Temporal Components of the Motor Patterns Expressed by the Human Spinal Cord Reflect Foot Kinematics

2003 ◽  
Vol 90 (5) ◽  
pp. 3555-3565 ◽  
Author(s):  
Yuri P. Ivanenko ◽  
Renato Grasso ◽  
Myrka Zago ◽  
Marco Molinari, ◽  
Giorgio Scivoletto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Injury ◽  
Activity Patterns ◽  
Building Blocks ◽  
Control Group ◽  
Motor Patterns ◽  
Foot Kinematics ◽  
Human Spinal Cord ◽  
Basic Set ◽  
Wide Range

What are the building blocks with which the human spinal cord constructs the motor patterns of locomotion? In principle, they could correspond to each individual activity pattern in dozens of different muscles. Alternatively, there could exist a small set of constituent temporal components that are common to all activation patterns and reflect global kinematic goals. To address this issue, we studied patients with spinal injury trained to step on a treadmill with body weight support. Patients learned to produce foot kinematics similar to that of healthy subjects but with activity patterns of individual muscles generally different from the control group. Hidden in the muscle patterns, we found a basic set of five temporal components, whose flexible combination accounted for the wide range of muscle patterns recorded in both controls and patients. Furthermore, two of the components were systematically related to foot kinematics across different stepping speeds and loading conditions. We suggest that the components are related to control signals output by spinal pattern generators, normally under the influence of descending and afferent inputs.

scholarly journals Harmonic Brain Modes: A Unifying Framework for Linking Space and Time in Brain Dynamics

2017 ◽  
Vol 24 (3) ◽  
pp. 277-293 ◽  
Author(s):  
Selen Atasoy ◽  
Gustavo Deco ◽  
Morten L. Kringelbach ◽  
Joel Pearson
Keyword(s):  
Neural Activity ◽  
Brain Activity ◽  
Activity Patterns ◽  
Structural Connectivity ◽  
Building Blocks ◽  
Mental States ◽  
Brain Dynamics ◽  
Space And Time ◽  
Wide Range ◽  
The Brain

A fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at “rest.” Here, we introduce the concept of harmonic brain modes—fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; that is, connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal, and network-level changes in the brain across different mental states ( wakefulness, sleep, anesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal, and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.

scholarly journals Expression of Connexins 37, 43 and 45 in Developing Human Spinal Cord and Ganglia

2020 ◽  
Vol 21 (24) ◽  
pp. 9356
Author(s):  
Marija Jurić ◽  
Julia Zeitler ◽  
Katarina Vukojević ◽  
Ivana Bočina ◽  
Maximilian Grobe ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Human Development ◽  
Developmental Stages ◽  
Activity Patterns ◽  
Expression Patterns ◽  
Human Spinal Cord ◽  
Spatio Temporal ◽  
Early Fetal Period ◽  
Areas Of Interest ◽  
Early Human

Direct intercellular communication via gap junctions has an important role in the development of the nervous system, ranging from cell migration and neuronal differentiation to the formation of neuronal activity patterns. This study characterized and compared the specific spatio-temporal expression patterns of connexins (Cxs) 37, 43 and 45 during early human developmental stages (since the 5th until the 10th developmental week) in the spinal cord (SC) and dorsal root ganglia (DRG) using double immunofluorescence and transmission electron microscopy. We found the expression of all three investigated Cxs during early human development in all the areas of interest, in the SC, DRG, developing paravertebral ganglia of the sympathetic trunk, notochord and all three meningeal layers, with predominant expression of Cx37. Comparing the expression of different Cxs between distinct developmental periods, we did not find significant differences. Specific spatio-temporal pattern of Cxs expression might reflect their relevance in the development of all areas of interest via cellular interconnectivity and synchronization during the late embryonic and early fetal period of human development.

scholarly journals Locomotor Training After Human Spinal Cord Injury: A Series of Case Studies

2000 ◽  
Vol 80 (7) ◽  
pp. 688-700 ◽  
Author(s):  
Andrea L Behrman ◽  
Susan J Harkema
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Sensory Information ◽  
Locomotor Training ◽  
Overground Walking ◽  
Thoracic Spinal Cord ◽  
Human Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

AbstractMany individuals with spinal cord injury (SCI) do not regain their ability to walk, even though it is a primary goal of rehabilitation. Mammals with thoracic spinal cord transection can relearn to step with their hind limbs on a treadmill when trained with sensory input associated with stepping. If humans have similar neural mechanisms for locomotion, then providing comparable training may promote locomotor recovery after SCI. We used locomotor training designed to provide sensory information associated with locomotion to improve stepping and walking in adults after SCI. Four adults with SCIs, with a mean postinjury time of 6 months, received locomotor training. Based on the American Spinal Injury Association (ASIA) Impairment Scale and neurological classification standards, subject 1 had a T5 injury classified as ASIA A, subject 2 had a T5 injury classified as ASIA C, subject 3 had a C6 injury classified as ASIA D, and subject 4 had a T9 injury classified as ASIA D. All subjects improved their stepping on a treadmill. One subject achieved overground walking, and 2 subjects improved their overground walking. Locomotor training using the response of the human spinal cord to sensory information related to locomotion may improve the potential recovery of walking after SCI.

scholarly journals Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

2015 ◽  
Vol 113 (7) ◽  
pp. 2447-2460 ◽  
Author(s):  
Maria Knikou ◽  
Andrew C. Smith ◽  
Chaithanya K. Mummidisetty
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Reciprocal Inhibition ◽  
H Reflex ◽  
Medial Gastrocnemius ◽  
Locomotor Training ◽  
Step Cycle ◽  
Human Spinal Cord ◽  
Cord Injury

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs.

scholarly journals A Panel of CSF and Serum Biomarkers Reflecting Injury Severity and Outcome in a Human Spinal Cord Injury Study

2021 ◽  
Author(s):  
Zhihui Yang ◽  
Yueqiang Fu ◽  
Sehajpreet Kaur ◽  
Iktej Singh Jabbal ◽  
Ahmed Moghieb ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Phase ◽  
Injury Severity ◽  
Spinal Injury ◽  
Serum Biomarkers ◽  
Breakdown Product ◽  
Serum Samples ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Acute spinal cord injury (SCI) results in catastrophic neurological impairment. We aimed to examine the temporal profile and severity correlation of biomarkers, and their relationship with the American Spinal Injury Association Scale (AIS) improvement in human SCI. 15 SCI and 10 non-SCI healthy subjects were classified according to the initial and discharge AIS grade. Serial cerebrospinal fluid (CSF) and serum samples were collected. Spectrin breakdown products (SBDP) 150, SBDP145, glial fibrillary acidic protein (GFAP), and GFAP breakdown product (GBDP) 38/44K were found to be elevated in the acute phase CSF samples in SCI patients on immunoblotting. SBDP150, ubiquitin C-terminal hydrolase-L1 (UCH-L1), GFAP, S100B, neurofilament light chain protein (NF-L), Tau & interleukin (IL) -6 were elevated in the acute phase CSF and serum samples on ELISA. CSF SBDP150, UCH-L1, GFAP, S100B and Tau were seen to peak on day 1 after injury, while CSF IL-6 and NF-L peaked on day 5. Serum SBDP150, IL-6, S100B, GFAP, UCHL-1 and Tau peaked on day 1, while serum NF-L peaked on day 5 post-injury. CSF alpha II-spectrin, SBDP150/145, and GBDP 44-38K levels (by immunoblots), CSF SBDP150, S100B, GFAP, UCHL-1 and Tau (ELISA) and serum UCHL-1 and Tau (ELISA) at specific time points showed SCI severity-correlation. CSF SBDP150, GFAP, and Tau and serum UCHL-1 and Tau (ELISA) were seen to have the best correlation with the severity at discharge. Receiver Operating Characteristic Curve analysis showed that CSF and serum biomarkers (SBDP150, IL-6, S100B, GFAP, NF-L, UCHL-1 and Tau) were associated with the severity of SCI.

scholarly journals Harmonic brain modes: a unifying framework for linking space and time in brain dynamics

2017 ◽  
Author(s):  
Selen Atasoy ◽  
Gustavo Deco ◽  
Morten L. Kringelbach ◽  
Joel Pearson
Keyword(s):  
Neural Activity ◽  
Brain Activity ◽  
Activity Patterns ◽  
Structural Connectivity ◽  
Building Blocks ◽  
Mental States ◽  
Brain Dynamics ◽  
Space And Time ◽  
Wide Range ◽  
The Brain

AbstractA fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at ‘rest’. Here, we introduce the concept of “harmonic brain modes” – fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; i.e. connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal and network-level changes in the brain across different mental states; (wakefulness, sleep, anaesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.

scholarly journals Increases in human motoneuron excitability after cervical spinal cord injury depend on the level of injury

2017 ◽  
Vol 117 (2) ◽  
pp. 684-691 ◽  
Author(s):  
Christine K. Thomas ◽  
Charlotte K. Häger ◽  
Cliff S. Klein
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Conduction Velocity ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Motor Units ◽  
M Wave ◽  
Human Spinal Cord ◽  
Motoneuron Excitability ◽  
Cord Injury

After human spinal cord injury (SCI), motoneuron recruitment and firing rate during voluntary and involuntary contractions may be altered by changes in motoneuron excitability. Our aim was to compare F waves in single thenar motor units paralyzed by cervical SCI to those in uninjured controls because at the single-unit level F waves primarily reflect the intrinsic properties of the motoneuron and its initial segment. With intraneural motor axon stimulation, F waves were evident in all 4 participants with C4-level SCI, absent in 8 with C5 or C6 injury, and present in 6 of 12 Uninjured participants ( P < 0.001). The percentage of units that generated F waves differed across groups (C4: 30%, C5 or C6: 0%, Uninjured: 16%; P < 0.001). Mean (±SD) proximal axon conduction velocity was slower after C4 SCI [64 ± 4 m/s ( n = 6 units), Uninjured: 73 ± 8 m/s ( n = 7 units); P = 0.037]. Mean distal axon conduction velocity differed by group [C4: 40 ± 8 m/s ( n = 20 units), C5 or C6: 49 ± 9 m/s ( n = 28), Uninjured: 60 ± 7 m/s ( n = 45); P < 0.001]. Motor unit properties (EMG amplitude, twitch force) only differed after SCI ( P ≤ 0.004), not by injury level. Motor units with F waves had distal conduction velocities, M-wave amplitudes, and twitch forces that spanned the respective group range, indicating that units with heterogeneous properties produced F waves. Recording unitary F waves has shown that thenar motoneurons closer to the SCI (C5 or C6) have reduced excitability whereas those further away (C4) have increased excitability, which may exacerbate muscle spasms. This difference in motoneuron excitability may be related to the extent of membrane depolarization following SCI. NEW & NOTEWORTHY Unitary F waves were common in paralyzed thenar muscles of people who had a chronic spinal cord injury (SCI) at the C4 level compared with uninjured people, but F waves did not occur in people that had SCI at the C5 or C6 level. These results highlight that intrinsic motoneuron excitability depends, in part, on how close the motoneurons are to the site of the spinal injury, which could alter the generation and strength of voluntary and involuntary muscle contractions.

Walking During Daily Life Can Be Validly and Responsively Assessed in Subjects With a Spinal Cord Injury

2008 ◽  
Vol 23 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Hubertus J. A. van Hedel ◽  
Volker Dietz ◽  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Daily Life ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Walking Capacity ◽  
European Multicenter Study ◽  
Walking Tests ◽  
Over Time

Objective. This study assessed the validity and responsiveness of the Spinal Cord Independence Measure (SCIM II) items indoor mobility, mobility for moderate distances, and outdoor mobility. Methods. The data of 886 spinal cord injury subjects were derived from the European Multicenter Study for Human Spinal Cord Injury (EM-SCI) and analyzed at 2 weeks and 1, 3, 6, and 12 months after injury. The SCIM II items were compared using the preferred walking speed and the Walking Index for Spinal Cord Injury (WISCI II). The responsiveness to assess differences over time was determined. The analyses were performed for subjects with varying impairment scales according to the American Spinal Injury Association (ASIA). Results. An initially moderate correlation between walking capacity and the SCIM II mobility items improved to excellent at 6 and 12 months after injury. The correlations were higher for indoor mobility compared with outdoor mobility. These correlations increased in ASIA C, but decreased over time in ASIA D subjects. The SCIM II mobility items showed initially positive responsiveness in ASIA A and B subjects. In ASIA C and D subjects, SCIM II responsiveness was significant within the first 6 months. Conclusions . The SCIM II items assess mobility (wheelchair and walking) during daily life. They show good validity and responsiveness, including postdischarge. They can be considered appropriate for evaluating the efficacy of new interventions on ambulatory function. Depending on the severity of the initial lesion and time of assessment, clinically applied walking tests can accurately predict walking performance during daily life.

Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured Göttingen minipigs

2021 ◽  
pp. 1-9
Author(s):  
Richard G. Fessler ◽  
Charles Y. Liu ◽  
Stephen McKenna ◽  
R. David Fessler ◽  
Jane S. Lebkowski ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Direct Injection ◽  
Tumor Formation ◽  
Control Group ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Human Spinal Cord ◽  
Histological Damage ◽  
Immunological Abnormalities

OBJECTIVE This study was conducted as a final proof-of-safety direct injection of oligodendrocyte progenitor cells into the uninjured spinal cord prior to translation to the human clinical trials. METHODS In this study, 107 oligodendrocyte progenitor cells (LCTOPC1, also known as AST-OPC1 and GRNOPC1) in 50-μL suspension were injected directly into the uninjured spinal cords of 8 immunosuppressed Göttingen minipigs using a specially designed stereotactic delivery device. Four additional Göttingen minipigs were given Hanks’ Balanced Salt Solution and acted as the control group. RESULTS Cell survival and no evidence of histological damage, abnormal inflammation, microbiological or immunological abnormalities, tumor formation, or unexpected morbidity or mortality were demonstrated. CONCLUSIONS These data strongly support the safety of intraparenchymal injection of LCTOPC1 into the spinal cord using a model anatomically similar to that of the human spinal cord. Furthermore, this research provides guidance for future clinical interventions, including mechanisms for precise positioning and anticipated volumes of biological payloads that can be safely delivered directly into uninjured portions of the spinal cord.

scholarly journals High Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Chronic Pain: 6-Month Australian Clinical Experience

2016 ◽  
Vol 4;19 (4;5) ◽  
pp. 267-280 ◽  
Author(s):  
Dr Marc A. Russo
Keyword(s):  
Spinal Cord ◽  
Pain Relief ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Leg Pain ◽  
Control Group ◽  
Intractable Pain ◽  
Positive Trial ◽  
Pain Clinics ◽  
Wide Range

Background: High frequency spinal cord stimulation at 10 kHz (HF10 therapy) represents a prominent advance in spinal cord stimulation (SCS) therapy, having demonstrated enhanced efficacy in patients with back and leg pain and pain relief without paresthesia that is sustained at 24 months post implant. Objective: To report on the effectiveness HF10 SCS therapy for a wide range of intractable pain conditions in clinical practice. Study Design: Retrospective investigation of 256 patients who trialed HF10 SCS for chronic intractable pain of various etiologies. Setting: Three Australian pain clinics. Methods: Two hundred fifty-six patients trialed HF10 SCS with view of a permanent implant if successful. Pain distributions included back + leg, back only, head ± neck, and neck ± arm/ shoulder. About 30% of patients had previously failed traditional low-frequency paresthesiabased stimulation, while the remaining cohort were either highly refractory to treatment or not recommended by the pain physician for traditional SCS. Pain scores (numerical pain rating scale – NPRS) and functional outcome measures (Oswestry Disability Index – ODI; and activity tolerance times) were assessed at baseline, post-trial, and at 3 and 6 months post-implant as available in the medical records. Results: Of the 256 patients, 189 (73%) reported a positive trial and were implanted. Patients with back + leg pain demonstrated the highest trial success rate (81%). A mean reduction in pain, among those for whom data were available, of 50% was sustained up to 6 months postimplant across the entire patient population. Sixty-eight percent of patients who failed traditional SCS reported a positive trial and mean pain relief at 6 months was 49% (P < 0.001). An 8.6 point reduction in ODI (21%) at 6 months and improved sitting, standing, and walking tolerances were also reported. Limitations: As data was collected retrospectively, missing data points were unavoidable; this was primarily due to inconsistent data collection and patients being lost to follow-up. Patient populations were diverse and a control group was not appropriate in this setting. Conclusions: These retrospective results demonstrate a significant advancement for patients suffering with chronic intractable pain and are consistent with recently published clinical results for HF10 SCS. HF10 SCS appears to be a viable, paresthesia-free alternative to traditional SCS, with high trial success rates, demonstrated effectiveness in a range of pain distributions including those typically difficult to treat with traditional SCS, and the possibility to restore pain control in patients who have previously failed traditional SCS. Key words: Spinal cord stimulation, high frequency stimulation, HF10, paresthesia-free stimulation, back pain, leg pain, cervical pain, neuromodulation

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