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Closed-loop control of epidural electrical stimulation to optimise spinal neuroprosthetic systems


E. Martin Moraud

Zurich, pp. 105

For several decades, epidural spinal-cord stimulation (EES) has been employed to alleviate chronic pain syndromes. Its therapeutic potential has more recently been broadened to improving motor execution and recovery in several neuromotor disorders. The understanding of the biological principles at the core of this intervention, and the spectacular achievements reported on experimental animals and human patients, have motivated the development of a myriad of complementary neurotechnologies. Implantable electronics, stretchable materials and versatile robotic interfaces have surged to improve neuromodulation strategies by providing more selective access to surviving spinal networks.

Yet to this point, EES has always been applied continuously, using parameters that are optimised based on visual observation only.

Conceptual and technical limitations have held back the development of stimulation strategies in closed-loop.

- First, the use of spinal-cord neuromodulation has operated under the assumption that the stimulation merely increases the general level of excitability within spinal circuits, and activates central pattern generators. As such, EES has always been employed continuously, with the aim to ‘passively’ maintain a constant level of excitation in the SC. Only recently has EES started to been viewed as a resource that may actively modulate motor output.

- Second, clear relationships between input parameters and features of gait have been completely lacking, mostly as a result of the low specificity of EES. Unlike stimulation approaches that specifically control particular muscles or joints, EES modulates the physiological state of complex networks of neurons with intrinsic dynamical properties. Adaptations in motor output only emerge indirectly, and involve whole-body changes of gait, posture and balance.

- Finally, closed-loop systems are critically contingent on biomarkers, which need to provide feedback about the biomechanical state of the subject reliably and in real-time.

In this thesis, we tackle these different issues simultaneously. We present complementary approaches combining (i) stimulation strategies that coordinate the triggering of multiple electrodes in order to reproduce the natural spatiotemporal patterns of activation that underlie healthy locomotion, and (ii) closed-loop strategies that control EES frequency based on movement feedback in order to correct key deficits of gait and balance in real-time.

For each approach, we present the design of necessary technical and algorithmic infrastructures to support to design of stimulation strategies ‘on demand’. Our results emphasize an very high degree of controllability of limb movements, consistently reproducible across animals and sessions. Closed-loop neuromodulation helped correct key impairments of gait, restored symmetry and balance, and reinforced the activation of spinal sub-circuits on the treadmill. This holds promises to improve locomotor training and promote task-dependent plasticity, and potentially to improve function after neurological injury. In addition, closed-loop EES enabled complex functional tasks over-ground, such as climbing stairs, avoiding obstacles or turning in a curve. Ultimately, these applications could help establish a library a functions to enable every-day activities out of laboratory environments.

Finally, the translation of our stimulation protocol onto implantable, wireless technologies is a pivotal requirement to bring its benefits to patients. A first step in this direction in presented in the conclusion, where we introduce the full integration of the aforementioned closed-loop strategies using technology that is now in the process of being approved for human use. We illustrate the complete validation of the system on non-human primates, and confirm its therapeutical potential to modulate gait with degrees of selectivity and controllability that are similar –or even greater– than what was observed in rodents.

These combined developments set the technological and conceptual basis for using closed-loop spinal neuromodulation to control gait, correct locomotor deficits and potentially improve rehabilitation after SCI and other neuromotor disorders.


Type of Publication:

(03)Ph.D. Thesis

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% Autogenerated BibTeX entry
@PhDThesis { Xxx:2014:IFA_5068,
    author={E. Martin Moraud},
    title={{Closed-loop control of epidural electrical stimulation to
	  optimise spinal neuroprosthetic systems}},
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