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Neural substrates for the motivational regulation of motor recovery after spinal-cord injury.

ABSTRACT: It is believed that depression impedes and motivation enhances functional recovery after neuronal damage such as spinal-cord injury and stroke. However, the neuronal substrate underlying such psychological effects on functional recovery remains unclear. A longitudinal study of brain activation in the non-human primate model of partial spinal-cord injury using positron emission tomography (PET) revealed a contribution of the primary motor cortex (M1) to the recovery of finger dexterity through the rehabilitative training. Here, we show that activity of the ventral striatum, including the nucleus accumbens (NAc), which plays a critical role in processing of motivation, increased and its functional connectivity with M1 emerged and was progressively strengthened during the recovery. In addition, functional connectivities among M1, the ventral striatum and other structures belonging to neural circuits for processing motivation, such as the orbitofrontal cortex, anterior cingulate cortex and pedunculopontine tegmental nucleus were also strengthened during the recovery. These results give clues to the neuronal substrate for motivational regulation of motor learning required for functional recovery after spinal-cord injury.

SUBMITTER: Nishimura Y

PROVIDER: S-EPMC3182173 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Neural substrates for the motivational regulation of motor recovery after spinal-cord injury.

Nishimura Yukio Y Onoe Hirotaka H Onoe Kayo K Morichika Yosuke Y Tsukada Hideo H Isa Tadashi T

PloS one 20110928 9

It is believed that depression impedes and motivation enhances functional recovery after neuronal damage such as spinal-cord injury and stroke. However, the neuronal substrate underlying such psychological effects on functional recovery remains unclear. A longitudinal study of brain activation in the non-human primate model of partial spinal-cord injury using positron emission tomography (PET) revealed a contribution of the primary motor cortex (M1) to the recovery of finger dexterity through th ...[more]

PMID: 21969864

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Project description:The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4-5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.

Project description:ObjectiveTo explore the hypothesis that earlier administration of acute gabapentinoids is beneficial to motor recovery after spinal cord injury in humans.MethodsThis is an observational study using a cohort from the European Multi-Centre Study about Spinal Cord Injury. Patient charts were reviewed to extract information regarding the administration and timing of gabapentinoid anticonvulsants. The primary outcome measure was motor scores, as measured by the International Standards for Neurological Classification of Spinal Cord Injury, collected longitudinally in the first year after injury. Sensory scores (light touch and pinprick) and functional measures (Spinal Cord Independence Measure) were secondary outcomes. Linear mixed effects regression models included a drug-by-time interaction to determine whether exposure to gabapentinoids altered recovery of muscle strength in the first year after injury.ResultsA total of 201 participants were included in the study and had a median age of 46 and baseline motor score of 50. Participants were mostly men (85%) with sensory and motor complete injuries (50%). Seventy individuals (35%) were administered gabapentinoids within the first 30 days after injury, and presented with similar demographics. In the longitudinal model, the administration of gabapentinoids within 30 days after injury was associated with improved motor recovery when compared to those who did not receive gabapentinoids during this time (3.69 additional motor points from 4 to 48 weeks after injury; p = 0.03). This effect size increased as administration occurred earlier after injury (i.e., a benefit of 4.68 points when administered within 5 days).ConclusionsThis retrospective, observational study provided evidence of the beneficial effect of gabapentinoid anticonvulsants on motor recovery after spinal cord injury. More critically, it highlighted a potential time dependence, suggesting that earlier intervention is associated with better outcomes.Classification of evidenceThis study provides Class IV evidence that gabapentinoids improve motor recovery for individuals with acute spinal cord injury.

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Neural substrates for the motivational regulation of motor recovery after spinal-cord injury.

Publications

Neural substrates for the motivational regulation of motor recovery after spinal-cord injury.

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