18 research outputs found

    Closed-Loop Deep Brain Stimulation for Essential Tremor Based on Thalamic Local Field Potentials.

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    BACKGROUND: High-frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor. OBJECTIVE: We proposed to close the loop of thalamic stimulation by detecting tremor-provoking movement states using local field potentials recorded from the same electrodes implanted for stimulation, so that the stimulation is only delivered when necessary. METHODS: Eight patients with essential tremor participated in this study. Patient-specific support vector machine classifiers were first trained using data recorded while the patient performed tremor-provoking movements. Then, the trained models were applied in real-time to detect these movements and triggered the delivery of stimulation. RESULTS: Using the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor-evoking movements were present. In comparison, the stimulation was switched on for 12.71 ± 7.06% of the time when the patients were at rest and tremor-free. Compared with continuous stimulation, a similar amount of tremor suppression was achieved while only delivering 36.62 ± 13.49% of the energy used in continuous stimulation. CONCLUSIONS: The results suggest that responsive thalamic stimulation for essential tremor based on tremor-provoking movement detection can be achieved without any requirement for external sensors or additional electrocorticography strips. Further research is required to investigate whether the decoding model is stable across time and generalizable to the variety of activities patients may engage with in everyday life. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

    Hyper-parameter tuning and feature extraction for asynchronous action detection from sub-thalamic nucleus local field potentials

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    Introduction: Decoding brain states from subcortical local field potentials (LFPs) indicative of activities such as voluntary movement, tremor, or sleep stages, holds significant potential in treating neurodegenerative disorders and offers new paradigms in brain-computer interface (BCI). Identified states can serve as control signals in coupled human-machine systems, e.g., to regulate deep brain stimulation (DBS) therapy or control prosthetic limbs. However, the behavior, performance, and efficiency of LFP decoders depend on an array of design and calibration settings encapsulated into a single set of hyper-parameters. Although methods exist to tune hyper-parameters automatically, decoders are typically found through exhaustive trial-and-error, manual search, and intuitive experience. Methods: This study introduces a Bayesian optimization (BO) approach to hyper-parameter tuning, applicable through feature extraction, channel selection, classification, and stage transition stages of the entire decoding pipeline. The optimization method is compared with five real-time feature extraction methods paired with four classifiers to decode voluntary movement asynchronously based on LFPs recorded with DBS electrodes implanted in the subthalamic nucleus of Parkinson’s disease patients. Results: Detection performance, measured as the geometric mean between classifier specificity and sensitivity, is automatically optimized. BO demonstrates improved decoding performance from initial parameter setting across all methods. The best decoders achieve a maximum performance of 0.74 ± 0.06 (mean ± SD across all participants) sensitivity-specificity geometric mean. In addition, parameter relevance is determined using the BO surrogate models. Discussion: Hyper-parameters tend to be sub-optimally fixed across different users rather than individually adjusted or even specifically set for a decoding task. The relevance of each parameter to the optimization problem and comparisons between algorithms can also be difficult to track with the evolution of the decoding problem. We believe that the proposed decoding pipeline and BO approach is a promising solution to such challenges surrounding hyper-parameter tuning and that the study’s findings can inform future design iterations of neural decoders for adaptive DBS and BCI

    Neuroimaging and electrophysiology meet invasive neurostimulation for causal interrogations and modulations of brain states

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    Deep brain stimulation (DBS) has developed over the last twenty years into a highly effective evidenced-based treatment option for neuropsychiatric disorders. Moreover, it has become a fascinating tool to provide illustrative insights into the functioning of brain networks. New anatomical and pathophysiological models of DBS action have accelerated our understanding of neurological and psychiatric disorders and brain functioning. The description of the brain networks arose through the unique ability to illustrate long-range interactions between interconnected brain regions as derived from state-of-the-art neuroimaging (structural, diffusion, and functional MRI) and the opportunity to record local and large-scale brain activity at millisecond temporal resolution (microelectrode recordings, local field potential, electroencephalography, and magnetoencephalography). In the first part of this review, we describe how neuroimaging techniques have led to current understanding of DBS effects, by identifying and refining the DBS targets and illustrate the actual view on the relationships between electrode locations and clinical effects. One step further, we discuss how neuroimaging has shifted the view of localized DBS effects to a modulation of specific brain circuits, which has been possible from the combination of electrode location reconstructions with recently introduced network imaging methods. We highlight how these findings relate to clinical effects, thus postulating neuroimaging as a key factor to understand the mechanisms of DBS action on behavior and clinical effects. In the second part, we show how invasive electrophysiology techniques have been efficiently integrated into the DBS set-up to precisely localize the neuroanatomical targets of DBS based on distinct region-specific patterns of neural activity. Next, we show how multi-site electrophysiological recordings have granted a real-time window into the aberrant brain circuits within and beyond DBS targets to quantify and map the dynamic properties of rhythmic oscillations. We also discuss how DBS alters the transient synchrony states of oscillatory networks in temporal and spatial domains during resting, task-based and motion conditions, and how this modulation of brain states ultimately shapes the functional response. Finally, we show how a successful decoding and management of electrophysiological proxies (beta bursts, phase-amplitude coupling) of aberrant brain circuits was translated into adaptive DBS stimulation paradigms for a targeted and state-dependent invasive electrical neuromodulation

    Human basal ganglia recordings from implanted deep brain stimulation electrodes and the microlesion effect

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    Computationally efficient algorithms and implementations of adaptive deep brain stimulation systems for Parkinson's disease

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    Clinical deep brain stimulation (DBS) is a tool used to mitigate pharmacologically intractable neurodegenerative diseases such as Parkinson's disease (PD), tremor and dystonia. Present implementations of DBS use continuous, high frequency voltage or current pulses so as to mitigate PD. This results in some limitations, among which there is stimulation induced side effects and shortening of pacemaker battery life. Adaptive DBS (aDBS) can be used to overcome a number of these limitations. Adaptive DBS is intended to deliver stimulation precisely only when needed. This thesis presents work undertaken to investigate, propose and develop novel algorithms and implementations of systems for adapting DBS. This thesis proposes four system implementations that could facilitate DBS adaptation either in the form of closed-loop DBS or spatial adaptation. The first method involved the use of dynamic detection to track changes in local field potentials (LFP) which can be indicative of PD symptoms. The work on dynamic detection included the synthesis of validation dataset using mainly autoregressive moving average (ARMA) models to enable the evaluation of a subset of PD detection algorithms for accuracy and complexity trade-offs. The subset of algorithms consisted of feature extraction (FE), dimensionality reduction (DR) and dynamic pattern classification stages. The combination with the best trade-off in terms of accuracy and complexity consisted of discrete wavelet transform (DWT) for FE, maximum ratio method (MRM) for DR and k-nearest neighbours (k-NN) for classification. The MRM is a novel DR method inspired by Fisher's separability criterion. The best combination achieved accuracy measures: F1-score of 97.9%, choice probability of 99.86% and classification accuracy of 99.29%. Regarding complexity, it had an estimated microchip area of 0.84 mmÂČ for estimates in 90 nm CMOS process. The second implementation developed the first known PD detection and monitoring processor. This was achieved using complementary detection, which presents a hardware-efficient method of implementing a PD detection processor for monitoring PD progression in Parkinsonian patients. Complementary detection is achieved by using a combination of weak classifiers to produce a classifier with a higher consistency and confidence level than the individual classifiers in the configuration. The PD detection processor using the same processing stages as the first implementation was validated on an FPGA platform. By mapping the implemented design on a 45 nm CMOS process, the most optimal implementation achieved a dynamic power per channel of 2.26 ÎŒW and an area per channel of 0.2384 mmÂČ. It also achieved mean accuracy measures: Mathews correlation coefficient (MCC) of 0.6162, an F1-score of 91.38%, and mean classification accuracy of 91.91%. The third implementation proposed a framework for adapting DBS based on a critic-actor control approach. This models the relationship between a trained clinician (critic) and a neuro-modulation system (actor) for modulating DBS. The critic was implemented and validated using machine learning models, and the actor was implemented using a fuzzy controller. Therapy is modulated based on state estimates obtained through the machine learning models. PD suppression was achieved in seven out of nine test cases. The final implementation introduces spatial adaptation for aDBS. Spatial adaptation adjusts to variation in lead position and/or stimulation focus, as poor stimulation focus has been reported to affect therapeutic benefits of DBS. The implementation proposes dynamic current steering systems as a power-efficient implementation for multi-polar multisite current steering, with a particular focus on the output stage of the dynamic current steering system. The output stage uses dynamic current sources in implementing push-pull current sources that are interfaced to 16 electrodes so as to enable current steering. The performance of the output stage was demonstrated using a supply of 3.3 V to drive biphasic current pulses of up to 0.5 mA through its electrodes. The preliminary design of the circuit was implemented in 0.18 ÎŒm CMOS technology

    29th Annual Computational Neuroscience Meeting: CNS*2020

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    Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202

    Heterogeneous recognition of bioacoustic signals for human-machine interfaces

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    Human-machine interfaces (HMI) provide a communication pathway between man and machine. Not only do they augment existing pathways, they can substitute or even bypass these pathways where functional motor loss prevents the use of standard interfaces. This is especially important for individuals who rely on assistive technology in their everyday life. By utilising bioacoustic activity, it can lead to an assistive HMI concept which is unobtrusive, minimally disruptive and cosmetically appealing to the user. However, due to the complexity of the signals it remains relatively underexplored in the HMI field. This thesis investigates extracting and decoding volition from bioacoustic activity with the aim of generating real-time commands. The developed framework is a systemisation of various processing blocks enabling the mapping of continuous signals into M discrete classes. Class independent extraction efficiently detects and segments the continuous signals while class-specific extraction exemplifies each pattern set using a novel template creation process stable to permutations of the data set. These templates are utilised by a generalised single channel discrimination model, whereby each signal is template aligned prior to classification. The real-time decoding subsystem uses a multichannel heterogeneous ensemble architecture which fuses the output from a diverse set of these individual discrimination models. This enhances the classification performance by elevating both the sensitivity and specificity, with the increased specificity due to a natural rejection capacity based on a non-parametric majority vote. Such a strategy is useful when analysing signals which have diverse characteristics, false positives are prevalent and have strong consequences, and when there is limited training data available. The framework has been developed with generality in mind with wide applicability to a broad spectrum of biosignals. The processing system has been demonstrated on real-time decoding of tongue-movement ear pressure signals using both single and dual channel setups. This has included in-depth evaluation of these methods in both offline and online scenarios. During online evaluation, a stimulus based test methodology was devised, while representative interference was used to contaminate the decoding process in a relevant and real fashion. The results of this research provide a strong case for the utility of such techniques in real world applications of human-machine communication using impulsive bioacoustic signals and biosignals in general

    A NEURAL BASIS FOR THE BEHAVIORAL EFFECTS OF ANXIETY

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    Anxiety represents a state of high arousal and negative valence that leads to enhanced vigilance in the absence of concrete and immediate threat. Anxiety has profound impacts on ongoing behaviors. It can be an adaptive reaction to stressful or unpredictable life events, but excessive and persistent anxiety produces adverse cognitive effects that disrupt ongoing behavior and contribute to the clinical manifestation of anxiety disorders. Numerous studies have associated anxiety with deficits in cognitive control of behavior, and with perseverative behavioral tendencies. In addition, the adverse impact of anxiety is characterized in part by deficits in reward-related behavioral domains such as anhedonia and aberrant reward-associated perception. This dissertation study focuses on the neural basis of the behavioral impacts of anxiety. The neural circuit, comprising the prefrontal cortex (PFC) and the ventral tegmental area (VTA), is thought to be critically involved in anxiety-induced behavioral disruptions. Numerous neurophysiological and neurochemical studies suggest that the mesoprefrontal circuit preferentially responds to aversive stimuli, stressors, and resultant anxiety. However, it is largely unknown how VTA and mPFC individual neurons and neuronal ensembles represent cognitive, motivational, and emotional behavioral changes in anxiety. To address this, we studied animals engaged in well-characterized motivated and cognitive behavioral tasks in the absence or presence of varying degrees of an anxiogenic perturbation. By electrophysiologically recording the activity of VTA and mPFC single neurons and local field potential (LFP) signals from the task-performing animals, we demonstrate that anxiety-related behavioral alterations can be attributed to specific changes in the activity of VTA and mPFC neurons and neuronal populations. Collectively, our neurophysiological findings suggest that anxiety “hijacks” the VTA-mPFC neural circuit by profoundly modulating the spontaneous and task-related neural activity at the individual neuron-, neural population-, and neural circuit levels. Anxiety-induced neural changes in the VTA-mPFC circuit were systematically associated with anxiety-like changes in motivated and cognitive behaviors, even on a single-trial basis, providing insights that could contribute to therapeutic interventions for the behavioral symptoms of anxiety disorders

    26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

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    This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)
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