Spinal cord injury therapy through active learning

Therapy employing epidural electrostimulation holds great potential for improving therapy for patients with spinal cord injury (SCI) (Harkema et al., 2011). Further promising results from combined therapies using electrostimulation have also been recently obtained (e.g., van den Brand et al., 2012). The devices being developed to deliver the stimulation are highly flexible, capable of delivering any individual stimulus among a combinatorially large set of stimuli (Gad et al., 2013). While this extreme flexibility is very useful for ensuring that the device can deliver an appropriate stimulus, the challenge of choosing good stimuli is quite substantial, even for expert human experimenters. To develop a fully implantable, autonomous device which can provide useful therapy, it is necessary to design an algorithmic method for choosing the stimulus parameters. Such a method can be used in a clinical setting, by caregivers who are not experts in the neurostimulator's use, and to allow the system to adapt autonomously between visits to the clinic. To create such an algorithm, this dissertation pursues the general class of active learning algorithms that includes Gaussian Process Upper Confidence Bound (GP-UCB, Srinivas et al., 2010), developing the Gaussian Process Batch Upper Confidence Bound (GP-BUCB, Desautels et al., 2012) and Gaussian Process Adaptive Upper Confidence Bound (GP-AUCB) algorithms. This dissertation develops new theoretical bounds for the performance of these and similar algorithms, empirically assesses these algorithms against a number of competitors in simulation, and applies a variant of the GP-BUCB algorithm in closed-loop to control SCI therapy via epidural electrostimulation in four live rats. The algorithm was tasked with maximizing the amplitude of evoked potentials in the rats' left tibialis anterior muscle. These experiments show that the algorithm is capable of directing these experiments sensibly, finding effective stimuli in all four animals. Further, in direct competition with an expert human experimenter, the algorithm produced superior performance in terms of average reward and comparable or superior performance in terms of maximum reward. These results indicate that variants of GP-BUCB may be suitable for autonomously directing SCI therapy.

Microelectrode Implants for Spinal Cord Stimulation in Rats

Paralysis is a debilitating condition afflicting millions of people across the globe, and is particularly deleterious to quality of life when motor function of the legs is severely impaired or completely absent. Fortunately, spinal cord stimulation has shown great potential for improving motor function after spinal cord injury and other pathological conditions. Many animal studies have shown stimulation of the neural networks in the spinal cord can improve motor ability so dramatically that the animals can even stand and step after a complete spinal cord transaction.

This thesis presents work to successfully provide a chronically implantable device for rats that greatly enhances the ability to control the site of spinal cord stimulation. This is achieved through the use of a parylene-C based microelectrode array, which enables a density of stimulation sites unattainable with conventional wire electrodes. While many microelectrode devices have been proposed in the past, the spinal cord is a particularly challenging environment due to the bending and movement it undergoes in a live animal. The developed microelectrode array is the first to have been implanted in vivo while retaining functionality for over a month. In doing so, different neural pathways can be selectively activated to facilitate standing and stepping in spinalized rats using various electrode combinations, and important differences in responses are observed.

An engineering challenge for the usability of any high density electrode array is connecting the numerous electrodes to a stimulation source. This thesis develops several technologies to address this challenge, beginning with a fully passive implant that uses one wire per electrode to connect to an external stimulation source. The number of wires passing through the body and the skin proved to be a hazard for the health of the animal, so a multiplexed implant was devised in which active electronics reduce the number of wires. Finally, a fully wireless implant was developed. As these implants are tested in vivo, encapsulation is of critical importance to retain functionality in a chronic experiment, especially for the active implants, and it was achieved without the use of costly ceramic or metallic hermetic packaging. Active implants were built that retained functionality 8 weeks after implantation, and achieved stepping in spinalized rats after just 8-10 days, which is far sooner than wire-based electrical stimulation has achieved in prior work.

From social to political. New forms of mobilization and democratization. Conference proceedings

In the recent evolution of contemporary social movements three phases can be identified. The first phase is marked by the labour movement and the systemic importance attributed to the labour conflict in industrial societies. This conflict has been interpreted as a consequence of the shortcoming of social integration mechanisms by Emile Durkheim, as a rational conflict by entrepreneurs’ and workers’ interests by Max Wener, and as a central class struggle for the transformation of society by Karl Marx. The second phase in this development was led by the new social movements of the post-industrial society of the 1960s and 1970s’ students, women and environmentalist movements. Two new analytical perspectives have explained these movements’ meaning and actions. Resource mobilization theory (McAdam and Tilly) has focuses on rational attitudes and conflicts. Actionalist sociology, in turn, has identified the new protagonists of social conflicts that replaced the labour movement in postindustrial societies. The third phase emerges in a world characterized by the ascendance of markets, the increasingly prominent role of financial capital flows, the closure of communities, and fundamentalism. In this context, human rights and pro-democratization movements constitute alternatives to global domination and the systemic conditioning of individual and groups.

Spinal circuits can accommodate interaction torques during multijoint limb movements

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals.

Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord

Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. In periphery, they contribute to sensory transmission, including that of nociception and pain. Here we characterized ASIC-like currents in dorsal horn neurons of the rat spinal cord and their functional modulation in pathological conditions. Reverse transcriptase-nested PCR and Western blotting showed that three ASIC isoforms, ASIC1a, ASIC2a, and ASIC2b, are expressed at a high level in dorsal horn neurons. Electrophysiological and pharmacological properties of the proton-gated currents suggest that homomeric ASIC1a and/or heteromeric ASIC1a + 2b channels are responsible for the proton-induced currents in the majority of dorsal horn neurons. Acidification-induced action potentials in these neurons were compatible in a pH-dependent manner with the pH dependence of ASIC-like current. Furthermore, peripheral complete Freund's adjuvant-induced inflammation resulted in increased expression of both ASIC1a and ASIC2a in dorsal horn. These results support the idea that the ASICs of dorsal horn neurons participate in central sensory transmission/modulation under physiological conditions and may play important roles in inflammation-related persistent pain.

Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity

Development of chronic pain involves alterations in peripheral nociceptors as well as elevated neuronal activity in multiple regions of the CNS. Previous pharmacological and behavioral studies suggest that peripheral acid-sensing ion channels (ASICs) cont

Strength mobilization in clays and silts

A large database of 115 triaxial, direct simple shear, and cyclic tests on 19 clays and silts is presented and analysed to develop an empirical framework for the prediction of the mobilization of the undrained shear strength, cu, of natural clays tested from an initially isotropic state of stress. The strain at half the peak undrained strength (γM=2) is used to normalize the shear strain data between mobilized strengths of 0.2cu and 0.8cu. A power law with an exponent of 0.6 is found to describe all the normalized data within a strain factor of 1.75 when a representative sample provides a value for γM=2. Multi-linear regression analysis shows that γM=2 is a function of cu, plasticity index Ip, and initial mean effective stress p′0. Of the 97 stress-strain curves for which cu, Ip, and p′0 were available, the observed values of γM=2 fell within a factor of three of the regression; this additional uncertainty should be acknowledged if a designer wished to limit immediate foundation settlements on the basis of an undrained strength profile and the plasticity index of the clay. The influence of stress history is also discussed. The application of these stress-strain relations to serviceability design calculations is portrayed through a worked example. The implications for geotechnical decision-making and codes of practice are considered.

Mobilization distance for upheaval buckling of shallowly buried pipelines

Buried pipelines may be subject to upheaval buckling because of thermally induced compressive stresses. As the buckling load of a strut decreases with increasing out of straightness, not only the maximum available resistance from the soil cover, but also the movement of the pipeline required to mobilize this are important factors in design. This paper will describe the results of 15 full-scale laboratory tests that have been carried out on pipeline uplift in both sandy and rocky backfills. The cover to diameter ratio ranged from 0.1 to 6. The results show that mobilization distance exhibits a linear relationship with H=D ratio and that the postpeak uplift force-displacement response can be accurately modeled using existing models. A tentative design approach is suggested; the maximum available uplift resistance may be reliably predicted from the postpeak response, and the mobilization distance may be predicted using the relationships described in this paper. © 2012 American Society of Civil Engineers.

Re-mobilization of pile shaft friction after an earthquake

During strong earthquakes, significant excess pore pressures can develop in saturated soils. After shaking ceases, the dissipation of these pressures can cause significant soil settlement, creating downward-acting frictional loads on piled foundations. Additionally, if the piles do not support the full axial load at the end of shaking, then the proportion of the superstructure's vertical loading carried by the piles may change as a result of the soil settlement, further altering the axial load distribution on piles as the soil consolidates. In this paper, the effect of hydraulic conductivity and initial post-shaking pile head loading is investigated in terms of the changing axial load distribution and settlement responses. The investigation is carried out by considering the results from four dynamic centrifuge experiments in which a 2 × 2 pile group was embedded in a two-layer profile and subjected to strong shaking. It is found that large contrasts in hydraulic conductivity between the two layers of the soil model affected both the pile group settlements and axial load distribution. Both these results stem from the differences in excess pore pressure dissipation, part of which took place very rapidly when the underlying soil layer had a large hydraulic conductivity.

Mobilization potential of heavy metals: A comparison between river and lake sediments

Toxic metals introduced into aquatic environments by human activities accumulation in sediments. A common notion is that the association of metals with acid volatile sulfides (AVS) affords a mechanism for partitioning metals from water to solid phase, thereby reducing biological availability. However, variation in environmental conditions can mobilize the sediment-bound metal and result in adverse environmental impacts. The AVS levels and the effect of AVS on the fate of Cu, Cd, Zn, Ni in sediments in the the Changjiang River, a suboxic river with sandy bottom sediment and the Donghu Lake, a anoxic lake with muddy sediment in China, were compared through aeration, static adsorption and release experiments in laboratory. Sips isotherm equation, kinetic equation and grade ion exchange theory were used to describe the heavy metal adsorb and release process. The results showed that AVS level in the lake sediment are higher than that of the river. Heavy metals in the overlying water can transfer to sediments incessantly as long as the sediment remains undisturbed. The metal release process is mainly related to AVS oxidation in lake sediment while also related to Org-C and Fe-Mn oxyhydroxide oxidation in river sediment. The effect of sulfides on Zn and Ni is high, followed by Cd, and Cu is easy bound to Org-C. AVS plays a major role in controlling metals activity in lake sediment and its presence increase the adsorption capacity both of the lake and river sediments.