Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats

Abstract

Unilateral damage to sensorimotor cortical (SMC) regions can profoundly impair skilled reaching function in the contralesional forelimb. Such damage also results in impairments and compensatory changes in the less-affected/ipsilesional forelimb, but these effects remain poorly understood. Furthermore, anesthetization of the ipsilesional hand in humans with cerebral infarcts has been reported to produce transient functional improvements in the paretic hand [14,48]. One aim of this study was to sensitively assay the bilateral effects of unilateral ischemic SMC damage on performance of a unimanual skilled reaching task (the single pellet retrieval task) that rats had acquired pre-operatively with each forelimb. The second aim was to determine whether partially recovered contralesional reaching function is influenced by anesthetization of the ipsilesional forelimb. Unilateral SMC lesions were found to result in transient ipsilesional impairments in reaching success and significant ipsilesional abnormalities in reaching movements compared with sham-operates. There were major contralesional reaching impairments which improved during a 4 week training period, but movements remained significantly abnormal. Anesthetization of the ipsilesional forelimb with lidocaine at this time attenuated the contralesional movement abnormalities. These findings indicate that unilateral ischemic SMC lesions impair skilled reaching behavior in both forelimbs. Furthermore, after partial recovery in the contralesional forelimb, additional improvements can be induced by transient anesthetization of the ipsilesional forelimb. This is consistent with the effects of unilateral anesthetization in humans which have been attributed to the modulation of competitive interhemispheric interactions. The present findings suggest that such interactions are also likely to influence skilled reaching function in rats.

Motor compensation and its effects on neural reorganization after stroke

“…In addition, disrupting the contralesional M1 or premotor cortex during the performance of more-complex motor tasks with the paretic hand disrupts the timing of movement with the paretic hand more so than it does in healthy controls 168 , suggesting that the contralesional hemisphere positively contributes to paretic hand function. Similarly contradictory roles of the contralesional hemisphere can be found in the animal literature 112,169–171 .…”

Maladaptive effects of learning with the less-affected forelimb after focal cortical infarcts in rats

“…This is consistent with there being subtle, interhemispheric motor learning interference effects that become exaggerated in rats with unilateral SMC lesions while re-learning to use the impaired forelimb. In both intact humans (Ward and Cohen, 2004) and rats (O'Bryant, Bernier, and Jones, 2007;Glazewski, Benedetti, and Barth, 2007), reduction in ipsilateral sensory activity has been found to improve function in the other body side. Sensory input from ipsilateral whiskers has been shown to result in a strong constraining influence on the receptive fields in the barrel field cortex (Glazewski, Benedetti, and Barth, 2007).…”

“…Sensory input from ipsilateral whiskers has been shown to result in a strong constraining influence on the receptive fields in the barrel field cortex (Glazewski, Benedetti, and Barth, 2007). Anesthetization of the less-affected hand improves performance of a finger tapping task with the paretic hand in stroke patients (Floel et al, 2004) and improves reaching function in the impaired forelimb in rats (O'Bryant, Bernier, and Jones, 2007). Moreover, the contralesional hemisphere can have an exaggerated inhibitory influence over the stroke-affected hemisphere during movements of the paretic hand compared with healthy subjects (Murase et al, 2004;Duque et al, 2005).…”

“…During movements of the paretic hand in humans with strokes, there is an abnormal interhemispheric inhibitory influence arising from the intact motor cortex (Murase et al, 2004;Duque et al, 2005). Anesthetization of the intact upper extremity in both humans (Voller et al, 2006) and rats (O'Bryant et al, 2007) transiently improves function in the stroke-impaired limb. These and related findings suggest that the intact hemisphere can negatively impact function of the impaired body side.…”

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

“…Motor impairments are among the most common and chronic consequences of stroke 25,26 , and are therefore the focus of a number of basic science research laboratories (e.g., [27][28][29][30][31][32] ). Skilled reaching tasks are the most commonly used tests of dexterous forelimb use in rodents, and have historically been most often used in rat models of injury (e.g., 11,19,28,33 ), although their use in mouse models is becoming quite frequent 34,35 .…”