Pedram Mohseni

Wireless multichannel biopotential recording using an integrated FM telemetry circuit

This paper presents a four-channel telemetric microsystem featuring on-chip alternating current amplification, direct current baseline stabilization, clock generation, time-division multiplexing, and wireless frequency-modulation transmission of microvolt- and millivolt-range input biopotentials in the very high frequency band of 94-98 MHz over a distance of /spl sim/0.5 m. It consists of a 4.84-mm/sup 2/ integrated circuit, fabricated using a 1.5-/spl mu/m double-poly double-metal n-well standard complementary metal-oxide semiconductor process, interfaced with only three off-chip components on a custom-designed printed-circuit board that measures 1.7/spl times/1.2/spl times/0.16 cm/sup 3/, and weighs 1.1 g including two miniature 1.5-V batteries. We characterize the microsystem performance, operating in a truly wireless fashion in single-channel and multichannel operation modes, via extensive benchtop and in vitro tests in saline utilizing two different micromachined neural recording microelectrodes, while dissipating /spl sim/2.2 mW from a 3-V power supply. Moreover, we demonstrate successful wireless in vivo recording of spontaneous neural activity at 96.2 MHz from the auditory cortex of an awake marmoset monkey at several transmission distances ranging from 10 to 50 cm with signal-to-noise ratios in the range of 8.4-9.5 dB.

A fully integrated neural recording amplifier with DC input stabilization

This paper presents a low-power low-noise fully integrated bandpass operational amplifier for a variety of biomedical neural recording applications. A standard two-stage CMOS amplifier in a closed-loop resistive feedback configuration provides a stable ac gain of 39.3 dB at 1 kHz. A subthreshold PMOS input transistor is utilized to clamp the large and random dc open circuit potentials that normally exist at the electrode-electrolyte interface. The low cutoff frequency of the amplifier is programmable up to 50 Hz, while its high cutoff frequency is measured to be 9.1 kHz. The tolerable dc input range is measured to be at least /spl plusmn/0.25 V with a dc rejection factor of at least 29 dB. The amplifier occupies 0.107 mm/sup 2/ in die area, and dissipates 115 /spl mu/W from a 3 V power supply. The total measured input-referred noise voltage in the frequency range of 0.1-10 kHz is 7.8 /spl mu/V/sub rms/. It is fabricated using AMI 1.5 /spl mu/m double-poly double-metal n-well CMOS process. This paper presents full characterization of the dc, ac, and noise performance of this amplifier through in vitro measurements in saline using two different neural recording electrodes.

Restoration of function after brain damage using a neural prosthesis

Significance Closed-loop systems, or brain–machine–brain interfaces (BMBIs), have not been widely developed for brain repair. In this study, we targeted spared motor and somatosensory regions of the rat brain after traumatic brain injury for establishment of a functional bridge using a battery-powered microdevice. The results show that by using discriminated action potentials as a trigger for stimulating a distant cortical location, rapid recovery of fine motor skills is facilitated. This study provides strong evidence that BMBIs can be used to bridge damaged neural pathways functionally and promote recovery after brain injury. Although this study is restricted to a rodent model of TBI, it is likely that the approach will also be applicable to other types of acquired brain injuries. Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury.

Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry: Technical note

OBJECT Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain. METHODS The FSCV study consisted of a triangle wave scanned between -0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 mum) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by approximately 100 microm. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system. RESULTS The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer); 2) Bluetooth transceiver; 3) microprocessor; and 4) direct-current battery. A Windows-XP laptop computer running custom software and equipped with a Universal Serial Bus-connected Bluetooth transceiver served as the base station. Computer software directed wireless data acquisition at 100 kilosamples/second and remote control of FSCV operation and adjustable waveform parameters. The WINCS provided reliable, high-fidelity measurements of dopamine and other neurochemicals such as serotonin, norepinephrine, and ascorbic acid by using FSCV at CFM and by flow injection analysis. In rats, the WINCS detected subsecond striatal dopamine release at the implanted sensor during high-frequency stimulation of ascending dopaminergic fibers. Overall, in vitro and in vivo testing demonstrated comparable signals to a conventional hardwired electrochemical system for FSCV. Importantly, the WINCS reduced susceptibility to electromagnetic noise typically found in an operating room setting. CONCLUSIONS Taken together, these results demonstrate that the WINCS is well suited for intraoperative neurochemical monitoring. It is anticipated that neurotransmitter measurements at an implanted chemical sensor will prove useful for advancing functional neurosurgery.

Evolution of Deep Brain Stimulation: Human Electrometer and Smart Devices Supporting the Next Generation of Therapy

Deep brain stimulation (DBS) provides therapeutic benefit for several neuropathologies, including Parkinson disease (PD), epilepsy, chronic pain, and depression. Despite well‐established clinical efficacy, the mechanism of DBS remains poorly understood. In this review, we begin by summarizing the current understanding of the DBS mechanism. Using this knowledge as a framework, we then explore a specific hypothesis regarding DBS of the subthalamic nucleus (STN) for the treatment of PD. This hypothesis states that therapeutic benefit is provided, at least in part, by activation of surviving nigrostriatal dopaminergic neurons, subsequent striatal dopamine release, and resumption of striatal target cell control by dopamine. While highly controversial, we present preliminary data that are consistent with specific predications testing this hypothesis. We additionally propose that developing new technologies (e.g., human electrometer and closed‐loop smart devices) for monitoring dopaminergic neurotransmission during STN DBS will further advance this treatment approach.

A battery-powered 8-channel wireless FM IC for biopotential recording applications

An 8-channel microsystem for transmission of 7 input biopotentials using wireless FM in the band of 94 to 98 MHz requires only 3 off-chip components. The 4.84 mm/sup 2/ IC is fabricated using a 1.5 /spl mu/m 2P2M CMOS process, dissipates /spl sim/2.05 mW at 3 V, and wirelessly reconstructs an 800 /spl mu/V neural spike over a distance of /spl sim/13 cm with an I/O correlation coefficient of /spl sim/96%.

An ultralight biotelemetry backpack for recording EMG signals in moths

A two-channel FM biopotential recording system fabricated on a foldable, lightweight, polyimide substrate is presented. Each channel consists of a biopotential amplifier followed by a Colpitts oscillator with operating frequency tunable in the 88-108 MHz commercial FM band. The overall system measures 10 mm/spl times/10 mm/spl times/3 mm, weighs 0.74 g, uses two 1.5-V batteries, dissipates about 2 mW, and has a transmission range of 2 m. Using this system, electromyogram signals have been recorded from the dorsal ventral muscle and the dorsal longitudinal muscle of a giant sphinx moth (Manduca sexta).

A low power fully integrated bandpass operational amplifier for biomedical neural recording applications

This paper presents a low power fully integrated bandpass amplifier for a variety of biomedical neural recording applications. A standard two-stage CMOS amplifier in a closed-loop resistive feedback configuration provides stable AC gain of 39.5 dB at 1 kHz. A PMOS input transistor, biased near the sub-threshold region acting as a high value resistor in the range of hundreds of mega ohms, is utilized to clamp the large and random DC open circuit potential that normally exists at the electrode-electrolyte interface. The 3 dB bandwidth of the amplifier is measured to be 26 Hz - 6.5 kHz and the tolerable DC input range is measured to be at least 1 V. The amplifier measures 0.107 mm/sup 2/ in die area and dissipates 133 /spl mu/W from a 3 V power supply. It is fabricated in MOSIS AMI 1.5 /spl mu/m double poly double metal n-well CMOS process. Bench tests show complete functionality of the amplifier in both light and dark conditions and for a wide range of recording electrode capacitance.

A Miniaturized System for Spike-Triggered Intracortical Microstimulation in an Ambulatory Rat

This paper reports on a miniaturized system for spike-triggered intracortical microstimulation (ICMS) in an ambulatory rat. The head-mounted microdevice comprises a previously developed application-specific integrated circuit fabricated in 0.35-μm two-poly four-metal complementary metal-oxide-semiconductor technology, which is assembled and packaged on a miniature rigid-flex substrate together with a few external components for programming, supply regulation, and wireless operation. The microdevice operates autonomously from a single 1.55-V battery, measures 3.6 cm × 1.3 cm × 0.6 cm, weighs 1.7 g (including the battery), and is capable of stimulating as well as recording the neural response to ICMS in biological experiments with anesthetized laboratory rats. Moreover, it has been interfaced with silicon microelectrodes chronically implanted in the cerebral cortex of an ambulatory rat and successfully delivers electrical stimuli to the second somatosensory area when triggered by neural activity from the rostral forelimb area with a user-adjustable spike-stimulus time delay. The spike-triggered ICMS is further shown to modulate the neuronal firing rate, indicating that it is physiologically effective.

A wireless IC for time-share chemical and electrical neural recording

Neurons communicate both electrically and chemically [1]. Extensive effort has been directed at monitoring these signals in awake animals to investigate the neural basis of behavior. While various measurement strategies have been employed in the past, electrophysiology (EPHYS) for single-unit recording [2] and voltammetry for neurotransmitter sensing [3] are established as the two best methods for probing neurotransmission at microscopic scales in real time.