research ◽  
Sequencing Analysis ◽  
Population Activity ◽  
Neuronal Populations ◽  
Custom Made ◽  
Facial Area

AbstractWe explore the link between on-going neuronal activity at primary motor cortex (M1) and face movement in awake mice. By combining custom-made behavioral sequencing analysis and fast volumetric Ca2+-imaging, we simultaneously tracked M1 population activity during many different facial motor sequences. We show that a facial area of M1 displays distinct trajectories of neuronal population dynamics across different spontaneous facial motor sequences, suggesting an underlying population dynamics code.Significance statementHow our brain controls a seemingly limitless diversity of body movements remains largely unknown. Recent research brings new light into this subject by showing that neuronal populations at the primary motor cortex display different dynamics during forelimb reaching movements versus grasping, which suggests that different motor sequences could be associated with distinct motor cortex population dynamics. To explore this possibility, we designed an experimental paradigm for simultaneously tracking the activity of neuronal populations in motor cortex across many different motor sequences. Our results support the concept that distinct population dynamics encode different motor sequences, bringing new insight into the role of motor cortex in sculpting behavior while opening new avenues for future research.

scholarly journals Efficacy of Repetitive Transcranial Magnetic Stimulation for Acute Central Post-stroke Pain: A Case Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Calogero Malfitano ◽  
Angela Rossetti ◽  
Stefano Scarano ◽  
Chiara Malloggi ◽  
Luigi Tesio
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Thermal Sensation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
The Body ◽  
Post Stroke ◽  
Thalamic Stroke ◽  
Motor Cortex Excitability

Although rare, central post-stroke pain remains one of the most refractory forms of neuropathic pain. Repetitive transcranial magnetic stimulation (rTMS) has been reported to be effective in chronic cases. However, there are no data on the effects in the acute and subacute phases after stroke. In this study, we present a case of a patient with thalamic stroke with acute onset of pain and paresthesia who was responsive to rTMS. After a right thalamic stroke, a 32-year-old woman presented with drug-resistant pain and paresthesia on the left side of the body. There were no motor or sensory deficits, except for blunted thermal sensation and allodynia on light touch. Ten daily sessions were performed, where 10 Hz rTMS was applied to the hand area of the right primary motor cortex, 40 days after stroke. Before rTMS treatment (T0), immediately after treatment conclusion (T1), and 1 month after treatment (T2), three pain questionnaires were administered, and cortical responses to single and paired-pulse TMS were assessed. Eight healthy participants served as controls. At T0, when the patient was experiencing the worst pain, the excitability of the ipsilesional motor cortex was reduced. At T1 and T2, the pain scores and paresthesia' spread decreased. The clinical improvement was paralleled by the recovery in motor cortex excitability of the affected hemisphere, in terms of both intra- and inter-hemispheric connections. In this subacute central post-stroke pain case, rTMS treatment was associated with decreased pain and motor cortex excitability changes.

scholarly journals Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

2018 ◽  
Vol 119 (1) ◽  
pp. 235-250 ◽  
Author(s):  
Boubker Zaaimi ◽  
Lauren R. Dean ◽  
Stuart N. Baker
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Reticular Formation ◽  
Upper Limb ◽  
Muscle Activation ◽  
Primary Motor Cortex ◽  
Cervical Spinal Cord ◽  
Motor Output ◽  
Natural Activity ◽  
Limb Muscles

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements.

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