A Low-Cost, Wireless, Multi-Channel Deep Brain Stimulation System for Rodents

We present a small (43mm x 24mm x 15mm), off-the-shelf wireless neurostimulator for rodent deep brain stimulation research. Our device enables researchers to wirelessly configure stimulator settings, such as amplitude, pulse width, channel selection, and frequency, via a phone app. The system uses impedance-independent current-mode stimulation and steers current to a selected channel. In addition to monophasic and biphasic stimulation, the system also supports arbitrary waveform stimulation using pre-stored lookup tables. The system uses a configurable grounding phase to clear residual charge and a stimulation compliance monitor to ensure safe operation. The compliance monitor wirelessly reports the current during stimulation, the amount of passive recharge current, and the DC voltage of the electrode interface. The 400mAh battery is easy to replace and can go over 40 hours between charges. The system can be built for less than $50 using easy-to-source components to support inexpensive, highly-parallel research applications

Wireless tools for neuromodulation

Epilepsy is a spectrum of diseases characterized by recurrent seizures. It is estimated that 50 million individuals worldwide are affected and 30% of cases are medically refractory or drug resistant. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are the only FDA approved device based therapies. Neither therapy offers complete seizure freedom in a majority of users. Novel methodologies are needed to better understand mechanisms and chronic nature of epilepsy. Most tools for neuromodulation in rodents are tethered. The few wireless devices use batteries or are inductively powered. The tether restricts movement, limits behavioral tests, and increases the risk of infection. Batteries are large and heavy with a limited lifetime. Inductive powering suffers from rapid efficiency drops due to alignment mismatches and increased distances. Miniature wireless tools that offer behavioral freedom, data acquisition, and stimulation are needed. This dissertation presents a platform of electrical, optical and radiofrequency (RF) technologies for device based neuromodulation. The platform can be configured with features including: two channels differential recording, one channel electrical stimulation, and one channel optical stimulation. Typical device operation consumes less than 4 mW. The analog front end has a bandwidth of 0.7 Hz - 1 kHz and a gain of 60 dB, and the constant current driver provides biphasic electrical stimulation. For use with optogenetics, the deep brain optical stimulation module provides 27 mW/mm2 of blue light (473 nm) with 21.01 mA. Pairing of stimulating and recording technologies allows closed-loop operation. A wireless powering cage is designed using the resonantly coupled filter energy transfer (RCFET) methodology. RF energy is coupled through magnetic resonance. The cage has a PTE ranging from 1.8-6.28% for a volume of 11 x 11 x 11 in3. This is sufficient to chronically house subjects. The technologies are validated through various in vivo preparations. The tools are designed to study epilepsy, SUDEP, and urinary incontinence but can be configured for other studies. The broad application of these technologies can enable the scientific community to better study chronic diseases and closed-loop therapies

A programmable closed-loop recording and stimulating wireless system for behaving small laboratory animals

A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays

A Closed-Loop Bidirectional Brain-Machine Interface System For Freely Behaving Animals

A brain-machine interface (BMI) creates an artificial pathway between the brain and the external world. The research and applications of BMI have received enormous attention among the scientific community as well as the public in the past decade. However, most research of BMI relies on experiments with tethered or sedated animals, using rack-mount equipment, which significantly restricts the experimental methods and paradigms. Moreover, most research to date has focused on neural signal recording or decoding in an open-loop method. Although the use of a closed-loop, wireless BMI is critical to the success of an extensive range of neuroscience research, it is an approach yet to be widely used, with the electronics design being one of the major bottlenecks. The key goal of this research is to address the design challenges of a closed-loop, bidirectional BMI by providing innovative solutions from the neuron-electronics interface up to the system level. Circuit design innovations have been proposed in the neural recording front-end, the neural feature extraction module, and the neural stimulator. Practical design issues of the bidirectional neural interface, the closed-loop controller and the overall system integration have been carefully studied and discussed.To the best of our knowledge, this work presents the first reported portable system to provide all required hardware for a closed-loop sensorimotor neural interface, the first wireless sensory encoding experiment conducted in freely swimming animals, and the first bidirectional study of the hippocampal field potentials in freely behaving animals from sedation to sleep. This thesis gives a comprehensive survey of bidirectional BMI designs, reviews the key design trade-offs in neural recorders and stimulators, and summarizes neural features and mechanisms for a successful closed-loop operation. The circuit and system design details are presented with bench testing and animal experimental results. The methods, circuit techniques, system topology, and experimental paradigms proposed in this work can be used in a wide range of relevant neurophysiology research and neuroprosthetic development, especially in experiments using freely behaving animals

Modulating microcircuits in depression

Major depressive disorder (MDD) is globally the leading cause of disability with a worldwide prevalence of 4.4 %, affecting 322 million people in 2015. The treatment of MDD includes antidepressant medication and psychological therapies. However, approximately one-third of treated patients do not respond adequately to these treatments. These patients suffer from treatment-resistant depression (TRD). Deep brain stimulation (DBS) is a therapy modality widely researched for TRD, however, study outcomes show inconsistent results. This thesis focuses on DBS in TRD and researches i) if it is possible to disentangle TRD into different microcircuits, ii) how clinical DBS outcomes can be improved and iii) if DBS can be refined with a non-invasive technique called magnetothermal DBS (mDBS) introducing nanomaterial-mediated neuromodulation. MDBS is researched in collaboration with the research group of prof. dr. P. Anikeeva at the research laboratory of electronics (rle) at the Massachusetts Institute of Technology (MIT) (Boston, USA)