An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction

Dynamic feedback based closed-loop medical devices offer a number of advantages for treatment of heterogeneous neurological conditions. Closed-loop devices integrate a level of neurobiological feedback, which allows for real-time adjustments to be made with the overarching aim of improving treatment efficacy and minimizing risks for adverse events. One target which has not been extensively explored as a potential feedback component in closed-loop therapies is mitochondrial function. Several neurodegenerative and psychiatric disorders including Parkinson’s disease, Major Depressive disorder and Bipolar disorder have been linked to perturbations in the mitochondrial respiratory chain. This paper investigates the potential to monitor this mitochondrial function as a method of feedback for closed-loop neuromodulation treatments. A generic model of the closed-loop treatment is developed to describe the high-level functions of any system designed to control neural function based on mitochondrial response to stimulation, simplifying comparison and future meta-analysis. This model has four key functional components including: a sensor, signal manipulator, controller and effector. Each of these components are described and several potential technologies for each are investigated. While some of these candidate technologies are quite mature, there are still technological gaps remaining. The field of closed-loop medical devices is rapidly evolving, and whilst there is a lot of interest in this area, widespread adoption has not yet been achieved due to several remaining technological hurdles. However, the significant therapeutic benefits offered by this technology mean that this will be an active area for research for years to come

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

A miniature closed-loop deep brain stimulation device

This paper presents a miniature light-weight closed-loop deep brain stimulation (DBS) device that delivers on-demand stimulation current pulses by monitoring and analysing local field potentials. The device includes monitoring and DBS units, each designed and fabricated on a separate small round circuit board. The closed-loop DBS device has been successfully validated by injecting a pre-recorded neural signal into its input, and collecting and analysing its output. The monitoring unit has an amplification gain of 113 dB in frequency range of 0.7-50 Hz. The DBS unit gives on-demand stimulation current pulses of duration 90 μs, frequency 130 Hz, and amplitude 200 μ. The total weight of the device including a 3V coin battery is 1.41 g. The diameter of the device is 11.4 mm. This portable head-mountable device is suitable for use in pre-clinical trials with small laboratory animals

Developing neurostimulation techniques to investigate antidepressant and mood modulating behaviors / by Rajas Prakash Kale

 My PhD consisted of a multidisciplinary approach towards primary research in the field of translational neuroscience. Incorporation of preclinical research, behavioral neuroscience, translational psychiatry, neural engineering, and biomedical device development techniques drives my continuing passion towards helping patients through innovation