Clinical applications of penetrating neural interfaces and Utah Electrode Array technologies

May combine two claims.

Silicon carbide has been shown to offer enhanced passivation of electrodes and electronic circuitry in saline environments and may provide long-term mechanical stability in vivo.

“Silicon carbide is one such material that has been shown to offer enhanced passivation of electrodes and electronic circuitry when tested in saline environments and may provide long-term mechanical stability in vivo (Faßbender et al 2000).”

• cites Faßbender et al 2000Not checked yet

  Not checked in the free run.

May combine two claims.

Attempting to push a UEA into the brain tends to compress the brain surface, and only perimeter electrodes implant, and only to a limited depth.

“attempting to push the array into the brain only tends to compress the surface of the brain; and only electrodes around the perimeter of the array experience implantation, and only to a limited depth.”

• cites Rousche and Normann 1992Not checked yet

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May combine two claims.

PEDOT is a polymeric conductor that has been shown to achieve impedance reductions, but protecting this coating from shear forces during electrode insertion into neural tissues is unresolved.

“PEDOT, is a polymeric conductor that has been shown to achieve such impedance reductions, but protecting this coating from the shear forces associated with electrode insertion into neural tissues is an unresolved problem (Frost et al 2012).”

• cites Frost et al 2012Not checked yet

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May combine two claims.

Implantation of a USEA into a peripheral nerve impales some vessels, causing a breach of the blood brain barrier and local accumulation of reactive microphages around the implanted electrodes.

“The spatial organization of the vasculature of the peripheral nerves cannot be predicted prior to implantation, and some vessels are likely to be impaled by the penetrating electrodes, causing a breach of the blood brain barrier and a local accumulation of reactive microphages around the implanted electrodes (Christensen et al 2014, Wark et al 2014).”

• cites Christensen et al 2014Not checked yet

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• cites Wark et al 2014Not checked yet

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• AssumptionRests on an assumption: The spatial organization of the vasculature of peripheral nerves cannot be predicted prior to implantation.

May combine two claims.

Several studies have shown that the ability of patients with tetraplegia to plan and imagine movements is usually intact and that it is possible to bypass damaged neural pathways with penetrating microelectrode arrays that record brain activity reflecting motor intention.

“Several studies have shown that the ability of patients with tetraplegia to plan and imagine movements is usually intact and that it is possible to bypass the damaged neural pathways with the use of penetrating microelectrode arrays that record the brain activity that reflects the individual's motor intention.”

• AssumptionThe authors state this as an assumption: There is a causative correlation between spatio-temporal neural activity patterns in motor cortex and a paralyzed subject's intent to perform particular volitional movements.

May combine two claims.

High density Utah slanted electrode arrays implanted in rat sciatic nerves caused transient impairment of peripheral nerve function, but normal wheel running was observed two weeks post-implantation.

“These high density electrode arrays have been implanted in rat sciatic nerves, and although wheel running measurements have shown a transient impairment of peripheral nerve function, normal levels of wheel running were observed in two weeks post-implantation (Wark et al 2014).”

• cites Wark et al 2014Not checked yet

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May combine two claims.

Sensorized hand prostheses with up to 23 degrees-of-freedom are presently available, or will soon become available.

“sensorized hand prostheses with up to 23 degrees-of-freedom are presently available, or will soon become available (Krausz et al 2015, Veer 2015).”

• cites Krausz et al 2015Not checked yet

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• cites Veer 2015Not checked yet

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May combine two claims.

Important limitations of the myoelectric approach include difficulty in recording suitable EMG signals and a shortage of information for control of multiple functions.

“However there are important limitations of this approach such as the difficulty in recording suitable EMG signals and the shortage of information for control of multiple functions (Schultz and Kuiken 2011).”

• cites Schultz and Kuiken 2011Not checked yet

  Not checked in the free run.

May combine two claims.

Patients with motor function impairments can use signals from motor regions of their brains to control a cursor on a screen or steer a robotic arm to reach, grasp, and manipulate an object or a glass.

“Thus patients with motor function impairments can use the signals from the motor regions of their brains to, for example, control a cursor on a screen so that they can efficiently interact with a computer, or, as shown in figure 8, to steer a robotic arm to reach out, grasp and manipulate an object or a glass in order to take a drink (Hochberg et al 2012, Collinger et al 2013).”

• cites Hochberg et al 2012Not checked yet

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• cites Collinger et al 2013Not checked yet

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• AssumptionThe authors state this as an assumption: There is a causative correlation between spatio-temporal neural activity patterns in motor cortex and a paralyzed subject's intent to perform particular volitional movements.

May combine two claims.

Most electrodes evoked a tingling sensation, while other electrodes evoked percepts of brushing along a finger or discrete proprioceptive percepts such as finger flexing.

“Most electrodes evoked a tingling sensation, but other electrodes evoked the percepts of 'brushing along a finger' or discrete proprioceptive percepts such as the flexing of a finger.”

May combine two claims.

USEAs can be implanted in severed peripheral nerves above the site of amputation, and the tips of the implanted electrodes will be distributed throughout the fascicles of the implanted nerves.

“USEAs can be implanted in severed peripheral nerves above the site of amputation, and the tips of the implanted electrodes will be distributed throughout the fascicles of the implanted nerves (Branner et al 2004, Wark et al 2014).”

• cites Branner et al 2004Not checked yet

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• cites Wark et al 2014Not checked yet

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May combine two claims.

Only a subset of implanted electrodes evoked sensory percepts because many did not abut sensory fibers.

“As many of the implanted electrodes did not abut sensory fibers, currents injected via only a subset of electrodes evoked these sensory percepts”

May combine two claims.

Continuous encapsulation produces an ever-growing barrier between electrode tips and surrounding neurons, causing single unit recording quality to deteriorate and the number of electrodes recording single units to decrease.

“This continuous encapsulation process produces an ever growing barrier between the electrode tips and the surrounding neurons, and single unit recording quality gradually deteriorates and the number of electrodes that successfully record single units also gradually decreases.”

May combine two claims.

For a 400 micron spaced USEA, no fiber in the nerve is further than 200 microns from an active electrode tip, and most fibers are much closer.

“Because of the gradient in electrode lengths, for a 400 micron spaced USEA, no fiber in the nerve is further than 200 microns from an active electrode tip, and most fibers are much closer.”

May combine two claims.

Inserting a complex three-dimensional structure into the highly vascularized cortex inevitably impales capillaries and compromises the blood-brain barrier.

“The cortical tissues are highly vascularized, so it is impossible to insert such a complex three-dimensional structure into the cortex without impaling capillaries, causing the blood-brain-barrier to be compromised by the implantation process.”

May combine two claims.

Penetrating microelectrode arrays implanted in paralyzed subjects allow unprecedented access to CNS neurons and provide insights into neural mechanisms of motor control that are only marginally available from surface field potentials.

“Penetrating microelectrode arrays, implanted in paralyzed subjects allow unprecedented access to the neurons of the CNS and provide insights into the neural mechanisms of motor control which is only marginally available from surface field potentials (Hatsopoulos and Donoghue 2009).”

• cites Hatsopoulos and Donoghue 2009Not checked yet

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• AssumptionThe authors state this as an assumption: There is a causative correlation between spatio-temporal neural activity patterns in motor cortex and a paralyzed subject's intent to perform particular volitional movements.

May combine two claims.

The UEA's thin substrate and lead wires give a very thin super-cortical profile when implanted in cortical tissue, allowing the skull of experimental animals to be closed after implantation.

“The 0.2 mm thick substrate and lead wires of the UEA provides a very thin super-cortical profile when the UEA is implanted in cortical tissue, allowing the skull of experimental animals to be closed after implantation.”

Probably not a substantial claim: may not pass S4 (based).

As penetrating electrodes become thinner, at some point they will not have the mechanical strength to withstand insertion without buckling and breaking.

“However, as the penetrating electrodes become thinner, at some point they will not have the mechanical strength to withstand insertion without buckling and breaking.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Fabrication processes and materials have yet to be discovered that passivate devices for the years required in clinical devices.

“Fabrication processes and materials have yet to be discovered that passivate the devices for the years that will be required in clinical devices.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Lower electrode impedances allow larger currents to be passed for a given electrode polarization and reduce noise in single- and multi-unit recordings.

“Lower electrode impedances allow larger currents to be passed via the electrode for a given electrode polarization, and reduce the noise in the single-and multi-unit recordings made with these devices.”

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

Present day upper limb prostheses are myoelectrically controlled, with EMG electrodes built into the cuff of the wearer's prosthesis.

“Traditional myoelectrically controlled prostheses take advantage of the neural information provided by muscle contractions and present day upper limb prostheses are myoelectrically controlled, with electromyography (EMG) electrodes built into the cuff of the wearer's prosthesis.”

Probably not a substantial claim: may not pass S4 (based).

Individuals with extant forearms achieve highly dexterous control of their hands and fingers partly because of somatosensory and tactile feedback from the fingers, muscles, and skin of the intact hand/forearm.

“Further, individuals with extant forearms are able to achieve highly dexterous control of their hands and fingers, in part because of somatosensory and tactile feedback originating in the fingers, muscles and skin of his/her intact hand/ forearm.”

May combine two claims.

Severed peripheral nerves above the level of amputation are a more direct site for neural control signals and have already been used for neural control of external devices.

“A more direct site for neural control signals are the severed peripheral nerves above the level of the amputation, and this site has been already used for neural control of external devices (Dhillon et al 2004, Horch et al 2011).”

• cites Dhillon et al 2004Not checked yet

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• cites Horch et al 2011Not checked yet

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May combine two claims.

The USEA can selectively contact small groups of axons within a nerve fascicle and could allow patients with tetraplegia to regain better control of hand movements for greater independence in daily activities.

“This penetrating neural interface can selectively contact small groups of axons within a nerve fascicle and could allow patients with tetraplegia to regain a better control of hand movements in order to achieve a greater measure of independence in daily activities.”

• AssumptionRests on an assumption: Intervening in the peripheral nervous system could offer many opportunities to restore sensory and/or motor function to those who have lost these functions.

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

Recent advances in hand prostheses include devices with multiple degrees of freedom and sensors on fingers and joints.

“Recent notable advances in the field of hand prostheses have included designing devices with multiple degrees of freedom and with various sensors located on the fingers and joints (Krausz et al 2015, Veer 2015).”

• cites Krausz et al 2015Not checked yet

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• cites Veer 2015Not checked yet

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May combine two claims.

Up to 13 separate finger or hand movements have been decoded from neural activity, with correlations between targeted and decoded movements exceeding 0.5.

“up to 13 separate finger/hand movements have been decoded with regressions between the targeted movements and the decoded movements greater than 0.5 (Davis et al 2016).”

• cites Davis et al 2016 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Electrodes abutting motor fibers can record neural activity evoked by the desire of the amputee to flex his or her elbow, whereas other electrodes can record the desire to flex or extend the wrist.

“The electrodes abutting motor fibers can be used to record neural activity evoked by the desire of the amputee to flex his or her elbow, whereas other electrodes can record, for example, the desire to flex or extend the wrist.”

May combine two claims.

The spatial-temporal neural activity pattern associated with intending to move a particular finger is robust and somewhat unique because severed motor nerves continue to send motor commands to missing muscles in the phantom forearm or hand.

“Because the severed motor nerves still are transmitting motor commands to missing muscles in the phantom forearm/hand, the spatial-temporal neural activity pattern associated with the intent to move a particular finger is robust and somewhat unique.”

• AssumptionRests on an assumption: Severed motor nerves continue to transmit motor commands to missing muscles in the phantom forearm or hand.

May combine two claims.

Direct connection of a prosthetic limb to the PNS can be safely implanted into humans and could provide a high degree of control of the actuators in prosthetic limbs.

“This form of direct connection of the prosthetic limb to the PNS can be safely implanted into humans (Normann 2007) and could provide a high degree of control of the actuators in the prosthetic limbs (Clark et al 2014).”

• cites Normann 2007Not checked yet

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• cites Clark et al 2014Not checked yet

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• AssumptionRests on an assumption: Intervening in the peripheral nervous system could offer many opportunities to restore sensory and/or motor function to those who have lost these functions.

Probably not a substantial claim: may not pass S4 (based).

Selective recording of volitionally evoked neural activity extends to electrodes selective for individual digit extension and flexion.

“This selective recording of volitionally evoked neural activity would extend to electrodes selective for individual digit extension and flexion”

May combine two claims.

Decoding these activity patterns is straightforward and requires only a minimal number of training sessions before subjects can control a robotic hand with volitional thoughts.

“As such, decoding these activity patterns is straightforward and requires only a minimal number of training sessions before the subjects are able to control the robotic hand with his/her volitional thoughts.”

Classified as probably not a substantial claim.

The aim of electrical brain stimulation is to shorten ictal phases by modulating the epileptogenic zone.

“The aim of electrical brain stimulation is to shorten ictal phases by modulating the epileptogenic zone (Fisher and Velasco 2014).”

• cites Fisher and Velasco 2014Not checked yet

  Not checked in the free run.

May combine two claims.

Most clinical applications described are still at very preliminary stages, but penetrating microelectronic devices are beginning to be considered as viable therapies for a broad range of patients with injury or disease of the nervous system.

“Although most of the clinical applications described below are still at very preliminary stages, these penetrating microelectronic devices are beginning to be considered as viable therapies for a broad range of patients with injury or disease of the nervous system.”

May combine two claims.

Some electrodes in a USEA implanted in a severed nerve abut afferent motor fibers and others abut efferent sensory fibers.

“Some electrodes abut afferent motor fibers and others abut efferent sensory fibers.”

May combine two claims.

The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function and stimulating it could have negative cardiac effects.

“The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function so that stimulating it could have negative cardiac effects (George et al 2000).”

• cites George et al 2000Not checked yet

  Not checked in the free run.

May combine two claims.

VNS stimulation turns off the immune/inflammatory response, improves left ventricular function and positively affects other key drivers of heart failure progression.

“VNS stimulation turns off the immune/inflammatory response, improves left ventricular function and positively affects other key drivers of heart failure progression (De Ferrari et al 2011, Sabbah 2011).”

• cites De Ferrari et al 2011Not checked yet

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• cites Sabbah 2011Not checked yet

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May combine two claims.

Most vagus nerve fibers originate from neurons in the nodose ganglion and project mostly to the nucleus of the solitary tract, with connections also to the medial reticular formation of the medulla, dorsal motor nucleus of the vagus, area postrema and nucleus cunneatus.

“Most of the fibers originate from neurons in the nodose ganglion and send their projections mostly to the nucleus of the solitary tract, but there are also connections to the medial reticular formation of the medulla, the dorsal motor nucleus of the vagus, the area postrema and the nucleus cunneatus (Rutecki 1990).”

• cites Rutecki 1990Not checked yet

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May combine two claims.

Clinical studies have shown that diaphragm pacing is a stable and effective method of long-term respiratory support in high-level cervical spinal cord injury patients, improving survival length and quality of life.

“Clinical studies have shown that diaphragm pacing is a stable and effective method of long-term respiratory support in high-level cervical spinal cord injury patients, improving the length of survival and the quality of life of these patients (Romero et al 2012, Posluszny et al 2014).”

• cites Romero et al 2012Not checked yet

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• cites Posluszny et al 2014Not checked yet

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May combine two claims.

The UEA has been used in research with epilepsy patients, and these studies demonstrated that it can record cortical circuit dynamics with excellent spatial and temporal resolution.

“In this context, the UEA has been recently used in research with epilepsy patients (Truccolo et al 2011, Weiss et al 2013, Weiss et al 2013, Kellis et al 2016) and the results of these studies have demonstrated that this penetrating microelectrode array is able to record the dynamics of the cortical circuits with excellent resolution in space and time.”

• cites Truccolo et al 2011Not checked yet

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• cites Weiss et al 2013Not checked yet

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• cites Kellis et al 2016Not checked yet

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May combine two claims.

Diaphragm pacing stimulation delays the need for ventilators and improves sleep in some patients with amyotrophic lateral sclerosis, increasing their survival.

“Furthermore diaphragm pacing stimulation delays the need for ventilators and improves sleep in some patients with amyotrophic lateral sclerosis, increasing their survival (Onders et al 2009, Gonzalez-Bermejo et al 2012).”

• cites Onders et al 2009Not checked yet

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• cites Gonzalez-Bermejo et al 2012Not checked yet

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May combine two claims.

Selective stimulation of these neural fibers can improve cardiac autonomic control and significantly attenuate heart failure.

“Consequently, selective stimulation of these neural fibers can improve cardiac autonomic control and significantly attenuate heart failure (Sabbah 2011).”

• cites Sabbah 2011Not checked yet

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

Several researchers have proposed that VNS has potential for treating other CNS conditions including involuntary movement disorders, depression, Alzheimer's disease, migraine and neuropsychiatric disorders.

“Moreover, several researches have proposed that VNS also has the potential for treatment of other clinical conditions affecting the CNS including involuntary movement disorders, depression, Alzheimer's disease, migraine and neuropsychiatric disorders (Groves and Brown 2005).”

• cites Groves and Brown 2005Not checked yet

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May combine two claims.

Cuff electrodes used to record bladder afferent nerve signals have drawbacks of low signal-to-noise ratios and interference from non-bladder activity.

“Cuff electrodes have been conventionally used to record the activity of bladder afferent nerve signals, but they present the drawback of low signal-tonoise ratios and interference from non-bladder activity (Kent and Grill 2013, Lee et al 2015).”

• cites Kent and Grill 2013Not checked yet

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• cites Lee et al 2015Not checked yet

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May combine two claims.

Adverse effects associated with VNS implantation and stimulation include hoarseness, cough, dyspnea, pain, paresthesia, nausea and headache, with hoarseness and dyspnea more likely on high stimulation than low stimulation.

“However there are some adverse effects associated with implantation and stimulation such as hoarseness, cough, dyspnea, pain, paresthesia, nausea and headache, with hoarseness and dyspnea more likely to occur on high stimulation than low stimulation (Panebianco et al 2015).”

• cites Panebianco et al 2015Not checked yet

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May combine two claims.

Intermittent or periodic stimulation with predetermined patterns and intensity tends to decrease anti-epileptic efficacy over time and cannot respond to changes in clinical symptoms or underlying disease.

“However clinical tests have revealed that intermittent or periodic stimulation with predetermined patterns and intensity tends to decrease its anti-epileptic efficacy over time and, furthermore, is not able to respond to changes in the patient's clinical symptoms or in the underlying disease (Sun and Morrell 2014).”

• cites Sun and Morrell 2014Not checked yet

  Not checked in the free run.

May combine two claims.

Responsive neurostimulation can truncate individual seizures at stimulus onset, reducing overall seizure frequency by 50%-60%.

“This paradigm, called responsive neurostimulation is able to truncate individual seizures at the onset of the stimulus, reaching a reduction of 50%-60% of the overall seizure frequency (Sun et al 2008).”

• cites Sun et al 2008Not checked yet

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May combine two claims.

The median percent reduction in seizures with the RNS System was 44% at one year and 53% at two years postimplant compared with baseline.

“The median percent reduction in seizures was 44% at one year and 53% at two years postimplant compared with baseline (Fisher and Velasco 2014).”

• cites Fisher and Velasco 2014Not checked yet

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May combine two claims.

Chronic stimulation for one year resulted in more than 90% reductions in seizure frequency while preserving motor function.

“Chronic stimulation for one year resulted in more than 90% reductions in seizure frequency while preserving motor function”

• cites Velasco et al 2009Not checked yet

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May combine two claims.

Microelectrode arrays such as USEA or HD-USEA can selectively record pudendal nerve activity corresponding to genitourinary stimuli and can also stimulate to restore urinary function.

“In this way microelectrodes arrays such as the USEA or the HD-USEA can selectively record neural activity in the pudendal nerves that correspond to various genitourinary stimuli, such as bladder filling or distention-evoked bladder contractions, and furthermore, can also work as stimulation electrodes to restore urinary function (Wark et al 2014, Wark et al 2015).”

• cites Wark et al 2014Not checked yet

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• cites Wark et al 2015Not checked yet

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May combine two claims.

Cochlear implant research has arguably been the most successful in restoring lost sensory function and has become a viable therapeutic option for many profoundly deaf patients.

“In terms of restoring lost sensory function, cochlear implant research has arguably been the most successful and has been translated into a viable therapeutic option for many profoundly deaf patients (Pena et al 2004).”

• cites Pena et al 2004Not checked yet

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May combine two claims.

Retinal diseases frequently reduce visual acuity and result in non-curable blindness, and several groups are developing prostheses for the remaining healthy retina, optic nerve and LGN.

“Since retinal diseases frequently reduce visual acuity and result in non-curable blindness, several groups worldwide are working on the development of various prostheses designed to interact with the remaining healthy retina (Stingl et al 2013, Chuang et al 2014, Picaud and Sahel 2014, Stronks and Dagnelie 2014), optic nerve (Brelen et al 2010) and LGN (Vurro et al 2014).”

• cites Stingl et al 2013Not checked yet

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• cites Chuang et al 2014Not checked yet

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• cites Picaud and Sahel 2014Not checked yet

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May combine two claims.

The output neurons of the eye, ganglion cells, often degenerate in many retinal blindnesses, so retinal, optic nerve or LGN prostheses are not expected to help blindness caused by glaucoma or optic atrophy or diseases of visual pathways.

“However the output neurons of the eye, the ganglion cells, often degenerate in many retinal blindnesses (Marc et al 2008), and therefore a retinal, optic nerve or even a LGN prosthesis are not expected to be helpful for blindness caused by glaucoma or optic atrophy nor for diseases of the visual pathways.”

• cites Marc et al 2008Not checked yet

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May combine two claims.

Electrodes implanted near the occipital pole or in extrastriate areas could elicit patterned perceptions and provide a limited but useful sense in blind subjects.

“and suggest that electrodes implanted near the occipital pole or in extrastriate areas could be able to elicit patterned perceptions and provide a limited but useful sense in blind subjects (Fernandez et al 2015).”

• cites Fernandez et al 2015Not checked yet

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May combine two claims.

Single-shank devices cannot activate neurons across the three-dimensional structure of the inferior colliculus with sufficient spatial and temporal resolution and do not achieve performance levels comparable to cochlear implants.

“Thus, these single shank devices cannot activate neurons across the three-dimensional structure of the inferior colliculus with sufficient spatial and temporal resolution and do not achieve performance levels comparable to cochlear implants (Lim et al 2009).”

• cites Lim et al 2009Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

Neural plasticity of the visual cortex should allow ever-improving correlation between the physical world and evoked phosphenes.

“Furthermore, the neural plasticity of the visual cortex should allow ever-improving correlation between the physical world and evoked phosphenes.”