Biomedical subjects

Jaimie F Borisoff

Publications and source records attributed to Jaimie F Borisoff.

10 recordsLinked to original sources

PubMed2006

Protracted myelin clearance hinders central primary afferent regeneration following dorsal rhizotomy and delayed neurotrophin-3 treatment.

Regeneration within or into the CNS is thwarted by glial inhibition at the site of a spinal cord injury and at the dorsal root entry zone (DREZ), respectively. At the DREZ, injured axons and their distal targets are separated by degenerating myelin and an astrocytic glia limitans. The different glial barriers to regeneration following dorsal rhizotomy are temporally and spatially distinct. The more peripheral astrocytic barrier develops first, and is surmountable by neurotrophin-3 (NT-3) treatment; the more central myelin-derived barrier, which prevents dorsal horn re-innervation by NT-3-treated axons, becomes significant only after the onset of myelin degeneration. Here we test the hypothesis that in the presence of NT-3, axonal regeneration is hindered by myelin degeneration products. To do so, we used the Long Evans Shaker (LES) rat, in which oligodendrocytes do not make CNS myelin, but do produce myelin-derived inhibitory proteins. We show that delaying NT-3 treatment for 1 week in normal (LE) rats, while allowing axonal penetration of the glia limitans and growth within degenerating myelin, results in misdirected regeneration with axons curling around presumptive degenerating myelin ovoids within the CNS compartment of the dorsal root. In contrast, delaying NT-3 treatment in LES rats resulted in straighter, centrally-directed regenerating axons. These results indicate that regeneration may be best optimized through a combination of neurotrophin treatment plus complete clearance of myelin debris.

Afferent Pathways↗

PubMed2006

Detection and classification of sensory information from acute spinal cord recordings.

One avenue of research for partial restoration of function following spinal cord injury is the use of neural prostheses, an example of which is functional electrical stimulation (FES) devices for motor functions. Neural prostheses may also be useful for the extraction of sensory information directly from the nervous system. We suggest the spinal cord as a possible site for the detection of peripheral sensory information from neural activity alone. Acute multichannel extracellular recordings were used to extract neural spike activity elicited from peripheral sensations from the spinal cords of rats. To test the recording method and classification potential, eight classes of sensory events were recorded consisting of electrical stimulation of seven locations on rat forepaws, and another class of data during which no stimulus was present. A dual-stage classification scheme using principal component analysis and k-Means clustering was devised to classify the sensory events during single trials. The eight tasks were correctly identified at a mean accuracy of 96%. Thus, we have shown the methodology to detect and classify peripheral sensory information from multichannel recordings of the spinal cord. These methods may be useful, for example, in a closed-loop FES for restoration of hand grasp.

Action Potentials↗

PubMed2006

Brain interface research for asynchronous control applications.

The Neil Squire Society has developed asynchronous, direct brain switches for self-paced control applications with mean activation rates of 73% and false positive error rates of 2%. This report summarizes our results to date, lessons learned, and current directions, including research into implanted brain interface designs.

Algorithms↗

PubMed2005

Deafferentation and neurotrophin-mediated intraspinal sprouting: a central role for the p75 neurotrophin receptor.

Axonal plasticity in the adult spinal cord is governed by intrinsic neuronal growth potential and by extracellular cues. The p75 receptor (p75(NTR)) binds growth-promoting neurotrophins (NTs) as well as the common receptor for growth-inhibiting myelin-derived proteins (the Nogo receptor) and so is well situated to gauge the balance of positive and negative influences on axonal plasticity. Using transgenic mice lacking the extracellular NT-binding domain of p75(NTR) (p75-/- mice), we have examined the influence of p75(NTR) on changes in the density of primary afferent (calcitonin gene-related peptide-expressing) and descending monoaminergic (serotonin- and tyrosine hydroxylase-expressing) projections to the dorsal horn after dorsal rhizotomy, with and without concomitant application of exogenous nerve growth factor and NT-3. We found that, in intact p75-/- mice, the axon density of all populations was equal to or less than that in wild-type mice but that rhizotomy-induced intraspinal sprouting was significantly augmented. Monoaminergic axon sprouting was enhanced in both nerve growth factor- and NT-3-treated p75-/- mice compared with similarly treated wild-type mice. Primary afferent sprouting was particularly robust in NT-3-treated p75-/- mice. These in vivo results illustrate the interactions of p75(NTR) with NTs, with their respective tropomyosin-related kinase receptors and with inhibitory myelin-derived molecules. Our findings illustrate the pivotal role of p75(NTR) in spinal axonal plasticity and identify it as a potential therapeutic target for spinal cord injury.

Afferent Pathways↗

PubMed2004

Rho-kinase inhibition enhances axonal plasticity and attenuates cold hyperalgesia after dorsal rhizotomy.

Dorsal rhizotomy results in primary deafferentation of the dorsal horn with concomitant sprouting of spared intraspinal monoaminergic axons. Because descending monoaminergic systems are thought to mitigate nociceptive transmission from the periphery and because dorsal rhizotomy can result in neuropathic pain, we sought to determine whether the rhizotomy-induced sprouting response could be further augmented. Because myelin-derived molecules mask endogenous plasticity of CNS axons and because myelin-inhibitory signaling occurs through the Rho-GTPase pathway, we inhibited Rho-pathway signaling after cervical dorsal rhizotomy in rats. An increase in the density of serotonergic- and tyrosine hydroxylase-positive fibers was seen in the dorsal horn 1 week after septuple rhizotomy, and axon density continued to increase for at least 1 month. One week after septuple rhizotomy, administration of intrathecal Y-27632, an antagonist of Rho-kinase (ROCK), increased the density of both fiber types over vehicle-treated controls. To examine behavioral effects of both cervical rhizotomy and ROCK inhibition, we examined responses to evoked pain: mechanical and thermal allodynia and cold hyperalgesia in the forepaw were examined after single, double, and quadruple rhizotomies of dorsal roots of the brachial plexus. The most notable behavioral outcome was the development of cold hyperalgesia in the affected forepaw after rhizotomies of the C7 and C8 dorsal roots. Application of Y-27632 both attenuated cold hyperalgesia and induced monoaminergic plasticity after C7/8 rhizotomy. Thus, inhibition of Rho-pathway signaling both promoted the sprouting of intact supraspinal monoaminergic fibers and alleviated pain after dorsal rhizotomy.

Amides↗

PubMed2004

Brain-computer interface design for asynchronous control applications: improvements to the LF-ASD asynchronous brain switch.

The low-frequency asynchronous switch design (LF-ASD) was introduced as a direct brain-computer interface (BCI) technology for asynchronous control applications. The LF-ASD operates as an asynchronous brain switch (ABS) which is activated only when a user intends control and maintains an inactive state output when the user is not meaning to control the device (i.e., they may be idle, thinking about a problem, or performing some other action). Results from LF-ASD evaluations have shown promise, although the reported error rates are too high for most practical applications. This paper presents the evaluation of four new LF-ASD designs with data collected from individuals with high-level spinal cord injuries and able-bodied subjects. These new designs incorporated electroencephalographic energy normalization and feature space dimensionality reduction. The error characteristics of the new ABS designs were significantly better than the LF-ASD design with true positive rate increases of approximately 33% for false positive rates in the range of 1%-2%. The results demonstrate that the dimensionality of the LF-ASD feature space can be reduced without performance degradation. The results also confirm previous findings that spinal cord-injured subjects can operate ABS designs to the same ability as able-bodied subjects.

Adult↗

PubMed2003

Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates.

Several molecules inhibit axonal growth cones and may account for the failure of central nervous system regeneration, including myelin proteins and various chondroitan sulfate proteoglycans expressed at the site of injury. Axonal growth inhibition by myelin and chondroitan sulfate proteoglycans may in part be controlled by Rho-GTPase, which mediates growth cone collapse. Here, we tested in vitro whether pharmacological inhibition of a major downstream effector of Rho, Rho-kinase, promotes axonal outgrowth from dorsal root ganglia grown on aggrecan. Aggrecan substrates stimulated Rho activity and were inhibitory to axonal growth. Y-27632 treatment promoted the growth of axons by 5- to 10-fold and induced "steamlined" growth cones with longer filopodia and smaller lamellipodia. Interestingly, more actin bundles reminiscent of stress fibers in the central domain of the growth cone were observed when grown on aggrecan compared to laminin. In addition, Y-27632 significantly promoted axonal growth on both myelin and adult rat spinal cord cryosections. Our data suggest that suppression of Rho-kinase activity may enhance axonal regeneration in the central nervous system.

Aggrecans↗

PubMed2003

Current trends in brain-computer interface research at the Neil Squire Foundation.

The Neil Squire Foundation (NSF) is a Canadian nonprofit organization whose purpose is to create opportunities for independence for individuals who have significant physical disabilities. Over the last ten years, our team in partnership with researchers at the Electrical and Computer Engineering Department, the University of British Columbia, has been working to develop a direct brain-controlled switch for individuals with significant physical disabilities. The NSF Brain Interface Project primarily focuses on the development of brain-computer interface switch technologies for intermittent (or asynchronous) control in natural environments. That is, technologies that will work when the User intends control but also remains in a stable off state when there is no intent to control. A prototype of such a switch has successfully been developed. This switch has demonstrated classification accuracies greater than 94%. The initial results are promising, but further research is required to improve switch accuracies and reliability and to test these switch technologies over a larger population of users and operating conditions. This paper provides an overview of the NSF brain-switch technologies and details our approach to future work in this area.

Adult↗

PubMed2002

Molecular targets for therapeutic intervention after spinal cord injury.

In an effort to develop therapies for promoting neurological recovery after spinal cord injury, much work has been done to identify the cellular and molecular factors that control axonal regeneration within the injured central nervous system. This review summarizes the current understanding of a number of the elements within the spinal cord environment that inhibit axonal growth and outlines the factors that influence the neuron's ability to regenerate its axon after injury. Recent insights in these areas have identified important molecular pathways that are potential targets for therapeutic intervention, raising hope for victims of spinal cord injury.

Animals↗

PubMedDate not supplied

Real-time control of a video game with a direct brain--computer interface.

Mason and Birch have developed a direct brain-computer interface for intermittent control of devices such as environmental control systems and neuroprotheses. This EEG-based brain switch, named the LF-ASD, has been used in several off-line studies, but little is known about its usability with real-world devices and computer applications. In this study, able-bodied individuals and people with high-level spinal injury used the LF-ASD brain switch to control a video game in real time. Both subject groups demonstrated switch activations varying from 30% to 78% and false-positive rates in the range of 0.5% to 2.2% over three 1-hour test sessions. These levels correspond to switch classification accuracies greater than 94% for all subjects. The results suggest that subjects with spinal cord injuries can operate the brain switch to the same ability as able-bodied subjects in a real-time control environment. These results support the findings of previous studies.

Adult↗