Neural Substrates for the Motivational Regulation of Motor Recovery after Spinal-Cord Injury

Nishimura, Yukio; Onoe, Hirotaka; Onoe, Kayo; Morichika, Yosuke; Tsukada, Hideo; Isa, Tadashi

doi:10.1371/journal.pone.0024854

Cited by 40 publications

(26 citation statements)

References 34 publications

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“…Remarkably, we also observed surface area expansions in the ventral striatum (i.e. nucleus accumbens), a region known to be involved in recovery of the dexterous finger movements after experimental SCI 4 , 36 .…”

Section: Discussionsupporting

confidence: 54%

Extrapyramidal plasticity predicts recovery after spinal cord injury

Huber

Hupp

Weiskopf

et al. 2020

Sci Rep

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Spinal cord injury (Sci) leads to widespread neurodegeneration across the neuroaxis. We explored trajectories of surface morphology, demyelination and iron concentration within the basal gangliathalamic circuit over 2 years post-SCI. This allowed us to explore the predictive value of neuroimaging biomarkers and determine their suitability as surrogate markers for interventional trials. changes in markers of surface morphology, myelin and iron concentration of the basal ganglia and thalamus were estimated from 182 MRI datasets acquired in 17 SCI patients and 21 healthy controls at baseline (1-month post injury for patients), after 3, 6, 12, and 24 months. Using regression models, we investigated group difference in linear and non-linear trajectories of these markers. Baseline quantitative MRI parameters were used to predict 24-month clinical outcome. Surface area contracted in the motor (i.e. lower extremity) and pulvinar thalamus, and striatum; and expanded in the motor thalamus and striatum in patients compared to controls over 2-years. In parallel, myelin-sensitive markers decreased in the thalamus, striatum, and globus pallidus, while iron-sensitive markers decreased within the left caudate. Baseline surface area expansions within the striatum (i.e. motor caudate) predicted better lower extremity motor score at 2-years. Extensive extrapyramidal neurodegenerative and reorganizational changes across the basal ganglia-thalamic circuitry occur early after Sci and progress over time; their magnitude being predictive of functional recovery. these results demonstrate a potential role of extrapyramidal plasticity during functional recovery after Sci. Spinal cord injury (SCI) leads to permanent functional deficits below the level of injury. Neurorehabilitation can foster sensorimotor recovery, but often only partial improvements can be achieved. Recovery is paralleled by a cascade of progressive neurodegenerative changes affecting the pyramidal, sensory and limbic system 1,2 ; its magnitude predicting functional recovery 1,2. In addition, compensatory changes within the extrapyramidal system might contribute to recovery as shown in the non-human primate model of SCI 3,4. For example, impaired information flow within the basal ganglia-thalamic circuit 5 and the motor cortex 6 was associated with abnormal activation patterns and increased functional connectivity in pallido-thalamocortical loops 6. However, in SCI patients, the role of the extrapyramidal system in sensorimotor recovery is understudied 7. To characterize structural trajectories of surface area and microstructural parameters, we modelled the MRI measures in terms of linear rate of change (reflecting degeneration/plasticity) and non-linear rate of change (reflecting acceleration/deceleration). In particularly, T1-weighted volumes were used to track trajectories of vertex-wise surface area contractions and expansions of the basal ganglia and thalamic subnuclei over 2-years. Myelin-sensitive magnetization transfer saturation (MT) and longitudinal relaxation ra...

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Section: Discussionsupporting

confidence: 54%

Extrapyramidal plasticity predicts recovery after spinal cord injury

Huber

Hupp

Weiskopf

et al. 2020

Sci Rep

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“…We recruited eight monkeys and then excluded two because the infection rate and/or expression of viral vectors in one monkey were judged to be obviously insufficient and the extent of lesion of the other monkey was too large; thus, the results of six monkeys are presented. The monkeys were first trained for a few weeks in a reach-and-grasp task described previously (15)(16)(17)(21)(22)(23) and in Supporting Information (SI Materials and Methods, Behavioral Testing, and Movie S1). The retrograde gene transfer vector (HiRet/FuG-E/NeuRet-TRE-EGFP.eTeNT) was then injected into the ventral horn of the spinal cord at C6-Th1 as previously described (23).…”

Section: Methodsmentioning

confidence: 99%

“…The authors also argued for partial compensation of grasping movements by the brainstemmediated descending pathways such as the rubrospinal tract (14). More recent studies on the neural basis of functional recovery following CST lesions revealed that a variety of plastic changes in neural circuits occurred in the supraspinal structures including the motor and premotor cortices (15), and in the connectivity from the nucleus accumbens to motor cortex (16,17). At the more caudal level, sprouting of the midline-crossing CST fibers was revealed in the lower cervical segment of monkeys with hemisected spinal cords (18).…”

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confidence: 99%

Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys

Tohyama

Kinoshita

Kobayashi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The direct cortico-motoneuronal connection is believed to be essential for the control of dexterous hand movements, such as precision grip in primates. It was reported, however, that even after lesion of the corticospinal tract (CST) at the C4-C5 segment, precision grip largely recovered within 1-3 mo, suggesting that the recovery depends on transmission through intercalated neurons rostral to the lesion, such as the propriospinal neurons (PNs) in the midcervical segments. To obtain direct evidence for the contribution of PNs to recovery after CST lesion, we applied a pathway-selective and reversible blocking method using double viral vectors to the PNs in six monkeys after CST lesions at C4-C5. In four monkeys that showed nearly full or partial recovery, transient blockade of PN transmission after recovery caused partial impairment of precision grip. In the other two monkeys, CST lesions were made under continuous blockade of PN transmission that outlasted the entire period of postoperative observation (3-4.5 mo). In these monkeys, precision grip recovery was not achieved. These results provide evidence for causal contribution of the PNs to recovery of hand dexterity after CST lesions; PN transmission is necessary for promoting the initial stage recovery; however, their contribution is only partial once the recovery is achieved.spinal cord injury | plasticity | neural circuit | nonhuman primates | viral vector A s a potential treatment for brain and spinal cord injury, regeneration of the injured axons has been attempted in animal models, often using rodents with corticospinal tract (CST) lesions. Regeneration of the injured CST fibers was facilitated by treatments such as peripheral nerve graft (1), application of an antibody against neurite growth inhibitors IN-1 (2), combined application of the antibody and neurotrophic factor NT-3 (3), and transplantation of neural stem cells derived from induced pluripotent stem cells (4). A more recent study showed that regenerated CST axons increased the connection to the spinal motoneurons (MNs) after spinal cord injury in monkeys (5). However, in these studies, the causal contribution of such regenerated fibers to the functional recovery was not directly demonstrated. Therefore, recent debates address the question whether these therapies should target repairing the injured CST fibers and/or facilitating compensation by indirect cortico-motoneuronal (CM) connections via other descending motor pathways (6-9).Traditionally, the neural control of dexterous hand movements in higher primates has primarily been associated with development of the direct pathway from the motor cortex to MNs, known as the CM pathway (10-12). Lesion of the CST at the brainstem level in nonhuman primates caused near-permanent loss of dexterous hand movements (13). The authors also argued for partial compensation of grasping movements by the brainstemmediated descending pathways such as the rubrospinal tract (14). More recent studies on the neural basis of functional recovery following CST lesions ...

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“…Additionally, a role of dopamine has also been suggested in motor skill learning in humans Sawaki et al 2002;Floel et al 2005a;Palminteri et al 2011;Lissek et al 2014). And recent studies show an effect of motivation and dopamine on rehabilitation of motor function after a central nervous system injury (Floel et al 2005b;Nishimura et al 2011;Lohse et al 2013).…”

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confidence: 99%

Motivational state, reward value, and Pavlovian cues differentially affect skilled forelimb grasping in rats

2016

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Motor skills represent high-precision movements performed at optimal speed and accuracy. Such motor skills are learned with practice over time. Besides practice, effects of motivation have also been shown to influence speed and accuracy of movements, suggesting that fast movements are performed to maximize gained reward over time as noted in previous studies. In rodents, skilled motor performance has been successfully modeled with the skilled grasping task, in which animals use their forepaw to grasp for sugar pellet rewards through a narrow window. Using sugar pellets, the skilled grasping task is inherently tied to motivation processes. In the present study, we performed three experiments modulating animals' motivation during skilled grasping by changing the motivational state, presenting different reward value ratios, and displaying Pavlovian stimuli. We found in all three studies that motivation affected the speed of skilled grasping movements, with the strongest effects seen due to motivational state and reward value. Furthermore, accuracy of the movement, measured in success rate, showed a strong dependence on motivational state as well. Pavlovian cues had only minor effects on skilled grasping, but results indicate an inverse Pavlovian-instrumental transfer effect on movement speed. These findings have broad implications considering the increasing use of skilled grasping in studies of motor system structure, function, and recovery after injuries.

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Neural Substrates for the Motivational Regulation of Motor Recovery after Spinal-Cord Injury

Cited by 40 publications

References 34 publications

Extrapyramidal plasticity predicts recovery after spinal cord injury

Extrapyramidal plasticity predicts recovery after spinal cord injury

Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys

Motivational state, reward value, and Pavlovian cues differentially affect skilled forelimb grasping in rats

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