[ARTICLE] Advances in closed-loop deep brain stimulation devices – Full Text

Abstract

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.

Background

Deep Brain Stimulation (DBS) can be classified into open-loop (also known as conventional) and closed-loop (also known as adaptive) paradigms. Closed-loop DBS employs a sensor to record a signal linked to symptoms while open-loop DBS does not use a sensor for recording the brain condition; therefore, stimulation parameters including duration, amplitude, and frequency of the pulse train remain constant in open-loop DBS regardless of fluctuations in the disease state. The recorded signal is known as a biomarker and can have varying nature, e.g. bioelectric, physiologic, biochemical, etc. In the open-loop DBS, a specialist tracks the patient’s clinical state and manually programs the device in a trial-and-error based manner. Adjustments of stimulation parameters are not conducted in real-time based on the ongoing neurophysiological variations in the brain; therefore, adverse effects on the patient may be induced due to the brain overstimulation. On the other hand, in the closed-loop DBS, the stimulation pulses are delivered when the brain is in an abnormal state, or they are automatically and dynamically adjusted based on the variations in the recorded signal over the time. Figure 1 compares open-loop and closed-loop DBS and illustrates how they act in different brain states.

Fig. 1 Overview of open-loop DBS (a) versus closed-loop DBS (b). In open-loop DBS, a neurologist manually adjusts the stimulation parameters every 3–12 months after DBS implantation. On the other hand, in closed-loop DBS, programming of the stimulation parameters is performed automatically based on the measured biomarker. c Demonstration of two different brain states and the action of open-loop and closed-loop DBS. When the brain enters a specific state, it remains in that state for a short or long time. Closed-loop DBS gets deactivated when the brain enters the normal state. Open-loop DBS continues the stimulation regardless of the brain state

Although the conventional DBS is a successful therapy, the closed-loop DBS is potentially capable of further and more efficient improvements in neurological diseases. A systematic review of the clinical literature by Hamani et al. [1] stated that adjusting the stimulation parameters of DBS devices could reduce or abolish adverse effects reported in 142 (19%) of 737 Parkinson’s disease (PD) patients treated with subthalamic nucleus (STN) DBS. In addition, Rosin et al. [2] demonstrated the superior function of closed-loop DBS, which automatically adjusts the stimulation parameters, to alleviate PD symptoms. Moreover, Little et al. [3] indicated that motor scores in eight PD patients improved by 50% (blinded) and 66% (unblinded) during closed-loop DBS, which were 27% (p = 0.005) to 29% (p = 0.03) higher than that of open-loop DBS. Besides these therapeutic benefits, they reported 56% reduction in stimulation time, as well as a decrease in the energy requirement of the closed-loop DBS compared to open-loop DBS. Therefore, patients may also benefit from fewer surgeries for replacement of the neurostimulator battery as a result of less power consumption in non-continuous stimulations [3]. Little et al. [3] and Wu et al. [4] reported that in order to obtain similar results from open-loop and closed-loop DBS, 44% less electrical stimulation is required using closed-loop DBS, which means higher efficiency, fewer surgery numbers, lower power consumption, and longer battery lifespan.

Although DBS is a successful therapy, its operation mechanism is mainly uncertain. Hess et al. [5] explained how the temporal pattern of stimulations might have key information for clarification of the DBS mechanism. A recent short review [6] on the physiological mechanism of DBS suggests the “disruption hypothesis” in which abnormal information is prevented from flowing into the stimulation site as a result of DBS dissociation effect on input and output signals. However, it is still under debate and remains to be confirmed by more pre-clinical research. Another review by Herrington et al. [7] accounts several non-exclusive mechanisms for DBS that depend on the condition being treated and the stimulation target. Despite the existence of different theories on the DBS mechanism, there are still questions in regard to the closed-loop DBS. Does adaptive control of DBS alter the DBS mechanism? If yes, how does it alter the DBS mechanism? These questions deserve consideration in the future experimental studies.

This paper presents a comprehensive review of portable closed-loop DBS devices. While there exists a number of excellent reviews on closed-loop DBS systems [8, 9, 10, 11, 12, 13, 14, 15, 16], this work differs from the existing works as described in the following. Among the published reviews, ref. [8] mainly highlights the applications of closed-loop DBS in the rehabilitation of movement disorders. Ref. [12] mainly describes the benefits of closed-loop DBS which using local field potentials (LFPs) as the feedback biomarker. Ref. [13] mainly reviews DBS (both open-loop and closed-loop) in terms of neurological aspects and clinical benefits. Ref. [9] indicates the available biomarkers for closing the feedback loop, and gives control strategies for manipulating measured signals relating to PD patient clinical state. Ref. [10] concentrates on emerging techniques in DBS including new electrode design, new stimulation patterns, and novel targeting techniques. Ref [16] has mainly focused on selection of biomarker and its benefits and problems. Ref. [14] introduces adaptive DBS, and outlines some technological advances in DBS including stimulation type and patterns, energy harvesting, and methods for increasing life quality of patients. Similarly, ref. [15] reviews some technological advancement such as surgical targeting, DBS parameters programming, and electrode design. On the other hand, ref. [11] highlights a range of issues associated with closed-loop DBS including biomarker sensing and processing, DBS parameters programming, control algorithm, wireless telemetry, and device size and power consumption.

This paper, on the other hand, provides a comprehensive review of closed-loop DBS devices, and covers a wider range of issues and advancements associated with such devices including: (i) biomarker selection, (ii) DBS parameters programming, (iii) stimulation type and pattern, (iv) control algorithms, (v) concurrent stimulation and recording, (vi) portability, (vii) battery-less technique, (viii) user-friendly interface, and (x) remote monitoring and wireless telemetry. The paper combines the key features of the current reviews going beyond devices that are used for specific disorders or biomarkers. It covers closed-loop DBS devices reported in the latest research publications not included in the existing reviews. The paper gives a brief history of closed-loop DBS. Next, it discusses different biomarkers for closing the feedback loop. Then, it reviews the algorithms developed for controlling stimulation parameters. After that, it highlights the current challenges and limitations for implementing closed-loop DBS. Also, it reviews the technological developments in closed-loop DBS. Then, it describes commercial closed-loop DBS systems. After that, it compares research-based closed-loop DBS devices highlighting future design expectations, and giving future directions and recommendations on closed-loop DBS devices. […]

Continue —> Advances in closed-loop deep brain stimulation devices | Journal of NeuroEngineering and Rehabilitation | Full Text

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