Publications of Pierre Sacré
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See detailModeling the interactions between stimulation and physiologically induced APs in a mammalian nerve fiber: dependence on frequency and fiber diameter
Sadashivaiah, Vijay; Sacré, Pierre ULiege; Guan, Yun et al

in Journal of Computational Neuroscience (2018)

Electrical stimulation of nerve fibers is used as a therapeutic tool to treat neurophysiological disorders. Despite efforts to model the effects of stimulation, its underlying mechanisms remain unclear ... [more ▼]

Electrical stimulation of nerve fibers is used as a therapeutic tool to treat neurophysiological disorders. Despite efforts to model the effects of stimulation, its underlying mechanisms remain unclear. Current mechanistic models quantify the effects that the electrical field produces near the fiber but do not capture interactions between action potentials (APs) initiated by stimulus and APs initiated by underlying physiological activity. In this study, we aim to quantify the effects of stimulation frequency and fiber diameter on AP interactions involving collisions and loss of excitability. We constructed a mechanistic model of a myelinated nerve fiber receiving two inputs: the underlying physiological activity at the terminal end of the fiber, and an external stimulus applied to the middle of the fiber. We define conduction reliability as the percentage of physiological APs that make it to the somatic end of the nerve fiber. At low input frequencies, conduction reliability is greater than 95% and decreases with increasing frequency due to an increase in AP interactions. Conduction reliability is less sensitive to fiber diameter and only decreases slightly with increasing fiber diameter. Finally, both the number and type of AP interactions significantly vary with both input frequencies and fiber diameter. Modeling the interactions between APs initiated by stimulus and APs initiated by underlying physiological activity in a nerve fiber opens opportunities towards understanding mechanisms of electrical stimulation therapies. [less ▲]

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See detailAn intracerebral exploration of functional connectivity during word production
Grappe, Amandine; Sarma, Sridevi V.; Sacré, Pierre ULiege et al

in Journal of Computational Neuroscience (2018)

Language is mediated by pathways connecting distant brain regions that have diverse functional roles. For word production, the network includes a ventral pathway, connecting temporal and inferior frontal ... [more ▼]

Language is mediated by pathways connecting distant brain regions that have diverse functional roles. For word production, the network includes a ventral pathway, connecting temporal and inferior frontal regions, and a dorsal pathway, connecting parietal and frontal regions. Despite the importance of word production for scientific and clinical purposes, the functional connectivity underlying this task has received relatively limited attention, and mostly from techniques limited in either spatial or temporal resolution. Here, we exploited data obtained from depth intra-cerebral electrodes stereotactically implanted in eight epileptic patients. The signal was recorded directly from various structures of the neocortex with high spatial and temporal resolution. The neurophysiological activity elicited by a picture naming task was analyzed in the time-frequency domain (10–150 Hz), and functional connectivity between brain areas among ten regions of interest was examined. Task related-activities detected within a network of the regions of interest were consistent with findings in the literature, showing task-evoked desynchronization in the beta band and synchronization in the gamma band. Surprisingly, long-range functional connectivity was not particularly stronger in the beta than in the high-gamma band. The latter revealed meaningful sub-networks involving, notably, the temporal pole and the inferior frontal gyrus (ventral pathway), and parietal regions and inferior frontal gyrus (dorsal pathway). These findings are consistent with the hypothesized network, but were not detected in every patient. Further research will have to explore their robustness with larger samples. [less ▲]

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See detailCharacterizing Complex Human Behaviors and Neural Responses Using Dynamic Models
Sarma, Sridevi V.; Sacré, Pierre ULiege

in Chen, Zhe; Sarma, Sridevi V. (Eds.) Dynamic Neuroscience: Statistics, Modeling, and Control (2018)

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See detailStudying the interactions in a mammalian nerve fiber: a functional modeling approach
Sadashivaiah, Vijay; Sacré, Pierre ULiege; Guan, Yun et al

in Proceedings of the 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2018)

Modern therapeutic interventions are increasingly favoring electrical stimulation to treat neurophysiological dis-orders. These therapies are associated with suboptimal efficacy since most ... [more ▼]

Modern therapeutic interventions are increasingly favoring electrical stimulation to treat neurophysiological dis-orders. These therapies are associated with suboptimal efficacy since most neurostimulation devices operate in an open-loop manner (i.e., stimulation settings like frequency, amplitude are preprogrammed). A closed-loop system can dynamically adjust stimulation parameters and may provide efficient therapies. Computational models used to design these systems vary in complexity which can adversely affect their real-time performance. In this study, we compare two models of varying degrees of complexity. We constructed two computational models of a myelinated nerve fiber (functional versus mechanistic) each receiving two inputs: the underlying physiological activity at one end of the fiber, and the external stimulus applied to the middle of the fiber. We then defined relay reliability as the percentage of physiological action potentials that make it to the other end of the nerve fiber. We applied the two inputs to the fiber at various frequencies and analyze reliability. We found that the functional model and the mechanistic model have similar reliability properties, but the functional model significantly decreases the computational complexity and simulation run time. This modeling effort is the first step towards understanding and designing closed loop, real-time neurostimulation devices. [less ▲]

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See detailSelective relay of afferent sensory-induced action potentials from peripheral nerve to brain and the effects of electrical stimulation
Sadashivaiah, Vijay; Sacré, Pierre ULiege; Guan, Yun et al

in Proceedings of the 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2018)

Electrical stimulation of peripheral nerve fibers and dorsal column fibers is used to treat acute and chronic pain. Recent studies have shown that sensitized A-fibers maybe involved in the relay of pain ... [more ▼]

Electrical stimulation of peripheral nerve fibers and dorsal column fibers is used to treat acute and chronic pain. Recent studies have shown that sensitized A-fibers maybe involved in the relay of pain information. These nerve fibers also carry sensory-induced action potentials (APs), such as proprioception, mechanoreception, etc. Electrical stimulation of these nerve fibers can result in interactions between sensory-induced APs and stimulation-induced APs. For example, the sensory-induced APs can collide with stimulus APs, and thus may never be relayed to the brain. In this study, we aimed to quantify the effects of stimulation frequency on these interactions. Specifically, we focused on the goal of stimulation to simultaneously (i) block noxious sensory signals while (ii) relaying innocuous sensory signals from the periphery to the brain via a myelinated nerve fiber. We defined a performance metric called the ``selective relay $(SR)$ '' measure. Specifically, we constructed a tractable model of a nerve fiber that receives two inputs: the underlying sensory activity at the bottom of the fiber (noxious or innocuous), and the external stimulus applied to the middle of the fiber. We then defined relay reliability, $R$, as the percentage of sensory APs that make it to the top of the fiber. $SR$ is then a product of relaying innocuous sensory information while blocking noxious pain stimuli, i.e., $SR=R_ s e n(1-R_ p a i n)$. We applied the two inputs to the fiber at various frequencies and analyzed relay reliability and then we studied selective relay assuming noxious and innocuous stimuli produce APs with distinct frequencies. We found that frequency stimulation between 50-100Hz effectively blocks relay of low-frequency pain signals, allowing mid-to-high frequency sensory signals to transmit to the brain. [less ▲]

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See detailThe Role of Associative Cortices and Hippocampus during Movement Perturbations
Kerr, Matthew; Sacré, Pierre ULiege; Kahn, Kevin et al

in Frontiers in Neural Circuits (2017), 11

Although motor control has been extensively studied, most research involving neural recordings has focused on primary motor cortex, pre-motor cortex, supplementary motor area, and cerebellum. These ... [more ▼]

Although motor control has been extensively studied, most research involving neural recordings has focused on primary motor cortex, pre-motor cortex, supplementary motor area, and cerebellum. These regions are involved during normal movements, however, associative cortices and hippocampus are also likely involved during perturbed movements as one must detect the unexpected disturbance, inhibit the previous motor plan, and create a new plan to compensate. Minimal data is available on these brain regions during such ``robust'' movements. Here, epileptic patients implanted with intracerebral electrodes performed reaching movements while experiencing occasional unexpected force perturbations allowing study of the fronto-parietal, limbic and hippocampal network at unprecedented high spatial and temporal scales. Areas including orbitofrontal cortex (OFC) and hippocampus showed increased activation during perturbed trials. These results, coupled with a visual novelty control task, suggest the hippocampal MTL-P300 novelty response is modality independent, and that the OFC is involved in modifying motor plans during robust movement. [less ▲]

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See detailModeling electrical stimulation of mammalian nerve fibers: A mechanistic versus probabilistic approach
Sadashivaiah, Vijay; Sacré, Pierre ULiege; Guan, Yun et al

in Proceedings of the 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2017)

Electrical neurostimulation is increasingly used over neuropharmacology to treat various diseases. Despite efforts to model the effects of electrical stimulation, its underlying mechanisms remain unclear ... [more ▼]

Electrical neurostimulation is increasingly used over neuropharmacology to treat various diseases. Despite efforts to model the effects of electrical stimulation, its underlying mechanisms remain unclear. This is because current mechanistic models just quantify the effects that the electrical field produces near the fiber and do not capture interactions between stimulus-initiated action potentials (APs) and underlying physiological activity initiated APs. In this study, we aim to quantify and compare these interactions. We construct two computational models of a nerve fiber of varying degrees of complexity (probabilistic versus mechanistic) each receiving two inputs: the underlying physiological activity at one end of the fiber, and the external stimulus applied to the middle of the fiber. We then define reliability, R, as the percentage of physiological APs that make it to the other end of the nerve fiber. We apply the two inputs to the fiber at various frequencies and analyze reliability. We find that the probabilistic model captures relay properties for low input frequencies (<; 10 Hz) but then differs from the mechanistic model if either input has a larger frequency. This is because the probabilistic model only accounts for only (i) inter signal loss of excitability and (ii) collisions between stimulus-initiated action potentials (APs) and underlying physiological activity initiated APs. This first step towards modeling the interactions in a nerve fiber opens up opportunities towards understanding mechanisms of electrical stimulation therapies. [less ▲]

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See detailNonmotor regions encode path-related information during movements
Breault, Macauley S.; Sacré, Pierre ULiege; Johnson, Jacob J. et al

in 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2017)

Sensorimotor control and the involvement of motor brain regions has been extensively studied, but the role nonmotor brain regions play during movements has been overlooked. This is particularly due to the ... [more ▼]

Sensorimotor control and the involvement of motor brain regions has been extensively studied, but the role nonmotor brain regions play during movements has been overlooked. This is particularly due to the difficulty of recording from multiple regions in the brain during motor control. In this study, we utilize stereoelectroencephalography (SEEG) recording techniques to explore the role nonmotor brain areas have on the way we move. Nine humans were implanted with SEEG depth electrodes for clinical purposes, which rendered access to local field potential (LFP) activity in deep and peripheral nonmotor structures. Participants performed fast and slow arm reaching movements using a robotic manipulandum. In this study, we explored whether neural activity in a given nonmotor brain structure correlated to movement path metrics including: path length, path deviation, and path speed. Statistical analysis revealed correlations between averaged neural activity in middle temporal gyrus, supramarginal gyrus, and fusiform gyrus and our path metrics both within and across the subjects. Furthermore, we split trials across subjects into two groups: one group consisted of trials with high values of each path metric and the other with low values. We then found significant differences in LFP power in specific frequency bands (e.g. beta) during movement between each group. These results suggest that nonmotor regions may dynamically encode path-related information during movement. [less ▲]

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See detailThe influences and neural correlates of past and present during gambling in humans
Sacré, Pierre ULiege; Subramanian, Sandya; Kerr, Matthew S. D. et al

in Scientific Reports (2017), 7

During financial decision-making tasks, humans often make “rational” decisions, where they maximize expected reward. However, this rationality may compete with a bias that reflects past outcomes. That is ... [more ▼]

During financial decision-making tasks, humans often make “rational” decisions, where they maximize expected reward. However, this rationality may compete with a bias that reflects past outcomes. That is, if one just lost money or won money, this may impact future decisions. It is unclear how past outcomes influence future decisions in humans, and how neural circuits encode present and past information. In this study, six human subjects performed a financial decision-making task while we recorded local field potentials from multiple brain structures. We constructed a model for each subject characterizing bets on each trial as a function of present and past information. The models suggest that some patients are more influenced by previous trial outcomes (i.e., previous return and risk) than others who stick to more fixed decision strategies. In addition, past return and present risk modulated with the activity in the cuneus; while present return and past risk modulated with the activity in the superior temporal gyrus and the angular gyrus, respectively. Our findings suggest that these structures play a role in decision-making beyond their classical functions by incorporating predictions and risks in humans’ decision strategy, and provide new insight into how humans link their internal biases to decisions. [less ▲]

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See detailThe role of nonmotor brain regions during human motor control
Johnson, Jacob J.; Breault, Macauley S.; Sacré, Pierre ULiege et al

in Proceedings of the 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) 2018-03-25 23:44:49 +0000 2018-03-25 23:44:53 +0000 (2017)

Neural prostheses have generally relied on signals from cortical motor regions to control reaching movements of a robotic arm. However, little work has been done in exploring the involvement of nonmotor ... [more ▼]

Neural prostheses have generally relied on signals from cortical motor regions to control reaching movements of a robotic arm. However, little work has been done in exploring the involvement of nonmotor cortical and associative regions during motor tasks. In this study, we identify regions which may encode direction during planning and movement of a center-out motor task. Local field potentials were collected using stereoelectroencephalography (SEEG) from nine epilepsy patients implanted with multiple depth electrodes for clinical purposes. Spectral analysis of the recorded data was performed using nonparametric statistical techniques to identify regions that may encode direction of movements during the motor task. The analysis revealed several nonmotor regions; including the right insular cortex, right temporal pole, right superior parietal lobule, and the right lingual gyrus, that encode directionality before and after movement onset. We observed that each of these regions encode direction in different frequency bands. This preliminary study suggests that nonmotor regions may be useful in assisting in neural prosthetic control. [less ▲]

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See detailNeuronal activity in human anterior cingulate cortex modulates with internal cognitive state during multi-source interference task
Sklar, Samuel; Walmer, Matthew; Sacré, Pierre ULiege et al

in Proceedings of the 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2017)

The dorsal anterior cingulate cortex (dACC) is thought to be essential for normal adaptation of one's behavior to difficult decisions, errors, and reinforcement. Here we examine single neurons from the ... [more ▼]

The dorsal anterior cingulate cortex (dACC) is thought to be essential for normal adaptation of one's behavior to difficult decisions, errors, and reinforcement. Here we examine single neurons from the human dACC in the context of a statistical model, including a cognitive state that varies with changes in cognitive interference induced by a Stroop-like task. We then include this cognitive state in point process models of single unit activity and subject reaction time. These results suggest that consideration of a latent cognitive state can explain additional variance in neural and behavioral dynamics. [less ▲]

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See detailSingularly perturbed phase response curves for relaxation oscillators
Sacré, Pierre ULiege; Franci, Alessio

in Proceedings of the 55th IEEE Conference on Decision and Control (CDC) (2016)

We exploit a novel geometric method to construct the global isochrones of relaxation oscillators and the associated phase response curve. This method complements the classical infinitesimal (local) phase ... [more ▼]

We exploit a novel geometric method to construct the global isochrones of relaxation oscillators and the associated phase response curve. This method complements the classical infinitesimal (local) phase response curve approach by constructively predicting the finite phase response curve near the singular limit of infinite timescale separations between the oscillator variables. We illustrate the power of our construction on the FitzHugh-Nagumo model of neuronal spike generation. Because of its global and constructive nature, not requiring extensive numerical simulations, the proposed approach is particularly suited to control design applications. [less ▲]

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See detailWinning versus losing during gambling and its neural correlates
Sacré, Pierre ULiege; Kerr, Matthew S. D.; Subramanian, Sandya et al

in Proceedings of the 2016 Annual Conference on Information Science and Systems (CISS) (2016)

Humans often make decisions which maximize an internal utility function. For example, humans often maximize their expected reward when gambling and this is considered as a “rational” decision. However ... [more ▼]

Humans often make decisions which maximize an internal utility function. For example, humans often maximize their expected reward when gambling and this is considered as a “rational” decision. However, humans tend to change their betting strategies depending on how they “feel”. If someone has experienced a losing streak, they may “feel” that they are more likely to win on the next hand even though the odds of the game have not changed. That is, their decisions are driven by their emotional state. In this paper, we investigate how the human brain responds to wins and losses during gambling. Using a combination of local field potential recordings in human subjects performing a financial decision-making task, spectral analyses, and non-parametric cluster statistics, we investigated whether neural responses in different cognitive and limbic brain areas differ between wins and losses after decisions are made. In eleven subjects, the neural activity modulated significantly between win and loss trials in one brain region: the anterior insula (p = 0.01). In particular, gamma activity (30-70 Hz) increased in the anterior insula when subjects just realized that they won. Modulation of metabolic activity in the anterior insula has been observed previously in functional magnetic resonance imaging studies during decision making and when emotions are elicited. However, our study is able to characterize temporal dynamics of electrical activity in this brain region at the millisecond resolution while decisions are made and after outcomes are revealed. [less ▲]

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See detailThe precuneus may encode irrationality in human gambling
Sacré, Pierre ULiege; Kerr, Matthew S. D.; Subramanian, Sandya et al

in Podeedings of the 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2016)

Humans often make irrational decisions, especially psychiatric patients who have dysfunctional cognitive and emotional circuitry. Understanding the neural basis of decision-making is therefore essential ... [more ▼]

Humans often make irrational decisions, especially psychiatric patients who have dysfunctional cognitive and emotional circuitry. Understanding the neural basis of decision-making is therefore essential towards patient management, yet current studies suffer from several limitations. Functional magnetic resonance imaging (fMRI) studies in humans have dominated decision-making neuroscience, but have poor temporal resolution and the blood oxygenation level-dependent signal is only a proxy for neural activity. On the other hand, lesion studies in humans used to infer functionality in decision-making lack characterization of neural activity altogether. Using a combination of local field potential recordings in human subjects performing a financial decision-making task, spectral analyses, and non-parametric cluster statistics, we analyzed the activity in the precuneus. In nine subjects, the neural activity modulated significantly between rational and irrational trials in the precuneus (p < 0.001). In particular, high-frequency activity (70-100 Hz) increased when irrational decisions were made. Although preliminary, these results suggest suppression of gamma rhythms via electrical stimulation in the precuneus as a therapeutic intervention for pathological decision-making. [less ▲]

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See detailLucky rhythms in orbitofrontal cortex bias gambling decisions in humans
Sacré, Pierre ULiege; Kerr, Matthew S. D.; Kahn, Kevin et al

in Scientific Reports (2016), 6

It is well established that emotions influence our decisions, yet the neural basis of this biasing effect is not well understood. Here we directly recorded local field potentials from the OrbitoFrontal ... [more ▼]

It is well established that emotions influence our decisions, yet the neural basis of this biasing effect is not well understood. Here we directly recorded local field potentials from the OrbitoFrontal Cortex (OFC) in five human subjects performing a financial decision-making task. We observed a striking increase in gamma-band (36–50 Hz) oscillatory activity that reflected subjects’ decisions to make riskier choices. Additionally, these gamma rhythms were linked back to mismatched expectations or “luck” occurring in past trials. Specifically, when a subject expected to win but lost, the trial was defined as “unlucky” and when the subject expected to lose but won, the trial was defined as “lucky”. Finally, a fading memory model of luck correlated to an objective measure of emotion, heart rate variability. Our findings suggest OFC may play a pivotal role in processing a subject’s internal (emotional) state during financial decision-making, a particularly interesting result in light of the more recent “cognitive map” theory of OFC function. [less ▲]

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See detailElectrical neurostimulation for chronic pain: on selective relay of sensory neural activities in myelinated nerve fibers
Sacré, Pierre ULiege; Sarma, Sridevi V.; Guan, Yun et al

in 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (2015)

Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and ... [more ▼]

Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and limited long-term success, as their mechanisms of action are unclear. Yet current computational models of pain transmission suffer from several limitations. In particular, dorsal column models do not include the fundamental underlying sensory activity traveling in these nerve fibers. We developed a (simple) simulation test bed of electrical neurostimulation of myelinated nerve fibers with underlying sensory activity. This paper reports our findings so far. Interactions between stimulation-evoked and underlying activities are mainly due to collisions of action potentials and losses of excitability due to the refractory period following an action potential. In addition, intuitively, the reliability of sensory activity decreases as the stimulation frequency increases. This first step opens the door to a better understanding of pain transmission and its modulation by neurostimulation therapies. [less ▲]

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See detailSensitivity analysis of oscillator models in the space of phase response curves: Oscillators as open systems
Sacré, Pierre ULiege; Sepulchre, Rodolphe ULiege

in IEEE Control Systems Magazine (2014), 34(2), 50-74

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See detailSensitivity analysis of circadian entrainment in the space of phase response curves
Sacré, Pierre ULiege; Sepulchre, Rodolphe ULiege

in Kulkarni, Vishwesh V.; Stan, Guy-Bart; Raman, Karthik (Eds.) A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems (2014)

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input–output ... [more ▼]

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input–output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical exploration of the parameter space. Application of this tool to a state-of-the-art model of circadian rhythms suggests that it can be useful and instrumental to biological investigations. [less ▲]

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See detailSystems analysis of oscillator models in the space of phase response curves
Sacré, Pierre ULiege

Doctoral thesis (2013)

Oscillators---whose steady-state behavior is periodic rather than constant---are observed in every field of science. While they have been studied for a long time as closed systems, they are increasingly ... [more ▼]

Oscillators---whose steady-state behavior is periodic rather than constant---are observed in every field of science. While they have been studied for a long time as closed systems, they are increasingly regarded as open systems, that is, systems that interact with their environment. Because their functions involve interconnection, the relevance of input--output systems theory to model, analyze, and control oscillators is obvious. Yet, due to the nonlinear nature of oscillators, methodological tools to study their systems properties remain scarce. In particular, few studies focus on the interface between two fundamental descriptions of oscillators, namely the (internal) state-space representation and the (external) circle representation. Starting with the pioneering work of Arthur Winfree, the phase response curve of an oscillator has emerged as the fundamental input--output characteristic linking both descriptions. The present dissertation aims at studying the systems properties of oscillators through the properties of their phase response curve. The main contributions of this dissertation are the following. We distinguish between two fundamental classes of oscillators. These classes differ in the local destabilizing mechanism that transforms the stable equilibrium of a globally dissipative system into a periodic orbit. To address input--output systems questions in the space of response curves, we equip this space with the right metrics and develop a (local) sensitivity analysis of infinitesimal phase response curves. This main contribution of the thesis is completed by the numerical tools required to turn the abstract developments into concrete algorithms. We illustrate how these analysis tools allow to address pertinent systems questions about models of circadian rhythms (robustness analysis and system identification) and of neural oscillators (model classification). These two biological rhythms are exemplative of both main classes of oscillators. We also design elementary control strategies to assign the phase of an oscillator. Motivated by an inherent limitation of infinitesimal methods for relaxation type of oscillators, we develop the novel geometric concept of ``singularly perturbed phase response curve' which exploits the time-scale separation to predict the phase response to finite perturbations. In conclusion, the present dissertation investigates input--output systems analysis of oscillators through their phase response curve at the interface between their external and internal descriptions, developing theoretical and numerical tools to study models arising in the biology of cellular rhythms. [less ▲]

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See detailSingularly perturbed phase response curves
Sacré, Pierre ULiege; Franci, Alessio ULiege; Sepulchre, Rodolphe ULiege

Conference (2013, March 26)

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