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Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion.

ABSTRACT: In the context of injury to the corticospinal tract (CST), brainstem-origin circuits may provide an alternative system of descending motor influence. However, subcortical circuits are largely under subconscious control. To improve volitional control over spared fibers after CST injury, we hypothesized that a combination of physical exercises simultaneously stimulating cortical and brainstem pathways above the injury would strengthen corticobulbar connections through Hebbian-like mechanisms. We sought to test this hypothesis in mice with unilateral CST lesions. Ten days after pyramidotomy, mice were randomized to four training groups: (1) postural exercises designed to stimulate brainstem pathways (BS); (2) distal limb-grip exercises preferentially stimulating CST pathways (CST); (3) simultaneous multimodal exercises (BS+CST); or (4) no training (NT). Behavioral and anatomical outcomes were assessed after 20 training sessions over 4 weeks. Mice in the BS+CST training group showed a trend toward greater improvements in skilled limb performance than mice in the other groups. There were no consistent differences between training groups in gait kinematics. Anatomically, multimodal BS+CST training neither increased corticobulbar fiber density of the lesioned CST rostral to the lesion nor collateral sprouting of the unlesioned CST caudal to the lesion. Further studies should incorporate electrophysiological assessment to gauge changes in synaptic strength of direct and indirect pathways between the cortex and spinal cord in response to multimodal exercises.

SUBMITTER: Harel NY

PROVIDER: S-EPMC3873870 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion.

Harel Noam Y NY Yigitkanli Kazim K Fu Yiguang Y Cafferty William B J WB Strittmatter Stephen M SM

Brain research 20130918

In the context of injury to the corticospinal tract (CST), brainstem-origin circuits may provide an alternative system of descending motor influence. However, subcortical circuits are largely under subconscious control. To improve volitional control over spared fibers after CST injury, we hypothesized that a combination of physical exercises simultaneously stimulating cortical and brainstem pathways above the injury would strengthen corticobulbar connections through Hebbian-like mechanisms. We s ...[more]

PMID: 24055330

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Project description:Brain lesion characteristics (timing, location, and extent) and the type of corticospinal tract (CST) wiring have been proposed as determinants of upper limb (UL) motor function in unilateral cerebral palsy (uCP), yet an investigation of the relative combined impact of these factors on both motor and sensory functions is still lacking. Here, we first investigated whether structural brain lesion characteristics could predict the underlying CST wiring and we explored the role of CST wiring and brain lesion characteristics to predict UL motor and sensory functions in uCP. Fifty-two participants with uCP (mean age (SD): 11 y and 3 m (3 y and 10 m)) underwent a single-pulse Transcranial Magnetic Stimulation session to determine CST wiring between the motor cortex and the more affected hand (n = 17 contralateral, n = 19 ipsilateral, and n = 16 bilateral) and an MRI to determine lesion timing (n = 34 periventricular (PV) lesion, n = 18 corticosubcortical (CSC) lesion), location, and extent. Lesion location and extent were evaluated with a semiquantitative scale. A standardized protocol included UL motor (grip strength, unimanual capacity, and bimanual performance) and sensory measures. A combination of lesion locations (damage to the PLIC and frontal lobe) significantly contributed to differentiate between the CST wiring groups, reclassifying the participants in their original group with 57% of accuracy. Motor and sensory functions were influenced by each of the investigated neurological factors. However, multiple regression analyses showed that motor function was predicted by the CST wiring (more preserved in individuals with contralateral CST (p < 0.01)), lesion extent, and damage to the basal ganglia and thalamus. Sensory function was predicted by the combination of a large and later lesion and an ipsilateral or bilateral CST wiring, which led to increased sensory deficits (p < 0.05). These novel insights contribute to a better understanding of the underlying pathophysiology of UL function and may be useful to delineate individualized treatment strategies.

Project description:Unilateral brachial plexus injury (BPI) impairs sensory and motor functions of the upper limb. This study aimed to map in detail brachial plexus sensory impairment both in the injured and the uninjured upper limb. Touch sensation was measured through Semmes-Weinstein monofilaments at the autonomous regions of the brachial plexus nerves, hereafter called points of exclusive innervation (PEIs). Seventeen BPI patients (31.35 years±6.9 SD) and 14 age-matched healthy controls (27.57 years±5.8 SD) were tested bilaterally at six selected PEIs (axillary, musculocutaneous, median, radial, ulnar, and medial antebrachial cutaneous [MABC]). As expected, the comparison between the control group and the brachial plexus patients' injured limb showed a robust difference for all PEIs (p ≤ 0.001). Moreover, the comparison between the control group and the brachial plexus uninjured limb revealed a difference for the median (p = 0.0074), radial (p = 0.0185), ulnar (p = 0.0404), and MABC (p = 0.0328) PEIs. After splitting the sample into two groups with respect to the dominance of the injured limb, higher threshold values were found for the uninjured side when it occurred in the right dominant limb compared to the control group at the median (p = 0.0456), radial (p = 0.0096), and MABC (p = 0.0078) PEIs. This effect was absent for the left, non-dominant arm. To assess the effect of the severity of sensory deficits observed in the injured limb upon the alterations of the uninjured limb, a K-means clustering algorithm (k = 2) was applied resulting in two groups with less or more severe sensory impairment. The less severely affected patients presented higher thresholds at the median (p = 0.0189), radial (p = 0.0081), ulnar (p = 0.0253), and MABC (p = 0.0187) PEIs in the uninjured limb in comparison with the control group, whereas higher thresholds at the uninjured limb were found only for the median PEI (p = 0.0457) in the more severely affected group. In conclusion, an expressive reduction in touch threshold was found for the injured limb allowing a precise mapping of the impairment caused by the BPI. Crucially, BPI also led to reduced tactile threshold in specific PEIs in the uninjured upper limb. These new findings suggest a superordinate model of representational plasticity occurring bilaterally in the brain after a unilateral peripheral injury.

Dataset Information

Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion.

Publications

Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion.

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