Time-Dependent Central Compensatory Mechanisms of Finger Dexterity After Spinal Cord Injury

Nishimura, Yukio; Onoe, Hirotaka; Morichika, Yosuke; Perfiliev, S.; Tsukada, Hideo; Isa, Tadashi

doi:10.1126/science.1147243

Cited by 217 publications

(238 citation statements)

References 29 publications

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“…The present behavioral tests, used since several years in our laboratory to quantify manual dexterity, are to some extent comparable to other tests of manual dexterity recently reported in the literature [24][25][26][27][28] . There is however a crucial need to standardize tests across different laboratories (for better comparison), which is a tentative goal of the present report.…”

Section: Figuresupporting

confidence: 50%

Behavioral Assessment of Manual Dexterity in Non-Human Primates

Schmidlin¹,

Kaeser²,

Gindrat³

et al. 2011

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The corticospinal (CS) tract is the anatomical support of the exquisite motor ability to skillfully manipulate small objects, a prerogative mainly of primates 1 . In case of lesion affecting the CS projection system at its origin (lesion of motor cortical areas) or along its trajectory (cervical cord lesion), there is a dramatic loss of manual dexterity (hand paralysis), as seen in some tetraplegic or hemiplegic patients. Although there is some spontaneous functional recovery after such lesion, it remains very limited in the adult. Various therapeutic strategies are presently proposed (e.g. cell therapy, neutralization of inhibitory axonal growth molecules, application of growth factors, etc), which are mostly developed in rodents. However, before clinical application, it is often recommended to test the feasibility, efficacy, and security of the treatment in non-human primates. This is especially true when the goal is to restore manual dexterity after a lesion of the central nervous system, as the organization of the motor system of rodents is different from that of primates 1,2 . Macaque monkeys are illustrated here as a suitable behavioral model to quantify manual dexterity in primates, to reflect the deficits resulting from lesion of the motor cortex or cervical cord for instance, measure the extent of spontaneous functional recovery and, when a treatment is applied, evaluate how much it can enhance the functional recovery.The behavioral assessment of manual dexterity is based on four distinct, complementary, reach and grasp manual tasks (use of precision grip to grasp pellets), requiring an initial training of adult macaque monkeys. The preparation of the animals is demonstrated, as well as the positioning with respect to the behavioral set-up. The performance of a typical monkey is illustrated for each task. The collection and analysis of relevant parameters reflecting precise hand manipulation, as well as the control of force, are explained and demonstrated with representative results. These data are placed then in a broader context, showing how the behavioral data can be exploited to investigate the impact of a spinal cord lesion or of a lesion of the motor cortex and to what extent a treatment may enhance the spontaneous functional recovery, by comparing different groups of monkeys (treated versus sham treated for instance). Advantages and limitations of the behavioral tests are discussed. The present behavioral approach is in line with previous reports emphasizing the pertinence of the non-human primate model in the context of nervous system diseases 2,3 . Video LinkThe video component of this article can be found at https://www.jove.com/video/3258/ ProtocolThe overall scheme of the experiment is depicted in Figure 1. Animal preparation and transfer to the behavioral laboratory1. In the laboratory, prepare the behavioral set-up: fill the wells of the different test boards (tests 1 to 3 below) with the pellets, which serve as reward during the behavioral tests. 2. Transfer the monkey from...

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Section: Figuresupporting

confidence: 50%

Behavioral Assessment of Manual Dexterity in Non-Human Primates

Schmidlin¹,

Kaeser²,

Gindrat³

et al. 2011

JoVE

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“…Indeed, regional correlations of glucose metabolism at rest between brain regions have been shown to be lower in long-term treated, older hypertensive relative to normotensive participants. 37 Observations supporting a compensation interpretation are as follows: (1) concurrent activation of disparate but task-relevant brain regions characterizes compensation 38,39 ; (2) compensatory changes within hippocampal circuits are documented in the animal literature 40 ; and (3) enhanced posttreatment correlations were not maladaptive in that cognitive performance was maintained or increased across our treatment period (data not shown). Our measures lack the resolution, however, to specifically relate our results to those in the animal literature (in which compensation can more readily be demonstrated).…”

Section: Discussionmentioning

confidence: 86%

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

et al. 2008

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Abstract-Hypertension is associated with mild decrements in cognition. In addition, regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults, who, compared with normotensive subjects, manifest greater correlation in blood flow response across task-related brain regions. Here, we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class. Treatment with lisinopril, an angiotensinconverting enzyme blocker, known to enhance vasodilative responsivity, was compared with treatment with atenolol, a ␤-blocker. Untreated hypertensive volunteers (nϭ28) were randomly assigned and treated for 1 year. Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide, a vasodilator, were assessed pretreatment and posttreatment. Peripheral brachial artery dilation during reactive hyperemia was also measured. Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection. Brachial artery flow-mediated dilation increased with treatment. No differences between medications were observed. In brain regions active in memory processing, however, regional cerebral blood flow responses were more highly correlated after treatment. Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension. This greater correlation among active brain regions, which is present as well in untreated hypertensive relative to normotensive volunteers, may represent compensation in the face of less region-specific responsivity in individuals with hypertension. M ild-to-moderate hypertension is associated with minor deficits in cognition. [1][2][3][4] Brain structure or function might account for these deficits. [5][6][7][8] Cognitive processing elicits a regional redistribution of blood flow, providing metabolic support to active neural areas. 9 Interference with this redistribution, blunting of regional blood flow, or structural loss because of poor perfusion might underlie the deficits of hypertensive individuals. Limited existing evidence supports all of these possibilities. [5][6][7][8]10 We demonstrated that, compared with normotensive individuals, those with hypertension have damped regional cerebral blood flow (CBF; rCBF) responses in parietal and thalamic areas (regions of interest [ROI]) during working memory tasks and greater correlation among rCBF responses across task-related regions. 7 Both observations might be because of a cerebrovascular adaptation to hypertension, most particularly, the remodeling of walls of small arteries, ie, thickening of the medial layer with or without a change in lumen diameter. 7 Antihypertensive medications have established influences on peripheral vascular function and may have similar effects on cerebrovascular...

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“…22-24, 30, 32, 135-138; Figure 2; and Figure 3, B and C). Functional studies show that relay circuits formed between supraspinal pathways and descending propriospinal neurons can relay supraspinal commands that control voluntary locomotion in rodents (31), and can mediate fine finger movements in nonhuman primates (138)(139)(140). Such observations provide a rationale for repair strategies that seek either to augment spontaneous relay circuit formation and efficacy after incomplete SCI ( Figure 3B), or to restore short-distance neural connectivity across anatomically complete SCI lesions ( Figure 3C).…”

Section: R E V I E W S E R I E S : G L I a A N D N E U R O D E G E N mentioning

confidence: 99%