Implantable neurotechnologies: a review of integrated circuit neural amplifiers

Probably not a substantial claim: may not pass S3 (load-bearing).

The size of IC neural amplifiers is an additional consideration for portable or implantable applications, which require a highly miniaturized integrated system with small IC area and overall footprint.

“In addition to noise and power considerations, the size of IC neural amplifiers is an additional consideration when they are used for portable or implantable applications. Both applications require a highly miniaturized integrated system with a small IC area and overall system footprint.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Power scheduling involves modulating the supply current of individual amplifier channels to reduce overall power consumption.

“Power scheduling involves modulating the supply current of individual amplifier channels to reduce the overall power consumption.”

May combine two claims.

The front-end amplifier should have the lowest input-referred noise and higher gain than later stages because the input-referred noise of later stages is referred back to the electrodes through this amplifier's gain.

“This amplifier should have the lowest input-referred noise and higher gain than the subsequent stages, as the RTI noise of all subsequent stages are referred back to the electrodes through the gain of this amplifier [52].”

• cites [52] Harrison RR (2008) The design of integrated circuits to observe brain activity. Proc IEEE 96(7):1203–1216 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Neural recording needs precise, low-noise amplifier systems to acquire and condition weak neural signals from electrode interfaces.

“Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces.”

May combine two claims.

For an electrode site with higher input noise, the corresponding front-end amplifier's power consumption can be reduced, and vice versa.

“For an electrode site that has higher input noise, the power consumption of the corresponding front-end amplifier can be reduced, and vice versa.”

May combine two claims.

Neural amplifiers require high gain and low noise because neural signals are small and span low to mid-range frequencies.

“Thus, neural amplifiers require high-gain and low-noise characteristics. Meeting these design requirements is technologically challenging and requires specialized design strategies.”

May combine two claims.

Because shielding lead wires and amplifiers is not always practical, a high CMRR is an important and desired characteristic.

“Although electrical shielding would reduce this common-mode interference by reducing the induced current coupled into the amplifier, it is not always practical to shield the lead wires and the amplifiers. Therefore, a high CMRR is an important and desired characteristic.”

• AssumptionRests on an assumption: Neural amplifiers typically have a common-mode rejection ratio between 70 and 120 dB, which is enough to suppress common-mode interference in most biopotential recordings.

May combine two claims.

Static electric charges typically encountered can produce voltages above 25 kV, so proper ESD design and correct device handling procedures are still required.

“Although most ICs are designed to meet standard ESD specifications [3, 4], the static electric charges that are typically encountered may result in voltages higher than 25 kV [115], and hence proper ESD design of the ICs and correct device handling procedures are still required.”

• cites [3] ANSI/ESD S5.3.1-2009 (2009) Electrostatic discharge sensitivity testing—charged device model (CDM)—component level. In: Electrostatic Discharge Association sourceNot checked yet

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• cites [4] ANSI/ESDA/JEDEC JS-001-2012 (2012) ESDA/JEDEC joint standard for electrostatic discharge sensitivity testing—human body model (HBM)—component level. Electrostatic Discharge AssociationNot checked yet

  Not checked in the free run.

• cites [115] Sadiku MNO, Akujuobi CM (2004) Electrostatic discharge (ESD). IEEE Potentials 22(5):39–41 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Custom-designed neural recording ICs have advantages over commercially available systems, including miniaturized form factor, low weight, and low power consumption, which enable portable and implantable neurodevices.

“However, custom-designed neural recording ICs offer several prime advantages, including miniaturized form factor, low weight and low power consumption. These properties allow for portable and implantable neurodevices.”

May combine two claims.

Al-ashmouny et al. reported a 128-input channel neural recording IC in which only 16 inputs were selectively routed to the front-end amplifiers, achieving power and area reduction.

“For example, Al-ashmouny et al. reported a 128-input channel neural recording IC [2] with only 16 inputs selectively routed to the front-end amplifiers, therefore achieving power and area reduction.”

• cites [2] Al-ashmouny KM, Chang S, Yoon E (2012) A 4 µW/Ch analog front-end module with moderate inversion and power-scalable sampling operation for 3-D neural microsystems. IEEE Trans Biomed Circuits Syst 6(5):403–413 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Lopez et al. multiplexed 455 electrode inputs to 52 amplifiers.

“Another recent work by Lopez et al. [77] adopted the same method and multiplexed 455 electrode inputs to 52 amplifiers.”

• cites [77] Lopez CM, Andrei A, Mitra S, Welkenhuysen M, Eberle W, Bartic C, Puers R, Yazicioglu RF, Gielen GGE (2014) An implantable 455-active-electrode 52-channel CMOS neural probe. IEEE J Solid State Circuits 49(1):248–261 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

A trade-off between IC die size and on-chip functionality is generally required.

“A trade-off between the IC die size and functionality is generally required.”

May combine two claims.

Multiplexing a high-density electrode array to a smaller amplifier array is a widely used resource-sharing technique that relies on not all electrode sites providing useful information after implantation or on necessary information being obtainable from a small subset, although the useful subset is not known in advance.

“The first widely used technique consists of multiplexing a high-density electrode array to a much smaller amplifier array. This strategy leverages the fact that not all electrode sites may provide useful information after implantation [97, 101, 145] or that the necessary information can be obtained from a small subset of electrodes, although the useful electrode subset is not known a priori [118].”

• cites [97] Olsson R, Wise K (2005) A three-dimensional neural recording microsystem with implantable data compression circuitry. IEEE J Solid State Circuits 40(12):2796–2804 sourceNot checked yet

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• cites [101] Perlin GE, Sodagar AM, Wise KD (2006) Neural recording front-end designs for fully implantable neuroscience applications and neural prosthetic microsystems. In: Proceedings of international conference on IEEE engineering in medicine biology society, 2982–2985 sourceNot checked yet

  Not checked in the free run.

• cites [145] Wise KD, Anderson DJ, Hetke JF, Kipke DR, Najafi K (2004) Wireless implantable microsystems: high-density electronic interfaces to the nervous system. Proc IEEE 92(1):76–97 sourceNot checked yet

  Not checked in the free run.

• cites [118] Sanchez JC, Carmena JM, Lebedev MA, Nicolelis MAL, Harris JG, Principe JC (2004) Ascertaining the importance of neurons to develop better brain-machine interfaces. IEEE Trans Biomed Eng 51(6):943–953 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Chae et al. described a method to minimize the power-area product of a neural recording system by properly selecting the number of channels that share a single ADC.

“Chae et al. [16] described a method to minimize the power–area product of a neural recording system though the proper selection of the number of channels that share a single ADC.”

• cites [16] Chae M, Yang Z, Yuce M, Hoang L, Liu W (2009) A 128-channel 6 mW wireless neural recording IC with spike feature extraction and UWB transmitter. IEEE Trans Neural Syst Rehabil Eng 17(4):312–321 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Miniaturized, low-power IC neural amplifiers are now used in emerging implantable neural prosthesis technologies.

“Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies.”

May combine two claims.

Neural signals are generally smaller in amplitude than cardiac and muscle electrical signals and span frequencies from below 100 Hz to tens of kHz.

“They are generally smaller in amplitude than electrical signals of the heart and muscle, and they span low- (below 100 Hz) to mid-range (10 s of kHz) frequencies.”

• cites [143] Webster JG (ed) (1998) Medical instrumentation: application and design. Wiley, New yorkNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

A dynamic voltage folding circuit remapped the amplifiers' large output swing to fit the ADC's limited input swing.

“A dynamic voltage folding circuit then remapped the large output swing of the amplifiers to fit the limited input swing of the ADC.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The gate area optimization technique proposed by Ng and Xu must be used to reduce input-referred noise from flicker noise and the capacitor transformer effect for complementary input pairs.

“Thus, the gate area optimization technique proposed by Ng and Xu [92] must be used to reduce the input-referred noise due to flicker noise and capacitor transformer effect for the complimentary input pairs.”

• cites [92] Ng KA, Xu YP (2013) A compact, low input capacitance neural recording amplifier. IEEE Trans Biomed Circuits Syst 7(5):610–620 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Pseudo-resistors formed by PMOS transistors help establish proper DC negative feedback bias and, together with Cfb, define the low-side 3-dB cutoff frequency of the neural amplifier.

“The pseudo-resistors formed by PMOS transistors help establish a proper DC negative feedback bias and together with Cfb also define the low-side 3-dB cutoff frequency of the neural amplifier.”

May combine two claims.

Wattanapanitch et al. proposed an NEF optimization scheme for low-voltage neural amplifiers using the folded cascode OTA, which was adopted in later studies.

“Wattanapanitch et al. [142] further proposed an NEF optimization scheme for low-voltage neural amplifiers implemented using the folded cascode OTA, which were adopted in later studies [103, 141].”

• cites [142] Wattanapanitch W, Fee M, Sarpeshkar R (2007) An energy-efficient micropower neural recording amplifier. IEEE Trans Biomed Circuits Syst 1(2):136–147 sourceNot checked yet

  Not checked in the free run.

• cites [103] Qian C, Parramon J, Sanchez-Sinencio E (2011) A micropower low-noise neural recording front-end circuit for epileptic seizure detection. IEEE J Solid State Circuits 46(6):1392–1405 sourceNot checked yet

  Not checked in the free run.

• cites [141] Wattanapanitch W, Sarpeshkar R (2011) A low-power 32-channel digitally programmable neural recording integrated circuit. IEEE Trans Biomed Circuits Syst 5(6):592–602 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The choice of front-end amplifier gain is influenced by the required application, whether CNS or PNS recording, and by the system's power supply.

“The choice of gain is influenced by the required application (CNS or PNS recording) and the system’s power supply [107].”

• cites [107] Rieger R, Schuettler M, Pal D, Clarke C, Langlois P, Taylor J, Donaldson N (2006) Very low-noise ENG amplifier system using CMOS technology. IEEE Trans Neural Syst Rehabil Eng 14(4):427–437 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The OTA's thermal noise is inversely related to the bias current supplied to the input differential pair, while flicker noise is inversely proportional to the active gate area of that pair.

“The thermal noise of the OTA is inversely related to the amount of bias current supplied to the input differential pair of the OTA (M1 and M2), whereas the flicker noise component is inversely proportional to the active gate area of the input different pair.”

May combine two claims.

To suppress noise from downstream signal processing stages, a high amplifier gain is desired and achieved by a high Cin/Cfb ratio, usually with a large Cin, but this increases silicon area and lowers input impedance.

“To suppress noise contributions from downstream signal processing stages, a high amplifier gain is desired and achieved by incorporating a high Cin/Cfb ratio (usually by using a large Cin), but at the expense of increased silicon area and lowered input impedance.”

May combine two claims.

Continued shrinking of fine-line CMOS processes has helped increase channel counts and add capabilities such as on-chip analog-to-digital conversion and digital radio transmission.

“The steady reduction in fine-line CMOS technologies has contributed to increased channel counts [6, 77] and expanded capabilities, such as on-chip analog-to-digital conversion [49, 156] and digital radio transmission [16, 67].”

• cites [6] Aziz JNY, Abdelhalim K, Shulyzki R, Genov R, Bardakjian BL, Derchansky M, Serletis D, Carlen PL (2009) 256-Channel neural recording and delta compression microsystem with 3D electrodes. IEEE J Solid State Circuits 44(3):995–1005 sourceNot checked yet

  Not checked in the free run.

• cites [77] Lopez CM, Andrei A, Mitra S, Welkenhuysen M, Eberle W, Bartic C, Puers R, Yazicioglu RF, Gielen GGE (2014) An implantable 455-active-electrode 52-channel CMOS neural probe. IEEE J Solid State Circuits 49(1):248–261 sourceNot checked yet

  Not checked in the free run.

• cites [49] Han D, Zheng Y, Rajkumar R, Dawe G, Je M (2014) A 0.45 V 100-channel neural-recording IC with sub-µW/channel consumption in 0.18 µm CMOS. IEEE Trans Biomed Circuits Syst 7(6):735–746 sourceNot checked yet

  Not checked in the free run.

• cites [156] Zou X, Liu L, Cheong JH, Yao L, Li P, Cheng MY, Goh WL, Rajkumar R, Dawe GS, Cheng KW, Je M (2013) A 100-channel 1-mW implantable neural recording IC. IEEE Trans Circuits Syst I 60(10):2584–2596 sourceNot checked yet

  Not checked in the free run.

• cites [16] Chae M, Yang Z, Yuce M, Hoang L, Liu W (2009) A 128-channel 6 mW wireless neural recording IC with spike feature extraction and UWB transmitter. IEEE Trans Neural Syst Rehabil Eng 17(4):312–321 sourceNot checked yet

  Not checked in the free run.

• cites [67] Lee SB, Lee H-M, Kiani M, Jow U-M, Ghovanloo M (2010) An inductively powered scalable 32-channel wireless neural recording system-on-a-chip for neuroscience applications. IEEE Trans Biomed Circuits Syst 4(6):360–371 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Recent works reported that careful design of the OTA A1 makes low current consumption and low input-referred noise easily achievable.

“Recent works have also reported that by carefully designing the OTA A1, low current consumption and low input-referred noise are easily achievable [63, 141, 142, 156].”

• cites [63] Johnson B, Molnar A (2013) An orthogonal current-reuse amplifier for multi-channel sensing. IEEE J Solid State Circuits 48(6):1487–1496 sourceNot checked yet

  Not checked in the free run.

• cites [141] Wattanapanitch W, Sarpeshkar R (2011) A low-power 32-channel digitally programmable neural recording integrated circuit. IEEE Trans Biomed Circuits Syst 5(6):592–602 sourceNot checked yet

  Not checked in the free run.

• cites [142] Wattanapanitch W, Fee M, Sarpeshkar R (2007) An energy-efficient micropower neural recording amplifier. IEEE Trans Biomed Circuits Syst 1(2):136–147 sourceNot checked yet

  Not checked in the free run.

• cites [156] Zou X, Liu L, Cheong JH, Yao L, Li P, Cheng MY, Goh WL, Rajkumar R, Dawe GS, Cheng KW, Je M (2013) A 100-channel 1-mW implantable neural recording IC. IEEE Trans Circuits Syst I 60(10):2584–2596 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The most common front-end amplifier for IC neural recordings was first proposed by Najafi and Wise and later refined by Harrison to its present circuit.

“The most common front-end amplifier for IC neural recordings was first proposed by Najafi and Wise [89] and then further refined by Harrison [52] to its present circuit shown in Fig. 4.”

• cites [89] Najafi K, Wise K (1986) An implantable multielectrode array with on-chip signal processing. IEEE J Solid State Circuits 21(6):1035–1044 sourceNot checked yet

  Not checked in the free run.

• cites [52] Harrison RR (2008) The design of integrated circuits to observe brain activity. Proc IEEE 96(7):1203–1216 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Although input transistor gate areas are usually large to reduce flicker noise, that reduction is counteracted by an increased capacitance multiplying effect from the parasitic gate area.

“Although the gate areas of the input transistors are usually large to reduce the flicker noise component, the flicker noise reduction is contradicted by the increased capacitance multiplying effect contributed by the parasitic gate area [92].”

• cites [92] Ng KA, Xu YP (2013) A compact, low input capacitance neural recording amplifier. IEEE Trans Biomed Circuits Syst 7(5):610–620 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Ng and Xu proposed relaxing the area-gain trade-off by introducing additional shunt elements onto the negative feedback network.

“However, Ng and Xu proposed relaxing this area–gain trade-off by introducing additional shunt elements onto the negative feedback network [92].”

• cites [92] Ng KA, Xu YP (2013) A compact, low input capacitance neural recording amplifier. IEEE Trans Biomed Circuits Syst 7(5):610–620 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The current-reuse technique doubles the gate capacitance of the input differential pair.

“Although this current-reuse technique is a promising method for reducing the thermal noise component, it doubles the gate capacitance of the input differential pair.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Al-ashmouny et al. reported an implementation in which the ADC supply voltage was scalable according to sampling rate, throttling power consumption.

“Similarly, Al-ashmouny et al. [2] reported an implementation where the supply voltage of the ADC was made scalable according to the sampling rate, throttling the power consumption.”

• cites [2] Al-ashmouny KM, Chang S, Yoon E (2012) A 4 µW/Ch analog front-end module with moderate inversion and power-scalable sampling operation for 3-D neural microsystems. IEEE Trans Biomed Circuits Syst 6(5):403–413 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Recent studies have attempted to reduce silicon area by using smaller unit capacitors or by reducing amplifier gain.

“Recent studies have attempted to reduce the silicon area by using smaller unit capacitors or reducing the amplifier gain [77, 78].”

• cites [77] Lopez CM, Andrei A, Mitra S, Welkenhuysen M, Eberle W, Bartic C, Puers R, Yazicioglu RF, Gielen GGE (2014) An implantable 455-active-electrode 52-channel CMOS neural probe. IEEE J Solid State Circuits 49(1):248–261 sourceNot checked yet

  Not checked in the free run.

• cites [78] Majidzadeh V, Schmid A, Leblebici Y (2011) Energy efficient low-noise neural recording amplifier with enhanced noise efficiency factor. IEEE Trans Biomed Circuits Syst 5(3):262–271 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Muller et al. introduced the power efficiency factor, which accounts for both operating current and supply voltage and therefore provides a better comparison of amplifier performance.

“Recently, Muller et al. [86] introduced the power efficiency factor (PEF), which takes into account both the operating current and the supply voltage and therefore provides a better comparison of the amplifier’s performance.”

• cites [86] Muller R, Gambini S, Rabaey JM (2013) A 0.013 mm 2, 5 µW, DC-Coupled neural signal acquisition IC With 0.5 V supply. IEEE J Solid State Circuits 47(1):232–243 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The gate areas of the input differential pair must be appropriately sized according to the method described by Ng and Xu.

“Hence, the gate areas of the input differential pair must be appropriately sized according to the method described by Ng and Xu [92].”

• cites [92] Ng KA, Xu YP (2013) A compact, low input capacitance neural recording amplifier. IEEE Trans Biomed Circuits Syst 7(5):610–620 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Front-end amplifier gains range from 200 to 10,000.

“Front-end amplifier gains range from 200 to 10,000.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Unlike an operational amplifier, an OTA has no power-consuming output driver circuit because it does not need to bias resistive elements other than the high-resistance pseudo-resistor in the feedback network.

“As opposed to an operational amplifier (OpAmp), the OTA does not have a power-consuming output driver circuit, as it does not need to bias any resistive elements other than the high-resistance pseudo-resistor in the feedback network in Fig. 4.”

May combine two claims.

For both the 2-stage Miller and symmetrical cascode OTAs, a significant part of total supply current is used for biasing and feedback stability at the second stages, leaving less current for the input differential stages and leading to higher NEF.

“For both types of OTAs, a significant part of the total supply current is only used for maintaining proper biasing and feedback stability at their second stages, leaving less current to bias their input differential stages and therefore leading to a higher NEF.”

May combine two claims.

Amplifier noise is typically designed to be lower than electrode noise and is maintained below 5 μVrms for CNS-recording amplifiers and below 1 μVrms for PNS-recording amplifiers.

“The noise introduced by the amplifier is typically designed to be lower than that introduced by the electrodes and, for a majority of neural applications, is maintained below 5 µVrms for amplifiers used to record CNS signals and less than 1 µVrms for PNS-recording amplifiers [76, 105].”

• cites [76] Loi D, Carboni C, Angius G, Angotzi GN, Barbaro M, Raffo L, Raspopovic S, Navarro X (2011) Peripheral neural activity recording and stimulation system. IEEE Trans Biomed Circuits Syst 5:368–379 sourceNot checked yet

  Not checked in the free run.

• cites [105] Rieger R, Taylor J, Demosthenous A, Donaldson N, Langlois PJ (2003) Design of a low-noise preamplifier for nerve cuff electrode recording. IEEE J Solid State Circuits 38(8):1373–1379 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Restricting an amplifier's recording band to the frequencies of interest markedly lowers the amplifier's noise contribution and thereby raises recording quality.

“By constraining the amplifiers to record only within the bandwidths of interest, the noise contribution from the amplifier is significantly reduced and therefore improves the recording quality.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Han et al. used 0.9 V and 0.45 V supply domains for the amplification stage and ADC, respectively.

“Finally, the chip reported by Han et al. [48] used 0.9 and 0.45 V supply domains for the amplification stage and ADC, respectively.”

• cites [48] Han D, Zheng Y, Rajkumar R, Dawe GS, Je M (2014) A 0.45 V 100-Channel neural-recording IC with sub-uW/channel consumption in 0.18 CMOS. IEEE Trans Biomed Circuits Syst 7(6):735–746 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The telescopic cascode OTA achieves the lowest NEF among the listed OTAs because all supply current is devoted to biasing the differential pair, allowing higher input gm and thus lower noise and NEF.

“The telescopic cascode OTA (Fig. 5c) achieves the lowest NEF among the listed OTAs, as all of the supply current is devoted to biasing the differential pair, allowing it to obtain a higher input gm (and hence lower noise and NEF) compared to the prior 2 OTAs.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Neuroscience studies commonly place electrodes into specific cortical regions to record neural electrical activity.

“Typical neuroscience studies involve inserting electrodes [10, 90, 144] into specific regions of the cortex to acquire neural electrical activity.”

• cites [10] “Blackrock microsystems.” [Online]. Available: http://www.blackrockmicro.com/Not checked yet

  Not checked in the free run.

• cites [90] “NeuroNexus Technologies.” [Online]. Available: http://www.neuronexustech.comNot checked yet

  Not checked in the free run.

• cites [144] Wise KD, Angell JB, Starr A (1970) An integrated-circuit approach to extracellular microelectrodes. IEEE Trans Bio-med Eng 17(3):238–247 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Advances in IC design and fabrication now allow neural recording systems to include wireless telemetry for data and sometimes wireless power transfer.

“With continuous improvements in IC design and fabrication technology, IC neural recording systems can be now integrated with wireless telemetry for data and, in some cases, wireless power transfer [67, 94].”

• cites [67] Lee SB, Lee H-M, Kiani M, Jow U-M, Ghovanloo M (2010) An inductively powered scalable 32-channel wireless neural recording system-on-a-chip for neuroscience applications. IEEE Trans Biomed Circuits Syst 4(6):360–371 sourceNot checked yet

  Not checked in the free run.

• cites [94] Ng KA, Xu L, Li X, Yen S, Je M, Xu YP, Tan TC (2012) An inductively powered CMOS multichannel bionic neural link for peripheral nerve function restoration. In: IEEE asian solid state circuits conference, 181–184 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Neuropace system is a commercially available device that performs closed-loop neurostimulation to treat epilepsy.

“For example, the Neuropace system (California, USA) [91] is a commercially available device that performs closed-loop neurostimulation for the treatment of epilepsy.”

• cites [91] “Neuropace Inc.” [Online]. Available: http://www.neuropace.com/product/overview.htmlNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Deep brain stimulation is especially effective for movement disorders including Parkinson's disease, dystonia and essential tremor.

“For example, deep brain stimulation (DBS) is particularly successful in treating movement disorders, such as Parkinson’s Disease, dystonia and essential tremor [5, 24, 83].”

• cites [5] Awan NR, Lozano A, Hamani C (2009) Deep brain stimulation: current and future perspectives. Neurosurg Focus 27:E2 sourceNot checked yet

  Not checked in the free run.

• cites [24] Coffey RJ (2009) Deep brain stimulation devices: a brief technical history and review. Artif Organs 33(3):208–220 sourceNot checked yet

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• cites [83] Miocinovic S, Somayajula S, Chitnis S, Vitek JL (2013) History, applications, and mechanisms of deep brain stimulation. JAMA Neurol 70(2):163–171 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

CNS-based neuroprostheses, or brain-machine interfaces, decode neural electrical activity to control robotic limbs or to stimulate muscles for restoring limb function.

“CNS-based neuroprostheses, or brain–machine interfaces (BMIs), are systems whereby neural electrical activities are decoded and used to control robotic limbs [76, 89, 105] or to stimulate muscles for restoring limb function [35].”

• cites [76] Loi D, Carboni C, Angius G, Angotzi GN, Barbaro M, Raffo L, Raspopovic S, Navarro X (2011) Peripheral neural activity recording and stimulation system. IEEE Trans Biomed Circuits Syst 5:368–379 sourceNot checked yet

  Not checked in the free run.

• cites [89] Najafi K, Wise K (1986) An implantable multielectrode array with on-chip signal processing. IEEE J Solid State Circuits 21(6):1035–1044 sourceNot checked yet

  Not checked in the free run.

• cites [105] Rieger R, Taylor J, Demosthenous A, Donaldson N, Langlois PJ (2003) Design of a low-noise preamplifier for nerve cuff electrode recording. IEEE J Solid State Circuits 38(8):1373–1379 sourceNot checked yet

  Not checked in the free run.

• cites [35] Ethier C, Oby ER, Bauman MJ, Miller LE (2012) Restoration of grasp following paralysis through brain-controlled stimulation of muscles. Nature 485(7398):368–371 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Closed-loop DBS has been proposed to deliver adaptive neuromodulation synchronized to each patient's real-time pathological brain state.

“Closed-loop DBS has been proposed to provide synchronous adaptive neuromodulation based on real-time pathological brain states in each patient [15, 83, 121].”

• cites [15] Carron R, Chaillet A, Filipchuk A, Pasillas-Lépine W, Hammond C (2013) Closing the loop of deep brain stimulation. Front Syst Neurosci 7(2):112Not checked yet

  Not checked in the free run.

• cites [83] Miocinovic S, Somayajula S, Chitnis S, Vitek JL (2013) History, applications, and mechanisms of deep brain stimulation. JAMA Neurol 70(2):163–171 sourceNot checked yet

  Not checked in the free run.

• cites [121] Santos FJ, Costa RM, Tecuapetla F (2011) Stimulation on demand: closing the loop on deep brain stimulation. Neuron 72:197–198 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Such recording systems are often powered by small lightweight batteries or by wireless power transfer.

“Often, such systems are powered using miniaturized and light-weight battery packs [36] or wireless power transfer systems [135].”

• cites [36] Fan D, Rich D, Holtzman T, Ruther P, Dalley JW, Lopez A et al. (2011) A wireless multi-channel recording system for freely behaving mice and rats. PLoS One 6(7):e22033. doi: 10.1371/journal.pone.0022033 sourceNot checked yet

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• cites [135] Thomas SJ, Harrison RR, Leonardo A, Reynolds MS (2012) A battery-free multichannel digital neural/EMG telemetry system for flying insects. IEEE Trans Biomed Circuits Syst 6(5):424–436 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Putting these modules on a single neuromodulation chip greatly reduces the form factor and simplifies implantation packaging.

“However, integration of these modules onto a single neuromodulation chip significantly decreases the form factor and simplifies the packaging required for implantation.”

May combine two claims.

The added battery weight that rodents must carry often causes fatigue and shortens experiments.

“This adds additional weight that the rodent subjects must bear, which often leads to animal fatigue and limits the duration of experiments.”

• AssumptionRests on an assumption: Battery weight on rodents often leads to animal fatigue and limits experiment duration.

May combine two claims.

So far, IC-based PNS amplifier implementations have been reported only rarely, and existing technologies have generally been used only in acute experiments.

“Until now, there have been limited reports of IC-based PNS amplifier implementations, and existing technologies have generally only been applied to acute experiments.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

DBS also serves as an alternative treatment for pharmacoresistant epilepsy, pain control and psychiatric disorders.

“DBS is also an alternative treatment for pharmacoresistant epilepsy, pain control and psychiatric disorders [5].”

• cites [5] Awan NR, Lozano A, Hamani C (2009) Deep brain stimulation: current and future perspectives. Neurosurg Focus 27:E2 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Current DBS treatments use open-loop configurations and need periodic clinician visits to adjust stimulation for best efficacy.

“However, current DBS therapies are conducted in open-loop configurations and require periodic visits with a clinician to make adjustments for optimal stimulation efficacy.”

May combine two claims.

Studies of patients implanted with this device have shown sustained significant seizure reductions and improved quality of life.

“Recent studies on patients implanted with this device have exhibited significant reductions in seizures over a sustained period of time, and hence, the patients experience an improved quality of life [8].”

• cites [8] Bergey GK, Morrell MJ, Mizrahi EM, Goldman A, King-Stephens D, Nair D, Srinivasan S, Jobst B, Gross RE, Shields DC, Barkley G, Salanova V, Olejniczak P, Cole A, Cash SS, Noe K, Wharen R, Worrell G, Murro AM, Edwards J, Duchowny M, Spencer D, Smith M, Geller E, Gwinn R, Skidmore C, Eisenschenk S, Berg M, Heck C, Van Ness P, Fountain N, Rutecki P, Massey A, O’Donovan C, Labar D, Duckrow RB, Hirsch LJ, Courtney T, Sun FT, Seale CG (2015) Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology 84(8):810–817 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The main aim of such studies is to learn how the activity of neuronal groups relates to sensation, behavior and cognition.

“The primary goal of such studies is to understand how the activities of groups of neurons are related to sensation, behavior and cognition [14, 117].”

• cites [14] Buzsáki G (2004) Large-scale recording of neuronal ensembles. Nat Neurosci 7(5):446–451 sourceNot checked yet

  Not checked in the free run.

• cites [117] Sahin NT, Pinker S, Cash SS, Schomer D, Halgren E (2009) Sequential processing of lexical, grammatical, and phonological information within Broca’s area. Science 326:445–449 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

These requirements demand more power-efficient ways to transmit recorded data off-chip.

“These needs require more power-efficient methods to send recorded data off-chip.”

Classified as probably not a substantial claim.

Studying naturally behaving animals demands recording systems that are highly miniaturized, small and light.

“This requires recording systems with a high degree of miniaturization, a small form factor and reduced weight.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The push to place more recording channels on one IC and to add more integrated features drives these design choices.

“These design choices are driven by the trend of packing increasingly higher numbers of recording channels on a single IC and the desire of researchers to have more integrated features.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Although miniature wireless recording ICs could simplify BMI interfaces, major regulatory approvals are needed before they can be safely used in humans, especially for implantable applications.

“Although many of the miniature and lightweight wireless recording systems ICs [12, 20, 40, 84, 120, 136, 151] discussed in the earlier sections of this review would simplify the BMI interface, major regulatory approvals (FCC, FDA, IEC) are needed before these devices can be safely applied to human use (especially for implantable applications).”

• AssumptionRests on an assumption: Major regulatory approvals (FCC, FDA, IEC) are required before wireless neural recording devices can be safely applied to human use.

May combine two claims.

Micera et al. used peripheral nerve stimulation to evoke graded sensory perceptions in a human amputee while decoding movement intention from residual muscle activity to actuate a robotic arm.

“Most recently, Micera et al. used peripheral nerve stimulation to evoke graded sensory perceptions in a human amputee subject while using the subject’s residual muscle activity to decode movement intention and actuate a robotic arm (Fig. 10) [82, 109].”

• cites [82] Micera S, Rossini PM, Rigosa J, Citi L, Carpaneto J, Raspopovic S, Tombini M, Cipriani C, Assenza G, Carrozza MC, Hoffmann K-P, Yoshida K, Navarro X, Dario P (2011) Decoding of grasping information from neural signals recorded using peripheral intrafascicular interfaces. J Neuroeng Rehabil 8:53 sourceNot checked yet

  Not checked in the free run.

• cites [109] Rossini PM, Micera S, Benvenuto A, Carpaneto J, Cavallo G, Citi L, Cipriani C, Denaro L, Denaro V, Di Pino G, Ferreri F, Guglielmelli E, Hoffmann KP, Raspopovic S, Rigosa J, Rossini L, Tombini M, Dario P (2010) Double nerve intraneural interface implant on a human amputee for robotic hand control. Clin Neurophysiol 121(5):777–783 sourceNot checked yet

  Not checked in the free run.