Closed-Loop Brain-Computer Interfaces for Memory Restoration Using Deep Brain Stimulation

The past two decades have witnessed the rapid growth of therapeutic brain-computer interfaces (BCI) targeting a diversity of brain dysfunctions. Among many neurosurgical procedures, deep brain stimulation (DBS) with neuromodulation technique has emerged as a fruitful treatment for neurodegenerative disorders such as epilepsy, Parkinson\u27s disease, post-traumatic amnesia, and Alzheimer\u27s disease, as well as neuropsychiatric disorders such as depression, obsessive-compulsive disorder, and schizophrenia. In parallel to the open-loop neuromodulation strategies for neuromotor disorders, recent investigations have demonstrated the superior performance of closed-loop neuromodulation systems for memory-relevant disorders due to the more sophisticated underlying brain circuitry during cognitive processes. Our efforts are focused on discovering unique neurophysiological patterns associated with episodic memories then applying control theoretical principles to achieve closed-loop neuromodulation of such memory-relevant oscillatory activity, especially, theta and gamma oscillations. First, we use a unique dataset with intracranial electrodes inserted simultaneously into the hippocampus and seven cortical regions across 40 human subjects to test for the presence of a pattern that the phase of hippocampal theta oscillation modulates gamma oscillations in the cortex, termed cross-regional phase-amplitude coupling (xPAC), representing a key neurophysiological mechanism that promotes the temporal organization of interregional oscillatory activities, which has not previously been observed in human subjects. We then establish that the magnitude of xPAC predicts memory encoding success along with other properties of xPAC. We find that strong functional xPAC occurs principally between the hippocampus and other mesial temporal structures, namely entorhinal and parahippocampal cortices, and that xPAC is overall stronger for posterior hippocampal connections. Next, we focus on hippocampal gamma power as a `biomarker\u27 and use a novel dataset in which open-loop DBS was applied to the posterior cingulate cortex (PCC) during the encoding of episodic memories. We evaluate the feasibility of modulating hippocampal power by a precise control of stimulation via a linear quadratic integral (LQI) controller based on autoregressive with exogenous input (ARX) modeling for in-vivo use. In the simulation framework, we demonstrate proposed BCI system achieves effective control of hippocampal gamma power in 15 out of 17 human subjects and we show our DBS pattern is physiologically safe with realistic time scales. Last, we further develop the PCC-applied binary-noise (BN) DBS paradigm targeting the neuromodulation of both hippocampal theta and gamma oscillatory power in 12 human subjects. We utilize a novel nonlinear autoregressive with exogenous input neural network (NARXNN) as the plant paired with a proportional–integral–derivative (PID) controller (NARXNN-PID) for delivering a precise stimulation pattern to achieve desired oscillatory power level. Compared to a benchmark consisted of a linear state-space model (LSSM) with a PID controller, we not only demonstrate that the superior performance of our NARXNN plant model but also show the greater capacity of NARXNN-PID architecture in controlling both hippocampal theta and gamma power. We outline further experimentation to test our BCI system and compare our findings to emerging closed-loop neuromodulation strategies

Wavelet-Based Artifact Identification and Separation Technique for EEG Signals during Galvanic Vestibular Stimulation

We present a new method for removing artifacts in electroencephalography (EEG) records during Galvanic Vestibular Stimulation (GVS). The main challenge in exploiting GVS is to understand how the stimulus acts as an input to brain. We used EEG to monitor the brain and elicit the GVS reflexes. However, GVS current distribution throughout the scalp generates an artifact on EEG signals. We need to eliminate this artifact to be able to analyze the EEG signals during GVS. We propose a novel method to estimate the contribution of the GVS current in the EEG signals at each electrode by combining time-series regression methods with wavelet decomposition methods. We use wavelet transform to project the recorded EEG signal into various frequency bands and then estimate the GVS current distribution in each frequency band. The proposed method was optimized using simulated signals, and its performance was compared to well-accepted artifact removal methods such as ICA-based methods and adaptive filters. The results show that the proposed method has better performance in removing GVS artifacts, compared to the others. Using the proposed method, a higher signal to artifact ratio of −1.625 dB was achieved, which outperformed other methods such as ICA-based methods, regression methods, and adaptive filters

Analysis of the structure of time-frequency information in electromagnetic brain signals

This thesis encompasses methodological developments and experimental work aimed at revealing information contained in time, frequency, and time–frequency representations of electromagnetic, specifically magnetoencephalographic, brain signals. The work can be divided into six endeavors. First, it was shown that sound slopes increasing in intensity from undetectable to audible elicit event-related responses (ERRs) that predict behavioral sound detection. This provides an opportunity to use non-invasive brain measures in hearing assessment. Second, the actively debated generation mechanism of ERRs was examined using novel analysis techniques, which showed that auditory stimulation did not result in phase reorganization of ongoing neural oscillations, and that processes additive to the oscillations accounted for the generation of ERRs. Third, the prerequisites for the use of continuous wavelet transform in the interrogation of event-related brain processes were established. Subsequently, it was found that auditory stimulation resulted in an intermittent dampening of ongoing oscillations. Fourth, information on the time–frequency structure of ERRs was used to reveal that, depending on measurement condition, amplitude differences in averaged ERRs were due to changes in temporal alignment or in amplitudes of the single-trial ERRs. Fifth, a method that exploits mutual information of spectral estimates obtained with several window lengths was introduced. It allows the removal of frequency-dependent noise slopes and the accentuation of spectral peaks. Finally, a two-dimensional statistical data representation was developed, wherein all frequency components of a signal are made directly comparable according to spectral distribution of their envelope modulations by using the fractal property of the wavelet transform. This representation reveals noise buried processes and describes their envelope behavior. These examinations provide for two general conjectures. The stability of structures, or the level of stationarity, in a signal determines the appropriate analysis method and can be used as a measure to reveal processes that may not be observable with other available analysis approaches. The results also indicate that transient neural activity, reflected in ERRs, is a viable means of representing information in the human brain.reviewe

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician

A systematic review on artifact removal and classification techniques for enhanced MEG-based BCI systems

Neurological disease victims may be completely paralyzed and unable to move, but they may still be able to think. Their brain activity is the only means by which they can interact with their environment. Brain-Computer Interface (BCI) research attempts to create tools that support subjects with disabilities. Furthermore, BCI research has expanded rapidly over the past few decades as a result of the interest in creating a new kind of human-to-machine communication. As magnetoencephalography (MEG) has superior spatial and temporal resolution than other approaches, it is being utilized to measure brain activity non-invasively. The recorded signal includes signals related to brain activity as well as noise and artifacts from numerous sources. MEG can have a low signal-to-noise ratio because the magnetic fields generated by cortical activity are small compared to other artifacts and noise. By using the right techniques for noise and artifact detection and removal, the signal-to-noise ratio can be increased. This article analyses various methods for removing artifacts as well as classification strategies. Additionally, this offers a study of the influence of Deep Learning models on the BCI system. Furthermore, the various challenges in collecting and analyzing MEG signals as well as possible study fields in MEG-based BCI are examined

A Python-based Brain-Computer Interface Package for Neural Data Analysis

Anowar, Md Hasan, A Python-based Brain-Computer Interface Package for Neural Data Analysis. Master of Science (MS), December, 2020, 70 pp., 4 tables, 23 figures, 74 references. Although a growing amount of research has been dedicated to neural engineering, only a handful of software packages are available for brain signal processing. Popular brain-computer interface packages depend on commercial software products such as MATLAB. Moreover, almost every brain-computer interface software is designed for a specific neuro-biological signal; there is no single Python-based package that supports motor imagery, sleep, and stimulated brain signal analysis. The necessity to introduce a brain-computer interface package that can be a free alternative for commercial software has motivated me to develop a toolbox using the python platform. In this thesis, the structure of MEDUSA, a brain-computer interface toolbox, is presented. The features of the toolbox are demonstrated with publicly available data sources. The MEDUSA toolbox provides a valuable tool to biomedical engineers and computational neuroscience researchers

Advances in closed-loop deep brain stimulation devices

BACKGROUND: Millions of patients around the world are affected by neurological and psychiatric disorders. Deep brain stimulation (DBS) is a device-based therapy that could have fewer side-effects and higher efficiencies in drug-resistant patients compared to other therapeutic options such as pharmacological approaches. Thus far, several efforts have been made to incorporate a feedback loop into DBS devices to make them operate in a closed-loop manner. METHODS: This paper presents a comprehensive investigation into the existing research-based and commercial closed-loop DBS devices. It describes a brief history of closed-loop DBS techniques, biomarkers and algorithms used for closing the feedback loop, components of the current research-based and commercial closed-loop DBS devices, and advancements and challenges in this field of research. This review also includes a comparison of the closed-loop DBS devices and provides the future directions of this area of research. RESULTS: Although we are in the early stages of the closed-loop DBS approach, there have been fruitful efforts in design and development of closed-loop DBS devices. To date, only one commercial closed-loop DBS device has been manufactured. However, this system does not have an intelligent and patient dependent control algorithm. A closed-loop DBS device requires a control algorithm to learn and optimize the stimulation parameters according to the brain clinical state. CONCLUSIONS: The promising clinical effects of open-loop DBS have been demonstrated, indicating DBS as a pioneer technology and treatment option to serve neurological patients. However, like other commercial devices, DBS needs to be automated and modernized

Machine learning based brain signal decoding for intelligent adaptive deep brain stimulation

Sensing enabled implantable devices and next-generation neurotechnology allow real-time adjustments of invasive neuromodulation. The identification of symptom and disease-specific biomarkers in invasive brain signal recordings has inspired the idea of demand dependent adaptive deep brain stimulation (aDBS). Expanding the clinical utility of aDBS with machine learning may hold the potential for the next breakthrough in the therapeutic success of clinical brain computer interfaces. To this end, sophisticated machine learning algorithms optimized for decoding of brain states from neural time-series must be developed. To support this venture, this review summarizes the current state of machine learning studies for invasive neurophysiology. After a brief introduction to the machine learning terminology, the transformation of brain recordings into meaningful features for decoding of symptoms and behavior is described. Commonly used machine learning models are explained and analyzed from the perspective of utility for aDBS. This is followed by a critical review on good practices for training and testing to ensure conceptual and practical generalizability for real-time adaptation in clinical settings. Finally, first studies combining machine learning with aDBS are highlighted. This review takes a glimpse into the promising future of intelligent adaptive DBS (iDBS) and concludes by identifying four key ingredients on the road for successful clinical adoption: i) multidisciplinary research teams, ii) publicly available datasets, iii) open-source algorithmic solutions and iv) strong world-wide research collaborations.Fil: Merk, Timon. Charité – Universitätsmedizin Berlin; AlemaniaFil: Peterson, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Matemática Aplicada del Litoral. Universidad Nacional del Litoral. Instituto de Matemática Aplicada del Litoral; Argentina. Harvard Medical School; Estados UnidosFil: Köhler, Richard. Charité – Universitätsmedizin Berlin; AlemaniaFil: Haufe, Stefan. Charité – Universitätsmedizin Berlin; AlemaniaFil: Richardson, R. Mark. Harvard Medical School; Estados UnidosFil: Neumann, Wolf Julian. Charité – Universitätsmedizin Berlin; Alemani

Electroencephalography-Based Brain–Machine Interfaces in Older Adults: A Literature Review

The aging process is a multifaceted phenomenon that affects cognitive-affective and physical functioning as well as interactions with the environment. Although subjective cognitive decline may be part of normal aging, negative changes objectified as cognitive impairment are present in neurocognitive disorders and functional abilities are most impaired in patients with dementia. Electroencephalography-based brain–machine interfaces (BMI) are being used to assist older people in their daily activities and to improve their quality of life with neuro-rehabilitative applications. This paper provides an overview of BMI used to assist older adults. Both technical issues (detection of signals, extraction of features, classification) and application-related aspects with respect to the users’ needs are considered