Biomedical subjects

Scott Barbay

Publications and source records attributed to Scott Barbay.

14 recordsLinked to original sources

PubMed2006

Effects of small ischemic lesions in the primary motor cortex on neurophysiological organization in ventral premotor cortex.

After a cortical lesion, cortical areas distant from the site of injury are known to undergo physiological and anatomical changes. However, the mechanisms through which reorganization of distant cortical areas is initiated are poorly understood. In a previous publication, we showed that the ventral premotor cortex (PMv) undergoes physiological reorganization after a lesion destroying the majority of the primary motor cortex (M1) distal forelimb representation (DFL). After large lesions destroying >50% of the M1 DFL, the PMv DFL invariably increased in size, and the amount of the increase was positively correlated with the size of lesion. To determine whether lesions destroying <50% of the M1 DFL followed a similar trajectory, we documented PMv reorganization using intracortical microstimulation techniques after small, ischemic lesions targeting subregions within the M1 DFL. In contrast to earlier results, lesions resulted in a reduction of the PMv DFL regardless of their location. Further, because recent anatomical findings suggest a segregation of PMv connectivity with M1, we examined two lesion characteristics that may drive alterations in PMv physiological reorganization: location of the lesion with respect to PMv connectivity and relative size of the lesion. The results suggest that after a lesion in the M1 DFL, the induction of representational plasticity in PMv, as evaluated using intracortical microstimulation, is related more to the size of the lesion than to the disruption of its intracortical connections.

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PubMed2006

VEGF protein associates to neurons in remote regions following cortical infarct.

Vascular endothelial growth factor (VEGF) is thought to contribute to both neuroprotection and angiogenesis after stroke. While increased expression of VEGF has been demonstrated in animal models after experimental ischemia, these studies have focused almost exclusively on the infarct and peri-infarct regions. The present study investigated the association of VEGF to neurons in remote cortical areas at three days after an infarct in primary motor cortex (M1). Although these remote areas are outside of the direct influence of the ischemic injury, remote plasticity has been implicated in recovery of function. For this study, intracortical microstimulation techniques identified primary and premotor cortical areas in a non-human primate. A focal ischemic infarct was induced in the M1 hand representation, and neurons and VEGF protein were identified using immunohistochemical procedures. Stereological techniques quantitatively assessed neuronal-VEGF association in the infarct and peri-infarct regions, M1 hindlimb, M1 orofacial, and ventral premotor hand representations, as well as non-motor control regions. The results indicate that VEGF protein significantly increased association to neurons in specific remote cortical areas outside of the infarct and peri-infarct regions. The increased association of VEGF to neurons was restricted to cortical areas that are functionally and/or behaviorally related to the area of infarct. There was no significant increase in M1 orofacial region or in non-motor control regions. We hypothesize that enhancement of neuronal VEGF in these functionally related remote cortical areas may be involved in recovery of function after stroke, through either neuroprotection or the induction of remote angiogenesis.

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PubMed2006

Ipsilateral connections of the ventral premotor cortex in a new world primate.

The present study describes the pattern of connections of the ventral premotor cortex (PMv) with various cortical regions of the ipsilateral hemisphere in adult squirrel monkeys. Particularly, we 1) quantified the proportion of inputs and outputs that the PMv distal forelimb representation shares with other areas in the ipsilateral cortex and 2) defined the pattern of PMv connections with respect to the location of the distal forelimb representation in primary motor cortex (M1), primary somatosensory cortex (S1), and supplementary motor area (SMA). Intracortical microstimulation techniques (ICMS) were used in four experimentally naïve monkeys to identify M1, PMv, and SMA forelimb movement representations. Multiunit recording techniques and myelin staining were used to identify the S1 hand representation. Then, biotinylated dextran amine (BDA; 10,000 MW) was injected in the center of the PMv distal forelimb representation. After tangential sectioning, the distribution of BDA-labeled cell bodies and terminal boutons was documented. In M1, labeling followed a rostrolateral pattern, largely leaving the caudomedial M1 unlabeled. Quantification of somata and terminals showed that two areas share major connections with PMv: M1 and frontal areas immediately rostral to PMv, designated as frontal rostral area (FR). Connections with this latter region have not been described previously. Moderate connections were found with PMd, SMA, anterior operculum, and posterior operculum/inferior parietal area. Minor connections were found with diverse areas of the precentral and parietal cortex, including S1. No statistical difference between the proportions of inputs and outputs for any location was observed, supporting the reciprocity of PMv intracortical connections.

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PubMed2006

An animal model of capsular infarct: endothelin-1 injections in the rat.

In this study stereotaxic injections of the vasoconstrictive peptide endothelin-1 (ET-1) were used to create infarcts in the white matter of the internal capsule underlying sensorimotor cortex in rats. Resulting deficits were assessed using established sensorimotor tests conducted on each rat before and after the ET-1-induced infarct. After a 14-day survival period, histological examination revealed tissue necrosis and demyelination in the infarcted white matter of ET-1-injected rats, but not saline-injected control rats. Infarcts resulted in measurable sensorimotor deficits in rats that received ET-1 injections. The same sensorimotor tests showed no deficits in surgical-control rats. The present model of white matter infarct should be valuable in examining the underlying mechanisms of subcortical ischemic stroke and to evaluate potential therapeutic interventions.

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PubMed2006

A single injection of D-amphetamine facilitates improvements in motor training following a focal cortical infarct in squirrel monkeys.

BACKGROUND: There is growing interest in the use of D-amphetamine (D-AMPH) as a pharmacological treatment to supplement rehabilitative therapy following stroke. Based on the success of earlier animal models, several clinical studies have demonstrated beneficial effects of applying physical rehabilitation while stroke patients are under the influence of D-AMPH. To begin to understand the neural mechanisms underlying this promising adjuvant therapy, the authors examined the effects of a single pairing of D-AMPH and rehabilitative training on motor performance after cortical infarct in squirrel monkeys. METHODS: Microelectrode stimulation techniques were used to delineate hand movement areas in the primary motor cortex prior to delivering a unilateral infarct to the complete hand representation. Postinfarct recovery was assessed for 3 groups of monkeys: D-AMPH + training, saline + training, and spontaneous recovery (SR). Postinfarct training groups received 14 consecutive days of motor skill training on a reach and retrieval task. A single injection of D-AMPH (0.25 mg/kg) or saline was given only on the 1st day of training (postinfarct day 10). Monkeys in the SR group had only minimal exposure to the training task once per week to monitor recovery. RESULTS: The results show that a single coupling of D-AMPH + training initiated 10 days after cortical infarct facilitated the rate of recovery and improved performance (68% improvement from 1st day of training) beyond the level achieved by the monkeys in the saline + training group (27% improved from 1st day of training). CONCLUSIONS: D-AMPH is a potent modulator of behavioral recovery following an ischemic infarct in nonhuman primates.

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PubMed2005

Behavioral and neurophysiological effects of delayed training following a small ischemic infarct in primary motor cortex of squirrel monkeys.

A focal injury within the cerebral cortex results in functional reorganization within the spared cortex through time-dependent metabolic and physiological reactions. Physiological changes are also associated with specific post-injury behavioral experiences. Knowing how these factors interact can be beneficial in planning rehabilitative intervention after a stroke. The purpose of this study was to assess the functional impact of delaying the rehabilitative behavioral experience upon movement representations within the primary motor cortex (M1) in an established nonhuman primate, ischemic infarct model. Five adult squirrel monkeys were trained on a motor-skill task prior to and 1 month after an experimental ischemic infarct was induced in M1. Movement representations of the hand were derived within M1 using standard electrophysiological procedures prior to the infarct and again one and two months after the infarct. The results of this study show that even though recovery of motor skills was similar to that of a previous study in squirrel monkeys after early training, unlike early training, delayed training did not result in maintenance of the spared hand representation within the M1 peri-infarct hand area. Instead, delaying training resulted in a large decrease in spared hand representation during the spontaneous recovery period that persisted following the delayed training. In addition, delayed training resulted in an increase of simultaneously evoked movements that are typically independent. These results indicate that post-injury behavioral experience, such as motor skill training, may modulate peri-infarct cortical plasticity in different ways in the acute versus chronic stages following stroke.

Analysis of Variance↗

PubMed2005

Extensive cortical rewiring after brain injury.

Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

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PubMed2005

Topographically divergent and convergent connectivity between premotor and primary motor cortex.

This study was undertaken to determine the topographic organization of connections between the forelimb representations of the ventral premotor cortex (PMv) and the primary motor cortex (M1). Intracortical microstimulation techniques were used in three experimentally naive squirrel monkeys to delineate the M1 and PMv forelimb representations in the hemisphere contralateral to the dominant hand. Small amounts of biotinylated dextran amine (BDA) were then injected in the PMv distal forelimb representation. Following tangential sectioning, the location of the injection core in PMv and BDA-labeled cell bodies and synaptic boutons in M1 were documented in relation to functional topography. Whereas the injection core was mainly located within the distal forelimb representation in PMv, BDA-labeled cell bodies and terminals were distributed over comparable proportions of proximal and distal forelimb representations in M1. These results suggest that neuronal populations within PMv send topographically divergent outputs to M1 and receive topographically convergent inputs from M1. Finally, we found that PMv projections to M1 were not evenly distributed but rather were directed consistently to three domains within the rostro-lateral portion of M1. To our knowledge, this is the first description of such a consistent clustering of PMv terminals within M1.

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PubMed2005

Dissociation of sensorimotor deficits after rostral versus caudal lesions in the primary motor cortex hand representation.

Primary motor cortex (M1) has traditionally been considered a motor structure. Although neurophysiologic studies have demonstrated that M1 is also influenced by somatosensory inputs (cutaneous and proprioceptive), the behavioral significance of these inputs has yet to be fully defined in primates. The present study describes differential sensory-related deficits after small ischemic lesions in either the rostral or caudal subregion of the M1 hand area in a nonhuman primate. Squirrel monkeys retrieved food pellets out of different sized wells drilled into a Plexiglas board. Before the lesion, monkeys retrieved pellets by directing the hand to the well, inserting fingers directly into it, and extracting the pellet. After a lesion to the rostral portion of M1, monkeys frequently failed to direct the hand accurately to the well. Instead, fingers contacted the surface of the board outside the well before entering the well. These aiming errors are consistent with both the large amount of proximal motor outputs and the predominant proprioceptive inputs of rostral M1. Overall, these aiming errors are suggestive of dysfunctional processing of proprioceptive information or the failure to integrate proprioceptive information with motor commands. In contrast, after a lesion to the caudal portion of M1, monkeys frequently examined their palm visually for the presence of the pellet after an attempted retrieval. These errors are consistent with both the large amount of distal motor outputs and the predominant cutaneous inputs of caudal M1. Thus these errors are suggestive of a deficit in processing of cutaneous information or the failure to integrate cutaneous information with motor commands. Rostral and caudal M1 lesions result in different deficits in sensory-dependent motor control that appear to correlate with broad segregation of motor outputs and previously described sensory inputs of M1.

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PubMed2003

A squirrel monkey model of poststroke motor recovery.

Nonhuman primate models of poststroke recovery have become increasingly rare primarily due to high purchase and maintenance costs and limited availability of nonhuman primate species. Despite this obstacle, nonhuman primate models may offer important advantages over rodent models for understanding many of the brain's mechanisms for self-repair due to greater similarity in cortical organization to humans. Since the mid-1990s, surgical, neurophysiological, and neuroanatomical methods have been developed to understand structural and functional remodeling of the cerebral cortex after an ischemic event, such as occurs in stroke. These methods require long surgical procedures and entail constant physiological monitoring. With careful attention to intraoperative and postsurgical monitoring, these procedures can be repeated multiple times in individual monkeys without untoward events. This model provides a statistically powerful approach for tracking brain plasticity in the ensuing weeks and months after a stroke-like injury, reducing the number of animals required for individual experiments. This methodology is described in detail, and many of the resulting findings that are relevant for understanding stroke recovery and the effects of rehabilitative and pharmacotherapeutic interventions are summarized.

Animals↗

PubMed2003

Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: a feasibility study in primates.

Stroke is often characterized by incomplete recovery and chronic motor impairments. A nonhuman primate model of cortical ischemia was used to evaluate the feasibility of using device-assisted cortical stimulation combined with rehabilitative training to enhance behavioral recovery and cortical plasticity. Following pre-infarct training on a unimanual motor task, maps of movement representations in primary motor cortex were derived. Then, an ischemic infarct was produced which destroyed the hand representation. Several weeks later, a second cortical map was derived to guide implantation of a surface electrode over peri-infarct motor cortex. After several months of spontaneous recovery, monkeys underwent subthreshold electrical stimulation combined with rehabilitative training for several weeks. Post-therapy behavioral performance was tracked for several additional months. A third cortical map was derived several weeks post-therapy to examine changes in motor representations. Monkeys showed significant improvements in motor performance (success, speed, and efficiency) following therapy, which persisted for several months. Cortical mapping revealed large-scale emergence of new hand representations in peri-infarct motor cortex, primarily in cortical tissue underlying the electrode. Results support the feasibility of using a therapy approach combining peri-infarct electrical stimulation with rehabilitative training to alleviate chronic motor deficits and promote recovery from cortical ischemic injury.

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PubMed2002

Motor learning-dependent synaptogenesis is localized to functionally reorganized motor cortex.

The regional specificity and functional significance of learning-dependent synaptogenesis within physiologically defined regions of the adult motor cortex are described. In comparison to rats in a motor activity control group, rats trained on a skilled reaching task exhibited an areal expansion of wrist and digit movement representations within the motor cortex. No expansion of hindlimb representations was seen. This functional reorganization was restricted to the caudal forelimb area, as no differences in the topography of movement representations were observed within the rostral forelimb area. Paralleling the physiological changes, trained animals also had significantly more synapses per neuron than controls within layer V of the caudal forelimb area. No differences in the number of synapses per neuron were found in either the rostral forelimb or hindlimb areas. This is the first demonstration of the co-occurrence of functional and structural plasticity within the same cortical regions and provides strong evidence that synapse formation may play a role in supporting learning-dependent changes in cortical function.

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PubMed2002

An index of topographic normality in rat somatosensory cortex: application to a sciatic nerve crush model.

Previous studies have demonstrated that peripheral denervation of the skin is reflected in the CNS as a reorganization of somatotopic representations. In cases in which peripheral nerve regeneration occurs there is a gradual reactivation of cortex by novel receptive fields that is reversed as regenerated nerves reestablish connections with the original skin surface. Functional recovery appears to depend on the pattern in which somatotopic organization in the cortex is reestablished. The relationship between functional recovery and cortical topography is not precise, however, since the descriptions of postinjury representations in the cortex have been largely descriptive and not quantitative. The purpose of this study was to derive an index to quantify deviations from normal somatotopic organization in the somatosensory cortex. Multiunit recordings of cutaneous representations in the somatosensory cortex (S1) of the rat were defined using Semmes-Weinstein monofilaments to stimulate the skin over the distal hindlimb of the rat 2 and 4 months after a sciatic nerve crush. To derive a sensitive index of topography, the sciatic nerve crush was selected as the injury model since nerve regeneration following crush injuries has been reported to reinstate preinjury cortical topography. Group comparisons were made with an intact control group. The results show that there were subtle, but significant differences in topography between rats with a regenerated sciatic nerve and normal rats. In addition, average thresholds for evoking cortical responses were higher than normal (but within normal range) 2 and 4 months after the crush. These results demonstrate that the index of topography derived for this study can reveal deviations that may not be distinguishable from normal topography when based on qualitative descriptions.

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PubMedDate not supplied

Effects of a rostral motor cortex lesion on primary motor cortex hand representation topography in primates.

BACKGROUND: Small lesions to rostral versus caudal portions of the hand representation in the primary motor cortex (M1) produce different behavioral deficits. The goal of the present study was to determine if rehabilitative training has similar effects on functional topography of the spared M1 after rostral versus previously reported caudal M1 lesions. METHODS: Following a lesion to the rostral M1 hand area, monkeys were trained for 1 h/day for 30 days to retrieve food pellets from small wells using their impaired hand. Electrophysiological maps of the M1 were derived in anesthetized monkeys before infarct and after rehabilitative training using intracortical microstimulation. RESULTS: After a lesion to the rostral M1 and rehabilitative training, the size of the spared hand representation decreased 1.2%. This change is not statistically different from the 9% increase seen after caudal M1 lesion and rehabilitative training (P > 0.2). CONCLUSION: Postlesion training spares peri-infarct hand area regardless of whether the lesion is in the rostral or caudal M1.

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