Integrated circuit design for implantable neural interfaces

Progress in microfabrication technology has opened the way for new possibilities in neuroscience and medicine. Chronic, biocompatible brain implants with recording and stimulation capabilities provided by embedded electronics have been successfully demonstrated. However, more ambitious applications call for improvements in every aspect of existing implementations. This thesis proposes two prototypes that advance the field in significant ways. The first prototype is a neural recording front-end with spectral selectivity capabilities that implements a design strategy that leads to the lowest reported power consumption as compared to the state of the art. The second one is a bidirectional front-end for closed-loop neuromodulation that accounts for self-interference and impedance mismatch thus enabling simultaneous recording and stimulation. The design process and experimental verification of both prototypes is presented herein

A 4-mode reconfigurable low noise amplifier for implantable neural recording channels

In this paper a reconfigurable implantable low noise amplifier for the recording of neural signals is presented. It is comprised by low-power and noise efficient current reuse OTAs in its direct path. The proposed architecture allows for an active feedback to set the high-pass corner in place of the commonly used pseudoresistor. Bandwidth selectivity is achieved by circuit reconfigurability which changes the pole frequencies of the system without impacting the total power consumption. Simulation results in AMS 0.18μm technology validate the proposed architecture in both nominal and corner process conditions with an estimated total power consumption of 454nW.Office of Naval Research (USA) N00014-14-1-0355Junta de Andalucía TIC 233

Design and Development of Smart Brain-Machine-Brain Interface (SBMIBI) for Deep Brain Stimulation and Other Biomedical Applications

Machine collaboration with the biological body/brain by sending electrical information back and forth is one of the leading research areas in neuro-engineering during the twenty-first century. Hence, Brain-Machine-Brain Interface (BMBI) is a powerful tool for achieving such machine-brain/body collaboration. BMBI generally is a smart device (usually invasive) that can record, store, and analyze neural activities, and generate corresponding responses in the form of electrical pulses to stimulate specific brain regions. The Smart Brain-Machine-Brain-Interface (SBMBI) is a step forward with compared to the traditional BMBI by including smart functions, such as in-electrode local computing capabilities, and availability of cloud connectivity in the system to take the advantage of powerful cloud computation in decision making. In this dissertation work, we designed and developed an innovative form of Smart Brain-Machine-Brain Interface (SBMBI) and studied its feasibility in different biomedical applications. With respect to power management, the SBMBI is a semi-passive platform. The communication module is fully passive—powered by RF harvested energy; whereas, the signal processing core is battery-assisted. The efficiency of the implemented RF energy harvester was measured to be 0.005%. One of potential applications of SBMBI is to configure a Smart Deep-Brain-Stimulator (SDBS) based on the general SBMBI platform. The SDBS consists of brain-implantable smart electrodes and a wireless-connected external controller. The SDBS electrodes operate as completely autonomous electronic implants that are capable of sensing and recording neural activities in real time, performing local processing, and generating arbitrary waveforms for neuro-stimulation. A bidirectional, secure, fully-passive wireless communication backbone was designed and integrated into this smart electrode to maintain contact between the smart electrodes and the controller. The standard EPC-Global protocol has been modified and adopted as the communication protocol in this design. The proposed SDBS, by using a SBMBI platform, was demonstrated and tested through a hardware prototype. Additionally the SBMBI was employed to develop a low-power wireless ECG data acquisition device. This device captures cardiac pulses through a non-invasive magnetic resonance electrode, processes the signal and sends it to the backend computer through the SBMBI interface. Analysis was performed to verify the integrity of received ECG data

In-body wireline interfacing platform for multi-module implantable microsystems

The recent evolution of implantable medical devicesfrom single-unit stimulators to modern implantable microsys-tems, has driven the need for distributed technologies, in whichboth the implant system and functions are partitioned across mul-tiple active devices. This multi-module approach is made possiblethanks to novel network architectures, allowing for in-body powerand data communications to be performed using implantableleads. This paper discusses the challenges in implementing suchinterfacing system and presents a platform based on one centralimplant (CI) and multiple peripheral implants (PIs) using a cus-tom 4WiCS communication protocol. This is implemented in PCBtechnology and tested to demonstrate intrabody communicationcapabilities and power transfer within the network. Measuredresults show CI-to-PI power delivery achieves 70%efficiency inexpected load condition, while establishing full-duplex data linkwith up to 4 PIs simultaneously

The neural engine: a reprogrammable low power platform for closed-loop optogenetics

Brain-machine Interfaces (BMI) hold great potential for treating neurological disorders such as epilepsy. Technological progress is allowing for a shift from open-loop, pacemaker-class, intervention towards fully closed-loop neural control systems. Low power programmable processing systems are therefore required which can operate within the thermal window of 2° C for medical implants and maintain long battery life. In this work, we developed a low power neural engine with an optimized set of algorithms which can operate under a power cycling domain. By integrating with custom designed brain implant chip, we have demonstrated the operational applicability to the closed-loop modulating neural activities in in-vitro brain tissues: the local field potentials can be modulated at required central frequency ranges. Also, both a freely-moving non-human primate (24-hour) and a rodent (1-hour) in-vivo experiments were performed to show system long-term recording performance. The overall system consumes only 2.93mA during operation with a biological recording frequency 50Hz sampling rate (the lifespan is approximately 56 hours). A library of algorithms has been implemented in terms of detection, suppression and optical intervention to allow for exploratory applications in different neurological disorders. Thermal experiments demonstrated that operation creates minimal heating as well as battery performance exceeding 24 hours on a freely moving rodent. Therefore, this technology shows great capabilities for both neuroscience in-vitro/in-vivo applications and medical implantable processing units

Acquisition systems and decoding algorithms of peripheral neural signals for prosthetic applications

During the years, neuroprosthetic applications have obtained a great deal of attention by the international research, especially in the bioengineering field, thanks to the huge investments on several proposed projects funded by the political institutions which consider the treatment of this particular disease of fundamental importance for the global community. The aim of these projects is to find a possible solution to restore the functionalities lost by a patient subjected to an upper limb amputation trying to develop, according to physiological considerations, a communication link between the brain in which the significant signals are generated and a motor prosthesis device able to perform the desired action. Moreover, the designed system must be able to give back to the brain a sensory feedback about the surrounding world in terms of pressure or temperature acquired by tactile biosensors placed at the surface of the cybernetic hand. It in fact allows to execute involuntarymovements when for example the armcomes in contact with hot objects. The development of such a closed-loop architecture involves the need to address some critical issues which depend on the chosen approach. Several solutions have been proposed by the researches of the field, each one differing with respect to where the neural signals are acquired, either at the central nervous systemor at the peripheral one,most of themfollowing the former even that the latter is always considered by the amputees amore natural way to handle the artificial limb. This research work is based on the use of intrafascicular electrodes directly implanted in the residual peripheral nerves of the stump which represents a good compromise choice in terms of invasiveness and selectivity extracting electroneurographic (ENG) signals from which it is possible to identify the significant activity of a quite limited number of neuronal cells. In the perspective of the hardware implementation of the resulting solution which can work autonomously without any intervention by the amputee in an adaptive way according to the current characteristics of the processed signal and by using batteries as power source allowing portability, it is necessary to fulfill the tight constraints imposed by the application under consideration involved in each of the various phases which compose the considered closed-loop system. Regarding to the recording phase, the implementation must be able to remove the unwanted interferences mainly due to the electro-stimulations of themuscles placed near the electrodes featured by an order of magnitude much greater in comparison to that of the signals of interest amplifying the frequency components belonging to the significant bandwidth, and to convert them with a high resolution in order to obtain good performance at the next processing phases. To this aim, a recording module for peripheral neural signals will be presented, based on the use of a sigma-delta architecture which is composed by two main parts: an analog front-end stage for neural signal acquisition, pre-filtering and sigma-delta modulation and a digital unit for sigma-delta decimation and system configuration. Hardware/software cosimulations exploiting the Xilinx System Generator tool in Matlab Simulink environment and then transistor-level simulations confirmed that the system is capable of recording neural signals in the order of magnitude of tens of μV rejecting the huge low-frequency noise due to electromyographic interferences. The same architecture has been then exploited to implement a prototype of an 8-channel implantable electronic bi-directional interface between the peripheral nervous system and the neuro-controlled hand prosthesis. The solution includes a custom designed Integrated Circuit (0.35μm CMOS technology), responsible of the signal pre-filtering and sigma-delta modulation for each channel and the neural stimuli generation (in the opposite path) based on the directives sent by a digital control systemmapped on a low-cost Xilinx FPGA Spartan-3E 1600 development board which also involves the multi-channel sigma-delta decimation with a high-order band-pass filter as first stage in order to totally remove the unwanted interferences. In this way, the analog chip can be implanted near the electrodes thanks to its limited size avoiding to add a huge noise to theweak neural signals due to longwires connections and to cause heat-related infections, shifting the complexity to the digital part which can be hosted on a separated device in the stump of the amputeewithout using complex laboratory instrumentations. The system has been successfully tested from the electrical point of view and with in-vivo experiments exposing good results in terms of output resolution and noise rejection even in case of critical conditions. The various output channels at the Nyquist sampling frequency coming from the acquisition system must be processed in order to decode the intentions of movements of the amputee, applying the correspondent electro-mechanical stimulation in input to the cybernetic hand in order to perform the desired motor action. Different decoding approaches have been presented in the past, the majority of them were conceived starting from the relative implementation and performance evaluation of their off-line version. At the end of the research, it is necessary to develop these solutions on embedded systems performing an online processing of the peripheral neural signals. However, it is often possible only by using complex hardware platforms clocked at very high operating frequencies which are not be compliant with the low-power requirements needed to allow portability for the prosthetic device. At present, in fact, the important aspect of the real-time implementation of sophisticated signal processing algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited resources of the former may have on the efficiency/effectiveness of any given algorithm. In this research work it has been addressed the optimization of a state-of-the-art algorithmfor PNS signals decoding that is a step forward for its real-time, full implementation onto a floating-point Digital Signal Processor (DSP). Beyond low-level optimizations, different solutions have been proposed at an high level in order to find the best trade-off in terms of effectiveness/efficiency. A latency model, obtained through cycle accurate profiling of the different code sections, has been drawn in order to perform a fair performance assessment. The proposed optimized real-time algorithmachieves up to 96% of correct classification on real PNS signals acquired through tf-LIFE electrodes on animals, and performs as the best off-line algorithmfor spike clustering on a synthetic cortical dataset characterized by a reasonable dissimilarity between the spikemorphologies of different neurons. When the real-time requirements are joined to the fulfilment of area and power minimization for implantable/portable applications, such as for the target neuroprosthetic devices, only custom VLSI implementations can be adopted. In this case, every part of the algorithmshould be carefully tuned. To this aim, the first preprocessing stage of the decoding algorithmbased on the use of aWavelet Denoising solution able to remove also the in-band noise sources has been deeply analysed in order to obtain an optimal hardware implementation. In particular, the usually overlooked part related to threshold estimation has been evaluated in terms of required hardware resources and functionality, exploiting the commercial Xilinx System Generator tool for the design of the architecture and the co-simulation. The analysis has revealed how the widely used Median Absolute Deviation (MAD) could lead o hardware implementations highly inefficient compared to other dispersion estimators demonstrating better scalability, relatively to the specific application. Finally, two different hardware implementations of the reference decoding algorithm have been presented highlighting pros and cons of each one of them. Firstly, a novel approach based on high-level dataflow description and automatic hardware generation is presented and evaluated on the on-line template-matching spike sorting algorithmwhich represents the most complex processing stage. It starts from the identification of the single kernels with the greater computational complexity and using their dataflow description to generate the HDL implementation of a coarse-grained reconfigurable global kernel characterized by theminimumresources in order to reduce the area and the energy dissipation for the fulfilment of the low-power requirements imposed by the application. Results in the best case have revealed a 71%of area saving compared tomore traditional solutions,without any accuracy penalty. With respect to single kernels execution, better latency performance are achievable stillminimizing the number of adopted resources. The performance in terms of latency can also be improved by tuning the implemented parallelismin the light of a defined number of channels and real-time constraints, by using more than one reconfigurable global kernel in order that they can be exploited to perform the same or different kernels at the same time in a parallel way, due to the fact that each one can execute the relative processing only in a sequential way. For this reason, a second FPGA-based prototype has been proposed based on the use of aMulti-Processor System-on-Chip (MPSoC) embedded architecture. This prototype is capable of respecting the real-time constraints posed by the application when clocked at less than 50 MHz, in comparison to 300 MHz of the previous DSP implementation. Considering that the application workload is extremely data dependent and unpredictable due to the sparsity of the neural signals, the architecture has to be dimensioned taking into account critical worst-case operating conditions in order to always ensure the correct functionality. To compensate the resulting overprovisioning of the system architecture, a software-controllable power management based on the use of clock gating techniques has been integrated in order tominimize the dynamic power consumption of the resulting solution. Summarizing, this research work can be considered a sort of proof-of-concept for the proposed techniques considering all the design issues which characterize each stage of the closed-loop system in the perspective of a portable low-power real-time hardware implementation of the neuro-controlled prosthetic device

Acquisition systems and decoding algorithms of peripheral neural signals for prosthetic applications

During the years, neuroprosthetic applications have obtained a great deal of attention by the international research, especially in the bioengineering field, thanks to the huge investments on several proposed projects funded by the political institutions which consider the treatment of this particular disease of fundamental importance for the global community. The aim of these projects is to find a possible solution to restore the functionalities lost by a patient subjected to an upper limb amputation trying to develop, according to physiological considerations, a communication link between the brain in which the significant signals are generated and a motor prosthesis device able to perform the desired action. Moreover, the designed system must be able to give back to the brain a sensory feedback about the surrounding world in terms of pressure or temperature acquired by tactile biosensors placed at the surface of the cybernetic hand. It in fact allows to execute involuntarymovements when for example the armcomes in contact with hot objects. The development of such a closed-loop architecture involves the need to address some critical issues which depend on the chosen approach. Several solutions have been proposed by the researches of the field, each one differing with respect to where the neural signals are acquired, either at the central nervous systemor at the peripheral one,most of themfollowing the former even that the latter is always considered by the amputees amore natural way to handle the artificial limb. This research work is based on the use of intrafascicular electrodes directly implanted in the residual peripheral nerves of the stump which represents a good compromise choice in terms of invasiveness and selectivity extracting electroneurographic (ENG) signals from which it is possible to identify the significant activity of a quite limited number of neuronal cells. In the perspective of the hardware implementation of the resulting solution which can work autonomously without any intervention by the amputee in an adaptive way according to the current characteristics of the processed signal and by using batteries as power source allowing portability, it is necessary to fulfill the tight constraints imposed by the application under consideration involved in each of the various phases which compose the considered closed-loop system. Regarding to the recording phase, the implementation must be able to remove the unwanted interferences mainly due to the electro-stimulations of themuscles placed near the electrodes featured by an order of magnitude much greater in comparison to that of the signals of interest amplifying the frequency components belonging to the significant bandwidth, and to convert them with a high resolution in order to obtain good performance at the next processing phases. To this aim, a recording module for peripheral neural signals will be presented, based on the use of a sigma-delta architecture which is composed by two main parts: an analog front-end stage for neural signal acquisition, pre-filtering and sigma-delta modulation and a digital unit for sigma-delta decimation and system configuration. Hardware/software cosimulations exploiting the Xilinx System Generator tool in Matlab Simulink environment and then transistor-level simulations confirmed that the system is capable of recording neural signals in the order of magnitude of tens of μV rejecting the huge low-frequency noise due to electromyographic interferences. The same architecture has been then exploited to implement a prototype of an 8-channel implantable electronic bi-directional interface between the peripheral nervous system and the neuro-controlled hand prosthesis. The solution includes a custom designed Integrated Circuit (0.35μm CMOS technology), responsible of the signal pre-filtering and sigma-delta modulation for each channel and the neural stimuli generation (in the opposite path) based on the directives sent by a digital control systemmapped on a low-cost Xilinx FPGA Spartan-3E 1600 development board which also involves the multi-channel sigma-delta decimation with a high-order band-pass filter as first stage in order to totally remove the unwanted interferences. In this way, the analog chip can be implanted near the electrodes thanks to its limited size avoiding to add a huge noise to theweak neural signals due to longwires connections and to cause heat-related infections, shifting the complexity to the digital part which can be hosted on a separated device in the stump of the amputeewithout using complex laboratory instrumentations. The system has been successfully tested from the electrical point of view and with in-vivo experiments exposing good results in terms of output resolution and noise rejection even in case of critical conditions. The various output channels at the Nyquist sampling frequency coming from the acquisition system must be processed in order to decode the intentions of movements of the amputee, applying the correspondent electro-mechanical stimulation in input to the cybernetic hand in order to perform the desired motor action. Different decoding approaches have been presented in the past, the majority of them were conceived starting from the relative implementation and performance evaluation of their off-line version. At the end of the research, it is necessary to develop these solutions on embedded systems performing an online processing of the peripheral neural signals. However, it is often possible only by using complex hardware platforms clocked at very high operating frequencies which are not be compliant with the low-power requirements needed to allow portability for the prosthetic device. At present, in fact, the important aspect of the real-time implementation of sophisticated signal processing algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited resources of the former may have on the efficiency/effectiveness of any given algorithm. In this research work it has been addressed the optimization of a state-of-the-art algorithmfor PNS signals decoding that is a step forward for its real-time, full implementation onto a floating-point Digital Signal Processor (DSP). Beyond low-level optimizations, different solutions have been proposed at an high level in order to find the best trade-off in terms of effectiveness/efficiency. A latency model, obtained through cycle accurate profiling of the different code sections, has been drawn in order to perform a fair performance assessment. The proposed optimized real-time algorithmachieves up to 96% of correct classification on real PNS signals acquired through tf-LIFE electrodes on animals, and performs as the best off-line algorithmfor spike clustering on a synthetic cortical dataset characterized by a reasonable dissimilarity between the spikemorphologies of different neurons. When the real-time requirements are joined to the fulfilment of area and power minimization for implantable/portable applications, such as for the target neuroprosthetic devices, only custom VLSI implementations can be adopted. In this case, every part of the algorithmshould be carefully tuned. To this aim, the first preprocessing stage of the decoding algorithmbased on the use of aWavelet Denoising solution able to remove also the in-band noise sources has been deeply analysed in order to obtain an optimal hardware implementation. In particular, the usually overlooked part related to threshold estimation has been evaluated in terms of required hardware resources and functionality, exploiting the commercial Xilinx System Generator tool for the design of the architecture and the co-simulation. The analysis has revealed how the widely used Median Absolute Deviation (MAD) could lead o hardware implementations highly inefficient compared to other dispersion estimators demonstrating better scalability, relatively to the specific application. Finally, two different hardware implementations of the reference decoding algorithm have been presented highlighting pros and cons of each one of them. Firstly, a novel approach based on high-level dataflow description and automatic hardware generation is presented and evaluated on the on-line template-matching spike sorting algorithmwhich represents the most complex processing stage. It starts from the identification of the single kernels with the greater computational complexity and using their dataflow description to generate the HDL implementation of a coarse-grained reconfigurable global kernel characterized by theminimumresources in order to reduce the area and the energy dissipation for the fulfilment of the low-power requirements imposed by the application. Results in the best case have revealed a 71%of area saving compared tomore traditional solutions,without any accuracy penalty. With respect to single kernels execution, better latency performance are achievable stillminimizing the number of adopted resources. The performance in terms of latency can also be improved by tuning the implemented parallelismin the light of a defined number of channels and real-time constraints, by using more than one reconfigurable global kernel in order that they can be exploited to perform the same or different kernels at the same time in a parallel way, due to the fact that each one can execute the relative processing only in a sequential way. For this reason, a second FPGA-based prototype has been proposed based on the use of aMulti-Processor System-on-Chip (MPSoC) embedded architecture. This prototype is capable of respecting the real-time constraints posed by the application when clocked at less than 50 MHz, in comparison to 300 MHz of the previous DSP implementation. Considering that the application workload is extremely data dependent and unpredictable due to the sparsity of the neural signals, the architecture has to be dimensioned taking into account critical worst-case operating conditions in order to always ensure the correct functionality. To compensate the resulting overprovisioning of the system architecture, a software-controllable power management based on the use of clock gating techniques has been integrated in order tominimize the dynamic power consumption of the resulting solution. Summarizing, this research work can be considered a sort of proof-of-concept for the proposed techniques considering all the design issues which characterize each stage of the closed-loop system in the perspective of a portable low-power real-time hardware implementation of the neuro-controlled prosthetic device

Integrated Circuits and Systems for Smart Sensory Applications

Connected intelligent sensing reshapes our society by empowering people with increasing new ways of mutual interactions. As integration technologies keep their scaling roadmap, the horizon of sensory applications is rapidly widening, thanks to myriad light-weight low-power or, in same cases even self-powered, smart devices with high-connectivity capabilities. CMOS integrated circuits technology is the best candidate to supply the required smartness and to pioneer these emerging sensory systems. As a result, new challenges are arising around the design of these integrated circuits and systems for sensory applications in terms of low-power edge computing, power management strategies, low-range wireless communications, integration with sensing devices. In this Special Issue recent advances in application-specific integrated circuits (ASIC) and systems for smart sensory applications in the following five emerging topics: (I) dedicated short-range communications transceivers; (II) digital smart sensors, (III) implantable neural interfaces, (IV) Power Management Strategies in wireless sensor nodes and (V) neuromorphic hardware