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Sample records for direct intracortical microstimulation

  1. Computational modeling of direct neuronal recruitment during intracortical microstimulation in somatosensory cortex

    NASA Astrophysics Data System (ADS)

    Overstreet, C. K.; Klein, J. D.; Helms Tillery, S. I.

    2013-12-01

    Objective. Electrical stimulation of cortical tissue could be used to deliver sensory information as part of a neuroprosthetic device, but current control of the location, resolution, quality, and intensity of sensations elicited by intracortical microstimulation (ICMS) remains inadequate for this purpose. One major obstacle to resolving this problem is the poor understanding of the neural activity induced by ICMS. Even with new imaging methods, quantifying the activity of many individual neurons within cortex is difficult. Approach. We used computational modeling to examine the response of somatosensory cortex to ICMS. We modeled the axonal arbors of eight distinct morphologies of interneurons and seven types of pyramidal neurons found in somatosensory cortex and identified their responses to extracellular stimulation. We then combined these axonal elements to form a multi-layered slab of simulated cortex and investigated the patterns of neural activity directly induced by ICMS. Specifically we estimated the number, location, and variety of neurons directly recruited by stimulation on a single penetrating microelectrode. Main results. The population of neurons activated by ICMS was dependent on both stimulation strength and the depth of the electrode within cortex. Strikingly, stimulation recruited interneurons and pyramidal neurons in very different patterns. Interneurons are primarily recruited within a dense, continuous region around the electrode, while pyramidal neurons were recruited in a sparse fashion both near the electrode and up to several millimeters away. Thus ICMS can lead to an unexpectedly complex spatial distribution of firing neurons. Significance. These results lend new insights to the complexity and range of neural activity that can be induced by ICMS. This work also suggests mechanisms potentially responsible for the inconsistency and unnatural quality of sensations initiated by ICMS. Understanding these mechanisms will aid in the design of

  2. The functional consequences of chronic, physiologically effective intracortical microstimulation.

    PubMed

    Parker, Rebecca A; Davis, Tyler S; House, Paul A; Normann, Richard A; Greger, Bradley

    2011-01-01

    Many studies have demonstrated the ability of chronically implanted multielectrode arrays (MEAs) to extract information from the motor cortex of both humans and nonhuman primates. Similarly, many studies have shown the ability of intracortical microstimulation to impart information to the brain via a single or a few electrodes acutely implanted in sensory cortex of nonhuman primates, but relatively few microstimulation studies characterizing chronically implanted MEAs have been performed. Additionally, device and tissue damage have been reported at the levels of microstimulation used in these studies. Whether the damage resulting from microstimulation impairs the ability of MEAs to chronically produce physiological effects, however, has not been directly tested. In this study, we examined the functional consequences of multiple months of periodic microstimulation via chronically implanted MEAs at levels capable of evoking physiological responses, that is, electromyogram (EMG) activity. The functionality of the MEA and neural tissue was determined by measuring impedances, the ability of microstimulation to evoke EMG responses, and the recording of action potentials. We found that impedances and the number of recorded action potentials followed the previously reported trend of decreasing over time in both animals that received microstimulation and those which did not receive microstimulation. Despite these trends, the ability to evoke EMG responses and record action potentials was retained throughout the study. The results of this study suggest that intracortical microstimulation via MEAs did not cause functional failure, suggesting that MEA-based microstimulation is ready to transition into subchronic (< 30 days) human trials to determine whether complex spatiotemporal sensory percepts can be evoked by patterned microstimulation. PMID:21867801

  3. Microstimulation with Chronically Implanted Intracortical Electrodes

    NASA Astrophysics Data System (ADS)

    McCreery, Douglas

    Stimulating microelectrodes that penetrate into the brain afford a means of accessing the basic functional units of the central nervous system. Microstimulation in the region of the cerebral cortex that subserve vision may be an alternative, or an adjunct, to a retinal prosthesis, and may be particularly attractive as a means of restoring a semblance of high-resolution central vision. There also is the intriguing possibility that such a prosthesis could convey higher order visual percepts, many of which are mediated by neural circuits in the secondary or "extra-striate" visual areas that surround the primary visual cortex. The technologies of intracortical stimulating microelectrodes and investigations of the effects of microstimulation on neural tissue have advanced to the point where a cortical-level prosthesis is at least feasible. The imperative of protecting neural tissue from stimulation-induced damage imposes constraints on the selection of stimulus parameters, as does the requirement that the stimulation not greatly affect the electrical excitability of the neurons that are to be activated. The latter is especially likely to occur when many adjacent microelectrodes are pulsed, as will be necessary in a visual prosthesis. However, data from animal studies indicates that these restrictions on stimulus parameter are compatible with those that can evoke visual percepts in humans and in experimental animals. These findings give cause to be optimistic about the prospects for realizing a visual prosthesis utilizing intracortical microstimulation.

  4. Virtual Active Touch Using Randomly Patterned Intracortical Microstimulation

    PubMed Central

    O’Doherty, Joseph E.; Lebedev, Mikhail A.; Li, Zheng; Nicolelis, Miguel A.L.

    2012-01-01

    Intracortical microstimulation (ICMS) has promise as a means for delivering somatosensory feedback in neuroprosthetic systems. Various tactile sensations could be encoded by temporal, spatial, or spatiotemporal patterns of ICMS. However, the applicability of temporal patterns of ICMS to artificial tactile sensation during active exploration is unknown, as is the minimum discriminable difference between temporally modulated ICMS patterns. We trained rhesus monkeys in an active exploration task in which they discriminated periodic pulse-trains of ICMS (200 Hz bursts at a 10 Hz secondary frequency) from pulse trains with the same average pulse rate, but distorted periodicity (200 Hz bursts at a variable instantaneous secondary frequency). The statistics of the aperiodic pulse trains were drawn from a gamma distribution with mean inter-burst intervals equal to those of the periodic pulse trains. The monkeys distinguished periodic pulse trains from aperiodic pulse trains with coefficients of variation 0.25 or greater. Reconstruction of movement kinematics, extracted from the activity of neuronal populations recorded in the sensorimotor cortex concurrent with the delivery of ICMS feedback, improved when the recording intervals affected by ICMS artifacts were removed from analysis. These results add to the growing evidence that temporally patterned ICMS can be used to simulate a tactile sense for neuroprosthetic devices. PMID:22207642

  5. Chronic intracortical microstimulation (ICMS) of cat sensory cortex using the Utah Intracortical Electrode Array.

    PubMed

    Rousche, P J; Normann, R A

    1999-03-01

    In an effort to assess the safety and efficacy of focal intracortical microstimulation (ICMS) of cerebral cortex with an array of penetrating electrodes as might be applied to a neuroprosthetic device to aid the deaf or blind, we have chronically implanted three trained cats in primary auditory cortex with the 100-electrode Utah Intracortical Electrode Array (UIEA). Eleven of the 100 electrodes were hard-wired to a percutaneous connector for chronic access. Prior to implant, cats were trained to "lever-press" in response to pure tone auditory stimulation. After implant, this behavior was transferred to "lever-presses" in response to current injections via single electrodes of the implanted arrays. Psychometric function curves relating injected charge level to the probability of response were obtained for stimulation of 22 separate electrodes in the three implanted cats. The average threshold charge/phase required for electrical stimulus detection in each cat was, 8.5, 8.6, and 11.6 nC/phase respectively, with a maximum charge/phase of 26 nC/phase and a minimum of 1.5 nC/phase thresholds were tracked for varying time intervals, and seven electrodes from two cats were tracked for up to 100 days. Electrodes were stimulated for no more than a few minutes each day. Neural recordings taken from the same electrodes before and after multiple electrical stimulation sessions were very similar in signal/noise ratio and in the number of recordable units, suggesting that the range of electrical stimulation levels used did not damage neurons in the vicinity of the electrodes. Although a few early implants failed, we conclude that ICMS of cerebral cortex to evoke a behavioral response can be achieved with the penetrating UIEA. Further experiments in support of a sensory cortical prosthesis based on ICMS are warranted. PMID:10188608

  6. A system for neural recording and closed-loop intracortical microstimulation in awake rodents.

    PubMed

    Venkatraman, Subramaniam; Elkabany, Ken; Long, John D; Yao, Yimin; Carmena, Jose M

    2009-01-01

    There is growing interest in intracortical microstimulation as a means of providing sensory input in neuroprosthetic systems. We believe that precisely controlling the timing and parameters of stimulation in closed loop can significantly improve the efficacy of this technique. Here, we present a system for closed-loop microstimulation in awake rodents chronically implanted with multielectrode arrays. The system interfaces with existing commercial recording and stimulating hardware. Using custom-made hardware, we can stimulate and record from electrodes on the same implanted array and significantly reduce the stimulation artifact. Stimulation sequences can either be preprogrammed or triggered by neural or behavioral events. Specifically, this system can provide feedback stimulation in response to action potentials or features in the local field potential recorded on any of the electrodes within 15 ms. It can also trigger stimulation based on behavioral events, such as real-time tracking of rat whiskers captured with high-speed video. We believe that this system, which can be recreated easily, will help to significantly refine the technique of intracortical microstimulation and advance the field of neuroprostheses. PMID:19224714

  7. The effect of chronic intracortical microstimulation on the electrode-tissue interface

    NASA Astrophysics Data System (ADS)

    Chen, Kevin H.; Dammann, John F.; Boback, Jessica L.; Tenore, Francesco V.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

    2014-04-01

    Objective. Somatosensation is critical for effective object manipulation, but current upper limb prostheses do not provide such feedback to the user. For individuals who require use of prosthetic limbs, this lack of feedback transforms a mundane task into one that requires extreme concentration and effort. Although vibrotactile motors and sensory substitution devices can be used to convey gross sensations, a direct neural interface is required to provide detailed and intuitive sensory feedback. The viability of intracortical microstimulation (ICMS) as a method to deliver feedback depends in part on the long-term reliability of implanted electrodes used to deliver the stimulation. The objective of the present study is to investigate the effects of chronic ICMS on the electrode-tissue interface. Approach. We stimulate the primary somatosensory cortex of three Rhesus macaques through chronically implanted electrodes for 4 h per day over a period of six months, with different electrodes subjected to different regimes of stimulation. We measure the impedance and voltage excursion as a function of time and of ICMS parameters. We also test the sensorimotor consequences of chronic ICMS by having animals grasp and manipulate small treats. Main results. We show that impedance and voltage excursion both decay with time but stabilize after 10-12 weeks. The magnitude of this decay is dependent on the amplitude of the ICMS and, to a lesser degree, the duration of individual pulse trains. Furthermore, chronic ICMS does not produce any deficits in fine motor control. Significance. The results suggest that chronic ICMS has only a minor effect on the electrode-tissue interface and may thus be a viable means to convey sensory feedback in neuroprosthetics.

  8. Behavioral assessment of sensitivity to intracortical microstimulation of primate somatosensory cortex

    PubMed Central

    Kim, Sungshin; Callier, Thierri; Tabot, Gregg A.; Gaunt, Robert A.; Tenore, Francesco V.; Bensmaia, Sliman J.

    2015-01-01

    Intracortical microstimulation (ICMS) is a powerful tool to investigate the functional role of neural circuits and may provide a means to restore sensation for patients for whom peripheral stimulation is not an option. In a series of psychophysical experiments with nonhuman primates, we investigate how stimulation parameters affect behavioral sensitivity to ICMS. Specifically, we deliver ICMS to primary somatosensory cortex through chronically implanted electrode arrays across a wide range of stimulation regimes. First, we investigate how the detectability of ICMS depends on stimulation parameters, including pulse width, frequency, amplitude, and pulse train duration. Then, we characterize the degree to which ICMS pulse trains that differ in amplitude lead to discriminable percepts across the range of perceptible and safe amplitudes. We also investigate how discriminability of pulse amplitude is modulated by other stimulation parameters—namely, frequency and duration. Perceptual judgments obtained across these various conditions will inform the design of stimulation regimes for neuroscience and neuroengineering applications. PMID:26504211

  9. Behavioral assessment of sensitivity to intracortical microstimulation of primate somatosensory cortex.

    PubMed

    Kim, Sungshin; Callier, Thierri; Tabot, Gregg A; Gaunt, Robert A; Tenore, Francesco V; Bensmaia, Sliman J

    2015-12-01

    Intracortical microstimulation (ICMS) is a powerful tool to investigate the functional role of neural circuits and may provide a means to restore sensation for patients for whom peripheral stimulation is not an option. In a series of psychophysical experiments with nonhuman primates, we investigate how stimulation parameters affect behavioral sensitivity to ICMS. Specifically, we deliver ICMS to primary somatosensory cortex through chronically implanted electrode arrays across a wide range of stimulation regimes. First, we investigate how the detectability of ICMS depends on stimulation parameters, including pulse width, frequency, amplitude, and pulse train duration. Then, we characterize the degree to which ICMS pulse trains that differ in amplitude lead to discriminable percepts across the range of perceptible and safe amplitudes. We also investigate how discriminability of pulse amplitude is modulated by other stimulation parameters-namely, frequency and duration. Perceptual judgments obtained across these various conditions will inform the design of stimulation regimes for neuroscience and neuroengineering applications. PMID:26504211

  10. Long-term stability of sensitivity to intracortical microstimulation of somatosensory cortex

    NASA Astrophysics Data System (ADS)

    Callier, Thierri; Schluter, Erik W.; Tabot, Gregg A.; Miller, Lee E.; Tenore, Francesco V.; Bensmaia, Sliman J.

    2015-10-01

    Objective. The dexterous manipulation of objects depends heavily on somatosensory signals from the limb. The development of anthropomorphic robotic arms and of algorithms to decode intended movements from neuronal signals has stimulated the need to restore somatosensation for use in upper-limb neuroprostheses. Without touch and proprioception, patients have difficulty controlling prosthetic limbs to a level that justifies the required invasive surgery. Intracortical microstimulation (ICMS) through chronically implanted electrode arrays has the potential to provide rich and intuitive sensory feedback. This approach to sensory restoration requires, however, that the evoked sensations remain stable over time. Approach. To investigate the stability of ICMS-evoked sensations, we measured the ability of non-human primates to detect ICMS over experimental sessions that spanned years. Main results. We found that the performance of the animals remained highly stable over time, even when they were tested with electrodes that had experienced extensive stimulation. Significance. Given the stability of the sensations that it evokes, ICMS may thus be a viable approach for sensory restoration.

  11. A miniaturized system for spike-triggered intracortical microstimulation in an ambulatory rat.

    PubMed

    Azin, Meysam; Guggenmos, David J; Barbay, Scott; Nudo, Randolph J; Mohseni, Pedram

    2011-09-01

    This paper reports on a miniaturized system for spike-triggered intracortical microstimulation (ICMS) in an ambulatory rat. The head-mounted microdevice comprises a previously developed application-specific integrated circuit fabricated in 0.35-μm two-poly four-metal complementary metal-oxide-semiconductor technology, which is assembled and packaged on a miniature rigid-flex substrate together with a few external components for programming, supply regulation, and wireless operation. The microdevice operates autonomously from a single 1.55-V battery, measures 3.6  cm × 1.3  cm × 0.6  cm, weighs 1.7  g (including the battery), and is capable of stimulating as well as recording the neural response to ICMS in biological experiments with anesthetized laboratory rats. Moreover, it has been interfaced with silicon microelectrodes chronically implanted in the cerebral cortex of an ambulatory rat and successfully delivers electrical stimuli to the second somatosensory area when triggered by neural activity from the rostral forelimb area with a user-adjustable spike-stimulus time delay. The spike-triggered ICMS is further shown to modulate the neuronal firing rate, indicating that it is physiologically effective. PMID:21690007

  12. The ventral tegmental area modulates intracortical microstimulation (ICMS)-evoked M1 activity in a time-dependent manner.

    PubMed

    Kunori, Nobuo; Kajiwara, Riichi; Takashima, Ichiro

    2016-03-11

    Intracortical microstimulation (ICMS)-evoked neural activity combined with ventral tegmental area (VTA) stimulation was studied in rat primary motor cortex (M1). We used voltage-sensitive dye (VSD) imaging to analyze the spatiotemporal dynamics of M1 activity following VTA-M1 paired stimulation. VTA stimulation was preceded by M1 ICMS at inter-stimulus intervals (ISIs) of 15-350ms. VSD imaging showed an excitatory-inhibitory sequence of neural activity after composing VTA stimulus- and ICMS-induced M1 neural activity. To evaluate the net ICMS M1 response, the optical response to unpaired VTA stimulation was subtracted from the VTA-M1 paired response. This revealed that the net ICMS-evoked M1 neural activity was inhibited when the ISI was 30-50ms, but highly facilitated when the ISI was 100-350ms. These results suggest that VTA modulates M1 excitability in the order of tens to hundreds of milliseconds and might directly affect the motor command generation process in the M1. PMID:26827719

  13. The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

    NASA Astrophysics Data System (ADS)

    Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

    2015-12-01

    Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

  14. The Duration of Motor Responses Evoked with Intracortical Microstimulation in Rats Is Primarily Modulated by Stimulus Amplitude and Train Duration

    PubMed Central

    Watson, Meghan; Sawan, Mohamad

    2016-01-01

    Microstimulation of brain tissue plays a key role in a variety of sensory prosthetics, clinical therapies and research applications, however the effects of stimulation parameters on the responses they evoke remain widely unknown. In particular, the effects of parameters when delivered in the form of a stimulus train as opposed to a single pulse are not well understood despite the prevalence of stimulus train use. We aimed to investigate the contribution of each parameter of a stimulus train to the duration of the motor responses they evoke in forelimb muscles. We used constant-current, biphasic, square wave pulse trains in acute terminal experiments under ketamine anaesthesia. Stimulation parameters were systematically tested in a pair-wise fashion in the caudal forelimb region of the motor cortex in 7 Sprague-Dawley rats while motor evoked potential (MEP) recordings from the forelimb were used to quantify the influence of each parameter in the train. Stimulus amplitude and train duration were shown to be the dominant parameters responsible for increasing the total duration of the MEP, while interphase interval had no effect. Increasing stimulus frequency from 100–200 Hz or pulse duration from 0.18–0.34 ms were also effective methods of extending response durations. Response duration was strongly correlated with peak time and amplitude. Our findings suggest that motor cortex intracortical microstimulations are often conducted at a higher frequency rate and longer train duration than necessary to evoke maximal response duration. We demonstrated that the temporal properties of the evoked response can be both predicted by certain response metrics and modulated via alterations to the stimulation signal parameters. PMID:27442588

  15. The Duration of Motor Responses Evoked with Intracortical Microstimulation in Rats Is Primarily Modulated by Stimulus Amplitude and Train Duration.

    PubMed

    Watson, Meghan; Sawan, Mohamad; Dancause, Numa

    2016-01-01

    Microstimulation of brain tissue plays a key role in a variety of sensory prosthetics, clinical therapies and research applications, however the effects of stimulation parameters on the responses they evoke remain widely unknown. In particular, the effects of parameters when delivered in the form of a stimulus train as opposed to a single pulse are not well understood despite the prevalence of stimulus train use. We aimed to investigate the contribution of each parameter of a stimulus train to the duration of the motor responses they evoke in forelimb muscles. We used constant-current, biphasic, square wave pulse trains in acute terminal experiments under ketamine anaesthesia. Stimulation parameters were systematically tested in a pair-wise fashion in the caudal forelimb region of the motor cortex in 7 Sprague-Dawley rats while motor evoked potential (MEP) recordings from the forelimb were used to quantify the influence of each parameter in the train. Stimulus amplitude and train duration were shown to be the dominant parameters responsible for increasing the total duration of the MEP, while interphase interval had no effect. Increasing stimulus frequency from 100-200 Hz or pulse duration from 0.18-0.34 ms were also effective methods of extending response durations. Response duration was strongly correlated with peak time and amplitude. Our findings suggest that motor cortex intracortical microstimulations are often conducted at a higher frequency rate and longer train duration than necessary to evoke maximal response duration. We demonstrated that the temporal properties of the evoked response can be both predicted by certain response metrics and modulated via alterations to the stimulation signal parameters. PMID:27442588

  16. The effects of prolonged intracortical microstimulation on the excitability of pyramidal tract neurons in the cat.

    PubMed

    McCreery, Douglas B; Agnew, William F; Bullara, Leo A

    2002-01-01

    This study was conducted to examine the excitability changes induced in cerebral cortical neurons during prolonged microstimulation with a spatially dense microelectrodes array. The arrays of 16 iridium microelectrodes were implanted chronically into the postcruciate gyrus of cats. Neuronal responses characteristic of single pyramidal tract axons (ULRs) were recorded in the medullary pyramid. 7 h of pulsing of individual electrodes at 50 Hz and at 4 nC/ph induced little or no change in the ULRs' electrical thresholds. The thresholds also were quite stable when 4 of the 16 microelectrodes were pulsed on each of 14 consecutive days. However, when all 16 microelectrodes were pulsed for 7 h at 4 nC/ph, the threshold of approximately half of the ULRs became elevated. Recovery of excitability required 2-18 days. Prolonged sequential (interleaved) pulsing of the 16 microelectrodes induced less depression of excitability than did simultaneous pulsing, but only when the stimulus amplitude was low (12 A, 1.8 nC/ph). Stimulation at a higher amplitude (15 nC/ph) induced much more depression of excitability. These findings imply that multiple processes mediate the stimulation-induced depression of neuronal excitability. The data also demonstrate that the depression can be reduced by employing a stimulus regimen in which the inherent spatial resolution of the array is maximized (sequential pulsing at an amplitude in which there is minimal overlap of the effective current fields). PMID:11874134

  17. Multiple factors may influence the performance of a visual prosthesis based on intracortical microstimulation: nonhuman primate behavioural experimentation.

    PubMed

    Torab, K; Davis, T S; Warren, D J; House, P A; Normann, R A; Greger, B

    2011-06-01

    We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts. PMID:21593550

  18. Multiple factors may influence the performance of a visual prosthesis based on intracortical microstimulation: nonhuman primate behavioural experimentation

    NASA Astrophysics Data System (ADS)

    Torab, K.; Davis, T. S.; Warren, D. J.; House, P. A.; Normann, R. A.; Greger, B.

    2011-06-01

    We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts.

  19. Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex

    PubMed Central

    Kunori, Nobuo; Murata, Yumi

    2016-01-01

    In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv. PMID:27494282

  20. Optimal space-time precoding of artificial sensory feedback through mutichannel microstimulation in bi-directional brain-machine interfaces

    NASA Astrophysics Data System (ADS)

    Daly, John; Liu, Jianbo; Aghagolzadeh, Mehdi; Oweiss, Karim

    2012-12-01

    Brain-machine interfaces (BMIs) aim to restore lost sensorimotor and cognitive function in subjects with severe neurological deficits. In particular, lost somatosensory function may be restored by artificially evoking patterns of neural activity through microstimulation to induce perception of tactile and proprioceptive feedback to the brain about the state of the limb. Despite an early proof of concept that subjects could learn to discriminate a limited vocabulary of intracortical microstimulation (ICMS) patterns that instruct the subject about the state of the limb, the dynamics of a moving limb are unlikely to be perceived by an arbitrarily-selected, discrete set of static microstimulation patterns, raising questions about the generalization and the scalability of this approach. In this work, we propose a microstimulation protocol intended to activate optimally the ascending somatosensory pathway. The optimization is achieved through a space-time precoder that maximizes the mutual information between the sensory feedback indicating the limb state and the cortical neural response evoked by thalamic microstimulation. Using a simplified multi-input multi-output model of the thalamocortical pathway, we show that this optimal precoder can deliver information more efficiently in the presence of noise compared to suboptimal precoders that do not account for the afferent pathway structure and/or cortical states. These results are expected to enhance the way microstimulation is used to induce somatosensory perception during sensorimotor control of artificial devices or paralyzed limbs.

  1. Ventral premotor-motor cortex interactions in the macaque monkey during grasp: response of single neurons to intracortical microstimulation.

    PubMed

    Kraskov, Alexander; Prabhu, Gita; Quallo, Marsha M; Lemon, Roger N; Brochier, Thomas

    2011-06-15

    Recent stimulation studies in monkeys and humans have shown strong interactions between ventral premotor cortex (area F5) and the hand area of primary motor cortex (M1). These short-latency interactions usually involve facilitation from F5 of M1 outputs to hand muscles, although suppression has also been reported. This study, performed in three awake macaque monkeys, sought evidence that these interactions could be mediated by short-latency excitatory and inhibitory responses of single M1 neurons active during grasping tasks. We recorded responses of these M1 neurons to single low-threshold (≤40 μA) intracortical microstimuli delivered to F5 sites at which grasp-related neurons were recorded. In 29 sessions, we tested 232 M1 neurons with stimuli delivered to between one and four sites in F5. Of the 415 responses recorded, 142 (34%) showed significant effects. The most common type of response was pure excitation (53% of responses), with short latency (1.8-3.0 ms) and brief duration (∼1 ms); purely inhibitory responses had slightly longer latencies (2-5 ms) and were of small amplitude and longer duration (5-7 ms). They accounted for 13% of responses, whereas mixed excitation then inhibition was seen in 34%. Remarkably, a rather similar set of findings applied to 280 responses of 138 F5 neurons to M1 stimulation; 109 (34%) responses showed significant effects. Thus, with low-intensity stimuli, the dominant interaction between these two cortical areas is one of short-latency, brief excitation, most likely mediated by reciprocal F5-M1 connections. Some neurons were tested with stimuli at both 20 and 40 μA; inhibition tended to dominate at the higher intensity. PMID:21677165

  2. Muscle synergies evoked by microstimulation are preferentially encoded during behavior

    PubMed Central

    Overduin, Simon A.; d'Avella, Andrea; Carmena, Jose M.; Bizzi, Emilio

    2014-01-01

    Electrical microstimulation studies provide some of the most direct evidence for the neural representation of muscle synergies. These synergies, i.e., coordinated activations of groups of muscles, have been proposed as building blocks for the construction of motor behaviors by the nervous system. Intraspinal or intracortical microstimulation (ICMS) has been shown to evoke muscle patterns that can be resolved into a small set of synergies similar to those seen in natural behavior. However, questions remain about the validity of microstimulation as a probe of neural function, particularly given the relatively long trains of supratheshold stimuli used in these studies. Here, we examined whether muscle synergies evoked during ICMS in two rhesus macaques were similarly encoded by nearby motor cortical units during a purely voluntary behavior involving object reach, grasp, and carry movements. At each microstimulation site we identified the synergy most strongly evoked among those extracted from muscle patterns evoked over all microstimulation sites. For each cortical unit recorded at the same microstimulation site, we then identified the synergy most strongly encoded among those extracted from muscle patterns recorded during the voluntary behavior. We found that the synergy most strongly evoked at an ICMS site matched the synergy most strongly encoded by proximal units more often than expected by chance. These results suggest a common neural substrate for microstimulation-evoked motor responses and for the generation of muscle patterns during natural behaviors. PMID:24634652

  3. Complex movement topography and extrinsic space representation in the rat forelimb motor cortex as defined by long-duration intracortical microstimulation.

    PubMed

    Bonazzi, Laura; Viaro, Riccardo; Lodi, Enrico; Canto, Rosario; Bonifazzi, Claudio; Franchi, Gianfranco

    2013-01-30

    Electrical stimulation of the motor cortex in the rat can evoke complex forelimb multi-joint movements, including movement of limb and paw. In this study, these movements have been quantified in terms of 3D displacement and kinematic variables of two markers positioned on the wrist and middle digits (limb and paw movement, respectively). Electrical microstimulation was applied to the motor cortex using a pulse train of 500 ms duration. Movements were measured using a high-resolution 3D optical system. Five classes of limb movements (abduction, adduction, extension, retraction, elevation) and four classes of paw movements (opening, closure, opening/closure sequence, supination) were described according to their kinematics. A consistent topography of these classes of movements was presented across the motor cortex together with a topography of spatial locations to which the paw was directed. In about one-half of cortical sites, a specific pattern of limb-paw movement combination did exist. Four categories of limb-paw movements resembling behavioral repertoire were identified: reach-shaping, reach-grasp sequence, bring-to-body, and hold-like movement. Overall, the forelimb motor region included: (1) a large caudal forelimb area dominated by reach-shaping movement representation; (2) a small rostral area containing reach-grasp sequence and bring-to-body movement representation; and (3) a more lateral portion where hold-like movement was represented. These results support the view that, in rats, the motor cortex controls forelimb movements at a relatively complex level and suggest that the orderly representation of complex movements and their dynamics/kinematics emerge from the principles of forelimb motor cortex organization. PMID:23365246

  4. Recovery of directed intracortical connectivity from fMRI data

    NASA Astrophysics Data System (ADS)

    Gilson, Matthieu; Ritter, Petra; Deco, Gustavo

    2016-06-01

    The brain exhibits complex spatio-temporal patterns of activity. In particular, its baseline activity at rest has a specific structure: imaging techniques (e.g., fMRI, EEG and MEG) show that cortical areas experience correlated fluctuations, which is referred to as functional connectivity (FC). The present study relies on our recently developed model in which intracortical white-matter connections shape noise-driven fluctuations to reproduce FC observed in experimental data (here fMRI BOLD signal). Here noise has a functional role and represents the variability of neural activity. The model also incorporates anatomical information obtained using diffusion tensor imaging (DTI), which estimates the density of white-matter fibers (structural connectivity, SC). After optimization to match empirical FC, the model provides an estimation of the efficacies of these fibers, which we call effective connectivity (EC). EC differs from SC, as EC not only accounts for the density of neural fibers, but also the concentration of synapses formed at their end, the type of neurotransmitters associated and the excitability of target neural populations. In summary, the model combines anatomical SC and activity FC to evaluate what drives the neural dynamics, embodied in EC. EC can then be analyzed using graph theory to understand how it generates FC and to seek for functional communities among cortical areas (parcellation of 68 areas). We find that intracortical connections are not symmetric, which affects the dynamic range of cortical activity (i.e., variety of states it can exhibit).

  5. Decoding the rat forelimb movement direction from epidural and intracortical field potentials

    NASA Astrophysics Data System (ADS)

    Slutzky, Marc W.; Jordan, Luke R.; Lindberg, Eric W.; Lindsay, Kevin E.; Miller, Lee E.

    2011-06-01

    Brain-machine interfaces (BMIs) use signals from the brain to control a device such as a computer cursor. Various types of signals have been used as BMI inputs, from single-unit action potentials to scalp potentials. Recently, intermediate-level signals such as subdural field potentials have also shown promise. These different signal types are likely to provide different amounts of information, but we do not yet know what signal types are necessary to enable a particular BMI function, such as identification of reach target location, control of a two-dimensional cursor or the dynamics of limb movement. Here we evaluated the performance of field potentials, measured either intracortically (local field potentials, LFPs) or epidurally (epidural field potential, EFPs), in terms of the ability to decode reach direction. We trained rats to move a joystick with their forepaw to control the motion of a sipper tube to one of the four targets in two dimensions. We decoded the forelimb reach direction from the field potentials using linear discriminant analysis. We achieved a mean accuracy of 69 ± 3% with EFPs and 57 ± 2% with LFPs, both much better than chance. Signal quality remained good up to 13 months after implantation. This suggests that using epidural signals could provide BMI inputs of high quality with less risk to the patient than using intracortical recordings.

  6. Asymmetric versus symmetric pulses for cortical microstimulation.

    PubMed

    Koivuniemi, Andrew S; Otto, Kevin J

    2011-10-01

    Intracortical microstimulation (ICMS), which has shown promise in the visual, auditory and somatosensory systems as a platform for sensory prostheses, typically relies on charged balanced, symmetric, biphasic stimulation. However, neural stimulation models as well as experiments conducted in cochlear implant users have suggested that charge balanced asymmetric pulses could generate lower detection thresholds for stimulation in terms of charge per phase. For this study, rats were chronically implanted with microelectrode arrays unilaterally in their right auditory cortex and then trained to detect ICMS delivered through a single electrode site in order to determine their behavioral threshold. This model was used in two experiments. The first experiment addressed the effect of lead phase direction, asymmetry, and phase duration on detection threshold. The second experiment fixed the cathode phase duration at 123 μs and varied only the phase asymmetry and lead phase direction. Taken together, the results of these experiments suggest that, for ICMS, the primary determinant of threshold level is cathode phase duration, and that asymmetry provides no significant advantage when compared to symmetric, cathode leading pulses. However, symmetric anode leading pulses of less than or equal to 205 μs per phase consistently showed higher thresholds when compared to all other pulses of equal cathode phase duration. PMID:21968793

  7. Vision Loss Shifts the Balance of Feedforward and Intracortical Circuits in Opposite Directions in Mouse Primary Auditory and Visual Cortices

    PubMed Central

    Petrus, Emily; Rodriguez, Gabriela; Patterson, Ryan; Connor, Blaine; Kanold, Patrick O.

    2015-01-01

    Loss of a sensory modality leads to widespread changes in synaptic function across sensory cortices, which are thought to be the basis for cross-modal adaptation. Previous studies suggest that experience-dependent cross-modal regulation of the spared sensory cortices may be mediated by changes in cortical circuits. Here, we report that loss of vision, in the form of dark exposure (DE) for 1 week, produces laminar-specific changes in excitatory and inhibitory circuits in the primary auditory cortex (A1) of adult mice to promote feedforward (FF) processing and also strengthens intracortical inputs to primary visual cortex (V1). Specifically, DE potentiated FF excitatory synapses from layer 4 (L4) to L2/3 in A1 and recurrent excitatory inputs in A1–L4 in parallel with a reduction in the strength of lateral intracortical excitatory inputs to A1–L2/3. This suggests a shift in processing in favor of FF information at the expense of intracortical processing. Vision loss also strengthened inhibitory synaptic function in L4 and L2/3 of A1, but via laminar specific mechanisms. In A1–L4, DE specifically potentiated the evoked synaptic transmission from parvalbumin-positive inhibitory interneurons to principal neurons without changes in spontaneous miniature IPSCs (mIPSCs). In contrast, DE specifically increased the frequency of mIPSCs in A1–L2/3. In V1, FF excitatory inputs were unaltered by DE, whereas lateral intracortical connections in L2/3 were strengthened, suggesting a shift toward intracortical processing. Our results suggest that loss of vision produces distinct circuit changes in the spared and deprived sensory cortices to shift between FF and intracortical processing to allow adaptation. PMID:26063913

  8. Vision loss shifts the balance of feedforward and intracortical circuits in opposite directions in mouse primary auditory and visual cortices.

    PubMed

    Petrus, Emily; Rodriguez, Gabriela; Patterson, Ryan; Connor, Blaine; Kanold, Patrick O; Lee, Hey-Kyoung

    2015-06-10

    Loss of a sensory modality leads to widespread changes in synaptic function across sensory cortices, which are thought to be the basis for cross-modal adaptation. Previous studies suggest that experience-dependent cross-modal regulation of the spared sensory cortices may be mediated by changes in cortical circuits. Here, we report that loss of vision, in the form of dark exposure (DE) for 1 week, produces laminar-specific changes in excitatory and inhibitory circuits in the primary auditory cortex (A1) of adult mice to promote feedforward (FF) processing and also strengthens intracortical inputs to primary visual cortex (V1). Specifically, DE potentiated FF excitatory synapses from layer 4 (L4) to L2/3 in A1 and recurrent excitatory inputs in A1-L4 in parallel with a reduction in the strength of lateral intracortical excitatory inputs to A1-L2/3. This suggests a shift in processing in favor of FF information at the expense of intracortical processing. Vision loss also strengthened inhibitory synaptic function in L4 and L2/3 of A1, but via laminar specific mechanisms. In A1-L4, DE specifically potentiated the evoked synaptic transmission from parvalbumin-positive inhibitory interneurons to principal neurons without changes in spontaneous miniature IPSCs (mIPSCs). In contrast, DE specifically increased the frequency of mIPSCs in A1-L2/3. In V1, FF excitatory inputs were unaltered by DE, whereas lateral intracortical connections in L2/3 were strengthened, suggesting a shift toward intracortical processing. Our results suggest that loss of vision produces distinct circuit changes in the spared and deprived sensory cortices to shift between FF and intracortical processing to allow adaptation. PMID:26063913

  9. Microstimulation: Principles, Techniques, and Approaches to Somatosensory Neuroprosthesis.

    PubMed

    Semework, Mulugeta

    2015-01-01

    The power of movement of electrically charged particles has been used to alleviate an array of illnesses and help control some human body parts. Microstimulation, the electrical current-driven excitation of neural elements, is now being aimed at brain-machine interfaces (BMIs), brain-controlled external devices that improve quality of life for people such as those who have lost the ability to use their limbs. This effort is motivated by behavioral experiments that indicate a direct link between microstimulation-induced sensory experience and behavior, pointing to the possibility of optimizing and controlling the outputs of BMIs. Several laboratories have focused on using electrical stimulation to return somatosensory feedback from prosthetic limbs directly to the user's central nervous system. However, the difficulty of the problem has led to limited success thus far, and there is a need for a better understanding of the basic principles of neural microstimulation. This article provides a review of the available literature and some recent work at Downstate Medical Center and Columbia University on microstimulation of the primate and rodent somatosensory (S1) cortex and the ventral posterolateral thalamus. It is aimed at contributing to the existing knowledge base to generate good behavioral responses and effective, BMI-appropriate somatosensory feedback. In general, the threshold for the particular brain tissue in response to current-amplitude has to be determined by rigorous experimentation. For consistently reproducible results, hardware and thresholds for microstimulation have to be specified. In addition, effects on motor functions, including unwanted side effects in response to the microstimulation of brain tissue, must be examined to take the field from bench to bedside. PMID:26351023

  10. Wireless Microstimulators for Neural Prosthetics

    PubMed Central

    Sahin, Mesut; Pikov, Victor

    2016-01-01

    One of the roadblocks in the field of neural prosthetics is the lack of microelectronic devices for neural stimulation that can last a lifetime in the central nervous system. Wireless multi-electrode arrays are being developed to improve the longevity of implants by eliminating the wire interconnects as well as the chronic tissue reactions due to the tethering forces generated by these wires. An area of research that has not been sufficiently investigated is a simple single-channel passive microstimulator that can collect the stimulus energy that is transmitted wirelessly through the tissue and immediately convert it into the stimulus pulse. For example, many neural prosthetic approaches to intraspinal microstimulation require only a few channels of stimulation. Wired spinal cord implants are not practical for human subjects because of the extensive flexions and rotations that the spinal cord experiences. Thus, intraspinal microstimulation may be a pioneering application that can benefit from submillimetersize floating stimulators. Possible means of energizing such a floating microstimulator, such as optical, acoustic, and electromagnetic waves, are discussed. PMID:21488815

  11. Neuron discharges in the rat auditory cortex during electrical intracortical stimulation.

    PubMed

    Maldonado, P E; Altman, J A; Gerstein, G L

    1998-01-01

    Studies were carried out in rats anesthetized with ketamine or nembutal, with recording of multicellular activity (with separate identification of responses from individual neurons) in the primary auditory cortex before and after electrical intracortical microstimulation. These experiments showed that about half of the set of neurons studied produced responses to short tonal bursts, these responses having two components-initial discharges arising in response to the sound, and afterdischarge occurring after pauses of 50-100 msec. Afterdischarges lasted at least several seconds, and were generally characterized by a rhythmic structure (with a frequency of 8-12 Hz). After electrical microstimulation, the level of spike activity increased, especially in afterdischarges, and this increase could last up to 4 h. Combined peristimulus histograms, cross-correlations, and gravitational analyses were used to demonstrate interactions of neurons, which increased after electrical stimulation and were especially pronounced in the response afterdischarges. PMID:9513978

  12. Intracortical Multiplication of Thalamocortical Signals in Mouse Auditory Cortex

    PubMed Central

    Li, Ling-yun; Li, Ya-tang; Zhou, Mu; Tao, Huizhong W.; Zhang, Li I.

    2013-01-01

    Cortical processing of sensory information initiates from the transformation of thalamically-relayed signals. By optogenetically silencing intracortical circuits to isolate thalamic inputs to layer 4 neurons, we show that intracortical excitation linearly amplifies thalamocortical responses underlying frequency and direction selectivity with preserved spectral range and tuning, and prolongs the response duration. This signal pre-amplification and prolongation enhances the salience of thalamocortically-relayed information and ensures its robust, faithful and more persistent representation. PMID:23933752

  13. Assessing direct paths of intracortical causal information flow of oscillatory activity with the isolated effective coherence (iCoh)

    PubMed Central

    Pascual-Marqui, Roberto D.; Biscay, Rolando J.; Bosch-Bayard, Jorge; Lehmann, Dietrich; Kochi, Kieko; Kinoshita, Toshihiko; Yamada, Naoto; Sadato, Norihiro

    2014-01-01

    Functional connectivity is of central importance in understanding brain function. For this purpose, multiple time series of electric cortical activity can be used for assessing the properties of a network: the strength, directionality, and spectral characteristics (i.e., which oscillations are preferentially transmitted) of the connections. The partial directed coherence (PDC) of Baccala and Sameshima (2001) is a widely used method for this problem. The three aims of this study are: (1) To show that the PDC can misrepresent the frequency response under plausible realistic conditions, thus defeating the main purpose for which the measure was developed; (2) To provide a solution to this problem, namely the “isolated effective coherence” (iCoh), which consists of estimating the partial coherence under a multivariate autoregressive model, followed by setting all irrelevant associations to zero, other than the particular directional association of interest; and (3) To show that adequate iCoh estimators can be obtained from non-invasively computed cortical signals based on exact low resolution electromagnetic tomography (eLORETA) applied to scalp EEG recordings. To illustrate the severity of the problem with the PDC, and the solution achieved by the iCoh, three examples are given, based on: (1) Simulated time series with known dynamics; (2) Simulated cortical sources with known dynamics, used for generating EEG recordings, which are then used for estimating (with eLORETA) the source signals for the final connectivity assessment; and (3) EEG recordings in rats. Lastly, real human recordings are analyzed, where the iCoh between six cortical regions of interest are calculated and compared under eyes open and closed conditions, using 61-channel EEG recordings from 109 subjects. During eyes closed, the posterior cingulate sends alpha activity to all other regions. During eyes open, the anterior cingulate sends theta-alpha activity to other frontal regions. PMID:24999323

  14. Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation

    NASA Astrophysics Data System (ADS)

    Yazdan-Shahmorad, A.; Lehmkuhle, M. J.; Gage, G. J.; Marzullo, T. C.; Parikh, H.; Miriani, R. M.; Kipke, D. R.

    2011-08-01

    While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation

  15. Effects of caudate microstimulation on spontaneous and purposive saccades.

    PubMed

    Watanabe, Masayuki; Munoz, Douglas P

    2013-07-01

    Electrical stimulation has been delivered to the basal ganglia (BG) to treat intractable symptoms of a variety of clinical disorders. However, it is still unknown how such treatments improve behavioral symptoms. A difficulty of this problem is that artificial signals created by electrical stimulation interact with intrinsic signals before influencing behavior, thereby making it important to understand how such interactions between artificial and intrinsic signals occur. We addressed this issue by analyzing the effects of electrical stimulation under the following two behavioral conditions that induce different states of intrinsic signals: 1) subjects behave spontaneously without task demands; and 2) subjects perform a behavioral paradigm purposefully. We analyzed saccadic eye movements in monkeys while delivering microstimulation to the head and body of the caudate nucleus, a major input stage of the oculomotor BG. When monkeys generated spontaneous saccades, caudate microstimulation biased saccade vector endpoints toward the contralateral direction of stimulation sites. However, when caudate microstimulation was delivered during a purposive prosaccade (look toward a visual stimulus) or an antisaccade (look away from a stimulus) paradigm, it created overall ipsilateral biases by suppressing contralateral saccades more strongly than ipsilateral saccades. These results suggest that the impact of BG electrical stimulation changes dynamically depending on the state of intrinsic signals that vary under a variety of behavioral demands in everyday life. PMID:23636720

  16. Modifying cognition and behavior with electrical microstimulation: implications for cognitive prostheses.

    PubMed

    Opris, Ioan; Ferrera, Vincent P

    2014-11-01

    A fundamental goal of cognitive neuroscience is to understand how brain activity generates complex mental states and behaviors. While neuronal activity may predict or correlate with behavioral responses in a cognitive task, the use of electrical microstimulation presents the possibility to augment such correlational findings with direct evidence for causal relationships. Although microstimulation has been used for many years as a tool for mapping sensory and motor function, its role in learning, memory and decision-making has emerged only recently. Focal microstimulation of higher cortical areas can produce complex mental states and sequences of action. However, the relationship between the locus of stimulation and the percepts or actions evoked is often stereotyped and inflexible. The challenge is to develop stimulation systems that do not have fixed output but can flexibly contribute to complex cognitive and behavioral tasks. We discuss how microstimulation has been instrumental in manipulating a wide spectrum of cognitive functions including working memory, perceptual decisions and executive control by enhancing attention, re-ordering temporal sequence of saccades, improving associative learning or cognitive performance. For example, stimulation in prefrontal, parietal and sensory cortices may establish causal effects on decision-making, while microstimulation of inferotemporal cortex or caudate nucleus enhances associative learning. Building cognitive prosthetics based on the insights gleaned from such studies may depend on the development of multiple-input, multiple-output (MIMO) devices that allow subjects to control stimulation with their own thoughts in a closed-loop system. PMID:25242103

  17. Primate reaching cued by multichannel spatiotemporal cortical microstimulation.

    PubMed

    Fitzsimmons, N A; Drake, W; Hanson, T L; Lebedev, M A; Nicolelis, M A L

    2007-05-23

    Both humans and animals can discriminate signals delivered to sensory areas of their brains using electrical microstimulation. This opens the possibility of creating an artificial sensory channel that could be implemented in neuroprosthetic devices. Although microstimulation delivered through multiple implanted electrodes could be beneficial for this purpose, appropriate microstimulation protocols have not been developed. Here, we report a series of experiments in which owl monkeys performed reaching movements guided by spatiotemporal patterns of cortical microstimulation delivered to primary somatosensory cortex through chronically implanted multielectrode arrays. The monkeys learned to discriminate microstimulation patterns, and their ability to learn new patterns and new behavioral rules improved during several months of testing. Significantly, information was conveyed to the brain through the interplay of microstimulation patterns delivered to multiple electrodes and the temporal order in which these electrodes were stimulated. This suggests multichannel microstimulation as a viable means of sensorizing neural prostheses. PMID:17522304

  18. Development of closed-loop neural interface technology in a rat model: combining motor cortex operant conditioning with visual cortex microstimulation.

    PubMed

    Marzullo, Timothy Charles; Lehmkuhle, Mark J; Gage, Gregory J; Kipke, Daryl R

    2010-04-01

    Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices. PMID:20144922

  19. Sensitivity to microstimulation of somatosensory cortex distributed over multiple electrodes

    PubMed Central

    Kim, Sungshin; Callier, Thierri; Tabot, Gregg A.; Tenore, Francesco V.; Bensmaia, Sliman J.

    2015-01-01

    Meaningful and repeatable tactile sensations can be evoked by electrically stimulating primary somatosensory cortex. Intracortical microstimulation (ICMS) may thus be a viable approach to restore the sense of touch in individuals who have lost it, for example tetraplegic patients. One of the potential limitations of this approach, however, is that high levels of current can damage the neuronal tissue if the resulting current densities are too high. The limited range of safe ICMS amplitudes thus limits the dynamic range of ICMS-evoked sensations. One way to get around this limitation would be to distribute the ICMS over multiple electrodes in the hopes of intensifying the resulting percept without increasing the current density experienced by the neuronal tissue. Here, we test whether stimulating through multiple electrodes is a viable solution to increase the dynamic range of ICMS-elicited sensations without increasing the peak current density. To this end, we compare the ability of non-human primates to detect ICMS delivered through one vs. multiple electrodes. We also compare their ability to discriminate pulse trains differing in amplitude when these are delivered through one or more electrodes. We find that increasing the number of electrodes through which ICMS is delivered only has a marginal effect on detectability or discriminability despite the fact that 2–4 times more current is delivered overall. Furthermore, the impact of multielectrode stimulation (or lack thereof) is found whether pulses are delivered synchronously or asynchronously, whether the leading phase of the pulses is cathodic or anodic, and regardless of the spatial configuration of the electrode groups. PMID:25914630

  20. Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording.

    PubMed

    Lee, Joonhee; Ozden, Ilker; Song, Yoon-Kyu; Nurmikko, Arto V

    2015-12-01

    Optogenetics, the selective excitation or inhibition of neural circuits by light, has become a transformative approach for dissecting functional brain microcircuits, particularly in in vivo rodent models, owing to the expanding libraries of opsins and promoters. Yet there is a lack of versatile devices that can deliver spatiotemporally patterned light while performing simultaneous sensing to map the dynamics of perturbed neural populations at the network level. We have created optoelectronic actuator and sensor microarrays that can be used as monolithic intracortical implants, fabricated from an optically transparent, electrically highly conducting semiconductor ZnO crystal. The devices can perform simultaneous light delivery and electrical readout in precise spatial registry across the microprobe array. We applied the device technology in transgenic mice to study light-perturbed cortical microcircuit dynamics and their effects on behavior. The functionality of this device can be further expanded to optical imaging and patterned electrical microstimulation. PMID:26457862

  1. Learning to Recognize Visual Objects With Microstimulation in Inferior Temporal Cortex

    PubMed Central

    Kawasaki, Keisuke; Sheinberg, David L.

    2008-01-01

    The malleability of object representations by experience is essential for adaptive behavior. It has been hypothesized that neurons in inferior temporal cortex (IT) in monkeys are pivotal in visual association learning, evidenced by experiments revealing changes in neural selectivity following visual learning, as well as by lesion studies, wherein functional inactivation of IT impairs learning. A critical question remaining to be answered is whether IT neuronal activity is sufficient for learning. To address this question directly, we conducted experiments combining visual classification learning with microstimulation in IT. We assessed the effects of IT microstimulation during learning in cases where the stimulation was exclusively informative, conditionally informative, and informative but not necessary for the classification task. The results show that localized microstimulation in IT can be used to establish visual classification learning, and the same stimulation applied during learning can predictably bias judgments on subsequent recognition. The effect of induced activity can be explained neither by direct stimulation-motor association nor by simple detection of cortical stimulation. We also found that the learning effects are specific to IT stimulation as they are not observed by microstimulation in an adjacent auditory area. Our results add the evidence that the differential activity in IT during visual association learning is sufficient for establishing new associations. The results suggest that experimentally manipulated activity patterns within IT can be effectively combined with ongoing visually induced activity during the formation of new associations. PMID:18463185

  2. Comparing temporal aspects of visual, tactile, and microstimulation feedback for motor control

    NASA Astrophysics Data System (ADS)

    Godlove, Jason M.; Whaite, Erin O.; Batista, Aaron P.

    2014-08-01

    Objectives. Current brain-computer interfaces (BCIs) rely on visual feedback, requiring sustained visual attention to use the device. Improvements to BCIs may stem from the development of an effective way to provide quick feedback independent of vision. Tactile stimuli, either delivered on the skin surface, or directly to the brain via microstimulation in somatosensory cortex, could serve that purpose. We examined the effectiveness of vibrotactile stimuli and microstimulation as a means of non-visual feedback by using a fundamental element of feedback: the ability to react to a stimulus while already in motion. Approach. Human and monkey subjects performed a center-out reach task which was, on occasion, interrupted with a stimulus cue that instructed a change in reach target. Main results. Subjects generally responded faster to tactile cues than to visual cues. However, when we delivered cues via microstimuation in a monkey, its response was slower on average than for both tactile and visual cues. Significance. Tactile and microstimulation feedback can be used to rapidly adjust movements mid-flight. The relatively slow speed of microstimulation is surprising and warrants further investigation. Overall, these results highlight the importance of considering temporal aspects of feedback when designing alternative forms of feedback for BCIs.

  3. A characterization of the effects on neuronal excitability due to prolonged microstimulation with chronically implanted microelectrodes.

    PubMed

    McCreery, D B; Yuen, T G; Agnew, W F; Bullara, L A

    1997-10-01

    Localized, long-lasting stimulation-induced depression of neuronal excitability (SIDNE) is a consequence of prolonged, high-frequency microstimulation in the central nervous system (CNS). It represents a persisting refractory state in the neurons and axons near the stimulating microelectrode, that occurs in the absence of histologically detectable tissue injury. It does not involve a change in synaptic efficacy and, in this respect, it differs from the more familiar phenomenon of long-term depression (LTD). Although SIDNE is ultimately reversible (after several days), it must be taken into account in the design of neural prostheses based on microstimulation in the central nervous system and in animal studies that require prolonged microstimulation in the CNS. In this study, we have characterized the phenomenon, using as the paradigm, iridium microelectrodes implanted chronically in the cat's posteroventral cochlear nucleus. Although the SIDNE may persist for several days after the end of the stimulation protocol, it does not become more severe from day to day when the stimulation protocol is repeated on successive days. The severity of the SIDNE is strongly dependent upon both the instantaneous frequency and the duty cycle of the electrical stimulation. The character of the SIDNE, including its localization to the immediate vicinity of the stimulating microelectrodes, suggests that the phenomenon is a direct consequence of the prolonged electrical excitation of the neurons close to the microelectrode. The problem of designing microstimulation systems that allow high-frequency stimulation of a neural substrate, while minimizing SIDNE are discussed. PMID:9311162

  4. Multiple manifestations of microstimulation in the optic tectum: eye movements, pupil dilations, and sensory priming.

    PubMed

    Netser, Shai; Ohayon, Shay; Gutfreund, Yoram

    2010-07-01

    It is well established that the optic tectum (or its mammalian homologue, the superior colliculus) is involved in directing gaze toward salient stimuli. However, salient stimuli typically induce orienting responses beyond gaze shifts. The role of the optic tectum in generating responses such as pupil dilation, galvanic responses, or covert shifts is not clear. In the present work, we studied the effects of microstimulation in the optic tectum of the barn owl (Tyto alba) on pupil diameter and on eye shifts. Experiments were conducted in lightly anesthetized head-restrained barn owls. We report that low-level microstimulation in the deep layers of the optic tectum readily induced pupil dilation responses (PDRs), as well as small eye movements. Electrically evoked PDRs, similar to acoustically evoked PDRs, were long-lasting and habituated to repeated stimuli. We further show that microstimulation in the external nucleus of the inferior colliculus also induced PDRs. Finally, in experiments in which tectal microstimulations were coupled with acoustic stimuli, we show a tendency of the microstimulation to enhance pupil responses and eye shifts to previously habituated acoustic stimuli. The enhancement was dependent on the site of stimulation in the tectal spatial map; responses to sounds with spatial cues that matched the site of stimulation were more enhanced compared with sounds with spatial cues that did not match. These results suggest that the optic tectum is directly involved in autonomic orienting reflexes as well as in gaze shifts, highlighting the central role of the optic tectum in mediating the body responses to salient stimuli. PMID:20427617

  5. Corticospinal and Intracortical Excitability of the Quadriceps in Patients with Knee Osteoarthritis

    PubMed Central

    Kittelson, Andrew J.; Thomas, Abbey C.; Kluger, Benzi M.; Stevens-Lapsley, Jennifer E.

    2015-01-01

    Deficits in voluntary activation of the quadriceps muscle are characteristic of knee osteoarthritis (OA), contributing to the quadriceps weakness that is also a hallmark of the disease. The mechanisms underlying this central activation deficit (CAD) are unknown, although cortical mechanisms may be involved. Here, we utilize transcranial magnetic stimulation (TMS) to assess corticospinal and intracortical excitability in patients with knee osteoarthritis (OA) and in a comparably aged group of healthy older adults, to quantify group differences and to examine associations between TMS measures and pain, quadriceps strength, and CAD. Seventeen patients with knee OA and 20 healthy controls completed testing. Motor evoked potentials (MEPs) were measured at the quadriceps by superficial electromyographic (EMG) recordings. Corticospinal excitability was assessed by measuring resting motor threshold (RMT) to TMS stimulation of the quadriceps representation at primary motor cortex, and intracortical excitability was assessed via paired pulse paradigms for short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). No statistically significant differences between patients with knee OA and healthy controls were found for RMT, SICI or ICF measures (p>0.05). For patients with knee OA, there were significant associations observed between pain and RMT, as well as between pain and ICF. No associations were observed between CAD and measures of corticospinal or intracortical excitability. These data suggest against direct involvement of corticospinal or intracortical pathways within primary motor cortex in the mechanisms of CAD. However, pain is implicated in the neural mechanisms of quadriceps motor control in patients with knee OA. PMID:25183161

  6. Injectable microstimulator for functional electrical stimulation.

    PubMed

    Loeb, G E; Zamin, C J; Schulman, J H; Troyk, P R

    1991-11-01

    A family of digitally controlled devices is constructed for functional electrical stimulation in which each module is an hermetically sealed glass capsule that is small enough to be injected through the lumen of a hypodermic needle. The overall design and component characteristics of microstimulators that receive power and command signals by inductive coupling from a single, externally worn coil are described. Each device stores power between stimulus pulses by charging an electrolytic capacitor formed by its two electrodes, made of sintered, anodised tantalum and electrochemically activated iridium, respectively. Externally, a highly efficient class E amplifier provides power and digitally encoded command signals to control the amplitude, duration and timing of pulses from up to 256 such microstimulators. PMID:1813741

  7. Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

    NASA Astrophysics Data System (ADS)

    Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

    2015-02-01

    To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.

  8. Progress Towards Biocompatible Intracortical Microelectrodes for Neural Interfacing Applications

    PubMed Central

    Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

    2015-01-01

    To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing. PMID:25460808

  9. Performance sustaining intracortical neural prostheses

    NASA Astrophysics Data System (ADS)

    Nuyujukian, Paul; Kao, Jonathan C.; Fan, Joline M.; Stavisky, Sergey D.; Ryu, Stephen I.; Shenoy, Krishna V.

    2014-12-01

    Objective. Neural prostheses, or brain-machine interfaces, aim to restore efficient communication and movement ability to those suffering from paralysis. A major challenge these systems face is robust performance, particularly with aging signal sources. The aim in this study was to develop a neural prosthesis that could sustain high performance in spite of signal instability while still minimizing retraining time. Approach. We trained two rhesus macaques implanted with intracortical microelectrode arrays 1-4 years prior to this study to acquire targets with a neurally-controlled cursor. We measured their performance via achieved bitrate (bits per second, bps). This task was repeated over contiguous days to evaluate the sustained performance across time. Main results. We found that in the monkey with a younger (i.e., two year old) implant and better signal quality, a fixed decoder could sustain performance for a month at a rate of 4 bps, the highest achieved communication rate reported to date. This fixed decoder was evaluated across 22 months and experienced a performance decline at a rate of 0.24 bps yr-1. In the monkey with the older (i.e., 3.5 year old) implant and poorer signal quality, a fixed decoder could not sustain performance for more than a few days. Nevertheless, performance in this monkey was maintained for two weeks without requiring additional online retraining time by utilizing prior days’ experimental data. Upon analysis of the changes in channel tuning, we found that this stability appeared partially attributable to the cancelling-out of neural tuning fluctuations when projected to two-dimensional cursor movements. Significance. The findings in this study (1) document the highest-performing communication neural prosthesis in monkeys, (2) confirm and extend prior reports of the stability of fixed decoders, and (3) demonstrate a protocol for system stability under conditions where fixed decoders would otherwise fail. These improvements to decoder

  10. Equilibrium-Based Movement Endpoints Elicited from Primary Motor Cortex Using Repetitive Microstimulation

    PubMed Central

    Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.

    2014-01-01

    High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) is increasingly being used to deduce how the brain encodes coordinated muscle activity and movement. However, the full movement repertoire that can be elicited from the forelimb representation of primary motor cortex (M1) using this method has not been systematically determined. Our goal was to acquire a comprehensive M1 forelimb representational map of movement endpoints elicited with HFLD-ICMS, using stimulus parameters optimal for evoking stable forelimb spatial endpoints. The data reveal a 3D forelimb movement endpoint workspace that is represented in a patchwork fashion on the 2D M1 cortical surface. Although cortical maps of movement endpoints appear quite disorderly with respect to movement space, we show that the endpoint locations in the workspace evoked with HFLD-ICMS of two adjacent cortical points are closer together than would be expected if the organization were random. Although there were few obvious consistencies in the endpoint maps across the two monkeys tested, one notable exception was endpoints bringing the hand to the mouth, which was located at the boundary between the hand and face representation. Endpoints at the extremes of the monkey's workspace and locations above the head were largely absent. Our movement endpoints are best explained as resulting from coactivation of agonist and antagonist muscles driving the joints toward equilibrium positions determined by the length–tension relationships of the muscles. PMID:25411500

  11. The olivocochlear reflex strength and cochlear sensitivity are independently modulated by auditory cortex microstimulation.

    PubMed

    Dragicevic, Constantino D; Aedo, Cristian; León, Alex; Bowen, Macarena; Jara, Natalia; Terreros, Gonzalo; Robles, Luis; Delano, Paul H

    2015-04-01

    In mammals, efferent projections to the cochlear receptor are constituted by olivocochlear (OC) fibers that originate in the superior olivary complex. Medial and lateral OC neurons make synapses with outer hair cells and with auditory nerve fibers, respectively. In addition to the OC system, there are also descending projections from the auditory cortex that are directed towards the thalamus, inferior colliculus, cochlear nucleus, and superior olivary complex. Olivocochlear function can be assessed by measuring a brainstem reflex mediated by auditory nerve fibers, cochlear nucleus neurons, and OC fibers. Although it is known that the OC reflex is activated by contralateral acoustic stimulation and produces a suppression of cochlear responses, the influence of cortical descending pathways in the OC reflex is largely unknown. Here, we used auditory cortex electrical microstimulation in chinchillas to study a possible cortical modulation of cochlear and auditory nerve responses to tones in the absence and presence of contralateral noise. We found that cortical microstimulation produces two different peripheral modulations: (i) changes in cochlear sensitivity evidenced by amplitude modulation of cochlear microphonics and auditory nerve compound action potentials and (ii) enhancement or suppression of the OC reflex strength as measured by auditory nerve responses, which depended on the intersubject variability of the OC reflex. Moreover, both corticofugal effects were not correlated, suggesting the presence of two functionally different efferent pathways. These results demonstrate that auditory cortex electrical microstimulation independently modulates the OC reflex strength and cochlear sensitivity. PMID:25663383

  12. Insights into cortical mechanisms of behavior from microstimulation experiments

    PubMed Central

    Histed, Mark H.; Ni, Amy M.; Maunsell, John H.R.

    2012-01-01

    Even the simplest behaviors depend on a large number of neurons that are distributed across many brain regions. Because electrical microstimulation can change the activity of localized subsets of neurons, it has provided valuable evidence that specific neurons contribute to particular behaviors. Here we review what has been learned about cortical function from behavioral studies using microstimulation in animals and humans. Experiments that examine how microstimulation affects the perception of stimuli have shown that the effects of microstimulation are usually highly specific and can be related to the stimuli preferred by neurons at the stimulated site. Experiments that ask subjects to detect cortical microstimulation in the absence of other stimuli have provided further insights. Although subjects typically can detect microstimulation of primary sensory or motor cortex, they are generally unable to detect stimulation of most of cortex without extensive practice. With practice, however, stimulation of any part of cortex can become detected. These training effects suggest that some patterns of cortical activity cannot be readily accessed to guide behavior, but that the adult brain retains enough plasticity to learn to process novel patterns of neuronal activity arising anywhere in cortex. PMID:22307059

  13. Aerobic exercise modulates intracortical inhibition and facilitation in a nonexercised upper limb muscle

    PubMed Central

    2014-01-01

    Background Despite growing interest in the relationship between exercise and short-term neural plasticity, the effects of exercise on motor cortical (M1) excitability are not well studied. Acute, lower-limb aerobic exercise may potentially modulate M1 excitability in working muscles, but the effects on muscles not involved in the exercise are unknown. Here we examined the excitability changes in an upper limb muscle representation following a single session of lower body aerobic exercise. Investigating the response to exercise in a non-exercised muscle may help to determine the clinical usefulness of lower-body exercise interventions for upper limb neurorehabilitation. Methods In this study, transcranial magnetic stimulation was used to assess input–output curves, short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF) in the extensor carpi radialis muscle in twelve healthy individuals following a single session of moderate stationary biking. Additionally, we examined whether the presence of a common polymorphism of the brain-derived neurotrophic factor (BDNF) gene would affect the response of these measures to exercise. Results We observed significant increases in ICF and decreases in SICI following exercise. No changes in LICI were detected, and no differences were observed in input–output curves following exercise, or between BDNF groups. Conclusions The current results demonstrate that the modulation of intracortical excitability following aerobic exercise is not limited to those muscles involved in the exercise, and that while exercise does not directly modulate the excitability of motor neurons, it may facilitate the induction of experience-dependent plasticity via a decrease in intracortical inhibition and increase in intracortical facilitation. These findings indicate that exercise may create favourable conditions for adaptive plasticity in M1 and may be an effective adjunct to

  14. Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.

    PubMed

    Liu, X; McCreery, D B; Carter, R R; Bullara, L A; Yuen, T G; Agnew, W F

    1999-09-01

    The stability of the interface between neural tissue and chronically implanted microelectrodes is very important for obtaining reliable control signals for neuroprosthetic devices. Stability is also crucial for chronic microstimulation of the cerebral cortex. However, changes of the electrode-tissue interface can be caused by a variety of mechanisms. In the present study, intracortical microelectrode arrays were implanted into the pericruciate gyrus of cats and neural activities were recorded on a regular basis for several months. An algorithm based on cluster analysis and interspike interval analysis was developed to sort the extracellular action potentials into single units. We tracked these units based on their waveform and their response to somatic stimulation or stereotypical movements by the cats. Our results indicate that, after implantation, the electrode-tissue interface may change from day-to-day over the first 1-2 weeks, week-to-week for 1-2 months, and become quite stable thereafter. A stability index is proposed to quantify the stability of the electrode-tissue interface. The reasons for the pattern of changes are discussed. PMID:10498377

  15. Microstimulation of visual cortex to restore vision.

    PubMed

    Tehovnik, Edward J; Slocum, Warren M; Smirnakis, Stelios M; Tolias, Andreas S

    2009-01-01

    This review argues that one reason why a functional visuo-cortical prosthetic device has not been developed to restore even minimal vision to blind individuals is because there is no animal model to guide the design and development of such a device. Over the past 8 years we have been conducting electrical microstimulation experiments on alert behaving monkeys with the aim of better understanding how electrical stimulation of the striate cortex (area V1) affects oculo- and skeleto-motor behaviors. Based on this work and upon review of the literature, we arrive at several conclusions: (1) As with the development of the cochlear implant, the development of a visuo-cortical prosthesis can be accelerated by using animals to test the perceptual effects of microstimulating V1 in intact and blind monkeys. (2) Although a saccade-based paradigm is very convenient for studying the effectiveness of delivering stimulation to V1 to elicit saccadic eye movements, it is less ideal for probing the volitional state of monkeys, as they perceive electrically induced phosphenes. (3) Electrical stimulation of V1 can delay visually guided saccades generated to a punctate target positioned in the receptive field of the stimulated neurons. We call the region of visual space affected by the stimulation a delay field. The study of delay fields has proven to be an efficient way to study the size and shape of phosphenes generated by stimulation of macaque V1. (4) An alternative approach to ascertain what monkeys see during electrical stimulation of V1 is to have them signal the detection of current with a lever press. Monkeys can readily detect currents of 1-2 microA delivered to V1. In order to evoke featured phosphenes currents of under 5 microA will be necessary. (5) Partially lesioning the retinae of monkeys is superior to completely lesioning the retinae when determining how blindness affects phosphene induction. We finish by proposing a future experimental paradigm designed to determine

  16. Implants and Decoding for Intracortical Brain Computer Interfaces

    PubMed Central

    Homer, Mark L.; Nurmikko, Arto V.; Donoghue, John P.; Hochberg, Leigh R.

    2014-01-01

    Intracortical brain computer interfaces (iBCIs) are being developed to enable a person to drive an output device, such as a computer cursor, directly from their neural activity. One goal of the technology is to help people with severe paralysis or limb loss. Key elements of an iBCI are the implanted sensor that records the neural signals and the software which decodes the user’s intended movement from those signals. Here, we focus on recent advances in these two areas, with special attention being placed on contributions that are or may soon be adopted by the iBCI research community. We discuss how these innovations increase the technology’s capability, accuracy, and longevity, all important steps that are expanding the range of possible future clinical applications. PMID:23862678

  17. Effects of Microstimulation in the Anterior Intraparietal Area during Three-Dimensional Shape Categorization

    PubMed Central

    Verhoef, Bram-Ernst; Vogels, Rufin; Janssen, Peter

    2015-01-01

    The anterior intraparietal area (AIP) of rhesus monkeys is part of the dorsal visual stream and contains neurons whose visual response properties are commensurate with a role in three-dimensional (3D) shape perception. Neuronal responses in AIP signal the depth structure of disparity-defined 3D shapes, reflect the choices of monkeys while they categorize 3D shapes, and mirror the behavioral variability across different stimulus conditions during 3D-shape categorization. However, direct evidence for a role of AIP in 3D-shape perception has been lacking. We trained rhesus monkeys to categorize disparity-defined 3D shapes and examined AIP's contribution to 3D-shape categorization by microstimulating in clusters of 3D-shape selective AIP neurons during task performance. We find that microstimulation effects on choices (monkey M1) and reaction times (monkey M1 and M2) depend on the 3D-shape preference of the stimulated site. Moreover, electrical stimulation of the same cells, during either the 3D-shape-categorization task or a saccade task, could affect behavior differently. Interestingly, in one monkey we observed a strong correlation between the strength of choice-related AIP activity (choice probabilities) and the influence of microstimulation on 3D-shape-categorization behavior (choices and reaction time). These findings propose AIP as part of the network responsible for 3D-shape perception. The results also show that the anterior intraparietal cortex contains cells with different tuning properties, i.e. 3D-shape- or saccade-related, that can be dynamically read out depending on the requirements of the task at hand. PMID:26295941

  18. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    NASA Astrophysics Data System (ADS)

    Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

    2013-08-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

  19. Effects of ketamine and propofol on motor evoked potentials elicited by intracranial microstimulation during deep brain stimulation

    PubMed Central

    Furmaga, Havan; Park, Hyun-Joo; Cooperrider, Jessica; Baker, Kenneth B.; Johnson, Matthew; Gale, John T.; Machado, Andre G.

    2014-01-01

    Few preclinical or clinical studies have evaluated the effect of anesthetics on motor evoked potentials (MEPs), either alone or in the presence of conditioning stimuli such as deep brain stimulation (DBS). In this study we evaluated the effects of two commonly used anesthetic agents, propofol and ketamine (KET), on MEPs elicited by intra-cortical microstimulation of the motor cortex in a rodent model with and without DBS of the dentatothalamocortical (DTC) pathway. The effects of propofol anesthesia on MEP amplitudes during DTC DBS were found to be highly dose dependent. Standard, but not high, dose propofol potentiated the facilitatory effects of 30 Hz DTC DBS on MEPs. This facilitation was sustained and phase-dependent indicating that, compared to high dose propofol, standard dose propofol has a beta-band excitatory effect on cortical networks. In contrast, KET anesthetic demonstrated a monotonic relationship with increasing frequencies of stimulation, such that the highest frequency of stimulation resulted in the greatest MEP amplitude. KET also showed phase dependency but less pronounced than standard dose propofol. The results underscore the importance of better understanding the complex effects of anesthetics on cortical networks and exogenous stimuli. Choice of anesthetic agents and dosing may significantly confound or even skew research outcomes, including experimentation in novel DBS indications and paradigms. PMID:24904312

  20. Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury.

    PubMed

    Shahdoost, Shahab; Frost, Shawn; Dunham, Caleb; DeJong, Stacey; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

    2015-08-01

    Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level. Using a combination of custom integrated circuit (IC) technology for corticospinal interfacing and field-programmable gate array (FPGA)-based technology for embedded signal processing, we demonstrate proof-of-concept of distinct muscle pattern activation via intraspinal microstimulation (ISMS) controlled in real time by intracortical neural spikes in an anesthetized laboratory rat. PMID:26736717

  1. Increased intracortical inhibition in hyperglycemic hemichorea-hemiballism.

    PubMed

    Li, Jie-Yuan; Chen, Robert

    2015-02-01

    Hemichorea-hemiballism (HC-HB) in uncontrolled diabetes mellitus is an uncommon manifestation of hyperglycemia. The pathophysiology of hyperglycemic HC-HB is not well understood. A previous report showed increased intracortical inhibition in the motor cortex in a patient with diabetes with HC-HB. The objective of this study is to investigate motor cortex excitability in patients with hyperglycemic HC-HB. We hypothesized that intracortical inhibition measured with transcranial magnetic stimulation, which likely reflects the excitability of cortical γ-aminobutyric acid (GABA)ergic circuits, would be impaired in patients with hyperglycemic HC-HB. We studied 15 patients with mean age 71.5 years (range, 48-94 y) and 12 age-matched healthy subjects. The motor cortex contralateral to the hemichorea was tested. Transcranial magnetic stimulation measures included motor evoked potential, recruitment curve, GABAA mediated short interval intracortical inhibition, intracortical facilitation, and GABAB mediated silent period duration and long interval intracortical inhibition. No significant difference was found in motor threshold, recruitment curve response, short interval intracortical inhibition, or intracortical facilitation in both rest and active conditions between patients with hyperglycemic HC-HB and normal subjects. However, long interval intracortical inhibition was significantly increased during muscle activation but not at rest in patients with hyperglycemic HC-HB. The silent period duration is also increased in patients with hyperglycemic HC-HB. We concluded that long interval intracortical inhibition and silent period are increased in the motor cortex contralateral to the hemichorea in hyperglycemic HC-HB, but only during muscle activation. Hemichorea-hemiballism may be associated with increased GABAB receptor-mediated inhibitory activity in the motor cortex. PMID:24919927

  2. Microstimulation of the human substantia nigra alters reinforcement learning.

    PubMed

    Ramayya, Ashwin G; Misra, Amrit; Baltuch, Gordon H; Kahana, Michael J

    2014-05-14

    Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning. PMID:24828643

  3. Task-dependent changes of intracortical inhibition.

    PubMed

    Liepert, J; Classen, J; Cohen, L G; Hallett, M

    1998-02-01

    The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1-6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10-15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movements involving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1-3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF

  4. Approaches for drug delivery with intracortical probes.

    PubMed

    Spieth, Sven; Schumacher, Axel; Trenkle, Fabian; Brett, Olivia; Seidl, Karsten; Herwik, Stanislav; Kisban, Sebastian; Ruther, Patrick; Paul, Oliver; Aarts, Arno A A; Neves, Hercules P; Rich, P Dylan; Theobald, David E; Holtzman, Tahl; Dalley, Jeffrey W; Verhoef, Bram-Ernst; Janssen, Peter; Zengerle, Roland

    2014-08-01

    Intracortical microprobes allow the precise monitoring of electrical and chemical signaling and are widely used in neuroscience. Microelectromechanical system (MEMS) technologies have greatly enhanced the integration of multifunctional probes by facilitating the combination of multiple recording electrodes and drug delivery channels in a single probe. Depending on the neuroscientific application, various assembly strategies are required in addition to the microprobe fabrication itself. This paper summarizes recent advances in the fabrication and assembly of micromachined silicon probes for drug delivery achieved within the EU-funded research project NeuroProbes. The described fabrication process combines a two-wafer silicon bonding process with deep reactive ion etching, wafer grinding, and thin film patterning and offers a maximum in design flexibility. By applying this process, three general comb-like microprobe designs featuring up to four 8-mm-long shafts, cross sections from 150×200 to 250×250 µm², and different electrode and fluidic channel configurations are realized. Furthermore, we discuss the development and application of different probe assemblies for acute, semichronic, and chronic applications, including comb and array assemblies, floating microprobe arrays, as well as the complete drug delivery system NeuroMedicator for small animal research. PMID:24101367

  5. Intracortical polyimide electrodes with a bioresorbable coating.

    PubMed

    Hassler, Christina; Guy, Julien; Nietzschmann, Max; Plachta, Dennis T T; Staiger, Jochen F; Stieglitz, Thomas

    2016-10-01

    Polyimide based shaft electrodes were coated with a bioresorbable layer to stiffen them for intracortical insertion and to reduce the mechanical mismatch between the target tissue and the implanted device after degradation of the coating. Molten saccharose was used as coating material. In a proof-of-concept study, the electrodes were implanted into the cortex of Wistar rats and the insertion forces during implantation were recorded. Electrochemical impedance spectroscopy was performed immediately after implantation and up to 13 weeks after implantation to monitor the tissue response to the implanted electrodes. The recorded spectra were modeled with an equivalent circuit to differentiate the influence of the single components. In one rat, a peak in the encapsulation resistance was observable after two weeks of implantation, indicating the peak of the acute inflammatory response. In another rat, the lowest resistances were observed after four weeks, indicating the termination of the acute inflammatory response. Multiunit activity was recorded with an adequate signal to noise ratio to allow spike sorting. Histology was performed after 7, 45 and 201 days of implantation. The results showed the highest tissue reaction after 45 days and confirmed impedance data that acute inflammatory reactions terminate over time. PMID:27534649

  6. A model for intracortical visual prosthesis research.

    PubMed

    Troyk, Philip; Bak, Martin; Berg, Joshua; Bradley, David; Cogan, Stuart; Erickson, Robert; Kufta, Conrad; McCreery, Douglas; Schmidt, Edward; Towle, Vernon

    2003-11-01

    In the field of visual prosthesis research, it has generally been held that animal models are limited to testing the safety of implantable hardware due to the inability of the animal to provide a linguistic report of perceptions. In contrast, vision scientists make extensive use of trained animal models to investigate the links between visual stimuli, neural activities, and perception. We describe an animal model for cortical visual prosthesis research in which novel animal psychophysical testing has been employed to compensate for the lack of a linguistic report. One hundred and fifty-two intracortical microelectrodes were chronically implanted in area V1 of a male macaque. Receptive field mapping was combined with eye-tracking to develop a reward-based training procedure. The animal was trained to use electrically induced point-flash percepts, called phosphenes, in performing a memory saccade task. It is our long-term goal to use this animal model to investigate stimulation strategies in developing a multichannel sensory cortical interface. PMID:14616519

  7. Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate+glutamine

    PubMed Central

    Tremblay, Sara; Beaulé, Vincent; Proulx, Sébastien; de Beaumont, Louis; Marjańska, Małgorzata; Doyon, Julien; Pascual-Leone, Alvaro; Lassonde, Maryse

    2013-01-01

    Transcranial magnetic stimulation (TMS) can provide an index of intracortical excitability/inhibition balance. However, the neurochemical substrate of these measures remains unclear. Pharmacological studies suggest the involvement of GABAA and GABAB receptors in TMS protocols aimed at measuring intracortical inhibition, but this link remains inferential. Proton magnetic resonance spectroscopy (1H-MRS) permits measurement of GABA and glutamate + glutamine (Glx) concentrations in the human brain and might help in the direct empirical assessment of the relationship between TMS inhibitory measures and neurotransmitter concentrations. In the present study, MRS-derived relative concentrations of GABA and Glx measured in the left M1 of healthy participants were correlated with TMS measures of intracortical inhibition. Glx levels were found to correlate positively with TMS-induced silent period duration, whereas no correlation was found between GABA concentration and TMS measures. The present data demonstrate that specific TMS measures of intracortical inhibition are linked to shifts in cortical Glx, rather than GABA neurotransmitter levels. Glutamate might specifically interact with GABAB receptors, where higher MRS-derived Glx concentrations seem to be linked to higher levels of receptor activity. PMID:23221412

  8. Self-recalibrating classifiers for intracortical brain-computer interfaces

    NASA Astrophysics Data System (ADS)

    Bishop, William; Chestek, Cynthia C.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Ryu, Stephen I.; Shenoy, Krishna V.; Yu, Byron M.

    2014-04-01

    Objective. Intracortical brain-computer interface (BCI) decoders are typically retrained daily to maintain stable performance. Self-recalibrating decoders aim to remove the burden this may present in the clinic by training themselves autonomously during normal use but have only been developed for continuous control. Here we address the problem for discrete decoding (classifiers). Approach. We recorded threshold crossings from 96-electrode arrays implanted in the motor cortex of two rhesus macaques performing center-out reaches in 7 directions over 41 and 36 separate days spanning 48 and 58 days in total for offline analysis. Main results. We show that for the purposes of developing a self-recalibrating classifier, tuning parameters can be considered as fixed within days and that parameters on the same electrode move up and down together between days. Further, drift is constrained across time, which is reflected in the performance of a standard classifier which does not progressively worsen if it is not retrained daily, though overall performance is reduced by more than 10% compared to a daily retrained classifier. Two novel self-recalibrating classifiers produce a \\mathord {\\sim }15% increase in classification accuracy over that achieved by the non-retrained classifier to nearly recover the performance of the daily retrained classifier. Significance. We believe that the development of classifiers that require no daily retraining will accelerate the clinical translation of BCI systems. Future work should test these results in a closed-loop setting.

  9. Orienting head movements resulting from electrical microstimulation of the brainstem tegmentum in the barn owl.

    PubMed

    Masino, T; Knudsen, E I

    1993-01-01

    The size and direction of orienting movements are represented systematically as a motor map in the optic tectum of the barn owl (du Lac and Knudsen, 1990). The optic tectum projects to several distinct regions in the medial brainstem tegmentum, which in turn project to the spinal cord (Masino and Knudsen, 1992). This study explores the hypothesis that a fundamental transformation in the neural representation of orienting movements takes place in the brainstem tegmentum. Head movements evoked by electrical microstimulation in the brainstem tegmentum of the alert barn owl were cataloged and the sites of stimulation were reconstructed histologically. Movements elicited from the brainstem tegmentum were categorized into one of six different classes: saccadic head rotations, head translations, facial movements, vocalizations, limb movements, and twitches. Saccadic head rotations could be further subdivided into two general categories: fixed-direction saccades and goal-directed saccades. Fixed-direction saccades, those whose direction was independent of initial head position, were elicited from the midbrain tegmentum. Goal-directed saccades, those whose direction changed with initial head position, were elicited from the central rhombencephalic reticular formation and from the efferent pathway of the cerebellum. Particular attention was paid to sites from which fixed-direction saccadic movements were elicited, as these movements appeared to represent components of orienting movements. Microstimulation in the medial midbrain tegmentum elicited fixed-direction saccades in one of six directions: rightward, leftward, upward, downward, clockwise roll, and counterclockwise roll. Stimulation in and around the interstitial nucleus of Cajal (InC; a complete list of anatomical abbreviations is given in the Appendix) produced ipsiversive horizontal saccades. Stimulation in the ventral InC and near the dorsal and medial edges of the red nucleus produced upward saccades. Stimulation

  10. Cortical Plasticity Induced by Spike-Triggered Microstimulation in Primate Somatosensory Cortex

    PubMed Central

    Song, Weiguo; Kerr, Cliff C.; Lytton, William W.; Francis, Joseph T.

    2013-01-01

    Electrical stimulation of the nervous system for therapeutic purposes, such as deep brain stimulation in the treatment of Parkinson’s disease, has been used for decades. Recently, increased attention has focused on using microstimulation to restore functions as diverse as somatosensation and memory. However, how microstimulation changes the neural substrate is still not fully understood. Microstimulation may cause cortical changes that could either compete with or complement natural neural processes, and could result in neuroplastic changes rendering the region dysfunctional or even epileptic. As part of our efforts to produce neuroprosthetic devices and to further study the effects of microstimulation on the cortex, we stimulated and recorded from microelectrode arrays in the hand area of the primary somatosensory cortex (area 1) in two awake macaque monkeys. We applied a simple neuroprosthetic microstimulation protocol to a pair of electrodes in the area 1 array, using either random pulses or pulses time-locked to the recorded spiking activity of a reference neuron. This setup was replicated using a computer model of the thalamocortical system, which consisted of 1980 spiking neurons distributed among six cortical layers and two thalamic nuclei. Experimentally, we found that spike-triggered microstimulation induced cortical plasticity, as shown by increased unit-pair mutual information, while random microstimulation did not. In addition, there was an increased response to touch following spike-triggered microstimulation, along with decreased neural variability. The computer model successfully reproduced both qualitative and quantitative aspects of the experimental findings. The physiological findings of this study suggest that even simple microstimulation protocols can be used to increase somatosensory information flow. PMID:23472086

  11. Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

    NASA Astrophysics Data System (ADS)

    Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

    2009-10-01

    Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

  12. Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

    PubMed Central

    Zimerman, Máximo; Wessel, Maximilian J.; Timmermann, Jan E.; Granström, Sofia; Gerloff, Christian; Mautner, Victor F.; Hummel, Friedhelm C.

    2015-01-01

    Background Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? Methods We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. Findings NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase. Interpretations Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as

  13. Reward modulates the effect of visual cortical microstimulation on perceptual decisions.

    PubMed

    Cicmil, Nela; Cumming, Bruce G; Parker, Andrew J; Krug, Kristine

    2015-01-01

    Effective perceptual decisions rely upon combining sensory information with knowledge of the rewards available for different choices. However, it is not known where reward signals interact with the multiple stages of the perceptual decision-making pathway and by what mechanisms this may occur. We combined electrical microstimulation of functionally specific groups of neurons in visual area V5/MT with performance-contingent reward manipulation, while monkeys performed a visual discrimination task. Microstimulation was less effective in shifting perceptual choices towards the stimulus preferences of the stimulated neurons when available reward was larger. Psychophysical control experiments showed this result was not explained by a selective change in response strategy on microstimulated trials. A bounded accumulation decision model, applied to analyse behavioural performance, revealed that the interaction of expected reward with microstimulation can be explained if expected reward modulates a sensory representation stage of perceptual decision-making, in addition to the better-known effects at the integration stage. PMID:26402458

  14. Current approaches to model extracellular electrical neural microstimulation

    PubMed Central

    Joucla, Sébastien; Glière, Alain; Yvert, Blaise

    2014-01-01

    Nowadays, high-density microelectrode arrays provide unprecedented possibilities to precisely activate spatially well-controlled central nervous system (CNS) areas. However, this requires optimizing stimulating devices, which in turn requires a good understanding of the effects of microstimulation on cells and tissues. In this context, modeling approaches provide flexible ways to predict the outcome of electrical stimulation in terms of CNS activation. In this paper, we present state-of-the-art modeling methods with sufficient details to allow the reader to rapidly build numerical models of neuronal extracellular microstimulation. These include (1) the computation of the electrical potential field created by the stimulation in the tissue, and (2) the response of a target neuron to this field. Two main approaches are described: First we describe the classical hybrid approach that combines the finite element modeling of the potential field with the calculation of the neuron's response in a cable equation framework (compartmentalized neuron models). Then, we present a “whole finite element” approach allowing the simultaneous calculation of the extracellular and intracellular potentials, by representing the neuronal membrane with a thin-film approximation. This approach was previously introduced in the frame of neural recording, but has never been implemented to determine the effect of extracellular stimulation on the neural response at a sub-compartment level. Here, we show on an example that the latter modeling scheme can reveal important sub-compartment behavior of the neural membrane that cannot be resolved using the hybrid approach. The goal of this paper is also to describe in detail the practical implementation of these methods to allow the reader to easily build new models using standard software packages. These modeling paradigms, depending on the situation, should help build more efficient high-density neural prostheses for CNS rehabilitation. PMID

  15. Intracortical Brain-Machine Interfaces Advance Sensorimotor Neuroscience

    PubMed Central

    Schroeder, Karen E.; Chestek, Cynthia A.

    2016-01-01

    Brain-machine interfaces (BMIs) decode brain activity to control external devices. Over the past two decades, the BMI community has grown tremendously and reached some impressive milestones, including the first human clinical trials using chronically implanted intracortical electrodes. It has also contributed experimental paradigms and important findings to basic neuroscience. In this review, we discuss neuroscience achievements stemming from BMI research, specifically that based upon upper limb prosthetic control with intracortical microelectrodes. We will focus on three main areas: first, we discuss progress in neural coding of reaches in motor cortex, describing recent results linking high dimensional representations of cortical activity to muscle activation. Next, we describe recent findings on learning and plasticity in motor cortex on various time scales. Finally, we discuss how bidirectional BMIs have led to better understanding of somatosensation in and related to motor cortex. PMID:27445663

  16. Virtual typing by people with tetraplegia using a self-calibrating intracortical brain-computer interface

    PubMed Central

    Jarosiewicz, Beata; Sarma, Anish A.; Bacher, Daniel; Masse, Nicolas Y.; Simeral, John D.; Sorice, Brittany; Oakley, Erin M.; Blabe, Christine; Pandarinath, Chethan; Gilja, Vikash; Cash, Sydney S.; Eskandar, Emad N.; Friehs, Gerhard; Henderson, Jaimie M.; Shenoy, Krishna V.; Donoghue, John P.; Hochberg, Leigh R.

    2016-01-01

    Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user’s self-selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis. PMID:26560357

  17. Mechanically-compliant intracortical implants reduce the neuroinflammatory response

    NASA Astrophysics Data System (ADS)

    Nguyen, Jessica K.; Park, Daniel J.; Skousen, John L.; Hess-Dunning, Allison E.; Tyler, Dustin J.; Rowan, Stuart J.; Weder, Christoph; Capadona, Jeffrey R.

    2014-10-01

    Objective. The mechanisms underlying intracortical microelectrode encapsulation and failure are not well understood. A leading hypothesis implicates the role of the mechanical mismatch between rigid implant materials and the much softer brain tissue. Previous work has established the benefits of compliant materials on reducing early neuroinflammatory events. However, recent studies established late onset of a disease-like neurodegenerative state. Approach. In this study, we implanted mechanically-adaptive materials, which are initially rigid but become compliant after implantation, to investigate the long-term chronic neuroinflammatory response to compliant intracortical microelectrodes. Main results. Three days after implantation, during the acute healing phase of the response, the tissue response to the compliant implants was statistically similar to that of chemically matched stiff implants with much higher rigidity. However, at two, eight, and sixteen weeks post-implantation in the rat cortex, the compliant implants demonstrated a significantly reduced neuroinflammatory response when compared to stiff reference materials. Chronically implanted compliant materials also exhibited a more stable blood-brain barrier than the stiff reference materials. Significance. Overall, the data show strikingly that mechanically-compliant intracortical implants can reduce the neuroinflammatory response in comparison to stiffer systems.

  18. Mechanically-Compliant Intracortical Implants Reduce the Neuroinflammatory Response

    PubMed Central

    Nguyen, Jessica K.; Park, Daniel J.; Skousen, John L.; Hess-Dunning, Allison E.; Tyler, Dustin J.; Rowan, Stuart J.; Weder, Christoph; Capadona, Jeffrey R.

    2014-01-01

    Objective The mechanisms underlying intracortical microelectrode encapsulation and failure are not well understood. A leading hypothesis implicates the role of the mechanical mismatch between rigid implant materials and the much softer brain tissue. Previous work has established the benefits of compliant materials on reducing early neuroinflammatory events. However, recent studies established late onset of a disease-like neurodegenerative state. Approach In this study, we implanted mechanically-adaptive materials, which are initially rigid but become compliant after implantation, to investigate the long-term chronic neuroinflammatory response to compliant intracortical microelectrodes. Main results Three days after implantation, during the acute healing phase of the response, the tissue response to the compliant implants was statistically similar to that of chemically matched stiff implants with much higher rigidity. However, at two, eight, and sixteen weeks post-implantation in the rat cortex, the compliant implants demonstrated a significantly reduced neuroinflammatory response when compared to stiff reference materials. Chronically implanted compliant materials also exhibited a more stable blood-brain barrier than the stiff reference materials. Significance Overall, the data show strikingly that mechanically-compliant intracortical implants can reduce the neuroinflammatory response in comparison to stiffer systems. PMID:25125443

  19. Characterization of a forebrain gaze field in the archistriatum of the barn owl: microstimulation and anatomical connections.

    PubMed

    Knudsen, E I; Cohen, Y E; Masino, T

    1995-07-01

    We present evidence that the archistriatum in the forebrain of the barn owl participates in gaze control, that it can mediate gaze changes independently of the optic tectum (OT), and that it projects in parallel to both the OT and to saccade-generating circuitry in the brainstem tegmentum. These properties are similar to those of the frontal eye fields (FEF) in the prefrontal cortex of primates. The forebrain was surveyed for sites where electrical microstimulation would induce head saccades. Head (and eye) saccades were elicited from the anterior 70% of the archistriatum, a region that we refer to as the archistriatal gaze fields (AGF). At single stimulation sites in the AGF, saccade amplitude tended to vary as a function of stimulation parameters (current strength, pulse frequency, and train duration) and starting head position. In contrast, saccade direction was largely independent of these parameters. Saccade direction did vary over a wide range of primarily contraversive directions with the site of stimulation in the AGF. Using anatomical pathway tracing techniques, we found that the archistriatum projects strongly and in parallel to the deep layers of the OT and to nuclei in the midline brainstem tegmentum. Previous work has shown that electrical microstimulation of either of these brainstem regions evokes saccadic movements of the head and/or eyes (du Lac and Knudsen, 1990; Masino and Knudsen, 1992b). Inactivation of the OT with lidocaine reduced the size but did not eliminate (or change the direction of) the saccades evoked by AGF stimulation. The direct anatomical pathway from the archistriatum to the midline tegmental nuclei can account for saccades that persist following OT inactivation. The similarities between the AGF in barn owls and the FEF in primates suggest that the same general plan of anatomical and functional organization supports the contribution of the forebrain to gaze control in a wide variety of species. PMID:7623141

  20. Bilateral force transients in the upper limbs evoked by single-pulse microstimulation in the pontomedullary reticular formation

    PubMed Central

    Hirschauer, Thomas J.

    2015-01-01

    Neurons in the pontomedullary reticular formation (PMRF) give rise to the reticulospinal tract. The motor output of the PMRF was investigated using stimulus-triggered averaging of electromyography (EMG) and force recordings in two monkeys (M. fascicularis). EMG was recorded from 12 pairs of upper limb muscles, and forces were detected using two isometric force-sensitive handles. Of 150 stimulation sites, 105 (70.0%) produced significant force responses, and 139 (92.5%) produced significant EMG responses. Based on the average flexor EMG onset latency of 8.3 ms and average force onset latency of 15.9 ms poststimulation, an electromechanical delay of ∼7.6 ms was calculated. The magnitude of force responses (∼10 mN) was correlated with the average change in EMG activity (P < 0.001). A multivariate linear regression analysis was used to estimate the contribution of each muscle to force generation, with flexors and extensors exhibiting antagonistic effects. A predominant force output pattern of ipsilateral flexion and contralateral extension was observed in response to PMRF stimulation, with 65.3% of significant ipsilateral force responses directed medially and posteriorly (P < 0.001) and 78.6% of contralateral responses directed laterally and anteriorly (P < 0.001). This novel approach permits direct measurement of force outputs evoked by central nervous system microstimulation. Despite the small magnitude of poststimulus EMG effects, low-intensity single-pulse microstimulation of the PMRF evoked detectable forces. The forces, showing the combined effect of all muscle activity in the arms, are consistent with reciprocal pattern of force outputs from the PMRF detectable with stimulus-triggered averaging of EMG. PMID:25652926

  1. Bilateral force transients in the upper limbs evoked by single-pulse microstimulation in the pontomedullary reticular formation.

    PubMed

    Hirschauer, Thomas J; Buford, John A

    2015-04-01

    Neurons in the pontomedullary reticular formation (PMRF) give rise to the reticulospinal tract. The motor output of the PMRF was investigated using stimulus-triggered averaging of electromyography (EMG) and force recordings in two monkeys (M. fascicularis). EMG was recorded from 12 pairs of upper limb muscles, and forces were detected using two isometric force-sensitive handles. Of 150 stimulation sites, 105 (70.0%) produced significant force responses, and 139 (92.5%) produced significant EMG responses. Based on the average flexor EMG onset latency of 8.3 ms and average force onset latency of 15.9 ms poststimulation, an electromechanical delay of ∼7.6 ms was calculated. The magnitude of force responses (∼10 mN) was correlated with the average change in EMG activity (P < 0.001). A multivariate linear regression analysis was used to estimate the contribution of each muscle to force generation, with flexors and extensors exhibiting antagonistic effects. A predominant force output pattern of ipsilateral flexion and contralateral extension was observed in response to PMRF stimulation, with 65.3% of significant ipsilateral force responses directed medially and posteriorly (P < 0.001) and 78.6% of contralateral responses directed laterally and anteriorly (P < 0.001). This novel approach permits direct measurement of force outputs evoked by central nervous system microstimulation. Despite the small magnitude of poststimulus EMG effects, low-intensity single-pulse microstimulation of the PMRF evoked detectable forces. The forces, showing the combined effect of all muscle activity in the arms, are consistent with reciprocal pattern of force outputs from the PMRF detectable with stimulus-triggered averaging of EMG. PMID:25652926

  2. Parameters of human motor unit twitches obtained by intramuscular microstimulation.

    PubMed

    Elek, J M; Kossev, A; Dengler, R; Schubert, M; Wohlfahrt, K; Wolf, W

    1992-01-01

    Intramuscular microstimulation of motor axons was used to study twitch responses of 209 motor units (MUs) in the first dorsal interosseus muscle (FDI) of 20 normal subjects. Twitch peak force (TF), maximum rate of rise of force (MRRF), contraction time (CT) and one-half relaxation time (HRT) were determined. The distributions of TF (mean 16.0 mN, median 10.3 mN) and MRRF (mean 0.88 N s-1, median 0.66 N s-1) were skewed to the right with the majority of the values lying in the lower ranges, whereas CT (mean 63 ms, median 62 ms) and HRT (mean 61 ms, median 58 ms) were approximately normally distributed. TF was significantly correlated with MRRF, but not with CT in contrast with studies of cat gastrocnemius muscle. TF values were similar to those obtained by spike-triggered averaging in the same muscle. The method proved to be reliable and appropriate for use in patients. Examples of MU twitch parameters from three patients with chronic partial denervation of the FDI are described. PMID:1483052

  3. Reanimating the arm and hand with intraspinal microstimulation

    NASA Astrophysics Data System (ADS)

    Zimmermann, Jonas B.; Seki, Kazuhiko; Jackson, Andrew

    2011-10-01

    To date, there is no effective therapy for spinal cord injury, and many patients could benefit dramatically from at least partial restoration of arm and hand function. Despite a substantial body of research investigating intraspinal microstimulation (ISMS) in frogs, rodents and cats, little is known about upper-limb responses to cervical stimulation in the primate. Here, we show for the first time that long trains of ISMS delivered to the macaque spinal cord can evoke functional arm and hand movements. Complex movements involving coordinated activation of multiple muscles could be elicited from a single electrode, while just two electrodes were required for independent control of reaching and grasping. We found that the motor responses to ISMS were described by a dual exponential model that depended only on stimulation history. We demonstrate that this model can be inverted to generate stimulus trains capable of eliciting arbitrary, graded motor responses, and could be used to restore volitional movements in a closed-loop brain-machine interface.

  4. Population Response Propagation to Extrastriate Areas Evoked by Intracortical Electrical Stimulation in V1

    PubMed Central

    Fehérvári, Tamás D.; Yagi, Tetsuya

    2016-01-01

    The mouse visual system has multiple extrastriate areas surrounding V1 each with a distinct representation of the visual field and unique functional and connectivity profiles, which are believed to form two parallel processing streams, similar to the ventral and dorsal streams in primates. At the same time, mouse visual areas have a high degree of interconnectivity, in particular V1 sends input to all higher visual areas. The study of these direct connections can further our understanding of the cortical processing of visual signals in the early mammalian cortex. Several studies have been published about the anatomy of these connections, but an in vivo electrophysiological characterization and comparison of the transmission to multiple extrastriate areas has not yet been reported. We used intracortical electrical stimulation combined with RH1691 VSD imaging in adult C57BL/6 mice in urethane anesthesia to analyze interareal transmission from V1 to extrastriate areas in superficial cortical layers. We found seven extrastriate response sites (five lateral, two medial) in a spatial pattern similar to area maps of the mouse visual cortex and, by shifting the location of V1 stimulation, demonstrated that the evoked responses in LM and AL were in accordance with the visuotopic mappings of these areas known from anatomy and in vivo studies. These two sites, considered to be gateways to their processing streams, had shorter latencies and faster transmission speeds than other extrastriate response sites. Short latency differences between response sites, and that TTX injection into LM reduced but did not eliminate other extrastriate responses indicated that the evoked cortical activity was, at least partially, transmitted directly from V1 to extrastriate areas. This study reports on analysis of interareal transmission from V1 to multiple extrastriate areas in mouse using intracortical electrical stimulation in vivo. PMID:26903816

  5. In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes

    PubMed Central

    Harris, J P; Hess, A E; Rowan, S J; Weder, C; Zorman, C A; Tyler, D J; Capadona, J R

    2012-01-01

    We recently introduced a series of stimuli-responsive, mechanically-adaptive polymer nanocomposites. Here, we report the first application of these bio-inspired materials as substrates for intracortical microelectrodes. Our hypothesis is that the ideal electrode should be initially stiff to facilitate minimal trauma during insertion into the cortex, yet becomes mechanically compliant to match the stiffness of the brain tissue and minimize forces exerted on the tissue, attenuating inflammation. Microprobes created from mechanically reinforced nanocomposites demonstrated a significant advantage compared to model microprobes composed of neat polymer only. The nanocomposite microprobes exhibit a higher storage modulus (E’ = ~5 GPa) than the neat polymer microprobes (E’ = ~2 GPa) and could sustain higher loads (~17 mN), facilitating penetration through the pia mater and insertion into the cerebral cortex of a rat. In contrast, the neat polymer microprobes mechanically failed under lower loads (~7 mN) before they were capable of inserting into cortical tissue. Further, we demonstrated the material’s ability to morph while in the rat cortex to more closely match the mechanical properties of the cortical tissue. Nanocomposite microprobes that were implanted into the rat cortex for up to 8 weeks demonstrated increased cell density at the microelectrode-tissue interface and a lack of tissue necrosis or excessive gliosis. This body of work introduces our nanocomposite-based microprobes as adaptive substrates for intracortical microelectrodes and potentially other biomedical applications. PMID:21654037

  6. Intracortical modulation of cortical-bulbar responses for the masseter muscle

    PubMed Central

    Ortu, Enzo; Deriu, Franca; Suppa, Antonio; Giaconi, Elena; Tolu, Eusebio; Rothwell, John C

    2008-01-01

    Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated in the masseter muscles of 12 subjects and the cortical silent period (SP) in nine subjects. Motor evoked potentials (MEPs) were recorded from contralateral (cMM) and ipsilateral (iMM) masseters, activated at 10% of maximal voluntary contraction (MVC). Interstimulus intervals (ISIs) were 2 and 3 ms for SICI, 10 and 15 ms for ICF. TMS of the left masseteric cortex induced MEPs that were larger in the cMM than the iMM; stimulation of right masseteric cortex produced a similar asymmetry in response amplitude. SICI was only observed using a CS intensity of 70% AMT and was equal in both cMM and iMM. SICI was stronger at higher TS intensities, was abolished by muscle activation greater than 10% MVC, and was unaffected by coil orientation changes. Control experiments confirmed that SICI was not contaminated by any inhibitory peripheral reflexes. However, ICF could not be obtained because it was masked by bilateral reflex depression of masseter EMG caused by auditory input from the coil discharge. The SP was bilateral and symmetric; its duration ranged from 35 to 70 ms depending on TS intensity and coil orientation. We conclude that SICI is present in the cortical representation of masseter muscles. The similarity of SICI in cMM and iMM suggests either that a single pool of inhibitory interneurons controls ipsi- and contralateral corticotrigeminal projections or that inhibition is directed to bilaterally projecting corticotrigeminal fibres. Finally, the corticotrigeminal projection seems to be weakly influenced by inhibitory interneurons mediating the cortical SP. PMID:18499727

  7. Advantages of closed-loop calibration in intracortical brain-computer interfaces for people with tetraplegia

    NASA Astrophysics Data System (ADS)

    Jarosiewicz, Beata; Masse, Nicolas Y.; Bacher, Daniel; Cash, Sydney S.; Eskandar, Emad; Friehs, Gerhard; Donoghue, John P.; Hochberg, Leigh R.

    2013-08-01

    Objective. Brain-computer interfaces (BCIs) aim to provide a means for people with severe motor disabilities to control their environment directly with neural activity. In intracortical BCIs for people with tetraplegia, the decoder that maps neural activity to desired movements has typically been calibrated using ‘open-loop’ (OL) imagination of control while a cursor automatically moves to targets on a computer screen. However, because neural activity can vary across contexts, a decoder calibrated using OL data may not be optimal for ‘closed-loop’ (CL) neural control. Here, we tested whether CL calibration creates a better decoder than OL calibration even when all other factors that might influence performance are held constant, including the amount of data used for calibration and the amount of elapsed time between calibration and testing. Approach. Two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial performed a center-out-back task using an intracortical BCI, switching between decoders that had been calibrated on OL versus CL data. Main results. Even when all other variables were held constant, CL calibration improved neural control as well as the accuracy and strength of the tuning model. Updating the CL decoder using additional and more recent data resulted in further improvements. Significance. Differences in neural activity between OL and CL contexts contribute to the superiority of CL decoders, even prior to their additional ‘adaptive’ advantage. In the near future, CL decoder calibration may enable robust neural control without needing to pause ongoing, practical use of BCIs, an important step toward clinical utility.

  8. Microstimulation Reveals Opposing Influences of Prelimbic and Infralimbic Cortex on the Expression of Conditioned Fear

    ERIC Educational Resources Information Center

    Vidal-Gonzalez, Ivan; Rauch, Scott L.; Quirk, Gregory J.; Vidal-Gonzalez, Benjamin

    2006-01-01

    Recent studies using lesion, infusion, and unit-recording techniques suggest that the infralimbic (IL) subregion of medial prefrontal cortex (mPFC) is necessary for the inhibition of conditioned fear following extinction. Brief microstimulation of IL paired with conditioned tones, designed to mimic neuronal tone responses, reduces the expression…

  9. Reward modulates the effect of visual cortical microstimulation on perceptual decisions

    PubMed Central

    Cicmil, Nela; Cumming, Bruce G; Parker, Andrew J; Krug, Kristine

    2015-01-01

    Effective perceptual decisions rely upon combining sensory information with knowledge of the rewards available for different choices. However, it is not known where reward signals interact with the multiple stages of the perceptual decision-making pathway and by what mechanisms this may occur. We combined electrical microstimulation of functionally specific groups of neurons in visual area V5/MT with performance-contingent reward manipulation, while monkeys performed a visual discrimination task. Microstimulation was less effective in shifting perceptual choices towards the stimulus preferences of the stimulated neurons when available reward was larger. Psychophysical control experiments showed this result was not explained by a selective change in response strategy on microstimulated trials. A bounded accumulation decision model, applied to analyse behavioural performance, revealed that the interaction of expected reward with microstimulation can be explained if expected reward modulates a sensory representation stage of perceptual decision-making, in addition to the better-known effects at the integration stage. DOI: http://dx.doi.org/10.7554/eLife.07832.001 PMID:26402458

  10. In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses

    PubMed Central

    2015-01-01

    Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters < 0.5 mm) and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards

  11. In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses.

    PubMed

    Becerra-Fajardo, Laura; Ivorra, Antoni

    2015-01-01

    Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters < 0.5 mm) and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards

  12. Responses of single corticospinal neurons to intracortical stimulation of primary motor and premotor cortex in the anesthetized macaque monkey.

    PubMed

    Maier, Marc A; Kirkwood, Peter A; Brochier, Thomas; Lemon, Roger N

    2013-06-01

    The responses of individual primate corticospinal neurons to localized electrical stimulation of primary motor (M1) and of ventral premotor cortex (area F5) are poorly documented. To rectify this and to study interactions between responses from these areas, we recorded corticospinal axons, identified by pyramidal tract stimulation, in the cervical spinal cord of three chloralose-anesthetized macaque monkeys. Single stimuli (≤400 μA) were delivered to the hand area of M1 or F5 through intracortical microwire arrays. Only 14/112 (13%) axons showed responses to M1 stimuli that indicated direct intracortical activation of corticospinal neurons (D-responses); no D-responses were seen from F5. In contrast, 62 axons (55%) exhibited consistent later responses to M1 stimulation, corresponding to indirect activation (I-responses), showing that single-pulse intracortical stimulation of motor areas can result in trans-synaptic activation of a high proportion of the corticospinal output. A combined latency histogram of all axon responses was nonperiodic, clearly different from the periodic surface-recorded corticospinal volleys. This was readily explained by correcting for conduction velocities of individual axons. D-responding axons, taken as originating in neurons close to the M1 stimulating electrodes, showed more I-responses from M1 than those without a D-response, and 8/10 of these axons also responded to F5 stimulation. Altogether, 33% of tested axons responded to F5 stimulation, most of which also showed I-responses from M1. These excitatory effects are in keeping with facilitation of hand muscles evoked from F5 being relayed via M1. This was further demonstrated by facilitation of test responses from M1 by conditioning F5 stimuli. PMID:23536718

  13. Biocompatible benzocyclobutene-based intracortical neural implant with surface modification

    NASA Astrophysics Data System (ADS)

    Lee, Keekeun; Massia, Stephen; He, Jiping

    2005-11-01

    This paper presents the fabrication of a benzocyclobutene (BCB) polymer-based intracortical neural implant for reliable and stable long-term implant function. BCB polymer has many attractive features for chronic implant application: flexibility, biocompatibility, low moisture uptake, low dielectric constant and easy surface modification. A 2 µm thick silicon backbone layer was attached underneath a flexible BCB electrode to improve mechanical stiffness. No insertion trauma was observed during penetrating into the dura of a rat. In vitro cytotoxicity tests of the completed BCB electrode revealed no toxic effects on cultured cells. The modified BCB surface with a dextran coating showed a significant reduction in 3T3 cell adhesion and spreading, indicating that this coating has the potential for lowering protein adsorption, minimizing inflammatory cell adhesion and glial scar formation in vivo, and thereby enhancing long-term implant performance.

  14. Contribution of intracortical inhibition in voluntary muscle relaxation.

    PubMed

    Motawar, Binal; Hur, Pilwon; Stinear, James; Seo, Na Jin

    2012-09-01

    Terminating a voluntary muscle contraction is an important aspect of motor control, and yet, its neurophysiology is unclear. The objective of this study was to determine the role of short-interval intracortical inhibition (SICI) by comparing SICIs during relaxation from a power grip versus during a sustained power grip at the matching muscle activity level. Right-handed healthy young adults gripped and relaxed from power grip following auditory cues. The relaxation period was determined as the time for the flexor digitorum superficialis (FDS) muscle to reach its pre-contraction baseline level after the cue to relax. SICI during relaxation was obtained at different times into the relaxation period in two separate studies (70, 80, 90 % into relaxation in Study 1; 25, 50, 75 % into relaxation in Study 2). In addition, SICI during sustained contraction was assessed while subjects maintained a power grip at the matching FDS EMG levels (obtained during relaxation, for both Studies). Results showed that the mean SICI was greater during relaxation than during sustained contraction at the matching muscle activity level in both Studies (p < 0.05), indicating increased activation of intracortical inhibitory circuits for muscle relaxation. SICI gradually increased from 25 to 50 and 75 % into relaxation (Study 2, p < 0.05), but did not change from 70 to 80 and 90 % into relaxation (Study 1). MEP decreased with progression of relaxation (p < 0.05) in both Studies, reflecting gradual decreases in corticomotor excitability. This work supports the hypothesis that relaxation from a voluntary muscle contraction involves inhibitory activity in the primary motor cortex. PMID:22791231

  15. Modulation of the Intracortical LFP during Action Execution and Observation

    PubMed Central

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N.; Kraskov, Alexander

    2015-01-01

    The activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter. Upper limb EMGs were recorded to control for covert muscle activity during observation. The movement-related potential (MRP), investigated as intracortical low-frequency LFP activity (<9 Hz), was modulated in both M1 and PMv, not only during action execution but also during action observation. Moreover, the temporal LFP modulations during execution and observation were highly correlated in both cortical areas. Beta power in both PMv and M1 was clearly modulated in both conditions. Although the MRP was detected only during dynamic periods of the task (reach/grasp/release), beta decreased during dynamic and increased during static periods (hold). Comparison of LFPs for different grasps provided evidence for partially nonoverlapping networks being active during execution and observation, which might be related to different inputs to motor areas during these conditions. We found substantial information about grasp in the MRP corroborating its suitability for brain–machine interfaces, although information about grasp was generally low during action observation. PMID:26041914

  16. Transspinal direct current stimulation immediately modifies motor cortex sensorimotor maps.

    PubMed

    Song, Weiguo; Truong, Dennis Q; Bikson, Marom; Martin, John H

    2015-04-01

    Motor cortex (MCX) motor representation reorganization occurs after injury, learning, and different long-term stimulation paradigms. The neuromodulatory approach of transspinal direct current stimulation (tsDCS) has been used to promote evoked cortical motor responses. In the present study, we used cathodal tsDCS (c-tsDCS) of the rat cervical cord to determine if spinal cord activation can modify the MCX forelimb motor map. We used a finite-element method model based on coregistered high-resolution rat MRI and microcomputed tomography imaging data to predict spinal current density to target stimulation to the caudal cervical enlargement. We examined the effects of cathodal and anodal tsDCS on the H-reflex and c-tsDCS on responses evoked by intracortical microstimulation (ICMS). To determine if cervical c-tsDCS also modified MCX somatic sensory processing, we examined sensory evoked potentials (SEPs) produced by wrist electrical stimulation and induced changes in ongoing activity. Cervical c-tsDCS enhanced the H-reflex, and anodal depressed the H-reflex. Using cathodal stimulation to examine cortical effects, we found that cervical c-tsDCS immediately modified the forelimb MCX motor map, with decreased thresholds and an expanded area. c-tsDCS also increased SEP amplitude in the MCX. The magnitude of changes produced by c-tsDCS were greater on the motor than sensory response. Cervical c-tsDCS more strongly enhanced forelimb than hindlimb motor representation and had no effect on vibrissal representation. The finite-element model indicated current density localized to caudal cervical segments, informing forelimb motor selectivity. Our results suggest that c-tsDCS augments spinal excitability in a spatially selective manner and may improve voluntary motor function through MCX representational plasticity. PMID:25673738

  17. Transspinal direct current stimulation immediately modifies motor cortex sensorimotor maps

    PubMed Central

    Song, Weiguo; Truong, Dennis Q.; Bikson, Marom

    2015-01-01

    Motor cortex (MCX) motor representation reorganization occurs after injury, learning, and different long-term stimulation paradigms. The neuromodulatory approach of transspinal direct current stimulation (tsDCS) has been used to promote evoked cortical motor responses. In the present study, we used cathodal tsDCS (c-tsDCS) of the rat cervical cord to determine if spinal cord activation can modify the MCX forelimb motor map. We used a finite-element method model based on coregistered high-resolution rat MRI and microcomputed tomography imaging data to predict spinal current density to target stimulation to the caudal cervical enlargement. We examined the effects of cathodal and anodal tsDCS on the H-reflex and c-tsDCS on responses evoked by intracortical microstimulation (ICMS). To determine if cervical c-tsDCS also modified MCX somatic sensory processing, we examined sensory evoked potentials (SEPs) produced by wrist electrical stimulation and induced changes in ongoing activity. Cervical c-tsDCS enhanced the H-reflex, and anodal depressed the H-reflex. Using cathodal stimulation to examine cortical effects, we found that cervical c-tsDCS immediately modified the forelimb MCX motor map, with decreased thresholds and an expanded area. c-tsDCS also increased SEP amplitude in the MCX. The magnitude of changes produced by c-tsDCS were greater on the motor than sensory response. Cervical c-tsDCS more strongly enhanced forelimb than hindlimb motor representation and had no effect on vibrissal representation. The finite-element model indicated current density localized to caudal cervical segments, informing forelimb motor selectivity. Our results suggest that c-tsDCS augments spinal excitability in a spatially selective manner and may improve voluntary motor function through MCX representational plasticity. PMID:25673738

  18. The importance of the intracortical canal network for murine bone mechanics.

    PubMed

    Schneider, Philipp; Voide, Romain; Stampanoni, Marco; Donahue, Leah Rae; Müller, Ralph

    2013-03-01

    As shown by recent data bone strength estimation can greatly be improved by including microarchitectural parameters in the analysis. Our previous results showed that intracortical canals (the living space of the vasculature and/or remodeling units) are a major contributor to cortical tissue porosity, and therefore, can be linked to mechanical bone properties. Consequently, the goal of this study was to investigate the importance of the intracortical canal network for murine bone mechanics. To study intracortical canals within murine femoral bone, we used a mouse model, including two mouse strains, C57BL/6J-Ghrhr(lit)/J (B6-lit/+) and C3.B6-Ghrhr(lit)/J (C3.B6-lit/+) representing low and high bone mass, respectively. The intracortical canal network was assessed by synchrotron radiation-based micro-computed tomography and the mechanical bone properties were derived from three-point bending experiments. Multiple linear regression models were built to explain the variation in ultimate force, work to fracture, and stiffness in terms of the morphometric parameters. The power to explain the variation in bone mechanics was increased significantly for most mechanical measures when including morphometric parameters of intracortical canals in addition to macroscopic morphometric measures. Specifically, we could derive generalized (mouse strain-independent) models for ultimate force, where the incorporation of intracortical canals in addition to macroscopic bone measures improved the explained variation in ultimate force considerably, which was confirmed by an increase in adjusted R(2) of 73% and 8% for B6-lit/+ and C3.B6-lit/+, respectively. Further, we observed that the heterogeneity of the morphometric measures for the individual canal branches play an important role for explaining the variation in ultimate force. Finally, the current study provides strong evidence that work to fracture of murine bone, which is triggered critically by microcracks, is affected by

  19. Accessing the tonotopic organization of the ventral cochlear nucleus by intranuclear microstimulation.

    PubMed

    McCreery, D B; Shannon, R V; Moore, J K; Chatterjee, M

    1998-12-01

    This study is part of a program to develop an auditory prosthesis for the profoundly deaf, based on multichannel microstimulation in the cochlear nucleus. The functionality of such a device is dependent on its ability to access the tonotopic axis of the human ventral cochlear nucleus in an orderly fashion. In these studies, we utilized the homologies between the human and feline ventral cochlear nuclei and the known tonotopic organization of the central nucleus of the inferior colliculus (IC). In anesthetized cats, stimuli were delivered to three or four locations along the dorsal-to-ventral axis of the posteroventral cochlear nucleus (PVCN), and for each stimulus location, we recorded the multiunit neuronal activity and the field potentials at 20 or more locations along the dorsolateral-ventromedial (tonotopic) axis of the IC. The current source-sink density (CSD), which delimits regions of neuronal activity, was computed from the sequence of field potentials recorded along this axis. The multiunit activity and the CSD analysis both showed that the tonotopic organization of the PVCN can be accessed in an orderly manner by intranuclear microstimulation in several regions of the PVCN, using the range of stimulus pulse amplitudes that have been shown in previous studies to be noninjurious during prolonged intranuclear microstimulation via chronically implanted microelectrodes. We discuss the applicability of these findings to the design of clinical auditory prostheses for implantation into the human cochlear nucleus. PMID:9865886

  20. Electrical microstimulation of the nucleus incertus induces forward locomotion and rotation in rats.

    PubMed

    Farooq, Usman; Kumar, Jigna Rajesh; Rajkumar, Ramamoorthy; Dawe, Gavin S

    2016-06-01

    Locomotion is essential for goal-oriented behavior. Theta frequency oscillations in the hippocampus have been associated with behavioral activation and initiation of movement. Recently, the nucleus incertus, a brainstem nucleus with widespread cortical and subcortical projections, has been reported to modulate the septo-hippocampal axis triggering theta activity in the hippocampus. This suggests that activation of the nucleus incertus would induce movement. In this study, we investigated the effects of electrical microstimulation of the nucleus incertus on locomotion in conscious rats. Rats chronically implanted with microelectrodes targeting the nucleus incertus were electrically stimulated while their behavior was tracked. High frequency electrical microstimulation of the nucleus incertus was sufficient to induce forward locomotion and rotation. The latencies of evoked locomotion were consistent with a role of the nucleus incertus in modulating premotor areas, possibly the septo-hippocampal axis. Electrical microstimulation of the nucleus incertus increased velocity, mobility and rotations during stimulation and post-stimulation. These results suggest that the nucleus incertus plays a role in behavioral activation and locomotion. PMID:27049117

  1. Intracortical inhibition is modulated by phase of prosthetic rehabilitation in transtibial amputees.

    PubMed

    Hordacre, Brenton; Bradnam, Lynley V; Barr, Christopher; Patritti, Benjamin L; Crotty, Maria

    2015-01-01

    Reorganization of primary motor cortex (M1) is well-described in long-term lower limb amputees. In contrast cortical reorganization during the rehabilitation period after amputation is poorly understood. Thirteen transtibial amputees and 13 gender matched control participants of similar age were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait variability at discharge was assessed as a functional measure. Compared to controls, amputees had reduced short-latency intracortical inhibition (SICI) for the ipsilateral M1 at admission (p = 0.01). Analysis across rehabilitation revealed SICI was reduced for the contralateral M1 at first walk compared to discharge (p = 0.003). For the ipsilateral M1 both short and long-latency intracortical inhibition were reduced at admission (p < 0.05) and prosthetic casting (p < 0.02). Analysis of the neurophysiology and gait function revealed several interesting relationships. For the contralateral M1, reduced inhibition at admission (p = 0.04) and first walk (p = 0.05) was associated with better gait function. For the ipsilateral M1, reduced inhibition at discharge (p = 0.05) was associated with poor gait function. This study characterized intracortical excitability in rehabilitating amputees. A dichotomous relationship between reduced intracortical inhibition for each M1 and gait function was observed at different times. Intracortical inhibition may be an appropriate cortical biomarker of gait function in lower limb amputees during rehabilitation, but requires further investigation. Understanding M1 intracortical excitability of amputees undertaking prosthetic rehabilitation provides insight into brain reorganization in the sub-acute post-amputation period and may guide future studies seeking to improve rehabilitation outcomes. PMID:26042015

  2. Intracortical inhibition is modulated by phase of prosthetic rehabilitation in transtibial amputees

    PubMed Central

    Hordacre, Brenton; Bradnam, Lynley V.; Barr, Christopher; Patritti, Benjamin L.; Crotty, Maria

    2015-01-01

    Reorganization of primary motor cortex (M1) is well-described in long-term lower limb amputees. In contrast cortical reorganization during the rehabilitation period after amputation is poorly understood. Thirteen transtibial amputees and 13 gender matched control participants of similar age were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait variability at discharge was assessed as a functional measure. Compared to controls, amputees had reduced short-latency intracortical inhibition (SICI) for the ipsilateral M1 at admission (p = 0.01). Analysis across rehabilitation revealed SICI was reduced for the contralateral M1 at first walk compared to discharge (p = 0.003). For the ipsilateral M1 both short and long-latency intracortical inhibition were reduced at admission (p < 0.05) and prosthetic casting (p < 0.02). Analysis of the neurophysiology and gait function revealed several interesting relationships. For the contralateral M1, reduced inhibition at admission (p = 0.04) and first walk (p = 0.05) was associated with better gait function. For the ipsilateral M1, reduced inhibition at discharge (p = 0.05) was associated with poor gait function. This study characterized intracortical excitability in rehabilitating amputees. A dichotomous relationship between reduced intracortical inhibition for each M1 and gait function was observed at different times. Intracortical inhibition may be an appropriate cortical biomarker of gait function in lower limb amputees during rehabilitation, but requires further investigation. Understanding M1 intracortical excitability of amputees undertaking prosthetic rehabilitation provides insight into brain reorganization in the sub-acute post-amputation period and may guide future studies seeking to improve rehabilitation outcomes. PMID:26042015

  3. Voltage Sensitive Dye Imaging Reveals Improved Topographic Activation of Cortex in Response to Manipulation of Thalamic Microstimulation Parameters

    PubMed Central

    Wang, Qi; Millard, Daniel C.; Zheng, He J.V.; Stanley, Garrett B.

    2012-01-01

    Voltage sensitive dye (VSD) imaging was used to quantify in-vivo, network level spatiotemporal cortical activation in response to electrical microstimulation of the thalamus in the rat vibrissa pathway. Thalamic microstimulation evoked a distinctly different cortical response than natural sensory stimulation, with the response to microstimulation spreading over a larger area of cortex and being topographically misaligned with the cortical column to which the stimulated thalamic region projects. Electrical stimulation with cathode-leading asymmetric waveforms reduced this topographic misalignment while simultaneously increasing the spatial specificity of the cortical activation. Systematically increasing the asymmetry of the microstimulation pulses revealed a continuum between symmetric and asymmetric stimulation that gradually reduced the topographic bias. These data strongly support the hypothesis that manipulation of the electrical stimulation waveform can be used to selectively activate specific neural elements. Specifically, our results are consistent with the prediction that cathode-leading asymmetric waveforms preferentially stimulating cell bodies over axons, while symmetric waveforms preferentially activate axons over cell bodies. The findings here provide some initial steps toward the design and optimization of microstimulation of neural circuitry, and open the door to more sophisticated engineering tools, such as nonlinear system identification techniques, to develop technologies for more effective control of activity in the nervous system. PMID:22327024

  4. Voltage-sensitive dye imaging reveals improved topographic activation of cortex in response to manipulation of thalamic microstimulation parameters

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Millard, Daniel C.; Zheng, He J. V.; Stanley, Garrett B.

    2012-04-01

    Voltage-sensitive dye imaging was used to quantify in vivo, network level spatiotemporal cortical activation in response to electrical microstimulation of the thalamus in the rat vibrissa pathway. Thalamic microstimulation evoked a distinctly different cortical response than natural sensory stimulation, with response to microstimulation spreading over a larger area of cortex and being topographically misaligned with the cortical column to which the stimulated thalamic region projects. Electrical stimulation with cathode-leading asymmetric waveforms reduced this topographic misalignment while simultaneously increasing the spatial specificity of the cortical activation. Systematically increasing the asymmetry of the microstimulation pulses revealed a continuum between symmetric and asymmetric stimulation that gradually reduced the topographic bias. These data strongly support the hypothesis that manipulation of the electrical stimulation waveform can be used to selectively activate specific neural elements. Specifically, our results are consistent with the prediction that cathode-leading asymmetric waveforms preferentially stimulate cell bodies over axons, while symmetric waveforms preferentially activate axons over cell bodies. The findings here provide some initial steps toward the design and optimization of microstimulation of neural circuitry, and open the door to more sophisticated engineering tools, such as nonlinear system identification techniques, to develop technologies for more effective control of activity in the nervous system.

  5. Intracortical remodeling parameters are associated with measures of bone robustness

    PubMed Central

    Goldman, Haviva M.; Hampson, Naomi A.; Guth, J. Jared; Lin, David; Jepsen, Karl J.

    2014-01-01

    Prior work identified a novel association between bone robustness and porosity, which may be part of a broader interaction whereby the skeletal system compensates for the natural variation in robustness (bone width relative to length) by modulating tissue-level mechanical properties to increase stiffness of slender bones and to reduce mass of robust bones. To further understand this association, we tested the hypothesis that the relationship between robustness and porosity is mediated through intracortical, BMU-based (basic multicellular unit) remodeling. We quantified cortical porosity, mineralization, and histomorphometry at two sites (38 and 66% of the length) in human cadaveric tibiae. We found significant correlations between robustness and several histomorphometric variables (e.g., % secondary tissue [R2 = 0.68, p < 0.004], total osteon area [R2=0.42, p<0.04]) at the 66% site. Although these associations were weaker at the 38% site, significant correlations between histological variables were identified between the two sites indicating that both respond to the same global effects and demonstrate a similar character at the whole bone level. Thus, robust bones tended to have larger and more numerous osteons with less infilling, resulting in bigger pores and more secondary bone area. These results suggest that local regulation of BMU-based remodeling may be further modulated by a global signal associated with robustness, such that remodeling is suppressed in slender bones but not in robust bones. Elucidating this mechanism further is crucial for better understanding the complex adaptive nature of the skeleton, and how inter-individual variation in remodeling differentially impacts skeletal aging and an individuals’ potential response to prophylactic treatments. PMID:24962664

  6. Spatial distribution of intracortical porosity varies across age and sex

    PubMed Central

    Nirody, Jasmine A.; Cheng, Karen P.; Parrish, Robin M.; Burghardt, Andrew J.; Majumdar, Sharmila; Link, Thomas M.; Kazakia, Galateia J.

    2015-01-01

    Cortical bone porosity is a major determinant of strength, stiffness, and fracture toughness of cortical tissue. The goal of this work was to investigate changes in spatial distribution and microstructure of cortical porosity associated with aging in men and women. The specific aims were to: 1) develop an automated technique for spatial analysis of cortical microstructure based on HR-pQCT data, and; 2) apply this technique to explore sex- and age-specific spatial distribution and microstructure of porosity within the cortex. We evaluated HR-pQCT images of the distal tibia from a cross-sectional cohort of 145 individuals, characterizing detectable pores as being in the endosteal, midcortical, or periosteal layers of the cortex. Metrics describing porosity, pore number, and pore size were quantifiedwithin each layer and compared across sexes, age groups, and cortical layers. The elderly cohort (65–78 years, n=22) displayed higher values than the young cohort (20–29 years, n=29) for all parameters both globally and within each layer. While all three layers displayed significant age-related porosity increases, the greatest difference in porosity between the young and elderly cohort was in the midcortical layer (+344%, p < 0.001). Similarly, the midcortical layer reflected the greatest differences between young and elderly cohorts in both pore number (+243%, p < 0.001) and size (+28%, p < 0.001). Females displayed greater age-related changes in porosity and pore number than males. Females and males displayed comparable small to non-significant changes with age in pore size. In summary, considerable variability exists in the spatial distribution of detectable cortical porosity at the distal tibia, and this variability is dependent on age and sex. Intracortical pore distribution analysis may ultimately provide insight into both mechanisms of pore network expansion and biomechanical consequences of pore distribution. PMID:25701139

  7. Selective Maturation of Temporal Dynamics of Intracortical Excitatory Transmission at the Critical Period Onset.

    PubMed

    Miao, Qinglong; Yao, Li; Rasch, Malte J; Ye, Qian; Li, Xiang; Zhang, Xiaohui

    2016-08-01

    Although the developmental maturation of cortical inhibitory synapses is known to be a critical factor in gating the onset of critical period (CP) for experience-dependent cortical plasticity, how synaptic transmission dynamics of other cortical synapses are regulated during the transition to CP remains unknown. Here, by systematically examining various intracortical synapses within layer 4 of the mouse visual cortex, we demonstrate that synaptic temporal dynamics of intracortical excitatory synapses on principal cells (PCs) and inhibitory parvalbumin- or somatostatin-expressing cells are selectively regulated before the CP onset, whereas those of intracortical inhibitory synapses and long-range thalamocortical excitatory synapses remain unchanged. This selective maturation of synaptic dynamics results from a ubiquitous reduction of presynaptic release and is dependent on visual experience. These findings provide an additional essential circuit mechanism for regulating CP timing in the developing visual cortex. PMID:27477277

  8. Cell-Targeted Optogenetics and Electrical Microstimulation Reveal the Primate Koniocellular Projection to Supra-granular Visual Cortex.

    PubMed

    Klein, Carsten; Evrard, Henry C; Shapcott, Katharine A; Haverkamp, Silke; Logothetis, Nikos K; Schmid, Michael C

    2016-04-01

    Electrical microstimulation and more recently optogenetics are widely used to map large-scale brain circuits. However, the neuronal specificity achieved with both methods is not well understood. Here we compare cell-targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1). Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers, and they indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain. PMID:27021172

  9. sLORETA intracortical lagged coherence during breath counting in meditation-naïve participants

    PubMed Central

    Milz, Patricia; Faber, Pascal L.; Lehmann, Dietrich; Kochi, Kieko; Pascual-Marqui, Roberto D.

    2013-01-01

    We investigated brain functional connectivity comparing no-task resting to breath counting (a meditation exercise but given as task without referring to meditation). Functional connectivity computed as EEG coherence between head-surface data suffers from localization ambiguity, reference dependence, and overestimation due to volume conduction. Lagged coherence between intracortical model sources addresses these criticisms. With this analysis approach, experienced meditators reportedly showed reduced coherence during meditation, meditation-naïve participants have not yet been investigated. 58-channel EEG from 23 healthy, right-handed, meditation-naïve males during resting [3 runs] and breath counting [2 runs] was computed into sLORETA time series of intracortical electrical activity in 19 regions of interest (ROI) corresponding to the cortex underlying 19 scalp electrode sites, for each of the eight independent EEG frequency bands covering 1.5–44 Hz. Intracortical lagged coherences and head-surface conventional coherences were computed between the 19 regions/sites. During breath counting compared to resting, paired t-tests corrected for multiple testing revealed four significantly lower intracortical lagged coherences, but four significantly higher head-surface conventional coherences. Lowered intracortical lagged coherences involved left BA 10 and right BAs 3, 10, 17, 40. In conclusion, intracortical lagged coherence can yield results that are inverted to those of head-surface conventional coherence. The lowered functional connectivity between cognitive control areas and sensory perception areas during meditation-type breath counting compared to resting conceivably reflects the attention to a bodily percept without cognitive reasoning. The reductions in functional connectivity were similar but not as widespread as the reductions reported during meditation in experienced meditators. PMID:24860483

  10. Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

    PubMed

    Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

    2016-07-01

    Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. PMID:27052583

  11. Point-and-Click Cursor Control With an Intracortical Neural Interface System by Humans With Tetraplegia

    PubMed Central

    Kim, Sung-Phil; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.; Friehs, Gerhard M.; Black, Michael J.

    2012-01-01

    We present a point-and-click intracortical neural interface system (NIS) that enables humans with tetraplegia to volitionally move a 2-D computer cursor in any desired direction on a computer screen, hold it still, and click on the area of interest. This direct brain–computer interface extracts both discrete (click) and continuous (cursor velocity) signals from a single small population of neurons in human motor cortex. A key component of this system is a multi-state probabilistic decoding algorithm that simultaneously decodes neural spiking activity of a small population of neurons and outputs either a click signal or the velocity of the cursor. The algorithm combines a linear classifier, which determines whether the user is intending to click or move the cursor, with a Kalman filter that translates the neural population activity into cursor velocity. We present a paradigm for training the multi-state decoding algorithm using neural activity observed during imagined actions. Two human participants with tetraplegia (paralysis of the four limbs) performed a closed-loop radial target acquisition task using the point-and-click NIS over multiple sessions. We quantified point-and-click performance using various human-computer interaction measurements for pointing devices. We found that participants could control the cursor motion and click on specified targets with a small error rate (<3% in one participant). This study suggests that signals from a small ensemble of motor cortical neurons (~40) can be used for natural point-and-click 2-D cursor control of a personal computer. PMID:21278024

  12. The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit

    PubMed Central

    Aedo, Cristian; Terreros, Gonzalo; León, Alex; Delano, Paul H.

    2016-01-01

    Background and Objective The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors. Methods We used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR). Results Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes. Conclusion These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses. PMID:27195498

  13. Comparison of spike sorting and thresholding of voltage waveforms for intracortical brain-machine interface performance

    PubMed Central

    Christie, Breanne P.; Tat, Derek M.; Irwin, Zachary T.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Ryu, Stephen I.; Shenoy, Krishna V.; Thompson, David E.; Chestek, Cynthia A.

    2015-01-01

    Objective For intracortical brain-machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials (“spikes”) requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials. Approach We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position. Results We found the highest performance for thresholding when placing a threshold between −3 to −4.5*VRMS. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data was thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded. Significance For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated. PMID:25504690

  14. Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

    PubMed Central

    Kozyrev, Vladislav; Eysel, Ulf T.; Jancke, Dirk

    2014-01-01

    Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this “basin of suppression” increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the “deceleration–acceleration” notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. PMID:25187557

  15. The Effect of Residual Endotoxin Contamination on the Neuroinflammatory Response to Sterilized Intracortical Microelectrodes

    PubMed Central

    Ravikumar, Madhumitha; Hageman, Daniel J.; Tomaszewski, William H.; Chandra, Gabriella M.; Skousen, John L.; Capadona, Jeffrey R.

    2014-01-01

    A major limitation to the use of microelectrode technologies in both research and clinical applications is our inability to consistently record high quality neural signals. There is increasing evidence that recording instability is linked, in part, to neuroinflammation. A number of factors including extravasated blood products and macrophage released soluble factors are believed to mediate neuroinflammation and the resulting recording instability. However, the roles of other inflammatory stimuli, such as residual endotoxin contamination, are poorly understood. Therefore, to determine the effect of endotoxin contamination we examined the brain tissue response of C57/BL6 mice to non-functional microelectrodes with a range of endotoxin levels. Endotoxin contamination on the sterilized microelectrodes was measured using a limulus amebocyte lysate test following FDA guidelines. Microelectrodes sterilized by autoclave, dry heat, or ethylene oxide gas, resulted in variable levels of residual endotoxins of 0.55 EU/mL, 0.22 EU/mL, and 0.11 EU/mL, respectively. Histological evaluation at two weeks showed a direct correlation between microglia/macrophage activation and endotoxin levels. Interestingly, astrogliosis, neuronal loss, and blood brain barrier dysfunction demonstrated a threshold-dependent response to bacterial endotoxins. However, at sixteen weeks, no histological differences were detected, regardless of initial endotoxin levels. Therefore, our results demonstrate that endotoxin contamination, within the range examined, contributes to initial but not chronic microelectrode associated neuroinflammation. Our results suggest that minimizing residual endotoxins may impact early recording quality. To this end, endotoxins should be considered as a potent stimulant to the neuroinflammatory response to implanted intracortical microelectrodes. PMID:24778808

  16. Comparison of spike sorting and thresholding of voltage waveforms for intracortical brain-machine interface performance

    NASA Astrophysics Data System (ADS)

    Christie, Breanne P.; Tat, Derek M.; Irwin, Zachary T.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Ryu, Stephen I.; Shenoy, Krishna V.; Thompson, David E.; Chestek, Cynthia A.

    2015-02-01

    Objective. For intracortical brain-machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials (‘spikes’) requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials. Approach. We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of Gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position. Main results. We found the highest performance for thresholding when placing a threshold between -3 and -4.5 × Vrms. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data were thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded. Significance. For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated.

  17. Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics.

    PubMed

    Kozyrev, Vladislav; Eysel, Ulf T; Jancke, Dirk

    2014-09-16

    Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this "basin of suppression" increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the "deceleration-acceleration" notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. PMID:25187557

  18. Fatigue microcracks that initiate fracture are located near elevated intracortical porosity but not elevated mineralization.

    PubMed

    Turnbull, Travis L; Baumann, Andrew P; Roeder, Ryan K

    2014-09-22

    In vivo microcracks in cortical bone are typically observed within more highly mineralized interstitial tissue, but postmortem investigations are inherently limited to cracks that did not lead to fracture which may be misleading with respect to understanding fracture mechanisms. We hypothesized that the one fatigue microcrack which initiates fracture is located spatially adjacent to elevated intracortical porosity but not elevated mineralization. Therefore, the spatial correlation between intracortical porosity, elevated mineralization, and fatigue microdamage was investigated by combining, for the first time, sequential, nondestructive, three-dimensional micro-computed tomography (micro-CT) measurements of each in cortical bone specimens subjected to compressive fatigue loading followed by a tensile overload to fracture. Fatigue loading resulted in significant microdamage accumulation and compromised mechanical properties upon tensile overload compared to control specimens. The microdamage that initiated fracture upon tensile overload was able to be identified in all fatigue-loaded specimens using contrast-enhanced micro-CT and registered images. Two-point (or pair) correlation functions revealed a spatial correlation between microdamage at the fracture initiation site and intracortical porosity, but not highly mineralized tissue, confirming the hypothesis. This difference was unique to the fracture initiation site. Intracortical porosity and highly mineralized tissue exhibited a significantly lower and higher probability, respectively, of being located spatially adjacent to all sites of microdamage compared to the fracture initiation site. Therefore, the results of this study suggest that human cortical bone is tolerant of most microcracks, which are generally compartmentalized within the more highly mineralized interstitial tissue, but a single microcrack of sufficient size located in spatial proximity to intracortical porosity can compromise fracture resistance

  19. Adaptive neuro-fuzzy sliding mode control of multi-joint movement using intraspinal microstimulation.

    PubMed

    Asadi, Ali-Reza; Erfanian, Abbas

    2012-07-01

    During the last decade, intraspinal microstimulation (ISMS) has been proposed as a potential technique for restoring motor function in paralyzed limbs. A major challenge to restoration of a desired functional limb movement through the use of ISMS is the development of a robust control strategy for determining the stimulation patterns. Accurate and stable control of limbs by functional intraspinal microstimulation is a very difficult task because neuromusculoskeletal systems have significant nonlinearity, time variability, large latency and time constant, and muscle fatigue. Furthermore, the controller must be able to compensate the effect of the dynamic interaction between motor neuron pools and electrode sites during ISMS. In this paper, we present a robust strategy for multi-joint control through ISMS in which the system parameters are adapted online and the controller requires no offline training phase. The method is based on the combination of sliding mode control with fuzzy logic and neural control. Extensive experiments on six rats are provided to demonstrate the robustness, stability, and tracking accuracy of the proposed method. Despite the complexity of the spinal neuronal networks, our results show that the proposed strategy could provide accurate tracking control with fast convergence and could generate control signals to compensate for the effects of muscle fatigue. PMID:22711783

  20. Short-term dynamics of causal information transfer in thalamocortical networks during natural inputs and microstimulation for somatosensory neuroprosthesis

    PubMed Central

    Semework, Mulugeta; DiStasio, Marcello

    2014-01-01

    Recording the activity of large populations of neurons requires new methods to analyze and use the large volumes of time series data thus created. Fast and clear methods for finding functional connectivity are an important step toward the goal of understanding neural processing. This problem presents itself readily in somatosensory neuroprosthesis (SSNP) research, which uses microstimulation (MiSt) to activate neural tissue to mimic natural stimuli, and has the capacity to potentiate, depotentiate, or even destroy functional connections. As the aim of SSNP engineering is artificially creating neural responses that resemble those observed during natural inputs, a central goal is describing the influence of MiSt on activity structure among groups of neurons, and how this structure may be altered to affect perception or behavior. In this paper, we demonstrate the concept of Granger causality, combined with maximum likelihood methods, applied to neural signals recorded before, during, and after natural and electrical stimulation. We show how these analyses can be used to evaluate the changing interactions in the thalamocortical somatosensory system in response to repeated perturbation. Using LFPs recorded from the ventral posterolateral thalamus (VPL) and somatosensory cortex (S1) in anesthetized rats, we estimated pair-wise functional interactions between functional microdomains. The preliminary results demonstrate input-dependent modulations in the direction and strength of information flow during and after application of MiSt. Cortico-cortical interactions during cortical MiSt and baseline conditions showed the largest causal influence differences, while there was no statistically significant difference between pre- and post-stimulation baseline causal activities. These functional connectivity changes agree with physiologically accepted communication patterns through the network, and their particular parameters have implications for both rehabilitation and brain

  1. Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

    PubMed Central

    Macefield, G; Gandevia, S C; Burke, D

    1990-01-01

    1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0.3-0.8 V, 0.1-0.2 ms, 1-100 Hz) or constant-current biphasic pulses (0.4-13.0 microA, 0.2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the

  2. Challenges and Opportunities for Next-Generation Intracortically Based Neural Prostheses

    PubMed Central

    Gilja, Vikash; Chestek, Cindy A.; Diester, Ilka; Henderson, Jaimie M.; Deisseroth, Karl

    2011-01-01

    Neural prosthetic systems aim to help disabled patients by translating neural signals from the brain into control signals for guiding computer cursors, prosthetic arms, and other assistive devices. Intracortical electrode arrays measure action potentials and local field potentials from individual neurons, or small populations of neurons, in the motor cortices and can provide considerable information for controlling prostheses. Despite several compelling proof-of-concept laboratory animal experiments and an initial human clinical trial, at least three key challenges remain which, if left unaddressed, may hamper the translation of these systems into widespread clinical use. We review these challenges: achieving able-bodied levels of performance across tasks and across environments, achieving robustness across multiple decades, and restoring able-bodied quality proprioception and somatosensation. We also describe some emerging opportunities for meeting these challenges. If these challenges can be largely or fully met, intracortically based neural prostheses may achieve true clinical viability and help increasing numbers of disabled patients. PMID:21257365

  3. Multiple EMG activity and intracortical inhibition and facilitation during a fine finger movement under pressure.

    PubMed

    Tanaka, Yoshifumi; Funase, Kozo; Sekiya, Hiroshi; Sasaki, Joyo; Takemoto, Toru

    2011-01-01

    The 1st purpose of this study was to examine multiple electromyography (EMG) during voluntary hand movements. A secondary purpose was to investigate possible effects of pressure on intracortical inhibition (ICI) and intracortical facilitation (ICF) functions of the motor cortex, using paired-pulse transcranial magnetic stimulation. Twelve participants traced a 15-cm diameter target circle using a small laser pointer attached to the right index finger. After 5 acquisition trials, they performed 3 nonpressure trials followed by 3 pressure trials. The results showed that pressure had effects not only on agonist EMG activity but also on multiple muscles, such as synergist. In addition, a decrease in ICI and an increase in ICF were both observed under pressure for muscles other than the agonist. PMID:21218324

  4. Model-based estimation of intra-cortical connectivity using electrophysiological data.

    PubMed

    Aram, P; Freestone, D R; Cook, M J; Kadirkamanathan, V; Grayden, D B

    2015-09-01

    This paper provides a new method for model-based estimation of intra-cortical connectivity from electrophysiological measurements. A novel closed-form solution for the connectivity function of the Amari neural field equations is derived as a function of electrophysiological observations. The resultant intra-cortical connectivity estimate is driven from experimental data, but constrained by the mesoscopic neurodynamics that are encoded in the computational model. A demonstration is provided to show how the method can be used to image physiological mechanisms that govern cortical dynamics, which are normally hidden in clinical data from epilepsy patients. Accurate estimation performance is demonstrated using synthetic data. Following the computational testing, results from patient data are obtained that indicate a dominant increase in surround inhibition prior to seizure onset that subsides in the cases when the seizures spread. PMID:26116963

  5. Intra-day signal instabilities affect decoding performance in an intracortical neural interface system

    NASA Astrophysics Data System (ADS)

    Perge, János A.; Homer, Mark L.; Malik, Wasim Q.; Cash, Sydney; Eskandar, Emad; Friehs, Gerhard; Donoghue, John P.; Hochberg, Leigh R.

    2013-06-01

    Objective. Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach. To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results. 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 ± 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 ± 6.5 µV or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional ‘bias’ in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions

  6. Intracortical Posterior Cingulate Myelin Content Relates to Error Processing: Results from T1- and T2-Weighted MRI Myelin Mapping and Electrophysiology in Healthy Adults.

    PubMed

    Grydeland, Håkon; Westlye, Lars T; Walhovd, Kristine B; Fjell, Anders M

    2016-06-01

    Myelin content of the cerebral cortex likely impacts cognitive functioning, but this notion has scarcely been investigated in vivo in humans. Here we tested for a relationship between intracortical myelin and a direct measure of neural activity in the form of the electrophysiological response error-related negativity (ERN). Using magnetic resonance imaging, myelin mapping was performed in 81 healthy adults aged 40-60 years by means of a T1- and T2-weighted (T1w/T2w) signal intensity ratio approach. Error trials on a version of the Eriksen flanker task triggered the ERN, a negative deflection of the event-related potential reflecting performance monitoring. Compelling evidence from neuroimaging, lesion, and source localization studies indicates that the ERN stems from the cingulate cortex. Vertex-wise analyses across the cingulate demonstrated that increased amplitude of the ERN was related to higher levels of intracortical myelin in the left posterior cingulate cortex. The association was independent of general ability level and subjacent white matter myelin. The results fit the notion that degree of myelin within the posterior cingulate cortex as measured by T1w/T2w signal intensity plays a role in error processing and cognitive control through the relationship with neural activity as measured by ERN amplitude, potentially by facilitating local neural synchronization. PMID:25840423

  7. A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion.

    PubMed

    Mazurek, Kevin A; Holinski, Bradley J; Everaert, Dirk G; Mushahwar, Vivian K; Etienne-Cummings, Ralph

    2016-08-01

    Neural pathways can be artificially activated through the use of electrical stimulation. For individuals with a spinal cord injury, intraspinal microstimulation, using electrical currents on the order of 125 μ A, can produce muscle contractions and joint torques in the lower extremities suitable for restoring walking. The work presented here demonstrates an integrated circuit implementing a state-based control strategy where sensory feedback and intrinsic feed forward control shape the stimulation waveforms produced on-chip. Fabricated in a 0.5 μ m process, the device was successfully used in vivo to produce walking movements in a model of spinal cord injury. This work represents progress towards an implantable solution to be used for restoring walking in individuals with spinal cord injuries. PMID:26978832

  8. A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion

    PubMed Central

    Mazurek, Kevin A.; Holinski, Bradley J.; Everaert, Dirk G.; Mushahwar, Vivian K.; Etienne-Cummings, Ralph

    2016-01-01

    Neural pathways can be artificially activated through the use of electrical stimulation. For individuals with a spinal cord injury, intraspinal microstimulation, using electrical currents on the order of 125 μA, can produce muscle contractions and joint torques in the lower extremities suitable for restoring walking. The work presented here demonstrates an integrated circuit implementing a state-based control strategy where sensory feedback and intrinsic feed forward control shape the stimulation waveforms produced on-chip. Fabricated in a 0.5 μm process, the device was successfully used in vivo to produce walking movements in a model of spinal cord injury. This work represents progress towards an implantable solution to be used for restoring walking in individuals with spinal cord injuries. PMID:26978832

  9. Mapping quantal touch using 7 Tesla functional magnetic resonance imaging and single-unit intraneural microstimulation.

    PubMed

    Sanchez Panchuelo, Rosa Maria; Ackerley, Rochelle; Glover, Paul M; Bowtell, Richard W; Wessberg, Johan; Francis, Susan T; McGlone, Francis

    2016-01-01

    Using ultra-high field 7 Tesla (7T) functional magnetic resonance imaging (fMRI), we map the cortical and perceptual responses elicited by intraneural microstimulation (INMS) of single mechanoreceptive afferent units in the median nerve, in humans. Activations are compared to those produced by applying vibrotactile stimulation to the unit's receptive field, and unit-type perceptual reports are analyzed. We show that INMS and vibrotactile stimulation engage overlapping areas within the topographically appropriate digit representation in the primary somatosensory cortex. Additional brain regions in bilateral secondary somatosensory cortex, premotor cortex, primary motor cortex, insula and posterior parietal cortex, as well as in contralateral prefrontal cortex are also shown to be activated in response to INMS. The combination of INMS and 7T fMRI opens up an unprecedented opportunity to bridge the gap between first-order mechanoreceptive afferent input codes and their spatial, dynamic and perceptual representations in human cortex. PMID:27154626

  10. BION microstimulators: a case study in the engineering of an electronic implantable medical device.

    PubMed

    Kane, Michael J; Breen, Paul P; Quondamatteo, Fabio; ÓLaighin, Gearóid

    2011-01-01

    The BION (Bionic Neuron) is a single channel implantable neurostimulator of unique design that can be delivered by injection. The development of the BION injectable neurostimulators exemplifies a challenging, but well posed medical design problem addressed with a successful strategy for prioritizing and resolving the biomedical and technological challenges. Though some performance requirements required post-evaluation revision, all fundamental goals were realized. A small number of significant design corrections occurred because the device requirements did not include the full scope of environmental demands. The design has spawned a number of variants optimized for diverse biomedical applications, and its clinical applications continue to evolve. The BION development history demonstrates design successes worth emulating and design pitfalls that may be avoidable for future medical device development teams. This paper serves as an introduction to the BION microstimulator technology and as an analysis of the design process used to develop the early clinical devices. PMID:21087890

  11. Effects of volitional contraction on intracortical inhibition and facilitation in the human motor cortex.

    PubMed

    Ortu, Enzo; Deriu, Franca; Suppa, Antonio; Tolu, Eusebio; Rothwell, John C

    2008-11-01

    Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) were assessed in the cortical motor area of the first dorsal interosseous muscle (FDI) of 16 healthy subjects. Paired-pulse TMS was delivered to the left hemisphere at the following interstimulus intervals (ISIs): 2 and 3 ms for SICI, 10 and 15 ms for ICF and 1-5 ms for SICF. Motor-evoked potentials were recorded from the resting and active right FDI. The effects exerted on SICI and ICF by four intensities (60-90% of active motor threshold, AMT) of the conditioning stimulus (S1) and by three levels of muscle contraction (10%, 25%, 50% of maximal voluntary contraction, MVC) were evaluated. The effects exerted on SICF were evaluated with two intensities (90% and 70% of AMT) of the test stimulus (S2) and with the same levels of muscle contraction. Results showed that: (i) during 10% MVC, maximum SICI was observed with S1 = 70% AMT; (ii) the amount of SICI obtained with S1 = 70% AMT was the same at rest as during 10% MVC, but decreased at higher contraction levels; (iii) ICF was observed only at rest with S1 = 90% AMT; (iv) SICF was facilitated at 10% and 25% MVC, but not at 50% MVC. We conclude that during muscle activation, intracortical excitability reflects a balance between activation of SICI and SICF systems. Part of the reduction in SICI during contraction is due to superimposed recruitment of SICF. Low intensity (70% AMT) conditioning stimuli can test SICI independently of effects on SICF at low contraction levels. PMID:18787036

  12. Intracortical inhibition and facilitation in different representations of the human motor cortex.

    PubMed

    Chen, R; Tam, A; Bütefisch, C; Corwell, B; Ziemann, U; Rothwell, J C; Cohen, L G

    1998-12-01

    Intracortical inhibition and facilitation in different representations of the human motor cortex. J. Neurophysiol. 80: 2870-2881, 1998. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the human motor cortex can be studied with paired transcranial magnetic stimulation (TMS). Plastic changes and some neurological disorders in humans are associated with changes in ICI and ICF. Although well characterized in the hand representation, it is not known if ICI and ICF vary across different body part representations. Therefore we studied ICI and ICF in different motor representations of the human motor cortex. The target muscles were rectus abdominus (RA), biceps brachii (BB), abductor pollicis brevis (APB), quadriceps femoris (QF), and abductor hallucis (AH). For each muscle, we measured the rest and active motor thresholds (MTs), the motor-evoked potential (MEP) stimulus-response curve (MEP recruitment), ICI, and ICF. The effects of different interstimulus intervals (ISIs) were studied with a conditioning stimulus (CS) intensity of 80% active MT. The effects of different CS intensities were studied at ISI of 2 ms for ICI and ISI of 15 ms for ICF. MT was lowest for APB, followed by BB, AH, and QF, and was highest for RA. Except for BB, MEP recruitment was generally steeper for muscles with lower MT. ICI and ICF were present in all the motor representations tested. The stimulus intensity necessary to elicit ICI was consistently lower than that required to elicit ICF, suggesting that they are mediated by separate mechanisms. Despite wide differences in MT and MEP recruitment, the absolute CS intensities (expressed as percentage of the stimulator's output) required to elicit ICI and ICF appear unrelated to MT and MEP recruitment in the different muscles tested. These findings suggest that the intracortical mechanisms for inhibition and facilitation in different motor representations are not related to the strength of corticospinal projections. PMID

  13. Microstimulators and Intramuscular Hook Electrodes for the Stimulation of Respiratory Muscles

    PubMed Central

    Walter, James S; Dunn, Robert B; Wurster, Robert D; Laghi, Franco

    2007-01-01

    Background/Objectives: We determined the feasibility of stimulating the major muscles of respiration with different types of electrodes. Intramuscular hook electrodes, model microstimulators (M-Micro) developed in our laboratory, and commercial radiofrequency microstimulators (RFM) (Alfred Mann Foundation, Valencia, CA), were employed in this investigation. Methods: In 8 anesthetized dogs, M-Micro were placed bilaterally on the diaphragm and in the abdominal muscles, and hook electrodes were placed in the 3rd and 5th intercostal regions adjacent to the intercostal nerves known to support inspiration. In 3 of the 8 animals, RFMs (Alfred Mann Foundation) in addition to the M-Micros were sutured to each hemidiaphragm at the same optimal site for phrenic nerve stimulation. During a hyperventilation-induced apnea, 2-second stimulations were applied to the diaphragm and with various combinations of diaphragm plus supporting muscles, both thoracic and abdominal. Results: Diaphragm stimulation alone provided tidal volumes adequate for basal alveolar ventilation. However, implantation of the RFM required greater contact with the muscle. Stimulating other respiratory muscles along with the diaphragm further increased tidal volumes. The hook electrodes, M-Micro, and RFM performed equally well. Conclusions: In the acute dog model, M-Micro and hook electrodes can provide an implant system for the maintenance of ventilation. Support of the intercostal and abdominal muscles has the potential to reduce the contraction requirements of the diaphragm with decreased likelihood of diaphragm fatigue and hypoventilation. Whether the electrodes under investigation could provide an implant system for long-term ventilation needs to be determined. PMID:17853655

  14. Improved Focalization of Electrical Microstimulation Using Microelectrode Arrays: A Modeling Study

    PubMed Central

    Joucla, Sébastien; Yvert, Blaise

    2009-01-01

    Extracellular electrical stimulation (EES) of the central nervous system (CNS) has been used empirically for decades, with both fundamental and clinical goals. Currently, microelectrode arrays (MEAs) offer new possibilities for CNS microstimulation. However, although focal CNS activation is of critical importance to achieve efficient stimulation strategies, the precise spatial extent of EES remains poorly understood. The aim of the present work is twofold. First, we validate a finite element model to compute accurately the electrical potential field generated throughout the extracellular medium by an EES delivered with MEAs. This model uses Robin boundary conditions that take into account the surface conductance of electrode/medium interfaces. Using this model, we determine how the potential field is influenced by the stimulation and ground electrode impedances, and by the electrical conductivity of the neural tissue. We confirm that current-controlled stimulations should be preferred to voltage-controlled stimulations in order to control the amplitude of the potential field. Second, we evaluate the focality of the potential field and threshold-distance curves for different electrode configurations. We propose a new configuration to improve the focality, using a ground surface surrounding all the electrodes of the array. We show that the lower the impedance of this surface, the more focal the stimulation. In conclusion, this study proposes new boundary conditions for the design of precise computational models of extracellular stimulation, and a new electrode configuration that can be easily incorporated into future MEA devices, either in vitro or in vivo, for a better spatial control of CNS microstimulation. PMID:19279677

  15. Twelve Months of Voluntary Heavy Alcohol Consumption in Male Rhesus Macaques Suppresses Intracortical Bone Remodeling

    PubMed Central

    Gaddini, Gino W.; Grant, Kathleen A.; Woodall, Andrew; Stull, Cara; Maddalozzo, Gianni F.; Zhang, Bo; Turner, Russell T.; Iwaniec, Urszula T.

    2015-01-01

    Chronic heavy alcohol consumption is a risk factor for cortical bone fractures in males. The increase in fracture risk may be due, in part, to reduced bone quality. Intracortical (osteonal) bone remodeling is the principle mechanism for maintaining cortical bone quality. However, it is not clear how alcohol abuse impacts intracortical bone remodeling. This study investigated the effects of long-duration heavy alcohol consumption on intracortical bone remodeling in a non-human primate model. Following a 4-month induction period, male rhesus macaques (Macaca mulatta, n = 21) were allowed to voluntarily self-administer water or alcohol (4% ethanol w/v) for 22 h/d, 7 d/wk for 12 months. Control monkeys (n = 13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3 days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7 ± 0.2 g alcohol/kg/d (mean ± SE) during the 12 months of self-administration, resulting in a mean daily blood alcohol concentration of 77 ± 9 mg/dl from samples taken at 7 h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250 mg/dl, modeling a binge-drinking pattern of alcohol consumption. The skeletal response to alcohol was determined by densitometry, microcomputed tomography and histomorphometry. Significant differences in tibial bone mineral content, bone mineral density, and cortical bone architecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and polar moment of inertia) in the tibial diaphysis were not detected with treatment. However, cortical porosity was lower (1.8 ± 0.5 % versus 0.6 ± 0.1 %, p = 0.021) and labeled osteon density was lower (0.41 ± 0.2/mm2 versus 0.04 ± 0.01/mm2, p < 0.003) in alcohol-consuming monkeys compared to controls, indicating a reduced rate of intracortical bone remodeling

  16. A low-power bidirectional telemetry device with a near-field charging feature for a cardiac microstimulator.

    PubMed

    Shuenn-Yuh Lee; Chih-Jen Cheng; Ming-Chun Liang

    2011-08-01

    In this paper, wireless telemetry using the near-field coupling technique with round-wire coils for an implanted cardiac microstimulator is presented. The proposed system possesses an external powering amplifier and an internal bidirectional microstimulator. The energy of the microstimulator is provided by a rectifier that can efficiently charge a rechargeable device. A fully integrated regulator and a charge pump circuit are included to generate a stable, low-voltage, and high-potential supply voltage, respectively. A miniature digital processor includes a phase-shift-keying (PSK) demodulator to decode the transmission data and a self-protective system controller to operate the entire system. To acquire the cardiac signal, a low-voltage and low-power monitoring analog front end (MAFE) performs immediate threshold detection and data conversion. In addition, the pacing circuit, which consists of a pulse generator (PG) and its digital-to-analog (D/A) controller, is responsible for stimulating heart tissue. The chip was fabricated by Taiwan Semiconductor Manufacturing Company (TSMC) with 0.35-μm complementary metal-oxide semiconductor technology to perform the monitoring and pacing functions with inductively powered communication. Using a model with lead and heart tissue on measurement, a -5-V pulse at a stimulating frequency of 60 beats per minute (bpm) is delivered while only consuming 31.5 μW of power. PMID:23851950

  17. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

    2014-06-01

    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  18. Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

    NASA Astrophysics Data System (ADS)

    Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

    2015-08-01

    Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

  19. Implications of Chronic Daily Anti-Oxidant Administration on the Inflammatory Response to Intracortical Microelectrodes

    PubMed Central

    Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

    2015-01-01

    Objective Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg/kg. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main Results Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes. PMID:26015427

  20. Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2013-01-01

    The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm(2) 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant's left middle temporal gyrus. In this participant, spectral power in 0.3-10 Hz, 20-55 Hz, and 125-250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly and

  1. Mapping quantal touch using 7 Tesla functional magnetic resonance imaging and single-unit intraneural microstimulation

    PubMed Central

    Sanchez Panchuelo, Rosa Maria; Ackerley, Rochelle; Glover, Paul M; Bowtell, Richard W; Wessberg, Johan

    2016-01-01

    Using ultra-high field 7 Tesla (7T) functional magnetic resonance imaging (fMRI), we map the cortical and perceptual responses elicited by intraneural microstimulation (INMS) of single mechanoreceptive afferent units in the median nerve, in humans. Activations are compared to those produced by applying vibrotactile stimulation to the unit’s receptive field, and unit-type perceptual reports are analyzed. We show that INMS and vibrotactile stimulation engage overlapping areas within the topographically appropriate digit representation in the primary somatosensory cortex. Additional brain regions in bilateral secondary somatosensory cortex, premotor cortex, primary motor cortex, insula and posterior parietal cortex, as well as in contralateral prefrontal cortex are also shown to be activated in response to INMS. The combination of INMS and 7T fMRI opens up an unprecedented opportunity to bridge the gap between first-order mechanoreceptive afferent input codes and their spatial, dynamic and perceptual representations in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12812.001 PMID:27154626

  2. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.

    PubMed

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  3. The Effects of Stimulation Strategy on Joint Movement Elicited by Intraspinal Microstimulation.

    PubMed

    Roshani, Amir; Erfanian, Abbas

    2016-07-01

    The goal of this study was to characterize the effects of stimulation parameters and multielectrode stimulation on selectivity, range of motion, recruitment characteristics, and fatigue during intraspinal microstimulation (ISMS). A custom-made multielectrode array was implanted into the activation pool of the rat dorsiflexor muscle where the stimulation produced the highest movement range on the ankle joint and the least effect on the other joints. The results show that the selectivity could be significantly enhanced using multielectrode stimulation strategy. Moreover, the fatigue was significantly reduced using multielectrode synchronous stimulation with respect to single-electrode stimulation. For a given charge, stimulation with higher current amplitude and shorter pulse duration produced greater range of motion than that with lower amplitude and longer pulse duration. However, the stimulation with shorter duration caused greater fatigue than that with longer. In addition, there was a significant difference in time constant of spinal response obtained with different pulse amplitudes during pulse width (PW) modulation. The time constant decreased with increasing pulse amplitude. However, there was no significant effect of pulse duration on time constant during pulse amplitude (PA) modulation. The results suggest that the motor neurons (MNs) within the spinal cord can be recruited according to size principle by appropriate selection of stimulation parameters. Based on these results an efficient stimulation strategy can be designed for control of movement performance (i.e., speed of movement, fatigue, range of motion, and selectivity) during ISMS. PMID:26685256

  4. Stimulus parameters affecting tissue injury during microstimulation in the cochlear nucleus of the cat.

    PubMed

    McCreery, D B; Yuen, T G; Agnew, W F; Bullara, L A

    1994-06-15

    We investigated the effects of continuous microstimulation in the cats' posteroventral cochlear nucleus, using chronically implanted activated iridium microelectrodes. We examined 51 electrode sites (39 pulsed sites, and 12 unpulsed sites). Seven hours of continuous stimulation at 500 Hz often produced tissue injury near the tips of the pulsed microelectrodes. The damage took the form of a region of vacuolated tissue extending 200 microns or more from the site of the electrode tip. Electron microscope studies showed the vacuoles to be severely edematous segments of myelinated axons. The statistical correlation between the amount of damaged tissue and the charge per phase was large and highly significant (P < 0.0001). When the electrodes were pulsed for 7 h at 500 Hz with charge-balanced biphasic pulse pairs, the threshold for the damage was approximately 3 nC/phase. The damage threshold was not appreciably lower than the stimulation protocol was extended to 35 h (7 h/day for 5 days). In contrast, the threshold for exciting neurons near the microelectrode is approximately 1 nC/phase, as determined by the evoked response recorded in the inferior colliculus. There was little correlation between the severity of the tissue damage and the geometric charge density at the surface of the electrodes, between the damage and amplitude of the cathodic phase of the voltage transient induced across the stimulating electrodes by the stimulus current pulses, or between the damage and the stimulus pulse duration. PMID:7928722

  5. FEF-microstimulation causes task-dependent modulation of occipital fMRI activity.

    PubMed

    Premereur, Elsie; Janssen, Peter; Vanduffel, Wim

    2013-02-15

    Electrical microstimulation of FEF (FEF-EM) modulates neuronal activity in area V4 (Moore and Armstrong, 2003) and elicits functional magnetic resonance imaging (fMRI) activations in visual cortex in a bottom-up dependent manner (Ekstrom et al., 2008). Here we test the hypothesis that FEF-EM-induced modulations of fMRI activity are also function of task demands, which would suggest top-down dependent gating of FEF signals in early visual cortex. We scanned two monkeys performing a visually guided saccade task; a passive fixation task with a very similar visual display; and a passive fixation task without peripheral dots. We found increased effects of FEF-EM on fMRI-activity in visual cortex during saccades compared to fixation, indicating that the FEF-EM induced modulation is task-dependent. Finally, the effect of FEF-EM is mainly present in voxels which were less activated by visual stimuli in the absence of electrical stimulation. Our results show that the FEF-EM-induced pattern of activation in early visual cortex is topographically specific and more pronounced during increased task demands. These results fit with models suggesting that FEF is an important source modulating activity in early sensory cortex and that these influences can be enhanced by coincident bottom-up or top-down signals. PMID:23186918

  6. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    PubMed Central

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  7. Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex.

    PubMed

    Wagener, Robin J; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F

    2016-02-01

    Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory "barrel" cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID:26564256

  8. Assessing intracortical myelin in the living human brain using myelinated cortical thickness

    PubMed Central

    Rowley, Christopher D.; Bazin, Pierre-Louis; Tardif, Christine L.; Sehmbi, Manpreet; Hashim, Eyesha; Zaharieva, Nadejda; Minuzzi, Luciano; Frey, Benicio N.; Bock, Nicholas A.

    2015-01-01

    Alterations in the myelination of the cerebral cortex may underlie abnormal cortical function in a variety of brain diseases. Here, we describe a technique for investigating changes in intracortical myelin in clinical populations on the basis of cortical thickness measurements with magnetic resonance imaging (MRI) at 3 Tesla. For this, we separately compute the thickness of the shallower, lightly myelinated portion of the cortex and its deeper, heavily myelinated portion (referred to herein as unmyelinated and myelinated cortex, respectively). Our expectation is that the thickness of the myelinated cortex will be a specific biomarker for disruptions in myeloarchitecture. We show representative atlases of total cortical thickness, T, unmyelinated cortical thickness, G, and myelinated cortical thickness, M, for a healthy group of 20 female subjects. We further demonstrate myelinated cortical thickness measurements in a preliminary clinical study of 10 bipolar disorder type-I subjects and 10 healthy controls, and report significant decreases in the middle frontal gyrus in T, G, and M in the disorder, with the largest percentage change occurring in M. This study highlights the potential of myelinated cortical thickness measurements for investigating intracortical myelin involvement in brain disease at clinically relevant field strengths and resolutions. PMID:26557052

  9. Muscle Relaxation of the Foot Reduces Corticospinal Excitability of Hand Muscles and Enhances Intracortical Inhibition

    PubMed Central

    Kato, Kouki; Muraoka, Tetsuro; Mizuguchi, Nobuaki; Nakagawa, Kento; Nakata, Hiroki; Kanosue, Kazuyuki

    2016-01-01

    The object of this study was to clarify the effects of foot muscle relaxation on activity in the primary motor cortex (M1) of the hand area. Subjects were asked to volitionally relax the right foot from sustained contraction of either the dorsiflexor (tibialis anterior; TA relaxation) or plantarflexor (soleus; SOL relaxation) in response to an auditory stimulus. Single- and paired-pulse transcranial magnetic stimulation (TMS) was delivered to the hand area of the left M1 at different time intervals before and after the onset of TA or SOL relaxation. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). MEP amplitudes of ECR and FCR caused by single-pulse TMS temporarily decreased after TA and SOL relaxation onset, respectively, as compared with those of the resting control. Furthermore, short-interval intracortical inhibition (SICI) of ECR evaluated with paired-pulse TMS temporarily increased after TA relaxation onset. Our findings indicate that muscle relaxation of the dorsiflexor reduced corticospinal excitability of the ipsilateral hand muscles. This is most likely caused by an increase in intracortical inhibition. PMID:27242482

  10. Effects of passive pedaling exercise on the intracortical inhibition in subjects with spinal cord injury.

    PubMed

    Nardone, Raffaele; Langthaler, Patrick B; Bathke, Arne C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Christova, Monica; Trinka, Eugen

    2016-06-01

    Cortical reorganization can be induced by exercise below the level of the lesion after spinal cord injury (SCI). The aim of the present study was to investigate the effect of passive and active pedaling exercise on leg motor cortical area excitability of subjects with traumatic SCI. Ten subjects with chronic cervical or thoracic SCI were enrolled in the study. We found a significant effect of pedaling on short-interval intracortical inhibition (SICI), which did not interact with the experimental condition (active vs. passive). This corresponded to a significant reduction of SICI in the subjects with SCI, together with no evidence that this pattern differed for passive vs. active pedaling. We found no significant effect of pedaling on intracortical facilitation. Our results showed that also passive cycling may be beneficial in activating motor cortical regions and possibly also facilitating motor recovery after SCI. The present study confirms and extends the findings of previous studies that have observed task-specific cortical activation during passive pedaling. Therefore passive exercise therapies when applied below the level of the lesion in subjects with SCI could promote cortical neuroplastic reorganization. PMID:27108543

  11. Muscle Relaxation of the Foot Reduces Corticospinal Excitability of Hand Muscles and Enhances Intracortical Inhibition.

    PubMed

    Kato, Kouki; Muraoka, Tetsuro; Mizuguchi, Nobuaki; Nakagawa, Kento; Nakata, Hiroki; Kanosue, Kazuyuki

    2016-01-01

    The object of this study was to clarify the effects of foot muscle relaxation on activity in the primary motor cortex (M1) of the hand area. Subjects were asked to volitionally relax the right foot from sustained contraction of either the dorsiflexor (tibialis anterior; TA relaxation) or plantarflexor (soleus; SOL relaxation) in response to an auditory stimulus. Single- and paired-pulse transcranial magnetic stimulation (TMS) was delivered to the hand area of the left M1 at different time intervals before and after the onset of TA or SOL relaxation. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). MEP amplitudes of ECR and FCR caused by single-pulse TMS temporarily decreased after TA and SOL relaxation onset, respectively, as compared with those of the resting control. Furthermore, short-interval intracortical inhibition (SICI) of ECR evaluated with paired-pulse TMS temporarily increased after TA relaxation onset. Our findings indicate that muscle relaxation of the dorsiflexor reduced corticospinal excitability of the ipsilateral hand muscles. This is most likely caused by an increase in intracortical inhibition. PMID:27242482

  12. A critical review of cell culture strategies for modelling intracortical brain implant material reactions.

    PubMed

    Gilmour, A D; Woolley, A J; Poole-Warren, L A; Thomson, C E; Green, R A

    2016-06-01

    The capacity to predict in vivo responses to medical devices in humans currently relies greatly on implantation in animal models. Researchers have been striving to develop in vitro techniques that can overcome the limitations associated with in vivo approaches. This review focuses on a critical analysis of the major in vitro strategies being utilized in laboratories around the world to improve understanding of the biological performance of intracortical, brain-implanted microdevices. Of particular interest to the current review are in vitro models for studying cell responses to penetrating intracortical devices and their materials, such as electrode arrays used for brain computer interface (BCI) and deep brain stimulation electrode probes implanted through the cortex. A background on the neural interface challenge is presented, followed by discussion of relevant in vitro culture strategies and their advantages and disadvantages. Future development of 2D culture models that exhibit developmental changes capable of mimicking normal, postnatal development will form the basis for more complex accurate predictive models in the future. Although not within the scope of this review, innovations in 3D scaffold technologies and microfluidic constructs will further improve the utility of in vitro approaches. PMID:26994876

  13. Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

    PubMed Central

    Wagener, Robin J.; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F.

    2016-01-01

    Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory “barrel” cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID:26564256

  14. Reprint of “Non-causal spike filtering improves decoding of movement intention for intracortical BCIs”☆

    PubMed Central

    Masse, Nicolas Y.; Jarosiewicz, Beata; Simeral, John D.; Bacher, Daniel; Stavisky, Sergey D.; Cash, Sydney S.; Oakley, Erin M.; Berhanu, Etsub; Eskandar, Emad; Friehs, Gerhard; Hochberg, Leigh R.; Donoghue, John P.

    2015-01-01

    Background Multiple types of neural signals are available for controlling assistive devices through brain–computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on “sorting” action potentials. New method We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4 ms lag between recording and filtering neural signals. Results Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant’s intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7° for participant S3, who was implanted 5.4 years prior to this study, and by 3.5° for participant T2, who was implanted 3 months prior to this study. PMID:25681017

  15. In vivo demonstration of injectable microstimulators based on charge-balanced rectification of epidermically applied currents

    NASA Astrophysics Data System (ADS)

    Ivorra, Antoni; Becerra-Fajardo, Laura; Castellví, Quim

    2015-12-01

    Objective. It is possible to develop implantable microstimulators whose actuation principle is based on rectification of high-frequency (HF) current bursts supplied through skin electrodes. This has been demonstrated previously by means of devices consisting of a single diode. However, previous single diode devices caused dc currents which made them impractical for clinical applications. Here flexible thread-like stimulation implants which perform charge balance are demonstrated in vivo. Approach. The implants weigh 40.5 mg and they consist of a 3 cm long tubular silicone body with a diameter of 1 mm, two electrodes at opposite ends, and, within the central section of the body, an electronic circuit made up of a diode, two capacitors, and a resistor. In the present study, each implant was percutaneously introduced through a 14 G catheter into either the gastrocnemius muscle or the cranial tibial muscle of a rabbit hindlimb. Then stimulation was performed by delivering HF bursts (amplitude <60 V, frequency 1 MHz, burst repetition frequency from 10 Hz to 200 Hz, duration = 200 μs) through a pair of textile electrodes strapped around the hindlimb and either isometric plantarflexion or dorsiflexion forces were recorded. Stimulation was also assayed 1, 2 and 4 weeks after implantation. Main results. The implants produced bursts of rectified current whose mean value was of a few mA and were capable of causing local neuromuscular stimulation. The implants were well-tolerated during the 4 weeks. Significance. Existing power supply methods, and, in particular inductive links, comprise stiff and bulky parts. This hinders the development of minimally invasive implantable devices for neuroprostheses based on electrical stimulation. The proposed methodology is intended to relieving such bottleneck. In terms of mass, thinness, and flexibility, the demonstrated implants appear to be unprecedented among the intramuscular stimulation implants ever assayed in vertebrates.

  16. A wireless implantable multichannel microstimulating system-on-a-chip with modular architecture.

    PubMed

    Ghovanloo, Maysam; Najafi, Khalil

    2007-09-01

    A 64-site wireless current microstimulator chip (Interestim-2B) and a prototype implant based on the same chip have been developed for neural prosthetic applications. Modular standalone architecture allows up to 32 chips to be individually addressed and operated in parallel to drive up to 2048 stimulating sites. The only off-chip components are a receiver inductive-capacitive (LC) tank, a capacitive low-pass filter for ripple rejection, and arrays of microelectrodes for interfacing with the neural tissue. The implant receives inductive power up to 50 mW and data at 2.5 Mb/s from a frequency shift keyed (FSK) 5/10 MHZ carrier to generate up to 65,800 stimulus pulses/s. Each Interestim-2B chip contains 16 current drivers with 270 microA full-scale current, 5-bit (32-steps) digital-to-analog converter (DAC) resolution, 100 M omega output impedance, and a voltage compliance that extends within 150 and 250 mV of the 5 V supply and ground rails, respectively. It can generate any arbitrary current waveform and supports a variety of monopolar and bipolar stimulation protocols. A common analog line provides access to each site potential, and exhausts residual stimulus charges for charge balancing. The chip has site potential measurement and in situ site impedance measurement capabilities, which help its users indicate defective sites or characteristic shifts in chronic stimulations. Interestim-2B chip is fabricated in the AMI 1.5 microm standard complementary metal-oxide-semiconductor (CMOS) process and measures 4.6 x 4.6 x 0.5 mm. The prototype implant size including test connectors is 19 x 14 x 6 mm, which can be shrunk down to < 0.5 CC. This paper also summarizes some of the in vitro and in vivo experiments performed using the Interestim-2B prototype implant. PMID:17894278

  17. A modular robust control framework for control of movement elicited by multi-electrode intraspinal microstimulation

    NASA Astrophysics Data System (ADS)

    Roshani, Amir; Erfanian, Abbas

    2016-08-01

    Objective. An important issue in restoring motor function through intraspinal microstimulation (ISMS) is the motor control. To provide a physiologically plausible motor control using ISMS, it should be able to control the individual motor unit which is the lowest functional unit of motor control. By focal stimulation only a small group of motor neurons (MNs) within a motor pool can be activated. Different groups of MNs within a motor pool can potentially be activated without involving adjacent motor pools by local stimulation of different parts of a motor pool via microelectrode array implanted into a motor pool. However, since the system has multiple inputs with single output during multi-electrode ISMS, it poses a challenge to movement control. In this paper, we proposed a modular robust control strategy for movement control, whereas multi-electrode array is implanted into each motor activation pool of a muscle. Approach. The controller was based on the combination of proportional-integral-derivative and adaptive fuzzy sliding mode control. The global stability of the controller was guaranteed. Main results. The results of the experiments on rat models showed that the multi-electrode control can provide a more robust control and accurate tracking performance than a single-electrode control. The control output can be pulse amplitude (pulse amplitude modulation, PAM) or pulse width (pulse width modulation, PWM) of the stimulation signal. The results demonstrated that the controller with PAM provided faster convergence rate and better tracking performance than the controller with PWM. Significance. This work represents a promising control approach to the restoring motor functions using ISMS. The proposed controller requires no prior knowledge about the dynamics of the system to be controlled and no offline learning phase. The proposed control design is modular in the sense that each motor pool has an independent controller and each controller is able to control ISMS

  18. Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

    NASA Astrophysics Data System (ADS)

    Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

    2013-06-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

  19. Strategies for generating prolonged functional standing using intramuscular stimulation or intraspinal microstimulation.

    PubMed

    Lau, Bernice; Guevremont, Lisa; Mushahwar, Vivian K

    2007-06-01

    Spinal cord injury (SCI) often results in the loss of the ability to stand. The goal of this study was to implement a functional electrical stimulation (FES) system for restoring prolonged periods of standing after SCI. For this purpose, we tested two control strategies: open-loop and closed-loop control, and two stimulation paradigms: non-interleaved intramuscular stimulation (IM-S) and interleaved intraspinal microstimulation (ISMS). The experiments were conducted in anesthetized cats. Stimulation was applied to the muscles through IM-S electrodes implanted in the main knee and ankle extensor muscles, or to the spinal cord through ultra-fine ISMS wires implanted within the ventral horn of the lumbosacral enlargement. The cats were partially supported over parallel force plates and accelerometers were secured to the hindlimbs above and below the ankle joint. Ground reaction forces and knee and ankle joint angles were measured by the force plates and accelerometers, respectively. The closed-loop controller used these feedback signals to modulate the amplitude of stimulation applied to the extensor muscles. The open-loop controller applied constant levels of stimulation which were determined before the onset of each trial. The duration of standing achieved using closed-loop control of IM-S was significantly longer than that achieved with open-loop control (approximately 2 times longer). The increase in the duration of standing corresponded with a decrease in the rate of force decay and a lower average injected current during closed-loop control. Standing was further improved with the use of ISMS. Closed-loop control of interleaved ISMS resulted in a period of standing > 3 times longer than the best trial generated using non-interleaved IM-S. There was also a significant improvement in the balance of force between the two hindlimbs. The results suggest that a system which uses closed-loop control in conjunction with interleaved ISMS could achieve prolonged FES

  20. Short-interval cortical inhibition and intracortical facilitation during submaximal voluntary contractions changes with fatigue.

    PubMed

    Hunter, Sandra K; McNeil, Chris J; Butler, Jane E; Gandevia, Simon C; Taylor, Janet L

    2016-09-01

    This study determined whether short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) change during a sustained submaximal isometric contraction. On 2 days, 12 participants (6 men, 6 women) performed brief (7-s) elbow flexor contractions before and after a 10-min fatiguing contraction; all contractions were performed at the level of integrated electromyographic activity (EMG) which produced 25 % maximal unfatigued torque. During the brief 7-s and 10-min submaximal contractions, single (test) and paired (conditioning-test) transcranial magnetic stimuli were applied over the motor cortex (5 s apart) to elicit motor-evoked potentials (MEPs) in biceps brachii. SICI and ICF were elicited on separate days, with a conditioning-test interstimulus interval of 2.5 and 15 ms, respectively. On both days, integrated EMG remained constant while torque fell during the sustained contraction by ~51.5 % from control contractions, perceived effort increased threefold, and MVC declined by 21-22 %. For SICI, the conditioned MEP during control contractions (74.1 ± 2.5 % of unconditioned MEP) increased (less inhibition) during the sustained contraction (last 2.5 min: 86.0 ± 5.1 %; P < 0.05). It remained elevated in recovery contractions at 2 min (82.0 ± 3.8 %; P < 0.05) and returned toward control at 7-min recovery (76.3 ± 3.2 %). ICF during control contractions (conditioned MEP 129.7 ± 4.8 % of unconditioned MEP) decreased (less facilitation) during the sustained contraction (last 2.5 min: 107.6 ± 6.8 %; P < 0.05) and recovered to 122.8 ± 4.3 % during contractions after 2 min of recovery. Both intracortical inhibitory and facilitatory circuits become less excitable with fatigue when assessed during voluntary activity, but their different time courses of recovery suggest different mechanisms for the fatigue-related changes of SICI and ICF. PMID:27165508

  1. Intracortical circuits amplify sound-evoked activity in primary auditory cortex following systemic injection of salicylate in the rat.

    PubMed

    Stolzberg, Daniel; Chrostowski, Michael; Salvi, Richard J; Allman, Brian L

    2012-07-01

    A high dose of sodium salicylate temporarily induces tinnitus, mild hearing loss, and possibly hyperacusis in humans and other animals. Salicylate has well-established effects on cochlear function, primarily resulting in the moderate reduction of auditory input to the brain. Despite decreased peripheral sensitivity and output, salicylate induces a paradoxical enhancement of the sound-evoked field potential at the level of the primary auditory cortex (A1). Previous electrophysiologic studies have begun to characterize changes in thalamorecipient layers of A1; however, A1 is a complex neural circuit with recurrent intracortical connections. To describe the effects of acute systemic salicylate treatment on both thalamic and intracortical sound-driven activity across layers of A1, we applied current-source density (CSD) analysis to field potentials sampled across cortical layers in the anesthetized rat. CSD maps were normally characterized by a large, short-latency, monosynaptic, thalamically driven sink in granular layers followed by a lower amplitude, longer latency, polysynaptic, intracortically driven sink in supragranular layers. Following systemic administration of salicylate, there was a near doubling of both granular and supragranular sink amplitudes at higher sound levels. The supragranular sink amplitude input/output function changed from becoming asymptotic at approximately 50 dB to sharply nonasymptotic, often dominating the granular sink amplitude at higher sound levels. The supragranular sink also exhibited a significant decrease in peak latency, reflecting an acceleration of intracortical processing of the sound-evoked response. Additionally, multiunit (MU) activity was altered by salicylate; the normally onset/sustained MU response type was transformed into a primarily onset response type in granular and infragranular layers. The results from CSD analysis indicate that salicylate significantly enhances sound-driven response via intracortical circuits

  2. Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

    NASA Astrophysics Data System (ADS)

    Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

    2012-12-01

    Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

  3. System identification of the nonlinear dynamics in the thalamocortical circuit in response to patterned thalamic microstimulation in-vivo

    PubMed Central

    Millard, Daniel C; Wang, Qi; Gollnick, Clare A; Stanley, Garrett B

    2013-01-01

    Objective Nonlinear system identification approaches were used to develop a dynamical model of the network level response to patterns of microstimulation in-vivo. Approach The thalamocortical circuit of the rodent vibrissa pathway was the model system, with voltage sensitive dye imaging capturing the cortical response to patterns of stimulation delivered from a single electrode in the ventral posteromedial thalamus. The results of simple paired stimulus experiments formed the basis for the development of a phenomenological model explicitly containing nonlinear elements observed experimentally. The phenomenological model was fit using datasets obtained with impulse train inputs, Poisson-distributed in time and uniformly varying in amplitude. Main Results The phenomenological model explained 58% of the variance in the cortical response to out of sample patterns of thalamic microstimulation. Furthermore, while fit on trial averaged data, the phenomenological model reproduced single trial response properties when simulated with noise added into the system during stimulus presentation. The simulations indicate that the single trial response properties were dependent on the relative sensitivity of the static nonlinearities in the two stages of the model, and ultimately suggest that electrical stimulation activates local circuitry through linear recruitment, but that this activity propagates in a highly nonlinear fashion to downstream targets. Significance The development of nonlinear dynamical models of neural circuitry will guide information delivery for sensory prosthesis applications, and more generally reveal properties of population coding within neural circuits. PMID:24162186

  4. Comparison of the contractile responses to irregular and regular trains of stimuli during microstimulation of single human motor axons.

    PubMed

    Leitch, Michael; Macefield, Vaughan G

    2014-04-01

    During voluntary contractions, human motoneurons discharge with a physiological variability of ∼20%. However, studies that have measured the contractile responses to microstimulation of single motor axons have used regular trains of stimuli with no variability. We tested the hypothesis that irregular (physiological) trains of stimuli produce greater contractile responses than regular (nonphysiological) trains of identical mean frequency but zero variability. High-impedance tungsten microelectrodes were inserted into the common peroneal nerve and guided into fascicles supplying a toe extensor muscle. Selective microstimulation was achieved for 14 single motor axons. Contractile responses were measured via an angular displacement transducer over the relevant toe. After the responses to regular trains of 10 stimuli extending from 2 to 100 Hz were recorded, irregular trains of 10 stimuli, based on the interspike intervals recorded from single motor units during voluntary contractions, were delivered. Finally, the stimulation sequences were repeated following a 2-min period of continuous stimulation at 10 Hz to induce muscle fatigue. Regular trains of stimuli generated a sigmoidal increase in displacement with frequency, whereas irregular trains, emulating the firing of volitionally driven motoneurons, displayed significantly greater responses over the same frequency range (8-24 Hz). This was maintained even in the presence of fatigue. We conclude that physiological discharge variability, which incorporates short and long interspike intervals, offers an advantage to the neuromuscular system by allowing motor units to operate on a higher level of the contraction-frequency curve and taking advantage of catch-like properties in skeletal muscle. PMID:24401713

  5. System identification of the nonlinear dynamics in the thalamocortical circuit in response to patterned thalamic microstimulation in vivo

    NASA Astrophysics Data System (ADS)

    Millard, Daniel C.; Wang, Qi; Gollnick, Clare A.; Stanley, Garrett B.

    2013-12-01

    Objective. Nonlinear system identification approaches were used to develop a dynamical model of the network level response to patterns of microstimulation in vivo. Approach. The thalamocortical circuit of the rodent vibrissa pathway was the model system, with voltage sensitive dye imaging capturing the cortical response to patterns of stimulation delivered from a single electrode in the ventral posteromedial thalamus. The results of simple paired stimulus experiments formed the basis for the development of a phenomenological model explicitly containing nonlinear elements observed experimentally. The phenomenological model was fit using datasets obtained with impulse train inputs, Poisson-distributed in time and uniformly varying in amplitude. Main results. The phenomenological model explained 58% of the variance in the cortical response to out of sample patterns of thalamic microstimulation. Furthermore, while fit on trial-averaged data, the phenomenological model reproduced single trial response properties when simulated with noise added into the system during stimulus presentation. The simulations indicate that the single trial response properties were dependent on the relative sensitivity of the static nonlinearities in the two stages of the model, and ultimately suggest that electrical stimulation activates local circuitry through linear recruitment, but that this activity propagates in a highly nonlinear fashion to downstream targets. Significance. The development of nonlinear dynamical models of neural circuitry will guide information delivery for sensory prosthesis applications, and more generally reveal properties of population coding within neural circuits.

  6. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

    NASA Astrophysics Data System (ADS)

    Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

    2014-03-01

    Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

  7. Generation of Locomotor-Like Activity in the Isolated Rat Spinal Cord Using Intraspinal Electrical Microstimulation Driven by a Digital Neuromorphic CPG.

    PubMed

    Joucla, Sébastien; Ambroise, Matthieu; Levi, Timothée; Lafon, Thierry; Chauvet, Philippe; Saïghi, Sylvain; Bornat, Yannick; Lewis, Noëlle; Renaud, Sylvie; Yvert, Blaise

    2016-01-01

    Neural prostheses based on electrical microstimulation offer promising perspectives to restore functions following lesions of the central nervous system (CNS). They require the identification of appropriate stimulation sites and the coordination of their activation to achieve the restoration of functional activity. On the long term, a challenging perspective is to control microstimulation by artificial neural networks hybridized to the living tissue. Regarding the use of this strategy to restore locomotor activity in the spinal cord, to date, there has been no proof of principle of such hybrid approach driving intraspinal microstimulation (ISMS). Here, we address a first step toward this goal in the neonatal rat spinal cord isolated ex vivo, which can display locomotor-like activity while offering an easy access to intraspinal circuitry. Microelectrode arrays were inserted in the lumbar region to determine appropriate stimulation sites to elicit elementary bursting patterns on bilateral L2/L5 ventral roots. Two intraspinal sites were identified at L1 level, one on each side of the spinal cord laterally from the midline and approximately at a median position dorso-ventrally. An artificial CPG implemented on digital integrated circuit (FPGA) was built to generate alternating activity and was hybridized to the living spinal cord to drive electrical microstimulation on these two identified sites. Using this strategy, sustained left-right and flexor-extensor alternating activity on bilateral L2/L5 ventral roots could be generated in either whole or thoracically transected spinal cords. These results are a first step toward hybrid artificial/biological solutions based on electrical microstimulation for the restoration of lost function in the injured CNS. PMID:27013936

  8. Generation of Locomotor-Like Activity in the Isolated Rat Spinal Cord Using Intraspinal Electrical Microstimulation Driven by a Digital Neuromorphic CPG

    PubMed Central

    Joucla, Sébastien; Ambroise, Matthieu; Levi, Timothée; Lafon, Thierry; Chauvet, Philippe; Saïghi, Sylvain; Bornat, Yannick; Lewis, Noëlle; Renaud, Sylvie; Yvert, Blaise

    2016-01-01

    Neural prostheses based on electrical microstimulation offer promising perspectives to restore functions following lesions of the central nervous system (CNS). They require the identification of appropriate stimulation sites and the coordination of their activation to achieve the restoration of functional activity. On the long term, a challenging perspective is to control microstimulation by artificial neural networks hybridized to the living tissue. Regarding the use of this strategy to restore locomotor activity in the spinal cord, to date, there has been no proof of principle of such hybrid approach driving intraspinal microstimulation (ISMS). Here, we address a first step toward this goal in the neonatal rat spinal cord isolated ex vivo, which can display locomotor-like activity while offering an easy access to intraspinal circuitry. Microelectrode arrays were inserted in the lumbar region to determine appropriate stimulation sites to elicit elementary bursting patterns on bilateral L2/L5 ventral roots. Two intraspinal sites were identified at L1 level, one on each side of the spinal cord laterally from the midline and approximately at a median position dorso-ventrally. An artificial CPG implemented on digital integrated circuit (FPGA) was built to generate alternating activity and was hybridized to the living spinal cord to drive electrical microstimulation on these two identified sites. Using this strategy, sustained left-right and flexor-extensor alternating activity on bilateral L2/L5 ventral roots could be generated in either whole or thoracically transected spinal cords. These results are a first step toward hybrid artificial/biological solutions based on electrical microstimulation for the restoration of lost function in the injured CNS. PMID:27013936

  9. Wireless control of intraspinal microstimulation in a rodent model of paralysis

    PubMed Central

    Kasasbeh, Aimen; Mallory, Grant W.; Hachmann, Jan T.; Dube, John R.; Kimble, Christopher J.; Lobel, Darlene A.; Bieber, Allan; Jeong, Ju Ho; Bennet, Kevin E.; Lujan, J. Luis

    2015-01-01

    OBJECT Despite a promising outlook, existing intraspinal microstimulation (ISMS) techniques for restoring functional motor control after spinal cord injury are not yet suitable for use outside a controlled laboratory environment. Thus, successful application of ISMS therapy in humans will require the use of versatile chronic neurostimulation systems. The objective of this study was to establish proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury. METHODS The lumbar spinal cord in each of 17 fully anesthetized Sprague-Dawley rats was stimulated via ISMS electrodes to evoke hindlimb function. Nine subjects underwent complete surgical transection of the spinal cord at the T-4 level 7 days before stimulation. Targeting for both groups (spinalized and control) was performed under visual inspection via dorsal spinal cord landmarks such as the dorsal root entry zone and the dorsal median fissure. Teflon-insulated stimulating platinum-iridium microwire electrodes (50 μm in diameter, with a 30- to 60-μm exposed tip) were implanted within the ventral gray matter to an approximate depth of 1.8 mm. Electrode implantation was performed using a free-hand delivery technique (n = 12) or a Kopf spinal frame system (n = 5) to compare the efficacy of these 2 commonly used targeting techniques. Stimulation was controlled remotely using a wireless neurostimulation control system. Hindlimb movements evoked by stimulation were tracked via kinematic markers placed on the hips, knees, ankles, and paws. Postmortem fixation and staining of the spinal cord tissue were conducted to determine the final positions of the stimulating electrodes within the spinal cord tissue. RESULTS The results show that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee, and hip muscles in 90% of the spinalized rats (n = 9) and 100% of the healthy control rats (n = 8). No functional differences

  10. Chronic microstimulation in the feline ventral cochlear nucleus: physiologic and histologic effects.

    PubMed

    McCreery, D B; Yuen, T G; Bullara, L A

    2000-11-01

    This study was conducted to help to establish the feasibility of a multi-channel auditory prosthesis based on microstimulation within the human ventral cochlear nucleus, and to define the range of stimulus parameters that can be used safely with such a device. We chronically implanted activated iridium microelectrodes into the feline ventral cochlear nucleus and, beginning 80-250 days after implantation, they were pulsed for 7 h/day, on up to 21 successive days. The stimulus was charge-balanced pulses whose amplitude was modulated by a simulated human voice. The pulse rate (250 Hz/electrode) and the maximum pulse amplitude were selected as those that are likely to provide a patient with useful auditory percepts. The changes in neuronal responses during the multi-day stimulation regimens were partitioned into long-lasting, stimulation-induced depression of neuronal excitability (SIDNE), and short-acting neuronal refractivity (SANR). Both SIDNE and SANR were quantified from the changes in the growth functions of the evoked potentials recorded in the inferior colliculus. All of the stimulation regimens that we tested induced measurable SIDNE and SANR. The combined effect of SIDNE and the superimposed SANR is to depress the neuronal response near threshold, and thereby, to depress the population response over the entire amplitude range of the stimulus pulses. SIDNE and SANR may cause the greatest degradation of the performance of a clinical device at the low end of the amplitude range, and this may represent an inherent limitation of this type of spatially localized, high-rate neuronal stimulation. We determined sets of stimulus parameters which preserved most of the dynamic range of the neuronal response, when using either long (150 micros/phase) or short (40 micros/phase) stimulus pulses. Increasing the amplitude of the stimulus was relatively ineffective as a means of increasing the dynamic range of neuronal response, since the greater stimulus amplitude induced

  11. Curcumin-releasing mechanically adaptive intracortical implants improve the proximal neuronal density and blood-brain barrier stability.

    PubMed

    Potter, Kelsey A; Jorfi, Mehdi; Householder, Kyle T; Foster, E Johan; Weder, Christoph; Capadona, Jeffrey R

    2014-05-01

    The cellular and molecular mechanisms by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remain active areas of research. We previously demonstrated that both the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress, contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically responsive, mechanically adaptive polymer implants based on poly(vinyl alcohol) (PVA), with the capability to also locally administer the antioxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and antioxidant release - leads to synergistic effects in vivo. Over the first 4weeks of the implantation, curcumin-releasing, mechanically adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat PVA controls. 12weeks post-implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically adaptive intracortical implants. PMID:24468582

  12. Descending Control of Nociceptive Processing in Knee Osteoarthritis Is Associated With Intracortical Disinhibition

    PubMed Central

    Tarragó, Maria da Graca L.; Deitos, Alícia; Brietzke, Aline Patrícia; Vercelino, Rafael; Torres, Iraci L. S.; Fregni, Felipe; Caumo, Wolnei

    2016-01-01

    Abstract Based on the hypothesis that an imbalance in excitatory and inhibitory input is a central mechanism of knee osteoarthritis chronic pain (KOACP), this exploratory study had the following aims: to compare whether the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system indexed by the motor-evoked potential (MEP) and the cortical salient period (CSP) in patients with severe osteoarthritis (OA) and healthy controls; and to determine if there is correlation between the measures of intracortical inhibition (CSP, MEP) with changes on the numerical pain scale (NPS [0–10]) in KOACP during a conditioned pain modulation (CPM)-task considering the effect of self-reported function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and analgesic use. In a cross-sectional study, we included females (n = 21), with disability by pain or stiffness due to KOACP and healthy controls (n = 10), aged 19 to 75 years. The motor cortex excitability parameters (MEP and CSP) were assessed using the transcranial magnetic stimulation. We assessed the pain and disability by the WOMAC, and change on NPS (0–10) during CPM-task. A Multivariate analysis of covariance revealed that the adjusted mean (SD) on the MEP amplitude was 13.53% higher in the OA than in healthy subjects (1.33 [0.49] vs 1.15 [0.13]), respectively (P = 0.16). The adjusted mean (SD) on the CSP observed in OA patients was 23.43% lower than in healthy subjects (54.54 [16.10] vs 70.94 [22.87]), respectively (P = 0.01). The function of the descending pain modulatory system assessed by change on NPS (0–10) during a CPM-task was negatively correlated with the cortical excitability parameter indexed by the CSP (P = 0.001). Also, the CSP was negatively correlated with the pain and disability assessed by the WOMAC index. These findings support the hypothesis that the change in cortical plasticity in

  13. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

    NASA Astrophysics Data System (ADS)

    Barrese, James C.; Rao, Naveen; Paroo, Kaivon; Triebwasser, Corey; Vargas-Irwin, Carlos; Franquemont, Lachlan; Donoghue, John P.

    2013-12-01

    Objective. Brain-computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach. Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results. Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed

  14. Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

    PubMed Central

    Barrese, James C; Aceros, Juan; Donoghue, John P

    2016-01-01

    Objective Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not

  15. Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

    NASA Astrophysics Data System (ADS)

    Barrese, James C.; Aceros, Juan; Donoghue, John P.

    2016-04-01

    Objective. Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach. We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results. SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does

  16. Delayed grip relaxation and altered modulation of intracortical inhibition with aging.

    PubMed

    Motawar, Binal; Stinear, James W; Lauer, Abigail W; Ramakrishnan, Viswanathan; Seo, Na Jin

    2016-04-01

    Grip relaxation is a voluntary action that requires an increase in short-interval intracortical inhibition (SICI) in healthy young adults, rather than a simple termination of excitatory drive. The way aging affects this voluntary inhibitory action and timing of grip relaxation is currently unknown. The objective of this study was to examine aging-related delays in grip relaxation and SICI modulation for the flexor digitorum superficialis muscle during grip relaxation. The main finding was that young adults increased SICI to relax their grips, whereas older adults did not increase SICI with a prolonged grip relaxation time (p < 0.05 for both SICI modulation and grip relaxation time). A secondary experiment showed that both young and older adults did not change H reflex excitability during grip relaxation. Our data suggest that grip relaxation is mediated by increased cortical inhibitory output in young adults, and aging-related impairment in increasing cortical inhibitory output may hamper timely cessation of muscle activity. Our data also suggest a lesser role of the spinal circuits in grip muscle relaxation. This knowledge may contribute to understanding of aging-related movement deterioration and development of interventions for improving modulation of SICI to improve muscle relaxation and movement coordination. PMID:26686531

  17. Brain computer interface learning for systems based on electrocorticography and intracortical microelectrode arrays

    PubMed Central

    Hiremath, Shivayogi V.; Chen, Weidong; Wang, Wei; Foldes, Stephen; Yang, Ying; Tyler-Kabara, Elizabeth C.; Collinger, Jennifer L.; Boninger, Michael L.

    2015-01-01

    A brain-computer interface (BCI) system transforms neural activity into control signals for external devices in real time. A BCI user needs to learn to generate specific cortical activity patterns to control external devices effectively. We call this process BCI learning, and it often requires significant effort and time. Therefore, it is important to study this process and develop novel and efficient approaches to accelerate BCI learning. This article reviews major approaches that have been used for BCI learning, including computer-assisted learning, co-adaptive learning, operant conditioning, and sensory feedback. We focus on BCIs based on electrocorticography and intracortical microelectrode arrays for restoring motor function. This article also explores the possibility of brain modulation techniques in promoting BCI learning, such as electrical cortical stimulation, transcranial magnetic stimulation, and optogenetics. Furthermore, as proposed by recent BCI studies, we suggest that BCI learning is in many ways analogous to motor and cognitive skill learning, and therefore skill learning should be a useful metaphor to model BCI learning. PMID:26113812

  18. Time Course of Corticospinal Excitability and Intracortical Inhibition Just before Muscle Relaxation

    PubMed Central

    Suzuki, Tomotaka; Sugawara, Kenichi; Ogahara, Kakuya; Higashi, Toshio

    2016-01-01

    Using transcranial magnetic stimulation (TMS), we investigated how short-interval intracortical inhibition (SICI) was involved with transient motor cortex (M1) excitability changes observed just before the transition from muscle contraction to muscle relaxation. Ten healthy participants performed a simultaneous relaxation task of the ipsilateral finger and foot, relaxing from 10% of their maximal voluntary contraction (MVC) force after the go signal. In the simple reaction time (RT) paradigm, single or paired TMS pulses were randomly delivered after the go signal, and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) muscle. We analyzed the time course prior to the estimated relaxation reaction time (RRT), defined here as the onset of voluntary relaxation. SICI decreased in the 80–100 ms before RRT, and MEPs were significantly greater in amplitude in the 60–80 ms period before RRT than in the other intervals in single-pulse trials. TMS pulses did not effectively increase RRT. These results show that cortical excitability in the early stage, before muscle relaxation, plays an important role in muscle relaxation control. SICI circuits may vary between decreased and increased activation to continuously maintain muscle relaxation during or after a relaxation response. With regard to M1 excitability dynamics, we suggest that SICI also dynamically changes throughout the muscle relaxation process. PMID:26858619

  19. Time Course of Corticospinal Excitability and Intracortical Inhibition Just before Muscle Relaxation.

    PubMed

    Suzuki, Tomotaka; Sugawara, Kenichi; Ogahara, Kakuya; Higashi, Toshio

    2016-01-01

    Using transcranial magnetic stimulation (TMS), we investigated how short-interval intracortical inhibition (SICI) was involved with transient motor cortex (M1) excitability changes observed just before the transition from muscle contraction to muscle relaxation. Ten healthy participants performed a simultaneous relaxation task of the ipsilateral finger and foot, relaxing from 10% of their maximal voluntary contraction (MVC) force after the go signal. In the simple reaction time (RT) paradigm, single or paired TMS pulses were randomly delivered after the go signal, and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) muscle. We analyzed the time course prior to the estimated relaxation reaction time (RRT), defined here as the onset of voluntary relaxation. SICI decreased in the 80-100 ms before RRT, and MEPs were significantly greater in amplitude in the 60-80 ms period before RRT than in the other intervals in single-pulse trials. TMS pulses did not effectively increase RRT. These results show that cortical excitability in the early stage, before muscle relaxation, plays an important role in muscle relaxation control. SICI circuits may vary between decreased and increased activation to continuously maintain muscle relaxation during or after a relaxation response. With regard to M1 excitability dynamics, we suggest that SICI also dynamically changes throughout the muscle relaxation process. PMID:26858619

  20. Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects.

    PubMed

    Fernández, Eduardo; Greger, Bradley; House, Paul A; Aranda, Ignacio; Botella, Carlos; Albisua, Julio; Soto-Sánchez, Cristina; Alfaro, Arantxa; Normann, Richard A

    2014-01-01

    The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns). However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology. PMID:25100989

  1. Developmental Sculpting of Intracortical Circuits by MHC Class I H2-Db and H2-Kb.

    PubMed

    Adelson, Jaimie D; Sapp, Richard W; Brott, Barbara K; Lee, Hanmi; Miyamichi, Kazunari; Luo, Liqun; Cheng, Sarah; Djurisic, Maja; Shatz, Carla J

    2016-04-01

    Synapse pruning is an activity-regulated process needed for proper circuit sculpting in the developing brain. Major histocompatibility class I (MHCI) molecules are regulated by activity, but little is known about their role in the development of connectivity in cortex. Here we show that protein for 2 MHCI molecules H2-Kb and H2-Db is associated with synapses in the visual cortex. Pyramidal neurons in mice lacking H2-Kb and H2-Db (KbDb KO) have more extensive cortical connectivity than normal. Modified rabies virus tracing was used to monitor the extent of pyramidal cell connectivity: Horizontal connectivity is greater in the visual cortex of KbDb KO mice. Basal dendrites of L2/3 pyramids, where many horizontal connections terminate, are more highly branched and have elevated spine density in the KO. Furthermore, the density of axonal boutons is elevated within L2/3 of mutant mice. These increases are accompanied by elevated miniature excitatory postsynaptic current frequency, consistent with an increase in functional synapses. This functional and anatomical increase in intracortical connectivity is also associated with enhanced ocular dominance plasticity that persists into adulthood. Thus, these MHCI proteins regulate sculpting of local cortical circuits and in their absence, the excess connectivity can function as a substrate for cortical plasticity throughout life. PMID:25316337

  2. Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal).

    PubMed

    Schmid, Anne-Christine; Chien, Jui-Hong; Greenspan, Joel D; Garonzik, Ira; Weiss, Nirit; Ohara, Shinji; Lenz, Frederick Arthur

    2016-06-01

    The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms. PMID:26864759

  3. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

    PubMed Central

    Barrese, James C; Rao, Naveen; Paroo, Kaivon; Triebwasser, Corey; Vargas-Irwin, Carlos; Franquemont, Lachlan; Donoghue, John P

    2016-01-01

    Objective Brain–computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed

  4. Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses

    NASA Astrophysics Data System (ADS)

    Woolley, Andrew J.; Desai, Himanshi A.; Otto, Kevin J.

    2013-04-01

    Objective. Brain-implanted microelectrode arrays show promise as future clinical devices. However, biological responses to various designs, compositions and locations of these implants have not been fully characterized, and may impact the long-term functionality of these devices. In order to improve our understanding of the tissue conditions at the interface of chronic brain-implanted microdevices, we proposed utilizing advanced histology and microscopy techniques to image implanted devices and surrounding tissue intact within brain slices. We then proposed utilizing these methods to examine whether depth within the cerebral cortex affected tissue conditions around implants. Approach. Histological data was collected from rodent brain slices containing intact, intracortical microdevices four weeks after implantation surgery. Thick tissue sections containing the chronic implants were processed with fluorescent antibody labels, and imaged in an optical clearing solution using laser confocal microscopy. Main Results. Tissue surrounding microdevices exhibited two major depth-related phenomena: a non-uniform microglial coating along the device length and a dense mass of cells surrounding the implant in cerebral cortical layers I and II. Detailed views of the monocyte-derived immune cells improve our understanding of the close and complex association that immune cells have with chronic brain implants, and illuminated a possible relationship between cortical depth and the intensity of a chronic monocyte response around penetrating microdevices. The dense mass of cells contained vimentin, a protein not typically expressed highly in CNS cells, evidence that non-CNS cells likely descended down the face of the penetrating devices from the pial surface. Significance. Image data of highly non-uniform and depth-dependent biological responses along a device provides novel insight into the complexity of the tissue response to penetrating brain-implanted microdevices. The presented

  5. Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta.

    PubMed

    Vardakastani, V; Saletti, D; Skalli, W; Marry, P; Allain, J M; Adam, C

    2014-12-01

    Osteogenesis imperfecta (OI) is a heritable disease occurring in one out of every 20,000 births. Although it is known that Type I collagen mutation in OI leads to increased bone fragility, the mechanism of this increased susceptibility to fracture is not clear. The aim of this study was to assess the microstructure of cortical bone fragments from patients with osteogenesis imperfecta (OI) using polarized light microscopy, and to correlate microstructural observations with the results of previously performed mechanical compression tests on bone from the same source. Specimens of cortical bone were harvested from the lower limbs of three (3) OI patients at the time of surgery, and were divided into two groups. Group 1 had been subjected to previous micro-mechanical compression testing, while Group 2 had not been subjected to any prior testing. Polarized light microscopy revealed disorganized bone collagen architecture as has been previously observed, as well as a large increase in the areal porosity of the bone compared to typical values for healthy cortical bone, with large (several hundred micron sized), asymmetrical pores. Importantly, the areal porosity of the OI bone samples in Group 1 appears to correlate strongly with their previously measured apparent Young's modulus and compressive strength. Taken together with prior nanoindentation studies on OI bone tissue, the results of this study suggest that increased intra-cortical porosity is responsible for the reduction in macroscopic mechanical properties of OI cortical bone, and therefore that in vivo imaging modalities with resolutions of ~100 μm or less could potentially be used to non-invasively assess bone strength in OI patients. Although the number of subjects in this study is small, these results highlight the importance of further studies in OI bone by groups with access to human OI tissue in order to clarify the relationship between increased porosity and reduced macroscopic mechanical integrity. PMID

  6. Intracortical distribution of number and volume of glomeruli during postnatal maturation in the dog

    PubMed Central

    Horster, Michael; Kemler, Barry J.; Valtin, Heinz

    1971-01-01

    Morphometric analysis was carried out on kidneys of neonatal dogs in which function of the entire kidney and of single nephrons had been evaluated. Measurements were begun after neogenesis of nephrons had been completed, i.e., at the end of the 3rd postnatal wk. They were continued to 74 days by which time glomerular function, expressed per unit of renal weight, had reached the mature level. For statistical analysis, the cortical histogram at each age was divided into eight zones of equal depth between the capsule and corticomedullary junction. The mean total number of glomeruli in this beagle strain was 589 × 103 per kidney. The fraction of the total number of glomeruli was lowest in the subcapsular layer (3.9%) and highest (24.5%) in the zone immediately beneath from where it decreased almost linearly to a value of 4.5% in the juxtamedullary region. This numerical distribution did not change with age, which suggests that growth of nonglomerular structures proceeded at the same rate in all cortical layers. Volume of the glomerular tuft rose slightly between the subcapsular and next layer and remained constant down to the juxtamedullary region where it increased sharply. The juxtamedullary glomerulus was about 45% larger in volume than the other glomeruli. This intracortical distribution of glomerular volume did not vary between 23 and 74 days, although the volume of an individual glomerulus at each level increased slightly with age. Total glomerular volume increased by 33% during the postnatal period studied, whereas simultaneously nonglomerular cortical volume rose by 235%. On the assumption that nonglomerular tissue consists mainly of tubules, the data suggest that the rate of tubular growth far exceeded that of glomerular growth. Despite this difference in glomerular and tubular growth rates, analysis of single nephrons in these dogs demonstrates constant and mature proximal fractional reabsorption of sodium and water. Images PMID:5547276

  7. Changes in Intracortical Microporosities Induced by Pharmaceutical Treatment of Osteoporosis as Detected by High Resolution Micro-CT

    PubMed Central

    Tommasini, Steven M.; Trinward, Andrea; Acerbo, Alvin S.; De Carlo, Francesco; Miller, Lisa M.; Judex, Stefan

    2012-01-01

    Bone’s microporosities play important biologic and mechanical roles. Here, we quantified 3D changes in cortical osteocyte-lacunae and other small porosities induced by estrogen withdrawal and two different osteoporosis treatments. Unlike 2D measurements, these data collected via synchrotron radiation-based μCT describe the size and 3D spatial distribution of a large number of porous structures. Six-month old female Sprague-Dawley rats were separated into four groups of age-matched controls, untreated OVX, OVX treated with PTH, and OVX treated with Alendronate (ALN). Intracortical microporosity of the medial quadrant of the femoral diaphysis was quantified at endosteal, intracortical, and periosteal regions of the samples, allowing the quantification of osteocyte lacunae that were formed primarily before versus after the start of treatment. Across the overall thickness of the medial cortex, lacunar volume fraction (Lc.V/TV) was significantly lower in ALN treated rats compared to PTH. In the endosteal region, average osteocyte lacunar volume () of untreated OVX rats was significantly lower than in age-matched controls, indicating a decrease in osteocyte lacunar size in bone formed on the endosteal surface after estrogen withdrawal. The effect of treatment (OVX, ALN, PTH) on the number of lacunae per tissue volume (Lc.N/TV) was dependent on the specific location within the cortex (endosteal, intracortical, periosteal). In both the endosteal and intracortical regions, Lc.N/TV was significantly lower in ALN than in untreated OVX, suggesting a site-specific effect in osteocyte lacuna density with ALN treatment. There also were a significantly greater number of small pores (5–100 μm3 in volume) in the endosteal region for PTH compared to ALN. The mechanical impact of this altered microporosity structure is unknown, but might serve to enhance, rather than deteriorate bone strength with PTH treatment, as smaller osteocyte lacunae may be better able to absorb

  8. Changes in intracortical microporosities induced by pharmaceutical treatment of osteoporosis as detected by high resolution micro-CT

    SciTech Connect

    Tommasini S. M.; Miller L.; Trinward, A.; Acerbo, A.S.; De Carlo F. and Judex, S.

    2011-12-28

    Bone's microporosities play important biologic and mechanical roles. Here, we quantified 3D changes in cortical osteocyte-lacunae and other small porosities induced by estrogen withdrawal and two different osteoporosistreatments. Unlike 2D measurements, these data collected via synchrotron radiation-based {mu}CT describe the size and 3D spatial distribution of a large number of porous structures. Six-month old female Sprague-Dawley rats were separated into four groups of age-matched controls, untreated OVX, OVX treated with PTH, and OVX treated with Alendronate (ALN). Intracortical microporosity of the medial quadrant of the femoral diaphysis was quantified at endosteal, intracortical, and periosteal regions of the samples, allowing the quantification of osteocyte lacunae that were formed primarily before versus after the start of treatment. Across the overall thickness of the medial cortex, lacunar volume fraction (Lc.V/TV) was significantly lower in ALN treated rats compared to PTH. In the endosteal region, average osteocyte lacunar volume (< Lc.V >) of untreated OVX rats was significantly lower than in age-matched controls, indicating a decrease in osteocyte lacunar size in bone formed on the endosteal surface after estrogen withdrawal. The effect of treatment (OVX, ALN, PTH) on the number of lacunae per tissue volume (Lc.N/TV) was dependent on the specific location within the cortex (endosteal, intracortical, periosteal). In both the endosteal and intracortical regions, Lc.N/TV was significantly lower in ALN than in untreated OVX, suggesting a site-specific effect in osteocyte lacuna density with ALN treatment. There also were a significantly greater number of small pores (5-100 {micro}m{sup 3} in volume) in the endosteal region for PTH compared to ALN. The mechanical impact of this altered microporosity structure is unknown, but might serve to enhance, rather than deteriorate bone strength with PTH treatment, as smaller osteocyte lacunae may be better able to

  9. The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted Intracortical microelectrodes

    PubMed Central

    Ravikumar, Madhumitha; Sunil, Smrithi; Black, James; Barkauskas, Deborah S.; Haung, Alex Y.; Miller, Robert H.; Selkirk, Stephen M.; Capadona, Jeffrey R.

    2014-01-01

    Resident microglia and blood-borne macrophages have both been implicated to play a dominant role in mediating the neuroinflammatory response affecting implanted intracortical microelectrodes. However, the distinction between each cell type has not been demonstrated due to a lack of discriminating cellular markers. Understanding the subtle differences of each cell population in mediating neuroinflammation can aid in determining the appropriate therapeutic approaches to improve microelectrode performance. Therefore, the goal of this study is to characterize the role of infiltrating blood-derived cells, specifically macrophages, in mediating neuroinflammation following intracortical microelectrode implantation. Interestingly, we found no correlation between microglia and neuron populations at the microelectrode-tissue interface. On the other hand, blood-borne macrophages consistently dominated the infiltrating cell population following microelectrode implantation. Most importantly, we found a correlation between increased populations of blood-derived cells (including the total macrophage population) and neuron loss at the microelectrode-tissue interface. Specifically, the total macrophage population was greatest at two and sixteen weeks post implantation, at the same time points when we observed the lowest densities of neuronal survival in closest proximity to the implant. Together, our results suggest a dominant role of infiltrating macrophages, and not resident microglia, in mediating neurodegeneration following microelectrode implantation. PMID:24973296

  10. The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.

    PubMed

    Ravikumar, Madhumitha; Sunil, Smrithi; Black, James; Barkauskas, Deborah S; Haung, Alex Y; Miller, Robert H; Selkirk, Stephen M; Capadona, Jeffrey R

    2014-09-01

    Resident microglia and blood-borne macrophages have both been implicated to play a dominant role in mediating the neuroinflammatory response affecting implanted intracortical microelectrodes. However, the distinction between each cell type has not been demonstrated due to a lack of discriminating cellular markers. Understanding the subtle differences of each cell population in mediating neuroinflammation can aid in determining the appropriate therapeutic approaches to improve microelectrode performance. Therefore, the goal of this study is to characterize the role of infiltrating blood-derived cells, specifically macrophages, in mediating neuroinflammation following intracortical microelectrode implantation. Interestingly, we found no correlation between microglia and neuron populations at the microelectrode-tissue interface. On the other hand, blood-borne macrophages consistently dominated the infiltrating cell population following microelectrode implantation. Most importantly, we found a correlation between increased populations of blood-derived cells (including the total macrophage population) and neuron loss at the microelectrode-tissue interface. Specifically, the total macrophage population was greatest at two and sixteen weeks post implantation, at the same time points when we observed the lowest densities of neuronal survival in closest proximity to the implant. Together, our results suggest a dominant role of infiltrating macrophages, and not resident microglia, in mediating neurodegeneration following microelectrode implantation. PMID:24973296

  11. Characteristics of sympathetic nerve activity in the rat sciatic nerve in response to microstimulation in a sympathetic fascicle in the contralateral side.

    PubMed

    Sato, Daisuke; Shiwaku, Yutaka; Nakamura, Ryoichi; Koizumi, Shuntaro; Feng, Zhonggang; Kusunoki, Masataka; Nakamura, Takao

    2013-01-01

    Microneurography is used for the monitor of various peripheral nerve activities. We recently reported that the electrical stimulation of peripheral sympathetic nerve fascicle via the microelectrode, i.e., microstimulation, temporarily reduced the blood glucose level in rats in case that the stimulation intensity was set high enough to induce small muscle contraction. However, the nature of microstimulation has little been clarified yet. Therefore, in the present study, we first detected sympathetic nerve signal microneurographically in the bilateral sciatic nerves of rats, and one of the microelectrodes was used for the microstimulation (0.25 ms-width pulse train at a rate of 1 Hz) while sympathetic nerve activity (SNA) was recorded in the contralateral side as a parameter of systemic sympathetic effects. The SNA, expressed as action potential rate, was transiently increased 150 ms after each stimulation pulse in case that the stimulation intensity was set not less than -0.1 V from the contraction threshold (around 0.32 V). To confirm that the increase was not caused by the activation of low threshold, thick fibers such as motor nerves in the vicinity of the microelectrode tip, next, a bipolar hook electrode, instead of the microelectrode, was then used in the stimulation side. As a result, the above-mentioned, transient increase in SNA was not observed any more in the contralateral side. These results suggest that systemic SNA could be enhanced with lower stimulation intensity than that inducing muscle contraction, and that thicker fibers may little affect the increase in the contralateral SNA. PMID:24111188

  12. Contribution of the motor cortex to the structure and the timing of hindlimb locomotion in the cat: a microstimulation study.

    PubMed

    Bretzner, Frédéric; Drew, Trevor

    2005-07-01

    We used microstimulation to examine the contribution of the motor cortex to the structure and timing of the hindlimb step cycle during locomotion in the intact cat. Stimulation was applied to the hindlimb representation of the motor cortex in 34 sites in three cats using either standard glass-insulated microelectrodes (16 sites in 1 cat) or chronically implanted microwire electrodes (18 sites in 2 cats). Stimulation at just suprathreshold intensities with the cat at rest produced multi-joint movements at a majority of sites (21/34, 62%) but evoked responses restricted to a single joint, normally the ankle, at the other 13/34 (38%) sites. Stimulation during locomotion generally evoked larger responses than the same stimulation at rest and frequently activated additional muscles. Stimulation at all 34 sites evoked phase-dependent responses in which stimulation in swing produced transient increases in activity in flexor muscles while stimulation during stance produced transient decreases in activity in extensors. Stimulation with long (200 ms) trains of stimuli in swing produced an increased level of activity and duration of flexor muscles without producing changes in cycle duration. In contrast, stimulation during stance decreased the duration of the extensor muscle activity and initiated a new and premature period of swing, resetting the step cycle. Stimulation of the pyramidal tract in two of these three cats as well as in two additional ones produced similar effects. The results show that the motor cortex is capable of influencing hindlimb activity during locomotion in a similar manner to that seen for the forelimb. PMID:15788518

  13. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with Osteogenesis Imperfecta

    PubMed Central

    Jameson, John; Smith, Peter; Harris, Gerald

    2015-01-01

    Osteogenesis Imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64–68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3–42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (p≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight towards understanding bone fragility and the role of intracortical porosity on the strength of bone

  14. Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

    PubMed

    Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

    2014-09-01

    Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3 and 42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (P≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone

  15. Paired-Pulse TMS and Fine-Wire Recordings Reveal Short-Interval Intracortical Inhibition and Facilitation of Deep Multifidus Muscle Fascicles

    PubMed Central

    Massé-Alarie, Hugo; Elgueta Cancino, Edith; Schneider, Cyril; Hodges, Paul

    2016-01-01

    Objective Paired-pulse transcranial magnetic stimulation (ppTMS) is used to probe inhibitory and excitatory networks within the primary motor cortex (M1). These mechanisms are identified for limb muscles but it is unclear whether they share properties with trunk muscles. The aim was to determine whether it was possible to test the intracortical inhibition and facilitation of the deep multifidus muscle fascicles (DM) and at which inter-stimulus intervals (ISI). Methods In ten pain-free individuals, TMS was applied over M1 and motor evoked potentials (MEP) were recorded using fine-wire electrodes in DM. MEPs were conditioned with subthreshold stimuli at ISIs of 1 to 12 ms to test short-interval intracortical inhibition (SICI) and at 15 ms for long-interval intracortical facilitation. Short-interval facilitation (SICF) was tested using 1-ms ISI. Results SICI of DM was consistently obtained with ISI of 1-, 3-, 4- and 12-ms. Facilitation of DM MEP was only identified using SICF paradigm. Conclusions A similar pattern of MEP modulation with ISI changes for deep trunk and limb muscles implies that M1 networks share some functional properties. Significance The ppTMS paradigm presents a potential to determine how M1 inhibitory and excitatory mechanisms participate in brain re-organization in back pain that affects control of trunk muscles. PMID:27509086

  16. A multi-channel telemetry system for brain microstimulation in freely roaming animals.

    PubMed

    Xu, Shaohua; Talwar, Sanjiv K; Hawley, Emerson S; Li, Lei; Chapin, John K

    2004-02-15

    A system is described that enables an experimenter to remotely deliver electrical pulse train stimuli to multiple different locations in the brains of freely moving rats. The system consists of two separate components: a transmitter base station that is controlled by a PC operator, and a receiver-microprocessor integrated pack worn on the back of the animals and which connects to suitably implanted brain locations. The backpack is small and light so that small animal subjects can easily carry it. Under remote command from the PC the backpack can be configured to provide biphasic pulse trains of arbitrarily specified parameters. A feature of the system is that it generates precise brain-stimulation behavioral effects using the direct constant-voltage TTL output of the backpack microprocessor. The system performs with high fidelity even in complex environments over a distance of about 300 m. Rat self-stimulation tests showed that this system produced the same behavioral responses as a conventional constant-current stimulator. This system enables a variety of multi-channel brain stimulation experiments in freely moving animals. We have employed it to develop a new animal behavior model ("virtual" conditioning) for the neurophysiological study of spatial learning, in which a rat can be accurately guided to navigate various terrains. PMID:14757345

  17. A complementary role of intracortical inhibition in age-related tactile degradation and its remodelling in humans.

    PubMed

    Pleger, Burkhard; Wilimzig, Claudia; Nicolas, Volkmar; Kalisch, Tobias; Ragert, Patrick; Tegenthoff, Martin; Dinse, Hubert R

    2016-01-01

    Many attempts are currently underway to restore age-related degraded perception, however, the link between restored perception and remodeled brain function remains elusive. To understand remodeling of age-related cortical reorganization we combined functional magnetic resonance imaging (fMRI) with assessments of tactile acuity, perceptual learning, and computational modeling. We show that aging leads to tactile degradation parallel to enhanced activity in somatosensory cortex. Using a neural field model we reconciled the empirical age-effects by weakening of cortical lateral inhibition. Using perceptual learning, we were able to partially restore tactile acuity, which however was not accompanied by the expected attenuation of cortical activity, but by a further enhancement. The neural field model reproduced these learning effects solely through a weakening of the amplitude of inhibition. These findings suggest that the restoration of age-related degraded tactile acuity on the cortical level is not achieved by re-strengthening lateral inhibition but by further weakening intracortical inhibition. PMID:27302219

  18. A complementary role of intracortical inhibition in age-related tactile degradation and its remodelling in humans

    PubMed Central

    Pleger, Burkhard; Wilimzig, Claudia; Nicolas, Volkmar; Kalisch, Tobias; Ragert, Patrick; Tegenthoff, Martin; Dinse, Hubert R.

    2016-01-01

    Many attempts are currently underway to restore age-related degraded perception, however, the link between restored perception and remodeled brain function remains elusive. To understand remodeling of age-related cortical reorganization we combined functional magnetic resonance imaging (fMRI) with assessments of tactile acuity, perceptual learning, and computational modeling. We show that aging leads to tactile degradation parallel to enhanced activity in somatosensory cortex. Using a neural field model we reconciled the empirical age-effects by weakening of cortical lateral inhibition. Using perceptual learning, we were able to partially restore tactile acuity, which however was not accompanied by the expected attenuation of cortical activity, but by a further enhancement. The neural field model reproduced these learning effects solely through a weakening of the amplitude of inhibition. These findings suggest that the restoration of age-related degraded tactile acuity on the cortical level is not achieved by re-strengthening lateral inhibition but by further weakening intracortical inhibition. PMID:27302219

  19. In vivo simultaneous cortical and intracortical monitoring of cerebral blood flow and mitochondrial redox state in experimental animals

    NASA Astrophysics Data System (ADS)

    Barbiro-Michaely, E.; Zuckerman, T.; Zarchin, N.; Rinkevich, S.; Knoller, N.; Hadani, M.; Mayevsky, A.

    2003-07-01

    Monitoring of intra-mitochondrial NADH redox state is a common in-vivo technique in experimental animals and is rare in clinical studies. The combination of NADH monitoring with the Laser Doppler flowmetry for cerebral blood flow monitoring was described in various publications. Until now, very small effort was made to monitor NADH and CBF inside the cortex of experimental animals. The significance of this monitoring is in its application to experimental models of Parkinson"s disease or to clinical monitoring situations in the intensive care unit, when ICP is monitored. Here we compared the responses of the gerbil or rat brain to oxygen deficiency, monitored on the brain surface and in different depths. After the animals were anesthetized, the two common carotid arteries (gerbil) were isolated and prepared for following occlusion. The brain was exposed and two optical probes were located on its surface. Ischemia was induced by occluding the two carotid arteries, and anoxia was preformed by inhalation of pure N2. After recovery, one of the probes was inserted into the cortex (0.5-3mm) and a second ischemia or anoxia was preformed. The results showed that: 1. It is possible to monitor both CBF and NADH on the brain surface simultaneously with intracortical location. 2. The responses of the brain to ischemia or anoxia was smaller inside the cortex comparing to brain surface. 3. Negative correlation was found between CBF and NADH in both locations and models. In conclusion, this new model of simultaneously monitoring of CBF and NADH in different cerebral locations can shed light on various pathophysiological situations.

  20. Estimation of Thalamocortical and Intracortical Network Models from Joint Thalamic Single-Electrode and Cortical Laminar-Electrode Recordings in the Rat Barrel System

    PubMed Central

    Blomquist, Patrick; Devor, Anna; Indahl, Ulf G.; Ulbert, Istvan; Einevoll, Gaute T.; Dale, Anders M.

    2009-01-01

    A new method is presented for extraction of population firing-rate models for both thalamocortical and intracortical signal transfer based on stimulus-evoked data from simultaneous thalamic single-electrode and cortical recordings using linear (laminar) multielectrodes in the rat barrel system. Time-dependent population firing rates for granular (layer 4), supragranular (layer 2/3), and infragranular (layer 5) populations in a barrel column and the thalamic population in the homologous barreloid are extracted from the high-frequency portion (multi-unit activity; MUA) of the recorded extracellular signals. These extracted firing rates are in turn used to identify population firing-rate models formulated as integral equations with exponentially decaying coupling kernels, allowing for straightforward transformation to the more common firing-rate formulation in terms of differential equations. Optimal model structures and model parameters are identified by minimizing the deviation between model firing rates and the experimentally extracted population firing rates. For the thalamocortical transfer, the experimental data favor a model with fast feedforward excitation from thalamus to the layer-4 laminar population combined with a slower inhibitory process due to feedforward and/or recurrent connections and mixed linear-parabolic activation functions. The extracted firing rates of the various cortical laminar populations are found to exhibit strong temporal correlations for the present experimental paradigm, and simple feedforward population firing-rate models combined with linear or mixed linear-parabolic activation function are found to provide excellent fits to the data. The identified thalamocortical and intracortical network models are thus found to be qualitatively very different. While the thalamocortical circuit is optimally stimulated by rapid changes in the thalamic firing rate, the intracortical circuits are low-pass and respond most strongly to slowly varying

  1. Testing the assumptions underlying fMRI adaptation using intracortical recordings in area MT.

    PubMed

    Kar, Kohitij; Krekelberg, Bart

    2016-07-01

    We investigated how neural activity in the middle temporal area of the macaque monkey changes after 3 sec of exposure to a visual stimulus and used this to gain insight into the assumptions underlying the fMRI adaptation method (fMRIa). We studied both changes in tuning curves following weak and strong motion stimuli (adaptation) and the differences between a first and second exposure to the same stimulus (repetition suppression). Typically, tuning curves had smaller amplitudes and narrower tuning widths after strong adaptation; this was true for single neurons, multi-unit activity (MUA), the evoked local field potential (LFP), as well as gamma band activity. Repetition typically led to reduced responses. This reduction was correlated with direction selectivity and not explained by neural fatigue. Our data, however, warn against a simplistic view of the consequences of adaptation. First, a considerable fraction of neurons and sites showed response enhancements after adaptation, especially when probed with a stimulus that moved opposite to the direction of the adapting stimulus. Second, adaptation was stimulus selective only on a time scale of ∼100 msec. Third, aggregate measures of neural activity (MUA, LFPs) had substantially different adaptation effects. Fourth, there were qualitative differences between our findings in MT and earlier findings in IT cortex. We conclude that selective adaptation effects in fMRIa are relatively easy to miss even when they exist (for instance by presenting stimuli for too long, or because neurons that enhance after adaptation cancel out the effect of neurons that suppress). Moreover, we argue that adaptation should be understood in the context of the computations that a neural circuit perform. Using fMRIa as a tool to uncover neural selectivity requires a better understanding of this circuitry and its consequences for adaptation. PMID:26856637

  2. A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

    PubMed Central

    Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

    2015-01-01

    Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS

  3. Classification of Intended Phoneme Production from Chronic Intracortical Microelectrode Recordings in Speech-Motor Cortex

    PubMed Central

    Brumberg, Jonathan S.; Wright, E. Joe; Andreasen, Dinal S.; Guenther, Frank H.; Kennedy, Philip R.

    2011-01-01

    We conducted a neurophysiological study of attempted speech production in a paralyzed human volunteer using chronic microelectrode recordings. The volunteer suffers from locked-in syndrome leaving him in a state of near-total paralysis, though he maintains good cognition and sensation. In this study, we investigated the feasibility of supervised classification techniques for prediction of intended phoneme production in the absence of any overt movements including speech. Such classification or decoding ability has the potential to greatly improve the quality-of-life of many people who are otherwise unable to speak by providing a direct communicative link to the general community. We examined the performance of three classifiers on a multi-class discrimination problem in which the items were 38 American English phonemes including monophthong and diphthong vowels and consonants. The three classifiers differed in performance, but averaged between 16 and 21% overall accuracy (chance-level is 1/38 or 2.6%). Further, the distribution of phonemes classified statistically above chance was non-uniform though 20 of 38 phonemes were classified with statistical significance for all three classifiers. These preliminary results suggest supervised classification techniques are capable of performing large scale multi-class discrimination for attempted speech production and may provide the basis for future communication prostheses. PMID:21629876

  4. Long-Range Temporal Correlations in the amplitude of alpha oscillations predict and reflect strength of intracortical facilitation: Combined TMS and EEG study.

    PubMed

    Fedele, Tommaso; Blagovechtchenski, Evgeny; Nazarova, Maria; Iscan, Zafer; Moiseeva, Victoria; Nikulin, Vadim V

    2016-09-01

    While variability of the motor responses to transcranial magnetic stimulation (TMS) is widely acknowledged, little is known about its central origin. One plausible explanation for such variability may relate to different neuronal states defining the reactivity of the cortex to TMS. In this study intrinsic spatio-temporal neuronal dynamics were estimated with Long-Range Temporal Correlations (LRTC) in order to predict the inter-individual differences in the strength of intra-cortical facilitation (ICF) and short-interval intracortical inhibition (SICI) produced by paired-pulse TMS (ppTMS) of the left primary motor cortex. LRTC in the alpha frequency range were assessed from multichannel electroencephalography (EEG) obtained at rest before and after the application of and single-pulse TMS (spTMS) and ppTMS protocols. For the EEG session, preceding TMS application, we showed a positive correlation across subjects between the strength of ICF and LRTC in the fronto-central and parietal areas. This in turn attests to the existence of subject-specific neuronal phenotypes defining the reactivity of the brain to ppTMS. In addition, we also showed that ICF was associated with the changes in neuronal dynamics in the EEG session after the application of the stimulation. This result provides a complementary evidence for the recent findings demonstrating that the cortical stimulation with sparse non-regular stimuli might have considerable long-lasting effects on the cortical activity. PMID:27318302

  5. Resistive and reactive changes to the impedance of intracortical microelectrodes can be mitigated with polyethylene glycol under acute in vitro and in vivo settings

    PubMed Central

    Sommakia, Salah; Gaire, Janak; Rickus, Jenna L.; Otto, Kevin J.

    2014-01-01

    The reactive response of brain tissue to implantable intracortical microelectrodes is thought to negatively affect their recordable signal quality and impedance, resulting in unreliable longitudinal performance. The relationship between the progression of the reactive tissue into a glial scar and the decline in device performance is unclear. We show that exposure to a model protein solution in vitro and acute implantation result in both resistive and capacitive changes to electrode impedance, rather than purely resistive changes. We also show that applying 4000 MW polyethylene glycol (PEG) prevents impedance increases in vitro, and reduces the percent change in impedance in vivo following implantation. Our results highlight the importance of considering the contributions of non-cellular components to the decline in neural microelectrode performance, and present a proof of concept for using a simple dip-coated PEG film to modulate changes in microelectrode impedance. PMID:25136315

  6. Spinal primitives and intra-spinal micro-stimulation (ISMS) based prostheses: a neurobiological perspective on the “known unknowns” in ISMS and future prospects

    PubMed Central

    Giszter, Simon F.

    2015-01-01

    The current literature on Intra-Spinal Micro-Stimulation (ISMS) for motor prostheses is reviewed in light of neurobiological data on spinal organization, and a neurobiological perspective on output motor modularity, ISMS maps, stimulation combination effects, and stability. By comparing published data in these areas, the review identifies several gaps in current knowledge that are crucial to the development of effective intraspinal neuroprostheses. Gaps can be categorized into a lack of systematic and reproducible details of: (a) Topography and threshold for ISMS across the segmental motor system, the topography of autonomic recruitment by ISMS, and the coupling relations between these two types of outputs in practice. (b) Compositional rules for ISMS motor responses tested across the full range of the target spinal topographies. (c) Rules for ISMS effects' dependence on spinal cord state and neural dynamics during naturally elicited or ISMS triggered behaviors. (d) Plasticity of the compositional rules for ISMS motor responses, and understanding plasticity of ISMS topography in different spinal cord lesion states, disease states, and following rehabilitation. All these knowledge gaps to a greater or lesser extent require novel electrode technology in order to allow high density chronic recording and stimulation. The current lack of this technology may explain why these prominent gaps in the ISMS literature currently exist. It is also argued that given the “known unknowns” in the current ISMS literature, it may be prudent to adopt and develop control schemes that can manage the current results with simple superposition and winner-take-all interactions, but can also incorporate the possible plastic and stochastic dynamic interactions that may emerge in fuller analyses over longer terms, and which have already been noted in some simpler model systems. PMID:25852454

  7. Spatiotemporal Profile of Voltage-Sensitive Dye Responses in the Visual Cortex of Tree Shrews Evoked by Electric Microstimulation of the Dorsal Lateral Geniculate and Pulvinar Nuclei

    PubMed Central

    Thomas, Sébastien; Petry, Heywood M.; Bickford, Martha E.; Casanova, Christian

    2015-01-01

    The primary visual cortex (V1) receives its main thalamic drive from the dorsal lateral geniculate nucleus (dLGN) through synaptic contacts terminating primarily in cortical layer IV. In contrast, the projections from the pulvinar nucleus to the cortex are less clearly defined. The pulvinar projects predominantly to layer I in V1, and layer IV in extrastriate areas. These projection patterns suggest that the pulvinar nucleus most strongly influences (drives) activity in cortical areas beyond V1. Should this hypothesis be true, one would expect the spatiotemporal responses evoked by pulvinar activation to be different in V1 and extrastriate areas, reflecting the different connectivity patterns. We investigated this issue by analyzing the spatiotemporal dynamics of cortical visual areas' activity following thalamic electrical microstimulation in tree shrews, using optical imaging and voltage-sensitive dyes. As expected, electrical stimulation of the dLGN induced fast and local responses in V1, as well as in extrastriate and contralateral cortical areas. In contrast, electrical stimulation of the pulvinar induced fast and local responses in extrastriate areas, followed by weak and diffuse activation in V1 and contralateral cortical areas. This study highlights spatiotemporal cortical activation characteristics induced by stimulation of first (dLGN) and high-order (pulvinar) thalamic nuclei. SIGNIFICANCE STATEMENT The pulvinar nucleus represents the main extrageniculate thalamic visual structure in higher-order mammals, but its exact role remains enigmatic. The pulvinar receive prominent inputs from virtually all visual cortical areas. Cortico-thalamo-cortical pathways through the pulvinar nuclei may then provide a complementary route for corticocortical information flow. One step toward the understanding of the role of transthalamic corticocortical pathways is to determine the nature of the signals transmitted between the cortex and the thalamus. By performing, for

  8. Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array.

    PubMed

    Simeral, J D; Kim, S-P; Black, M J; Donoghue, J P; Hochberg, L R

    2011-04-01

    The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point

  9. Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

    NASA Astrophysics Data System (ADS)

    Simeral, J. D.; Kim, S.-P.; Black, M. J.; Donoghue, J. P.; Hochberg, L. R.

    2011-04-01

    The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point

  10. Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

    PubMed Central

    Simeral, J D; Kim, S-P; Black, M J; Donoghue, J P; Hochberg, L R

    2013-01-01

    The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point

  11. Large-scale cortical reorganization following forelimb deafferentation in rat does not involve plasticity of intracortical connections.

    PubMed

    Pearson, P P; Arnold, P B; Oladehin, A; Li, C X; Waters, R S

    2001-05-01

    Physiological mapping of the body representation 1 month or longer after forelimb removal in adult rats revealed new pockets of shoulder representation in the forepaw barrel subfield (FBS) in the first somatosensory cortex (SI). These "new" shoulder representations have longer evoked response latencies than sites in the shoulder representation within the trunk subfield, hereafter referred to as the "original" shoulder representation. We postulated that the "new" shoulder representations in the FBS were relayed from the "original" shoulder representation. We investigated this hypothesis by studying anatomical connectivity between the "original" shoulder representation and the FBS in intact control and forelimb deafferented adult rats using Phaseolus vulgaris leucoagglutinin (PHA-L), biocytin, and biotin dextran-amine (BDA) as anterograde tracers. The retrograde tracer cholera toxin beta subunit (CT-B) injected into the FBS was also used to study connectivity between the "original" shoulder representation and the FBS. Using these anatomical tracing techniques, we were unable to show the existence of a direct corticocortical connection between the "original" shoulder representation in the trunk subfield and the FBS in either intact or deafferented rats. Functional connectivity between the two cortical regions was studied by ablating the "original" shoulder representation alone or in combination with the shoulder representation in the second somatosensory cortex (SII) while recording evoked responses in the FBS following electrical stimulation of the shoulder. Both ablations failed to eliminate the evoked responses at the "new" shoulder sites in the FBS, suggesting that SI and SII are not necessary for "new" shoulder input in the FBS. It is suggested that subcortical sites may play a major role in large-scale cortical reorganization. Results of projections from the "original" shoulder representation to parietal medial (PM), parietal lateral (PL), SII, parietal ventral

  12. Comparable patterns of muscle facilitation evoked by individual corticomotoneuronal (CM) cells and by single intracortical microstimuli in primates: evidence for functional groups of CM cells.

    PubMed

    Cheney, P D; Fetz, E E

    1985-03-01

    We compared the averaged responses of forelimb muscles to action potentials of single motor cortex cells and to single intracortical microstimuli (S-ICMS). Activity of precentral neurons and 12 identified forelimb muscles (6 flexors and 6 extensors of wrist and fingers) was recorded in macaques while they performed alternating ramp-and-hold wrist movements. Action potentials of cells that covaried reliably with wrist flexion or extension were used to compile spike-triggered averages (spike-TAs) of rectified electromyographic (EMG) activity of six synergistically coactivated muscles. Cells whose spikes were followed by a clear postspike facilitation (PSF) of rectified muscle activity were designated corticomotoneuronal (CM) cells. CM cells typically facilitated a subset of the coactivated muscles called the cell's target muscles. The relative strength of the PSF in different target muscles ranged from clear increases above base-line fluctuations to weak but significant effects. For each CM cell we characterized the "PSF profile" of facilitation across different muscles, defined as the relative strength of PSF in each of the coactivated agonist muscles. After identifying the CM cell's target muscles, we delivered S-ICMS through the microelectrode at the same site. Biphasic stimuli were delivered during the same wrist movements in which the recorded CM cell had been active. Stimulus intensities were too weak (typically 5-10 microA) and their repetition rate too slow (5-15 Hz) to evoke muscle excitation evident in the raw EMG record. However, stimulus-triggered averages (stimulus-TAs) of the rectified EMGs of coactivated muscles revealed consistent patterns of poststimulus facilitation (PStimF). In most cases the muscles facilitated by the CM cell in spike-TAs (n = 60) were also facilitated by S-ICMS in stimulus-TAs. At sites of CM cells the threshold stimulus intensities for evoking a statistically significant effect were between 0.5 and 2 microA. S-ICMS of 5 micro

  13. Intracortical and Thalamocortical Connections of the Hand and Face Representations in Somatosensory Area 3b of Macaque Monkeys and Effects of Chronic Spinal Cord Injuries.

    PubMed

    Chand, Prem; Jain, Neeraj

    2015-09-30

    Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at cervical levels undergo large-scale reorganization. Reorganization results in expansion of intact chin inputs, which reactivate neurons in the deafferented hand representation in the primary somatosensory cortex (area 3b), ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A likely contributing mechanism for this large-scale plasticity is sprouting of axons across the hand-face border. Here we determined whether such sprouting takes place in area 3b. We first determined the extent of intrinsic corticocortical connectivity between the hand and the face representations in normal area 3b. Small amounts of neuroanatomical tracers were injected in these representations close to the electrophysiologically determined hand-face border. Locations of the labeled neurons were mapped with respect to the detailed electrophysiological somatotopic maps and histologically determined hand-face border revealed in sections of the flattened cortex stained for myelin. Results show that intracortical projections across the hand-face border are few. In monkeys with chronic unilateral lesions of the dorsal columns and expanded chin representation, connections across the hand-face border were not different compared with normal monkeys. Thalamocortical connections from the hand and face representations in the ventroposterior nucleus to area 3b also remained unaltered after injury. The results show that sprouting of intrinsic connections in area 3b or the thalamocortical inputs does not contribute to large-scale cortical plasticity. Significance statement: Long-term injuries to dorsal spinal cord in adult primates result in large-scale somatotopic reorganization due to which chin inputs expand into the deafferented hand region. Reorganization takes place in multiple cortical areas, and thalamic and medullary nuclei. To what extent this brain reorganization due to dorsal column injuries

  14. Different Current Intensities of Anodal Transcranial Direct Current Stimulation Do Not Differentially Modulate Motor Cortex Plasticity

    PubMed Central

    Kidgell, Dawson J.; Daly, Robin M.; Young, Kayleigh; Lum, Jarrod; Tooley, Gregory; Jaberzadeh, Shapour; Zoghi, Maryam; Pearce, Alan J.

    2013-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities. PMID:23577272

  15. Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis

    PubMed Central

    Grahn, Peter J.; Mallory, Grant W.; Berry, B. Michael; Hachmann, Jan T.; Lobel, Darlene A.; Lujan, J. Luis

    2014-01-01

    Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. PMID:25278830

  16. Rewiring Neural Interactions by Micro-Stimulation

    PubMed Central

    Rebesco, James M.; Stevenson, Ian H.; Körding, Konrad P.; Solla, Sara A.; Miller, Lee E.

    2010-01-01

    Plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. In vitro, associative pairing of presynaptic spiking and stimulus-induced postsynaptic depolarization causes changes in the synaptic efficacy of the presynaptic neuron, when activated by extrinsic stimulation. In vivo, such paradigms can alter the responses of whole groups of neurons to stimulation. Here, we used in vivo spike-triggered stimulation to drive plastic changes in rat forelimb sensorimotor cortex, which we monitored using a statistical measure of functional connectivity inferred from the spiking statistics of the neurons during normal, spontaneous behavior. These induced plastic changes in inferred functional connectivity depended on the latency between trigger spike and stimulation, and appear to reflect a robust reorganization of the network. Such targeted connectivity changes might provide a tool for rerouting the flow of information through a network, with implications for both rehabilitation and brain–machine interface applications. PMID:20838477

  17. An implantable neural stimulator for intraspinal microstimulation.

    PubMed

    Troyk, Philip R; Mushahwar, Vivian K; Stein, Richard B; Suh, Sungjae; Everaert, Dirk; Holinski, Brad; Hu, Zhe; DeMichele, Glenn; Kerns, Douglas; Kayvani, Kevin

    2012-01-01

    This paper reports on a wireless stimulator device for use in animal experiments as part of an ongoing investigation into intraspinal stimulation (ISMS) for restoration of walking in humans with spinal cord injury. The principle behind using ISMS is the activation of residual motor-control neural networks within the spinal cord ventral horn below the level of lesion following a spinal cord injury. The attractiveness to this technique is that a small number of electrodes can be used to induce bilateral walking patterns in the lower limbs. In combination with advanced feedback algorithms, ISMS has the potential to restore walking for distances that exceed that produced by other types of functional electrical stimulation. Recent acute animal experiments have demonstrated the feasibility of using ISMS to produce the coordinated walking patterns. Here we described a wireless implantable stimulation system to be used in chronic animal experiments and for providing the basis for a system suitable for use in humans. Electrical operation of the wireless system is described, including a demonstration of reverse telemetry for monitoring the stimulating electrode voltages. PMID:23366038

  18. Approaches to a cortical vision prosthesis: implications of electrode size and placement

    NASA Astrophysics Data System (ADS)

    Christie, Breanne P.; Ashmont, Kari R.; House, Paul A.; Greger, Bradley

    2016-04-01

    Objective. In order to move forward with the development of a cortical vision prosthesis, the critical issues in the field must be identified. Approach. To begin this process, we performed a brief review of several different cortical and retinal stimulation techniques that can be used to restore vision. Main results. Intracortical microelectrodes and epicortical macroelectrodes have been evaluated as the basis of a vision prosthesis. We concluded that an important knowledge gap necessitates an experimental in vivo performance evaluation of microelectrodes placed on the surface of the visual cortex. A comparison of the level of vision restored by intracortical versus epicortical microstimulation is necessary. Because foveal representation in the primary visual cortex involves more cortical columns per degree of visual field than does peripheral vision, restoration of foveal vision may require a large number of closely spaced microelectrodes. Based on previous studies of epicortical macrostimulation, it is possible that stimulation via surface microelectrodes could produce a lower spatial resolution, making them better suited for restoring peripheral vision. Significance. The validation of epicortical microstimulation in addition to the comparison of epicortical and intracortical approaches for vision restoration will fill an important knowledge gap and may have important implications for surgical strategies and device longevity. It is possible that the best approach to vision restoration will utilize both epicortical and intracortical microstimulation approaches, applying them appropriately to different visual representations in the primary visual cortex.

  19. Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex

    NASA Astrophysics Data System (ADS)

    Perge, János A.; Zhang, Shaomin; Malik, Wasim Q.; Homer, Mark L.; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N.; Donoghue, John P.; Hochberg, Leigh R.

    2014-08-01

    Objective. Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach. We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results. We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). Significance. Field potentials provided comparable

  20. An online brain-machine interface using decoding of movement direction from the human electrocorticogram

    NASA Astrophysics Data System (ADS)

    Milekovic, Tomislav; Fischer, Jörg; Pistohl, Tobias; Ruescher, Johanna; Schulze-Bonhage, Andreas; Aertsen, Ad; Rickert, Jörn; Ball, Tonio; Mehring, Carsten

    2012-08-01

    A brain-machine interface (BMI) can be used to control movements of an artificial effector, e.g. movements of an arm prosthesis, by motor cortical signals that control the equivalent movements of the corresponding body part, e.g. arm movements. This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single neurons. We show that the same approach can be realized using brain activity measured directly from the surface of the human cortex using electrocorticography (ECoG). Five subjects, implanted with ECoG implants for the purpose of epilepsy assessment, took part in our study. Subjects used directionally dependent ECoG signals, recorded during active movements of a single arm, to control a computer cursor in one out of two directions. Significant BMI control was achieved in four out of five subjects with correct directional decoding in 69%-86% of the trials (75% on average). Our results demonstrate the feasibility of an online BMI using decoding of movement direction from human ECoG signals. Thus, to achieve such BMIs, ECoG signals might be used in conjunction with or as an alternative to intracortical neural signals.

  1. Perceiving invisible light through a somatosensory cortical prosthesis.

    PubMed

    Thomson, Eric E; Carra, Rafael; Nicolelis, Miguel A L

    2013-01-01

    Sensory neuroprostheses show great potential for alleviating major sensory deficits. It is not known, however, whether such devices can augment the subject's normal perceptual range. Here we show that adult rats can learn to perceive otherwise invisible infrared light through a neuroprosthesis that couples the output of a head-mounted infrared sensor to their somatosensory cortex (S1) via intracortical microstimulation. Rats readily learn to use this new information source, and generate active exploratory strategies to discriminate among infrared signals in their environment. S1 neurons in these infrared-perceiving rats respond to both whisker deflection and intracortical microstimulation, suggesting that the infrared representation does not displace the original tactile representation. Hence, sensory cortical prostheses, in addition to restoring normal neurological functions, may serve to expand natural perceptual capabilities in mammals. PMID:23403583

  2. Directing 101.

    ERIC Educational Resources Information Center

    Pintoff, Ernest

    Providing an introduction to anyone considering directing as a field of study or career, this book takes a broad look at the process of directing and encourages students and professionals alike to look outside of the movie industry for inspiration. Chapters in the book discuss selecting and acquiring material; budgeting and financing; casting and…

  3. Advance directives

    PubMed Central

    O’Sullivan, Rory; Mailo, Kevin; Angeles, Ricardo; Agarwal, Gina

    2015-01-01

    Abstract Objective To establish the prevalence of patients with advance directives in a family practice, and to describe patients’ perspectives on a family doctor’s role in initiating discussions about advance directives. Design A self-administered patient questionnaire. Setting A busy urban family medicine teaching clinic in Hamilton, Ont. Participants A convenience sample of adult patients attending the clinic over the course of a typical business week. Main outcome measures The prevalence of advance directives in the patient population was determined, and the patients’ expectations regarding the role of their family doctors were elucidated. Results The survey population consisted of 800 participants (a response rate of 72.5%) well distributed across age groups; 19.7% had written advance directives and 43.8% had previously discussed the topic of advance directives, but only 4.3% of these discussions had occurred with family doctors. In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents believed patients should initiate the discussion. Patients who considered advance directives extremely important were significantly more likely to want their family doctors to start the conversation (odds ratio 3.98; P < .05). Conclusion Advance directives were not routinely addressed in the family practice. Most patients preferred to initiate the discussion of advance directives. However, patients who considered the subject extremely important wanted their family doctors to initiate the discussion. PMID:25873704

  4. Resonance of cortico-cortical connections of the motor system with the observation of goal directed grasping movements.

    PubMed

    Koch, Giacomo; Versace, Viviana; Bonnì, Sonia; Lupo, Federica; Lo Gerfo, Emanuele; Oliveri, Massimiliano; Caltagirone, Carlo

    2010-10-01

    Goal directed movements require the activation of parietal, premotor and primary motor areas. In monkeys, neurons of these areas become active also during the observation of movements performed by others, especially for coding the goal of the action (mirror system). Using bifocal transcranial magnetic stimulation (TMS) in healthy subjects, we tested whether the observation of goal directed reach to grasp actions may lead to specific changes in the short-latency connections linking key areas of the mirror system, such as the anterior intraparietal cortex (AIP) and the ventral premotor cortex (PMv), with the primary motor cortex (M1). We found that AIP-M1 and PMv-M1 cortico-cortical interactions were specifically activated when observing successful reaching to grasp goal directed actions, in which the hand posture was congruent with the goal of the action performed by the actor. On the other hand they were not modified when the same goal directed actions were performed wrongly with an inappropriate grasping posture. A similar profile of excitability was observed when testing specific intracortical facilitatory circuits in M1 (I(2)-waves), known to reflect the activity in cortico-cortical pathways transmitting information from PMv. We conclude that the simple observation of others' goal directed actions is able to induce specific neurophysiological changes in some cortico-cortical circuits of the human motor system. PMID:20691198

  5. TMS reveals a direct influence of spinal projections from human SMAp on precise force production.

    PubMed

    Entakli, Jonathan; Bonnard, Mireille; Chen, Sophie; Berton, Eric; De Graaf, Jozina B

    2014-01-01

    The corticospinal (CS) system plays an important role in fine motor control, especially in precision grip tasks. Although the primary motor cortex (M1) is the main source of the CS projections, other projections have been found, especially from the supplementary motor area proper (SMAp). To study the characteristics of these CS projections from SMAp, we compared muscle responses of an intrinsic hand muscle (FDI) evoked by stimulation of human M1 and SMAp during an isometric static low-force control task. Subjects were instructed to maintain a small cursor on a target force curve by applying a pressure with their right precision grip on a force sensor. Neuronavigated transcranial magnetic stimulation was used to stimulate either left M1 or left SMAp with equal induced electric field values at the defined cortical targets. The results show that the SMAp stimulation evokes reproducible muscle responses with similar latencies and amplitudes as M1 stimulation, and with a clear and significant shorter silent period. These results suggest that (i) CS projections from human SMAp are as rapid and efficient as those from M1, (ii) CS projections from SMAp are directly involved in control of the excitability of spinal motoneurons and (iii) SMAp has a different intracortical inhibitory circuitry. We conclude that human SMAp and M1 both have direct influence on force production during fine manual motor tasks. PMID:24164635

  6. DIRECTIONAL COUPLERS

    DOEpatents

    Nigg, D.J.

    1961-12-01

    A directional coupler of small size is designed. Stripline conductors of non-rectilinear configuration, and separated from each other by a thin dielectric spacer. cross each other at least at two locations at right angles, thus providing practically pure capacitive coupling which substantially eliminates undesirable inductive coupling. The conductors are sandwiched between a pair of ground planes. The coupling factor is dependent only on the thickness and dielectric constant of the dielectric spacer at the point of conductor crossover. (AEC)

  7. DIRECTIONAL ANTENNA

    DOEpatents

    Bittner, B.J.

    1958-05-20

    A high-frequency directional antenna of the 360 d scaring type is described. The antenna has for its desirable features the reduction in both size and complexity of the mechanism for rotating the antenna through its scanning movement. These advantages result from the rotation of only the driven element, the reflector remaining stationary. The particular antenna structure comprises a refiector formed by a plurality of metallic slats arranged in the configuration of an annular cage having the shape of a zone of revolution. The slats are parallel to each other and are disposed at an angle of 45 d to the axis of the cage. A directional radiator is disposed inside the cage at an angle of 45 d to the axis of the cage in the same direction as the reflecting slats which it faces. As the radiator is rotated, the electromagnetic wave is reflected from the slats facing the radiator and thereafter passes through the cage on the opposite side, since these slats are not parallel with the E vector of the wave.

  8. Modulation of Cortical Inhibitory Circuits after Cathodal Transcranial Direct Current Stimulation over the Primary Motor Cortex

    PubMed Central

    Sasaki, Ryoki; Miyaguchi, Shota; Kotan, Shinichi; Kojima, Sho; Kirimoto, Hikari; Onishi, Hideaki

    2016-01-01

    Here, we aimed to evaluate whether cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and primary somatosensory cortex (S1) can modulate cortical inhibitory circuits. Sixteen healthy subjects participated in this study. Cathodal tDCS was positioned over the left M1 (M1 cathodal) or left S1 (S1 cathodal) with an intensity of 1 mA for 10 min. Sham tDCS was applied for 10 min over the left M1 (sham). Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were recorded from the right abductor pollicis brevis (APB) muscle before the intervention (pre) and 10 and 30 min after the intervention (post 1 and post 2, respectively). Cortical inhibitory circuits were evaluated using short-interval intracortical inhibition (SICI) and short-latency afferent inhibition (SAI). M1 cathodal decreased single-pulse MEP amplitudes at post 1 and decreased SAI at post 1 and post 2; however, SICI did not exhibit any change. S1 cathodal and sham did not show any changes in MEP amplitudes at any of the three time points. These results demonstrated that cathodal tDCS over the M1 not only decreases the M1 excitability but also affects the cortical inhibitory circuits related to SAI. PMID:26869909

  9. Direct ELISA.

    PubMed

    Lin, Alice V

    2015-01-01

    First described by Engvall and Perlmann, the enzyme-linked immunosorbent assay (ELISA) is a rapid and sensitive method for detection and quantitation of an antigen using an enzyme-labeled antibody. Besides routine laboratory usage, ELISA has been utilized in medical field and food industry as diagnostic and quality control tools. Traditionally performed in 96-well or 384-well polystyrene plates, the technology has expanded to other platforms with increase in automation. Depending on the antigen epitope and availability of specific antibody, there are variations in ELISA setup. The four basic formats are direct, indirect, sandwich, and competitive ELISAs. Direct ELISA is the simplest format requiring an antigen and an enzyme-conjugated antibody specific to the antigen. This chapter describes the individual steps for detection of a plate-bound antigen using a horseradish peroxidase (HRP)-conjugated antibody and luminol-based enhanced chemiluminescence (ECL) substrate. The methodological approach to optimize the assay by chessboard titration is also provided. PMID:26160564

  10. Direct cervicoplasty.

    PubMed

    Jordan, J Randall

    2012-02-01

    The sagging neck, or "turkey gobbler" deformity, is one of the more common reasons that patients present to facial plastic surgeons. Although many of these patients might be best improved by a full rhytidectomy with periauricular incisions, skin flap undermining, and platysmal tightening, there are some patients who do not wish to undergo a full rhytidectomy. Some of these patients may be reasonably well served by a direct cervicoplasty or submentoplasty. The advantages of this approach include shorter operative time, faster recovery, and lower complication rates. The primary disadvantage is an anterior cervical incision that may be visible under some conditions. This article will review the options for skin incisions as well as technical details that may lead to a successful rejuvenation of the submental region. PMID:22418816

  11. Future direction of direct writing

    NASA Astrophysics Data System (ADS)

    Kim, Nam-Soo; Han, Kenneth N.

    2010-11-01

    Direct write technology using special inks consisting of finely dispersed metal nanoparticles in liquid is receiving an undivided attention in recent years for its wide range of applicability in modern electronic industry. The application of this technology covers radio frequency identification-tag (RFID-tag), flexible-electronics, organic light emitting diodes (OLED) display, e-paper, antenna, bumpers used in flip-chip, underfilling, frit, miniresistance applications and biological uses, artificial dental applications and many more. In this paper, the authors have reviewed various direct write technologies on the market and discussed their advantages and shortfalls. Emphasis has given on microdispensing deposition write (MDDW), maskless mesoscale materials deposition (M3D), and ink-jet technologies. All of these technologies allow printing various patterns without employing a mask or a resist with an enhanced speed with the aid of computer. MDDW and M3D are capable of drawing patterns in three-dimension and MDDW, in particular, is capable of writing nanoinks with high viscosity. However, it is still far away for direct write to be fully implemented in the commercial arena. One of the hurdles to overcome is in manufacturing conductive inks which are chemically and physically stable, capable of drawing patterns with acceptable conductivity, and also capable of drawing patterns with acceptable adhesiveness with the substrates. The authors have briefly discussed problems involved in manufacturing nanometal inks to be used in various writing devices. There are numerous factors to be considered in manufacturing such inks. They are reducing agents, concentrations, oxidation, compact ability allowing good conductivity, and stability in suspension.

  12. Direct cervicoplasty.

    PubMed

    Jordan, J Randall; Yellin, Seth

    2014-08-01

    Rejuvenation of the aging neck is one of the common reasons for the patients presented to facial plastic surgeons. In the author's opinion, most of these patients will be best served by a full rhytidectomy approach with periauricular incisions, skin flap undermining, and platysmaplasty. There is a subset of patients, however, who presented with complaints limited to the so-called Turkey Gobbler deformity, and who do not wish to undergo a full rhytidectomy approach. These patients may be well served by a lesser procedure such as a direct cervicoplasty or submentoplasty. The advantages of this approach include shorter operative time, faster recovery, and lower complication rates. The primary disadvantage of these more limited approaches is that there is an anterior cervical scar that may be visible under some conditions. This article will review the multiple options for skin incisions as well as details of the technique that the authors have found may lead to a successful rejuvenation of the submental region. PMID:25076453

  13. The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity

    PubMed Central

    Amadi, Ugwechi; Allman, Claire; Johansen-Berg, Heidi; Stagg, Charlotte J.

    2015-01-01

    Background The relative timing of plasticity-induction protocols is known to be crucial. For example, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability and typically enhances plasticity, can impair performance if it is applied before a motor learning task. Such timing-dependent effects have been ascribed to homeostatic plasticity, but the specific synaptic site of this interaction remains unknown. Objective We wished to investigate the synaptic substrate, and in particular the role of inhibitory signaling, underpinning the behavioral effects of anodal tDCS in homeostatic interactions between anodal tDCS and motor learning. Methods We used transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibitory signaling following tDCS and motor learning. Each subject participated in four experimental sessions and data were analyzed using repeated measures ANOVAs and post-hoc t-tests as appropriate. Results As predicted, we found that anodal tDCS prior to the motor task decreased learning rates. This worsening of learning after tDCS was accompanied by a correlated increase in GABAA activity, as measured by TMS-assessed short interval intra-cortical inhibition (SICI). Conclusion This provides the first direct demonstration in humans that inhibitory synapses are the likely site for the interaction between anodal tDCS and motor learning, and further, that homeostatic plasticity at GABAA synapses has behavioral relevance in humans. PMID:26279408

  14. Behavioral demonstration of a somatosensory neuroprosthesis.

    PubMed

    Berg, J A; Dammann, J F; Tenore, F V; Tabot, G A; Boback, J L; Manfredi, L R; Peterson, M L; Katyal, K D; Johannes, M S; Makhlin, A; Wilcox, R; Franklin, R K; Vogelstein, R J; Hatsopoulos, N G; Bensmaia, S J

    2013-05-01

    Tactile sensation is critical for effective object manipulation, but current prosthetic upper limbs make no provision for delivering somesthetic feedback to the user. For individuals who require use of prosthetic limbs, this lack of feedback transforms a mundane task into one that requires extreme concentration and effort. Although vibrotactile motors and sensory substitution devices can be used to convey gross sensations, a direct neural interface is required to provide detailed and intuitive sensory feedback. In light of this, we describe the implementation of a somatosensory prosthesis with which we elicit, through intracortical microstimulation (ICMS), percepts whose magnitude is graded according to the force exerted on the prosthetic finger. Specifically, the prosthesis consists of a sensorized finger, the force output of which is converted into a regime of ICMS delivered to primary somatosensory cortex through chronically implanted multi-electrode arrays. We show that the performance of animals (Rhesus macaques) on a tactile task is equivalent whether stimuli are delivered to the native finger or to the prosthetic finger. PMID:23475375

  15. Review of Brain-Machine Interfaces Used in Neural Prosthetics with New Perspective on Somatosensory Feedback through Method of Signal Breakdown.

    PubMed

    Vidal, Gabriel W Vattendahl; Rynes, Mathew L; Kelliher, Zachary; Goodwin, Shikha Jain

    2016-01-01

    The brain-machine interface (BMI) used in neural prosthetics involves recording signals from neuron populations, decoding those signals using mathematical modeling algorithms, and translating the intended action into physical limb movement. Recently, somatosensory feedback has become the focus of many research groups given its ability in increased neural control by the patient and to provide a more natural sensation for the prosthetics. This process involves recording data from force sensitive locations on the prosthetics and encoding these signals to be sent to the brain in the form of electrical stimulation. Tactile sensation has been achieved through peripheral nerve stimulation and direct stimulation of the somatosensory cortex using intracortical microstimulation (ICMS). The initial focus of this paper is to review these principles and link them to modern day applications such as restoring limb use to those who lack such control. With regard to how far the research has come, a new perspective for the signal breakdown concludes the paper, offering ideas for more real somatosensory feedback using ICMS to stimulate particular sensations by differentiating touch sensors and filtering data based on unique frequencies. PMID:27313959

  16. [Artificial Feedback for Invasive Brain-Computer Interfaces].

    PubMed

    Badakva, A M; Miller, N V; Zobova, L N

    2016-01-01

    During the last two decades, considerable progress has been made in the studies of brain-computer interfaces (BCIs)--devices in which motor signals from the brain are registered by multi-electrode arrays and transformed into commands for articial actuators such as cursors and robotic devices. This review is focused on one problem. Voluntary motor control is based on neurophysiological processes which depend heavily on the afferent innervation of skin, muscles and joints. Thus, invasive BCI has to be based on a bidirectional system in which motor control signals are registered by multi-channel micro-electrodes implanted in motor areas, while tactile, proprioceptive and other useful signals are transported back to the brain through spatial-temporal patterns of intracortical microstimulation (ICMS) delivered to sensory areas. In general, the studies of invasive BCIs have advanced in several directions. The progress of BCIs with articial sensory feedback will not only help patients, but will also expand knowledge base in the field of human cortical functions. PMID:27188155

  17. Review of Brain-Machine Interfaces Used in Neural Prosthetics with New Perspective on Somatosensory Feedback through Method of Signal Breakdown

    PubMed Central

    Vidal, Gabriel W. Vattendahl; Rynes, Mathew L.; Kelliher, Zachary; Goodwin, Shikha Jain

    2016-01-01

    The brain-machine interface (BMI) used in neural prosthetics involves recording signals from neuron populations, decoding those signals using mathematical modeling algorithms, and translating the intended action into physical limb movement. Recently, somatosensory feedback has become the focus of many research groups given its ability in increased neural control by the patient and to provide a more natural sensation for the prosthetics. This process involves recording data from force sensitive locations on the prosthetics and encoding these signals to be sent to the brain in the form of electrical stimulation. Tactile sensation has been achieved through peripheral nerve stimulation and direct stimulation of the somatosensory cortex using intracortical microstimulation (ICMS). The initial focus of this paper is to review these principles and link them to modern day applications such as restoring limb use to those who lack such control. With regard to how far the research has come, a new perspective for the signal breakdown concludes the paper, offering ideas for more real somatosensory feedback using ICMS to stimulate particular sensations by differentiating touch sensors and filtering data based on unique frequencies. PMID:27313959

  18. Active tactile exploration using a brain-machine-brain interface.

    PubMed

    O'Doherty, Joseph E; Lebedev, Mikhail A; Ifft, Peter J; Zhuang, Katie Z; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A L

    2011-11-10

    Brain-machine interfaces use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses. PMID:21976021

  19. Voltage-sensitive dye imaging of primary motor cortex activity produced by ventral tegmental area stimulation.

    PubMed

    Kunori, Nobuo; Kajiwara, Riichi; Takashima, Ichiro

    2014-06-25

    The primary motor cortex (M1) receives dopaminergic projections from the ventral tegmental area (VTA) through the mesocortical dopamine pathway. However, few studies have focused on changes in M1 neuronal activity caused by VTA activation. To address this issue, we used voltage-sensitive dye imaging (VSD) to reveal the spatiotemporal dynamics of M1 activity induced by single-pulse stimulation of VTA in anesthetized rats. VSD imaging showed that brief electrical stimulation of unilateral VTA elicited a short-latency excitatory-inhibitory sequence of neuronal activity not only in the ipsilateral but also in the contralateral M1. The contralateral M1 response was not affected by pharmacological blockade of ipsilateral M1 activity, but it was completely abolished by corpus callosum transection. Although the VTA-evoked neuronal activity extended throughout the entire M1, we found the most prominent activity in the forelimb area of M1. The 6-OHDA-lesioned VTA failed to evoke M1 activity. Furthermore, both excitatory and inhibitory intact VTA-induced activity was entirely extinguished by blocking glutamate receptors in the target M1. When intracortical microstimulation of M1 was paired with VTA stimulation, the evoked forelimb muscle activity was facilitated or inhibited, depending on the interval between the two stimuli. These findings suggest that VTA neurons directly modulate the excitability of M1 neurons via fast glutamate signaling and, consequently, may control the last cortical stage of motor command processing. PMID:24966388

  20. Building an organic computing device with multiple interconnected brains.

    PubMed

    Pais-Vieira, Miguel; Chiuffa, Gabriela; Lebedev, Mikhail; Yadav, Amol; Nicolelis, Miguel A L

    2015-01-01

    Recently, we proposed that Brainets, i.e. networks formed by multiple animal brains, cooperating and exchanging information in real time through direct brain-to-brain interfaces, could provide the core of a new type of computing device: an organic computer. Here, we describe the first experimental demonstration of such a Brainet, built by interconnecting four adult rat brains. Brainets worked by concurrently recording the extracellular electrical activity generated by populations of cortical neurons distributed across multiple rats chronically implanted with multi-electrode arrays. Cortical neuronal activity was recorded and analyzed in real time, and then delivered to the somatosensory cortices of other animals that participated in the Brainet using intracortical microstimulation (ICMS). Using this approach, different Brainet architectures solved a number of useful computational problems, such as discrete classification, image processing, storage and retrieval of tactile information, and even weather forecasting. Brainets consistently performed at the same or higher levels than single rats in these tasks. Based on these findings, we propose that Brainets could be used to investigate animal social behaviors as well as a test bed for exploring the properties and potential applications of organic computers. PMID:26158615

  1. Building an organic computing device with multiple interconnected brains

    PubMed Central

    Pais-Vieira, Miguel; Chiuffa, Gabriela; Lebedev, Mikhail; Yadav, Amol; Nicolelis, Miguel A. L.

    2015-01-01

    Recently, we proposed that Brainets, i.e. networks formed by multiple animal brains, cooperating and exchanging information in real time through direct brain-to-brain interfaces, could provide the core of a new type of computing device: an organic computer. Here, we describe the first experimental demonstration of such a Brainet, built by interconnecting four adult rat brains. Brainets worked by concurrently recording the extracellular electrical activity generated by populations of cortical neurons distributed across multiple rats chronically implanted with multi-electrode arrays. Cortical neuronal activity was recorded and analyzed in real time, and then delivered to the somatosensory cortices of other animals that participated in the Brainet using intracortical microstimulation (ICMS). Using this approach, different Brainet architectures solved a number of useful computational problems, such as discrete classification, image processing, storage and retrieval of tactile information, and even weather forecasting. Brainets consistently performed at the same or higher levels than single rats in these tasks. Based on these findings, we propose that Brainets could be used to investigate animal social behaviors as well as a test bed for exploring the properties and potential applications of organic computers. PMID:26158615

  2. Active tactile exploration enabled by a brain-machine-brain interface

    PubMed Central

    O’Doherty, Joseph E.; Lebedev, Mikhail A.; Ifft, Peter J.; Zhuang, Katie Z.; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A. L.

    2011-01-01

    Brain-machine interfaces (BMIs)1,2 use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. While BMIs aim to restore the normal sensorimotor functions of the limbs, so far they have lacked tactile sensation. Here we demonstrate the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and enables the signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex (S1). Monkeys performed an active-exploration task in which an actuator (a computer cursor or a virtual-reality hand) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in primary motor cortex (M1). ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search and discriminate one out of three visually undistinguishable objects, using the virtual hand to identify the unique artificial texture (AT) associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic, or even virtual prostheses. PMID:21976021

  3. A Flexible Base Electrode Array for Intraspinal Microstimulation

    PubMed Central

    Khaled, I.; Elmallah, S.; Cheng, C.; Moussa, W.A.; Mushahwar, V.K.; Elias, A.L.

    2013-01-01

    In this paper, we report the development of a flexible base array of penetrating electrodes which can be used to interface with the spinal cord. A customizable and feasible fabrication protocol is described. The flexible base arrays were fabricated and implanted into surrogate cords which were elongated by 12%. The resulting strains were optically measured across the cord and compared to those associated with two types of electrodes arrays (one without a base and one with a rigid base connecting the electrodes). The deformation behavior of cords implanted with the flexible base arrays resembled the behavior of cords implanted with individual microwires that were not connected through a base. The results of the strain test were used to validate a 2D finite element model. The validated model was used to assess the stresses induced by the electrodes of the 3 types of arrays on the cord, and to examine how various design parameters (thickness, base modulus, etc.) impact the mechanical behavior of the electrode array. Rigid base arrays induced higher stresses on the cord than the flexible base arrays which in turn imposed higher stresses than the individual microwire implants. The developed flexible base array showed improvement over the rigid base array; however, its stiffness needs to be further reduced to emulate the mechanical behavior of individual microwire arrays without a base. PMID:23744656

  4. Getting signals into the brain: visual prosthetics through thalamic microstimulation

    PubMed Central

    Pezaris, John S.; Eskandar, Emad N.

    2010-01-01

    Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface. PMID:19569894

  5. Multivariate autoregressive models with exogenous inputs for intracerebral responses to direct electrical stimulation of the human brain

    PubMed Central

    Chang, Jui-Yang; Pigorini, Andrea; Massimini, Marcello; Tononi, Giulio; Nobili, Lino; Van Veen, Barry D.

    2012-01-01

    A multivariate autoregressive (MVAR) model with exogenous inputs (MVARX) is developed for describing the cortical interactions excited by direct electrical current stimulation of the cortex. Current stimulation is challenging to model because it excites neurons in multiple locations both near and distant to the stimulation site. The approach presented here models these effects using an exogenous input that is passed through a bank of filters, one for each channel. The filtered input and a random input excite a MVAR system describing the interactions between cortical activity at the recording sites. The exogenous input filter coefficients, the autoregressive coefficients, and random input characteristics are estimated from the measured activity due to current stimulation. The effectiveness of the approach is demonstrated using intracranial recordings from three surgical epilepsy patients. We evaluate models for wakefulness and NREM sleep in these patients with two stimulation levels in one patient and two stimulation sites in another resulting in a total of 10 datasets. Excellent agreement between measured and model-predicted evoked responses is obtained across all datasets. Furthermore, one-step prediction is used to show that the model also describes dynamics in pre-stimulus and evoked recordings. We also compare integrated information—a measure of intracortical communication thought to reflect the capacity for consciousness—associated with the network model in wakefulness and sleep. As predicted, higher information integration is found in wakefulness than in sleep for all five cases. PMID:23226122

  6. Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.

    PubMed

    Molina-Luna, Katiuska; Buitrago, Manuel M; Hertler, Benjamin; Schubring, Maximilian; Haiss, Florent; Nisch, Wilfried; Schulz, Jörg B; Luft, Andreas R

    2007-03-30

    Stimulation mapping of motor cortex is an important tool for assessing motor cortex physiology. Existing techniques include intracortical microstimulation (ICMS) which has high spatial resolution but damages cortical integrity by needle penetrations, and transcranial stimulation which is non-invasive but lacks focality and spatial resolution. A minimally invasive epidural microstimulation (EMS) technique using chronically implanted polyimide-based thin-film microelectrode arrays (72 contacts) was tested in rat motor cortex and compared to ICMS within individual animals. Results demonstrate reliable mapping with high reproducibility and validity with respect to ICMS. No histological evidence of cortical damage and the absence of motor deficits as determined by performance of a motor skill reaching task, demonstrate the safety of the method. EMS is specifically suitable for experiments integrating electrophysiology with behavioral and molecular biology techniques. PMID:17178423

  7. Evaluation of the stability of intracortical microelectrode arrays.

    PubMed

    Liu, Xindong; McCreery, Douglas B; Bullara, Leo A; Agnew, William F

    2006-03-01

    In order to use recorded neural activities from the brain as control signals for neuroprosthesis devices, it is important to maintain a stable interface between chronically implanted microelectrodes and neural tissue. Our previous paper introduced a method to quantify the stability of the recording microelectrodes. In this paper, the method is refined 1) by incorporating stereotypical behavioral patterns into the spike sorting program and 2) by using a classifier based on Bayes theorem for assigning the recorded action potentials to the underlying neural generators. An improved method for calculating stability index is proposed. The results for the stability of microelectrode arrays that differ in structure are presented. PMID:16562636

  8. Direct Antiglobulin Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Direct Antiglobulin Test Share this page: Was this page helpful? Also known as: DAT; Direct Coombs Test; Direct Anti-human Globulin Test Formal ...

  9. An Additional Motor-Related Field in the Lateral Frontal Cortex of Squirrel Monkeys

    PubMed Central

    Duric, Vanja; Barbay, Scott; Frost, Shawn B.; Stylianou, Antonis; Nudo, Randolph J.

    2008-01-01

    Our earlier efforts to document the cortical connections of the ventral premotor cortex (PMv) revealed dense connections with a field rostral and lateral to PMv, an area we called the frontal rostral field (FR). Here, we present data collected in FR using electrophysiological and anatomical methods. Results show that FR contains an isolated motor representation of the forelimb that can be differentiated from PMv based on current thresholds and latencies to evoke electromyographic activity using intracortical microstimulation techniques. In addition, FR has a different pattern of cortical connections compared with PMv. Together, these data support that FR is an additional, previously undescribed motor-related area in squirrel monkeys. PMID:18424778

  10. Use of functional near-infrared spectroscopy to evaluate the effects of anodal transcranial direct current stimulation on brain connectivity in motor-related cortex.

    PubMed

    Yan, Jiaqing; Wei, Yun; Wang, Yinghua; Xu, Gang; Li, Zheng; Li, Xiaoli

    2015-04-01

    Transcranial direct current stimulation (tDCS) is a noninvasive, safe and convenient neuro-modulatory technique in neurological rehabilitation, treatment, and other aspects of brain disorders. However, evaluating the effects of tDCS is still difficult. We aimed to evaluate the effects of tDCS using hemodynamic changes using functional near-infrared spectroscopy (fNIRS). Five healthy participants were employed and anodal tDCS was applied to the left motor-related cortex, with cathodes positioned on the right dorsolateral supraorbital area. fNIRS data were collected from the right motor-related area at the same time. Functional connectivity (FC)between intracortical regions was calculated between fNIRS channels using a minimum variance distortion-less response magnitude squared coherence (MVDR-MSC) method. The levels of Oxy-HbO change and the FC between channels during the prestimulation, stimulation, and poststimulation stages were compared. Results showed no significant level difference, but the FC measured by MVDR-MSC significantly decreased during tDCS compared with pre-tDCS and post-tDCS, although the FC difference between pre-tDCS and post-tDCS was not significant. We conclude that coherence calculated from resting state fNIRS may be a useful tool for evaluating the effects of anodal tDCS and optimizing parameters for tDCS application. PMID:25894253