Frontal and frontoparietal injury differentially affect the ipsilateral corticospinal projection from the nonlesioned hemisphere in monkey (Macaca mulatta)

Abstract

Upper extremity hemiplegia is a common consequence of unilateral cortical stroke. Understanding the role of the unaffected cerebral hemisphere in the motor recovery process has been encouraged, in part, by the presence of ipsilateral corticospinal projections. We examined the neuroplastic response of the ipsilateral corticospinal projection (iCSP) from the contralesional primary motor cortex (cM1) hand/arm area to spinal levels C5-T1 after spontaneous long-term recovery from isolated frontal lobe injury and isolated frontoparietal injury. High-resolution tract tracing, stereological, and behavioral methodologies were applied. Recovery from frontal motor injury resulted in enhanced numbers of terminal labeled boutons in the iCSP from cM1 compared to controls. Increases occurred in lamina VIII and the adjacent ventral sectors of lamina VII, which are involved in axial/proximal limb sensorimotor processing. Larger frontal lobe lesions were associated with greater numbers of terminal boutons than smaller frontal lobe lesions. In contrast, frontoparietal injury blocked this response, as total bouton number was similar to controls, demonstrating that disruption of somatosensory input to one hemisphere has a suppressive effect on the iCSP from the non-lesioned hemisphere. However, compared to controls, elevated bouton numbers occurred in lamina VIII, at the expense of lamina VII bouton labeling. Lamina IX boutons were also elevated in two frontoparietal lesion cases with extensive cortical injury. Since lamina VIII and IX collectively harbor axial, proximal, and distal motoneurons, therapeutic intervention targeting the ipsilateral corticospinal linkage from cM1 may promote proximal, and possibly distal, upper limb motor recovery following frontal and frontoparietal injury.

Role of primary motor cortex in the control of manual dexterity assessed via sequential bilateral lesion in the adult macaque monkey: A case study

“…Moreover, reversible inactivation with a low dose of muscimol does not allow for the observation of the effects of long-term inactivation of intact M1. In both studies (Liu and Rouiller, 1999;present study), the possibility that a contribution of the intact M1 in the functional recovery after unilateral M1 lesion was not observed may be due to the moderate size of the primary M1 lesion, leaving open the possibility that recovery from a larger lesion may possibly involve intact M1, as suggested in previous reports (Liu and Rouiller, 1999;Biernaskie et al, 2005) and supported by a recent tract-tracing study in monkeys subjected to large unilateral cortical lesion (Morecraft et al, 2016).…”

“…These data suggest that the size of the unilateral M1 lesion may trigger different mechanisms of recovery, involving or not the intact M1. As reported recently (Morecraft et al, 2016), the size of the lesion in the frontal lobe as well as the spread of the lesion in the parietal lobe determined the degree of impact of the intact contralesional M1 in the functional recovery in rhesus monkeys. Nevertheless, the notion that the intact contralesional M1 provides systematic, full, and direct support for the spontaneous functional recovery occurring following a stroke appears to be controversial, albeit there is evidence supporting an additional contribution of the intact M1 to that of ipsilesional non-primary motor areas (Jaillard et al, 2005;Dancause, 2006;Dancause et al, 2015).…”

“…A plastic reorganization of neural circuits, involving non-primary motor areas, has been shown to take place (Dancause et al, 2005;McNeal et al, 2010;Hamadjida et al, 2012). There is recent evidence for a cortical somatosensory influence on the mechanisms of functional recovery after frontal lobe lesion including M1 (Morecraft et al, 2015(Morecraft et al, , 2016.…”

“…Rizzolatti and Luppino, 2001;Shelton and Reding, 2001;Olivier et al, 2007;Brown and Teskey, 2014). In monkeys, alterations of hand movements have been reported after unilateral transient inactivation or permanent lesion of M1 followed by the occurrence of compensatory strategies, affecting motor parameters such as force (Brochier et al, 1999), trajectory (Cirstea and Levin, 2000), precision grip (Brochier et al, 1999;Darling et al, 2009Darling et al, , 2011bDarling et al, , 2013Darling et al, , 2014Kermadi et al, 1997;Liu and Rouiller, 1999;Kaeser et al, 2010;Hoogewoud et al, 2013;Morecraft et al, 2015Morecraft et al, , 2016Wyss et al, 2013;Murata et al, 2015), flexion-extension (Schieber and Poliakov, 1998) and wrist movement (Hoffman and Strick, 1995). Depending on the size and location of the injury, spontaneous recovery occurs to a variable extent, though it is generally incomplete.…”

Motor compensation and its effects on neural reorganization after stroke

“…Surviving cortical neurons of the injured hemisphere can also contribute to the re-innervation of the same targets 97,98,115 . In macaques, the sprouting of ipsilesional and contralesional projections into denervated regions of the spinal cord has been found to vary depending on cortical lesion size and territory 175 . The relative importance of the two sources of re-innervation has not been thoroughly dissected.…”