Imbalanced Corticospinal and Reticulospinal Contributions to Spasticity in Humans with Spinal Cord Injury

Sangari, Sina; Perez, Monica A.

doi:10.1523/jneurosci.1106-19.2019

Cited by 49 publications

(49 citation statements)

References 83 publications

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“…Recent work in spinal cord injury survivors suggests that high spasticity is associated with limited residual corticospinal connections and enhanced reticulospinal output below the lesion 36 , 37 ; this accords with clinical experience associating spasticity with the RST. 38 Against this background, it might be thought that our intervention, which aimed to strengthen reticulospinal outputs, could have risked increasing spasticity.…”

Section: Discussionsupporting

confidence: 60%

A Novel Wearable Device for Motor Recovery of Hand Function in Chronic Stroke Survivors

Choudhury

Singh

Shobhana

et al. 2020

Neurorehabil Neural Repair

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Background. In monkey, reticulospinal connections to hand and forearm muscles are spontaneously strengthened following corticospinal lesions, likely contributing to recovery of function. In healthy humans, pairing auditory clicks with electrical stimulation of a muscle induces plastic changes in motor pathways (probably including the reticulospinal tract), with features reminiscent of spike-timing dependent plasticity. In this study, we tested whether pairing clicks with muscle stimulation could improve hand function in chronic stroke survivors. Methods. Clicks were delivered via a miniature earpiece; transcutaneous electrical stimuli at motor threshold targeted forearm extensor muscles. A wearable electronic device (WD) allowed patients to receive stimulation at home while performing normal daily activities. A total of 95 patients >6 months poststroke were randomized to 3 groups: WD with shock paired 12 ms before click; WD with clicks and shocks delivered independently; standard care. Those allocated to the device used it for at least 4 h/d, every day for 4 weeks. Upper-limb function was assessed at baseline and weeks 2, 4, and 8 using the Action Research Arm Test (ARAT), which has 4 subdomains (Grasp, Grip, Pinch, and Gross). Results. Severity across the 3 groups was comparable at baseline. Only the paired stimulation group showed significant improvement in total ARAT (median baseline: 7.5; week 8: 11.5; P = .019) and the Grasp subscore (median baseline: 1; week 8: 4; P = .004). Conclusion. A wearable device delivering paired clicks and shocks over 4 weeks can produce a small but significant improvement in upper-limb function in stroke survivors.

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Section: Discussionsupporting

confidence: 60%

A Novel Wearable Device for Motor Recovery of Hand Function in Chronic Stroke Survivors

Choudhury

Singh

Shobhana

et al. 2020

Neurorehabil Neural Repair

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“…The reduction in the MEP amplitude size was also correlated with spasticity as one of the most common signs in humans with an SCI [ 58 ]. Spasticity causes muscle spasms, and increases muscle tone, hyperreflexia, and involuntary movements.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with an incomplete SCI and spastic muscles, the contribution of the corticospinal tract was demonstrated by TMS. Results showed that smaller MEP amplitude sizes over the area of M1 were found in patients with higher spasticity compared to healthy controls and patients with low spasticity [ 58 ]. A previous study showed that a high frequency of rTMS could effectively decrease spasticity in patients with multiple sclerosis and stroke [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Neuromodulatory effects of repetitive transcranial magnetic stimulation on neural plasticity and motor functions in rats with an incomplete spinal cord injury: A preliminary study

et al. 2021

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We investigated the effects of intermittent theta-burst stimulation (iTBS) on locomotor function, motor plasticity, and axonal regeneration in an animal model of incomplete spinal cord injury (SCI). Aneurysm clips with different compression forces were applied extradurally around the spinal cord at T10. Motor plasticity was evaluated by examining the motor evoked potentials (MEPs). Long-term iTBS treatment was given at the post-SCI 5th week and continued for 2 weeks (5 consecutive days/week). Time-course changes in locomotor function and the axonal regeneration level were measured by the Basso Beattie Bresnahan (BBB) scale, and growth-associated protein (GAP)-43 expression was detected in brain and spinal cord tissues. iTBS-induced potentiation was reduced at post-1-week SCI lesion and had recovered by 4 weeks post-SCI lesion, except in the severe group. Multiple sessions of iTBS treatment enhanced the motor plasticity in all SCI rats. The locomotor function revealed no significant changes between pre- and post-iTBS treatment in SCI rats. The GAP-43 expression level in the spinal cord increased following 2 weeks of iTBS treatment compared to the sham-treatment group. This preclinical model may provide a translational platform to further investigate therapeutic mechanisms of transcranial magnetic stimulation and enhance the possibility of the potential use of TMS with the iTBS scheme for treating SCIs.

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“…A critical question is how these contributions might take place. For example, we recently showed lesser corticospinal and larger reticulospinal influences to spastic muscles in humans with SCI (Sangari and Perez, 2019), suggesting that the contributions from corticospinal and reticulospinal tracts are imbalanced when spasticity is present (Owen et al, 2017;McPherson et al, 2018;Choudhury et al, 2019). Here, we tested SCI participants who did not have spasticity in biceps or triceps to avoid the effect of this variable on our results.…”

Section: Functional Considerationsmentioning

confidence: 97%

Distinct Corticospinal and Reticulospinal Contributions to Voluntary Control of Elbow Flexor and Extensor Muscles in Humans with Tetraplegia

Sangari

Pérez

2020

J. Neurosci.

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Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps.

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Imbalanced Corticospinal and Reticulospinal Contributions to Spasticity in Humans with Spinal Cord Injury

Cited by 49 publications

References 83 publications

A Novel Wearable Device for Motor Recovery of Hand Function in Chronic Stroke Survivors

A Novel Wearable Device for Motor Recovery of Hand Function in Chronic Stroke Survivors

Neuromodulatory effects of repetitive transcranial magnetic stimulation on neural plasticity and motor functions in rats with an incomplete spinal cord injury: A preliminary study

Distinct Corticospinal and Reticulospinal Contributions to Voluntary Control of Elbow Flexor and Extensor Muscles in Humans with Tetraplegia

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