Science.gov

Sample records for direct intracortical microstimulation

  1. A Brain-Machine Interface Instructed by Direct Intracortical Microstimulation

    PubMed Central

    O'Doherty, Joseph E.; Lebedev, Mikhail A.; Hanson, Timothy L.; Fitzsimmons, Nathan A.; Nicolelis, Miguel A. L.

    2009-01-01

    Brain–machine interfaces (BMIs) establish direct communication between the brain and artificial actuators. As such, they hold considerable promise for restoring mobility and communication in patients suffering from severe body paralysis. To achieve this end, future BMIs must also provide a means for delivering sensory signals from the actuators back to the brain. Prosthetic sensation is needed so that neuroprostheses can be better perceived and controlled. Here we show that a direct intracortical input can be added to a BMI to instruct rhesus monkeys in choosing the direction of reaching movements generated by the BMI. Somatosensory instructions were provided to two monkeys operating the BMI using either: (a) vibrotactile stimulation of the monkey's hands or (b) multi-channel intracortical microstimulation (ICMS) delivered to the primary somatosensory cortex (S1) in one monkey and posterior parietal cortex (PP) in the other. Stimulus delivery was contingent on the position of the computer cursor: the monkey placed it in the center of the screen to receive machine–brain recursive input. After 2 weeks of training, the same level of proficiency in utilizing somatosensory information was achieved with ICMS of S1 as with the stimulus delivered to the hand skin. ICMS of PP was not effective. These results indicate that direct, bi-directional communication between the brain and neuroprosthetic devices can be achieved through the combination of chronic multi-electrode recording and microstimulation of S1. We propose that in the future, bidirectional BMIs incorporating ICMS may become an effective paradigm for sensorizing neuroprosthetic devices. PMID:19750199

  2. 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

  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. A computational model that predicts behavioral sensitivity to intracortical microstimulation

    NASA Astrophysics Data System (ADS)

    Kim, Sungshin; Callier, Thierri; Bensmaia, Sliman J.

    2017-02-01

    Objective. Intracortical microstimulation (ICMS) is a powerful tool to investigate the neural mechanisms of perception and can be used to restore sensation for patients who have lost it. While sensitivity to ICMS has previously been characterized, no systematic framework has been developed to summarize the detectability of individual ICMS pulse trains or the discriminability of pairs of pulse trains. Approach. We develop a simple simulation that describes the responses of a population of neurons to a train of electrical pulses delivered through a microelectrode. We then perform an ideal observer analysis on the simulated population responses to predict the behavioral performance of non-human primates in ICMS detection and discrimination tasks. Main results. Our computational model can predict behavioral performance across a wide range of stimulation conditions with high accuracy (R 2 = 0.97) and generalizes to novel ICMS pulse trains that were not used to fit its parameters. Furthermore, the model provides a theoretical basis for the finding that amplitude discrimination based on ICMS violates Weber’s law. Significance. The model can be used to characterize the sensitivity to ICMS across the range of perceptible and safe stimulation regimes. As such, it will be a useful tool for both neuroscience and neuroprosthetics.

  5. Discriminability of Single and Multichannel Intracortical Microstimulation within Somatosensory Cortex.

    PubMed

    Overstreet, Cynthia K; Hellman, Randall B; Ponce Wong, Ruben D; Santos, Veronica J; Helms Tillery, Stephen I

    2016-01-01

    The addition of tactile and proprioceptive feedback to neuroprosthetic limbs is expected to significantly improve the control of these devices. Intracortical microstimulation (ICMS) of somatosensory cortex is a promising method of delivering this sensory feedback. To date, the main focus of somatosensory ICMS studies has been to deliver discriminable signals, corresponding to varying intensity, to a single location in cortex. However, multiple independent and simultaneous streams of sensory information will need to be encoded by ICMS to provide functionally relevant feedback for a neuroprosthetic limb (e.g., encoding contact events and pressure on multiple digits). In this study, we evaluated the ability of an awake, behaving non-human primate (Macaca mulatta) to discriminate ICMS stimuli delivered on multiple electrodes spaced within somatosensory cortex. We delivered serial stimulation on single electrodes to evaluate the discriminability of sensations corresponding to ICMS of distinct cortical locations. Additionally, we delivered trains of multichannel stimulation, derived from a tactile sensor, synchronously across multiple electrodes. Our results indicate that discrimination of multiple ICMS stimuli is a challenging task, but that discriminable sensory percepts can be elicited by both single and multichannel ICMS on electrodes spaced within somatosensory cortex.

  6. Discriminability of Single and Multichannel Intracortical Microstimulation within Somatosensory Cortex

    PubMed Central

    Overstreet, Cynthia K.; Hellman, Randall B.; Ponce Wong, Ruben D.; Santos, Veronica J.; Helms Tillery, Stephen I.

    2016-01-01

    The addition of tactile and proprioceptive feedback to neuroprosthetic limbs is expected to significantly improve the control of these devices. Intracortical microstimulation (ICMS) of somatosensory cortex is a promising method of delivering this sensory feedback. To date, the main focus of somatosensory ICMS studies has been to deliver discriminable signals, corresponding to varying intensity, to a single location in cortex. However, multiple independent and simultaneous streams of sensory information will need to be encoded by ICMS to provide functionally relevant feedback for a neuroprosthetic limb (e.g., encoding contact events and pressure on multiple digits). In this study, we evaluated the ability of an awake, behaving non-human primate (Macaca mulatta) to discriminate ICMS stimuli delivered on multiple electrodes spaced within somatosensory cortex. We delivered serial stimulation on single electrodes to evaluate the discriminability of sensations corresponding to ICMS of distinct cortical locations. Additionally, we delivered trains of multichannel stimulation, derived from a tactile sensor, synchronously across multiple electrodes. Our results indicate that discrimination of multiple ICMS stimuli is a challenging task, but that discriminable sensory percepts can be elicited by both single and multichannel ICMS on electrodes spaced within somatosensory cortex. PMID:27995126

  7. Spike Time-Dependent Plasticity Induced by Intra-Cortical Microstimulation in the Auditory Cortex

    NASA Astrophysics Data System (ADS)

    Takahashi, Hirokazu; Yokota, Ryo; Suzrikawa, Jun; Kanzaki, Ryohei

    Intrinsic plastic properties in the auditory cortex can cause dynamic remodeling of the functional organization according to trainings. Neurorehabilitation will therefore potentially benefit from electrical stimulation that can modify synaptic strength as desired. Here we show that the auditory cortex of rats can be modified by intracortical microstimulation (ICMS) associated with tone stimuli on the basis of the spike time-dependent plasticity (STDP). Two kinds of ICMS were applied; a pairing ICMS following a tone-induced excitatory synaptic input and an anti-paring ICMS preceding a tone-induced input. The pairing and anti-pairing ICMS produced potentiation and depression, respectively, in responses to the paired tones with a particular test frequency, and thereby modified the tuning property of the auditory cortical neurons. In addition, we demonstrated that our experimental setup has a potential to directly measure how anesthetic agents and pharmacological manipulation affect ICMS-induced plasticity, and thus will serve as a powerful platform to investigate the neural basis of the plasticity.

  8. Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.

    PubMed

    Hussin, Ahmed T; Boychuk, Jeffery A; Brown, Andrew R; Pittman, Quentin J; Teskey, G Campbell

    2015-01-01

    Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used. The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons. We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors. With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation. Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Intracortical microstimulation of supplementary eye field impairs ability of monkeys to make serially ordered saccades

    PubMed Central

    Olson, Carl R.

    2014-01-01

    Neurons in the supplementary eye field (SEF) of the macaque monkey exhibit rank selectivity, firing differentially as a function of the phase attained during the performance of a task requiring the execution of saccades to a series of objects in fixed order. The activity of these neurons is commonly thought to represent ordinal position in the service of serial-order performance. However, there is little evidence causally linking neuronal activity in the SEF to sequential behavior. To explore the role of the SEF in serial-order performance, we delivered intracortical microstimulation while monkeys performed a task requiring them to make saccades to three objects in a fixed order on each trial. Microstimulation, considered on average across all SEF sites and all phases of the trial, affected saccadic kinematics. In particular, it prolonged the reaction time, increased the peak velocity, and slightly increased the amplitude of saccades. In addition, it interfered with the monkeys' ability to select the target appropriate to a given phase of the trial. The pattern of the errors was such as would be expected if microstimulation shifted the neural representation of ordinal position toward a later phase of the trial. PMID:24453278

  10. 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.

  11. 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.

  12. Analysis on bilateral hindlimb mapping in motor cortex of the rat by an intracortical microstimulation method.

    PubMed

    Seong, Han Yu; Cho, Ji Young; Choi, Byeong Sam; Min, Joong Kee; Kim, Yong Hwan; Roh, Sung Woo; Kim, Jeong Hoon; Jeon, Sang Ryong

    2014-04-01

    Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%± 11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

  13. Psychophysical correspondence between vibrotactile intensity and intracortical microstimulation for tactile neuroprostheses in rats

    NASA Astrophysics Data System (ADS)

    Devecioğlu, İsmail; Güçlü, Burak

    2017-02-01

    Objective. Recent studies showed that intracortical microstimulation (ICMS) generates artificial sensations which can be utilized as somatosensory feedback in cortical neuroprostheses. To mimic the natural psychophysical response, ICMS parameters are modulated according to psychometric equivalence functions (PEFs). PEFs match the intensity levels of ICMS and mechanical stimuli, which elicit equal detection probabilities, but they typically do not include the frequency as a control variable. We aimed to establish frequency-dependent PEFs for vibrotactile stimulation of the glabrous skin and ICMS in the primary somatosensory cortex of awake freely behaving rats. Approach. We collected psychometric data for vibrotactile and ICMS detection at three stimulation frequencies (40, 60 and 80 Hz). The psychometric data were fitted with a model equation of two independent variables (stimulus intensity and frequency) and four subject-dependent parameters. For each rat, we constructed a separate PEF which was used to estimate the ICMS current amplitude for a given displacement amplitude and frequency. The ICMS frequency was set equal to the vibrotactile frequency. We validated the PEFs in a modified task which included randomly selected probe trials presented either with a vibrotactile or an ICMS stimulus, and also at frequencies and intensity levels not tested before. Main results. The PEFs were generally successful in estimating the ICMS current intensities (no significant differences between vibrotactile and ICMS trials in Kolmogorov-Smirnov tests). Specifically, hit rates from both trial conditions were significantly correlated in 86% of the cases, and 52% of all data had perfect match in linear regression. Significance. The psychometric correspondence model presented in this study was constructed based on surface functions which define psychophysical detection probability as a function of stimulus intensity and frequency. Therefore, it may be used for the real

  14. 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.

  15. 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

  16. 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.

  17. Intracortical Microstimulation Maps of Motor, Somatosensory, and Posterior Parietal Cortex in Tree Shrews (Tupaia belangeri) Reveal Complex Movement Representations.

    PubMed

    Baldwin, Mary K L; Cooke, Dylan F; Krubitzer, Leah

    2017-02-01

    Long-train intracortical microstimulation (LT-ICMS) is a popular method for studying the organization of motor and posterior parietal cortex (PPC) in mammals. In primates, LT-ICMS evokes both multijoint and multiple-body-part movements in primary motor, premotor, and PPC. In rodents, LT-ICMS evokes complex movements of a single limb in motor cortex. Unfortunately, very little is known about motor/PPC organization in other mammals. Tree shrews are closely related to both primates and rodents and could provide insights into the evolution of complex movement domains in primates. The present study investigated the extent of cortex in which movements could be evoked with ICMS and the characteristics of movements elicited using both short train (ST) and LT-ICMS in tree shrews. We demonstrate that LT-ICMS and ST-ICMS maps are similar, with the movements elicited with ST-ICMS being truncated versions of those elicited with LT-ICMS. In addition, LT-ICMS-evoked complex movements within motor cortex similar to those in rodents. More complex movements involving multiple body parts such as the hand and mouth were also elicited in motor cortex and PPC, as in primates. Our results suggest that complex movement networks present in PPC and motor cortex were present in mammals prior to the emergence of primates.

  18. Voltage-sensitive-dye imaging of microstimulation-evoked neural activity through intracortical horizontal and callosal connections in cat visual cortex

    NASA Astrophysics Data System (ADS)

    Suzurikawa, Jun; Tani, Toshiki; Nakao, Masayuki; Tanaka, Shigeru; Takahashi, Hirokazu

    2009-12-01

    Recently, intrinsic signal optical imaging has been widely used as a routine procedure for visualizing cortical functional maps. We do not, however, have a well-established imaging method for visualizing cortical functional connectivity indicating spatio-temporal patterns of activity propagation in the cerebral cortex. In the present study, we developed a novel experimental setup for investigating the propagation of neural activities combining the intracortical microstimulation (ICMS) technique with voltage sensitive dye (VSD) imaging, and demonstrated the feasibility of this setup applying to the measurement of time-dependent intra- and inter-hemispheric spread of ICMS-evoked excitation in the cat visual cortices, areas 17 and 18. A microelectrode array for the ICMS was inserted with a specially designed easy-to-detach electrode holder around the 17/18 transition zones (TZs), where the left and right hemispheres were interconnected via the corpus callosum. The microelectrode array was stably anchored in agarose without any holder, which enabled us to visualize evoked activities even in the vicinity of penetration sites as well as in a wide recording region that covered a part of both hemispheres. The VSD imaging could successfully visualize ICMS-evoked excitation and subsequent propagation in the visual cortices contralateral as well as ipsilateral to the ICMS. Using the orientation maps as positional references, we showed that the activity propagation patterns were consistent with previously reported anatomical patterns of intracortical and interhemispheric connections. This finding indicates that our experimental system can serve for the investigation of cortical functional connectivity.

  19. 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.

  20. The Organization of the Forelimb Representation of the C57BL/6 Mouse Motor Cortex as Defined by Intracortical Microstimulation and Cytoarchitecture

    PubMed Central

    Adkins, DeAnna L.; Donlan, Nicole A.; Asay, Aaron L.; Thomas, Nagheme; Kleim, Jeffrey A.

    2011-01-01

    The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor–somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations. PMID:20739477

  1. A 1.5-to-5 V converter for a battery-powered activity-dependent intracortical microstimulation SoC.

    PubMed

    Azin, Meysam; Mohseni, Pedram

    2012-01-01

    This paper reports on the design, analysis, implementation, and testing of a 1.5-to-5 V converter as part of a battery-powered activity-dependent intracortical microstimulation (ICMS) system-on-chip (SoC) that converts extracellular neural spikes recorded from one cortical area to electrical stimuli delivered to another cortical area in real time. The highly integrated voltage converter is intended to generate a 5-V supply for the stimulating back-end on the SoC from a miniature primary battery that powers the entire system. It is implemented in AMS 0.35 µm two-poly four-metal (2P/4M) complementary metal-oxide-semiconductor (CMOS) technology, employs only one external capacitor (1 µF) for storage, and delivers a maximum dc load current of ~88 µA with power efficiency of 31% with its output voltage adjusted to 5.05 V. This current drive capability affords simultaneous stimulation on all eight channels of the SoC with current amplitude up to ~100 µA and average stimulus rate >500 Hz, which is comfortably higher than firing rate of cortical neurons (<150 spikes per second). The measurement results also agree favorably with theoretical derivations from the analysis of converter operation.

  2. 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

  3. 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.

  4. Multiple representations of body movements in mesial area 6 and the adjacent cingulate cortex: an intracortical microstimulation study in the macaque monkey.

    PubMed

    Luppino, G; Matelli, M; Camarda, R M; Gallese, V; Rizzolatti, G

    1991-09-22

    The mesial agranular frontal cortex that lies rostral to area 4 (F1) is formed by two distinct cytoarchitectonic areas: F3, located caudally, and F6, located rostrally. In the present experiments we investigated the organization of F3 and F6 by observing the motor responses evoked by their intracortical electrical microstimulation. Our main purpose was to find out whether the cytoarchitectonic subdivision of the mesial agranular frontal cortex into two areas has a physiological counterpart. The result showed that F3 (the caudal area) contains a complete motor representation with hindlimb movements located caudally, forelimb movements located centrally, and orofacial movements located rostrally. The great majority of limb movements involved proximal joints. With respect to F1, F3 showed the following functional characteristics: (1) lack of segregation between proximal and distal movements, (2) larger percentage of complex movements, and (3) higher excitability threshold. Movements were more difficult to elicit from F6 (the rostral area) than from F3. However, by using a longer stimulus train duration (100 ms) 39.3% of tested sites produced body movements. This percentage increased (50.5%) when the electrical stimulation was applied during monkey natural movements instead of when the monkey was still in its chair. Most of the evoked movements concerned the forelimb. More rarely, neck and upper face movements were observed. Unlike F1 and F3 where most movements were fast, slow movements were frequently observed with stimulation of F6. Many of them mimicked natural movements of the animal. Eye movements were evoked from F7 (superior area 6) but not from F6. An additional motor representation was found in the dorsocaudal part of area 24 (24d). This area is topographically organized with a forelimb representation located caudally and ventrally and a hindlimb representation located rostrally and dorsally. The excitability threshold of area 24d is higher than that of F1

  5. 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.

  6. 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).

  7. High-side Digitally Current Controlled Biphasic Bipolar Microstimulator

    PubMed Central

    Hanson, Timothy L.; Ómarsson, Björn; O'Doherty, Joseph E.; Peikon, Ian D.; Lebedev, Mikhail; Nicolelis, Miguel AL.

    2012-01-01

    Electrical stimulation of nervous tissue has been extensively used as both a tool in experimental neuroscience research and as a method for restoring of neural functions in patients suffering from sensory and motor disabilities. In the central nervous system, intracortical microstimulation (ICMS) has been shown to be an effective method for inducing or biasing perception, including visual and tactile sensation. ICMS also holds promise for enabling brain-machine-brain interfaces (BMBIs) by directly writing information into the brain. Here we detail the design of a high-side, digitally current-controlled biphasic, bipolar microstimulator, and describe the validation of the device in vivo. As many applications of this technique, including BMBIs, require recording as well as stimulation, we pay careful attention to isolation of the stimulus channels and parasitic current injection. With the realized device and standard recording hardware - without active artifact rejection - we are able to observe stimulus artifacts of less than 2 ms in duration. PMID:22328184

  8. High-side digitally current controlled biphasic bipolar microstimulator.

    PubMed

    Hanson, Timothy L; Ómarsson, Björn; O'Doherty, Joseph E; Peikon, Ian D; Lebedev, Mikhail A; Nicolelis, Miguel A L

    2012-05-01

    Electrical stimulation of nervous tissue has been extensively used as both a tool in experimental neuroscience research and as a method for restoring of neural functions in patients suffering from sensory and motor disabilities. In the central nervous system, intracortical microstimulation (ICMS) has been shown to be an effective method for inducing or biasing perception, including visual and tactile sensation. ICMS also holds promise for enabling brain-machine-brain interfaces (BMBIs) by directly writing information into the brain. Here we detail the design of a high-side, digitally current-controlled biphasic, bipolar microstimulator, and describe the validation of the device in vivo. As many applications of this technique, including BMBIs, require recording as well as stimulation, we pay careful attention to isolation of the stimulus channels and parasitic current injection. With the realized device and standard recording hardware-without active artifact rejection-we are able to observe stimulus artifacts of less than 2 ms in duration.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Mapping Horizontal Spread of Activity in Monkey Motor Cortex Using Single Pulse Microstimulation

    PubMed Central

    Riehle, Alexa; Brochier, Thomas G.

    2016-01-01

    Anatomical studies have demonstrated that distant cortical points are interconnected through long range axon collaterals of pyramidal cells. However, the functional properties of these intrinsic synaptic connections, especially their relationship with the cortical representations of body movements, have not been systematically investigated. To address this issue, we used multielectrode arrays chronically implanted in the motor cortex of two rhesus monkeys to analyze the effects of single-pulse intracortical microstimulation (sICMS) applied at one electrode on the neuronal activities recorded at all other electrodes. The temporal and spatial distribution of the evoked responses of single and multiunit activities was quantified to determine the properties of horizontal propagation. The typical responses were characterized by a brief excitatory peak followed by inhibition of longer duration. Significant excitatory responses to sICMS could be evoked up to 4 mm away from the stimulation site, but the strength of the response decreased exponentially and its latency increased linearly with the distance. We then quantified the direction and strength of the propagation in relation to the somatotopic organization of the motor cortex. We observed that following sICMS the propagation of neural activity is mainly directed rostro-caudally near the central sulcus but follows medio-lateral direction at the most anterior electrodes. The fact that these interactions are not entirely symmetrical may characterize a critical functional property of the motor cortex for the control of upper limb movements. Overall, these results support the assumption that the motor cortex is not functionally homogeneous but forms a complex network of interacting subregions. PMID:28018182

  14. 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

  15. Neuronal expression of c-Fos after epicortical and intracortical electric stimulation of the primary visual cortex.

    PubMed

    Neyazi, Belal; Schwabe, Kerstin; Alam, Mesbah; Krauss, Joachim K; Nakamura, Makoto

    2016-11-01

    Electrical stimulation of the primary visual cortex (V1) is an experimental approach for visual prostheses. We here compared the response to intracortical and epicortical stimulation of the primary visual cortex by using c-Fos immunoreactivity as a marker for neuronal activation. The primary visual cortex of male Sprague Dawley rats was unilaterally stimulated for four hours using bipolar electrodes placed either intracortically in layer IV (n=26) or epicortically (n=20). Four different current intensities with a constant pulse width of 200μs and a constant frequency of 10Hz were used, for intracortical stimulation with an intensity of 0μA (sham-stimulation), 10μA, 20μA and 40μA, and for epicortical stimulation 0μA, 400μA, 600μA and 800μA. Subsequently all animals underwent c-Fos immunostaining and c-Fos expression was assessed in layer I-VI of the primary visual cortex within 200μm and 400μm distance to the stimulation site. C-Fos expression was higher after intracortical stimulation compared to epicortical stimulation, even though ten times lower current intensities were applied. Furthermore intracortical stimulation resulted in more focal neuronal activation than epicortical stimulation. C-Fos expression was highest after intracortical stimulation with 20μA compared to all other intensities. Epicortical stimulation showed a linear increase of c-Fos expression with the highest expression at 800μA. Sham stimulation showed similar expression of c-Fos in both hemispheres. The contralateral hemisphere was not affected by intracortical or epicortical stimulation of either intensities. In summary, intracortical stimulation resulted in more focal neuronal activation with less current than epicortical stimulation. This model may be used as a simple but reliable model to evaluate electrodes for microstimulation of the primary visual cortex before testing in more complex settings.

  16. 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

  17. Implantable multiprogrammable microstimulator dedicated to bladder control.

    PubMed

    Arabi, K; Sawan, M

    1996-01-01

    An implantable multiprogrammable microstimulator that is intended to restore normal bladder functions (retention and incontinence) to spinal cord injured patients is presented. The implantable microstimulator circuitry is externally controlled and is powered by a single encoded radio frequency carrier and has four bipolar (eight monopolar) independently controlled channels. It offers a higher degree of reprogrammability and flexibility and can be used in any neuromuscular applications. The implant system is adaptable to the patient's needs and to future developments in stimulation algorithms, without changing the implant. Features of the microstimulator include its capabilities to generate a wide range of waveforms and to combine up to four different programmable frequencies in each wave train. By using a forward error detection and correction communication protocol, the reliability of the implant is increased. The chip has been designed for structural testability by means of a scan-based test approach and uses circuit techniques to reduce power consumption and ensure long-term stability.

  18. 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.

  19. Effects of Cortical Microstimulation on Confidence in a Perceptual Decision

    PubMed Central

    Fetsch, Christopher R.; Kiani, Roozbeh; Newsome, William T.; Shadlen, Michael N.

    2014-01-01

    SUMMARY Decisions are often associated with a degree of certainty, or confidence — an estimate of the probability that the chosen option will be correct. Recent neurophysiological results suggest that the central processing of evidence leading to a perceptual decision also establishes a level of confidence. Here we provide a causal test of this hypothesis by electrically stimulating areas of the visual cortex involved in motion perception. Monkeys discriminated the direction of motion in a noisy display, and were sometimes allowed to opt out of the direction choice if their confidence was low. Microstimulation did not reduce overall confidence in the decision but instead altered confidence in a manner that mimicked a change in visual motion, plus a small increase in sensory noise. The results suggest that the same sensory neural signals support choice, reaction time and confidence in a decision, and that artificial manipulation of these signals preserves the quantitative relationship between accumulated evidence and confidence. PMID:25123306

  20. Microstimulation of the midbrain tegmentum creates learning signals for saccade adaptation.

    PubMed

    Kojima, Yoshiko; Yoshida, Kaoru; Iwamoto, Yoshiki

    2007-04-04

    Error signals are vital to motor learning. However, we know little about pathways that transmit error signals for learning in voluntary movements. Here we show that microstimulation of the midbrain tegmentum can induce learning in saccadic eye movements in monkeys. Weak electrical stimuli delivered approximately 200 ms after saccades in one horizontal direction produced gradual and marked changes in saccade gain. The spatial and temporal characteristics of the produced changes were similar to those of adaptation induced by real visual error. When stimulation was applied after saccades in two different directions, endpoints of these saccades gradually shifted in the same direction in two dimensions. We conclude that microstimulation created powerful learning signals that dictate the direction of adaptive shift in movement endpoints. Our findings suggest that the error signals for saccade adaptation are conveyed in a pathway that courses through the midbrain tegmentum.

  1. 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.

  2. Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury.

    PubMed

    Mercier, L M; Gonzalez-Rothi, E J; Streeter, K A; Posgai, S S; Poirier, A S; Fuller, D D; Reier, P J; Baekey, D M

    2017-02-01

    Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5-21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100-200 μA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable "closed-loop-like" ISMS approaches to sustain ventilation after severe SCI.NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals. Copyright © 2017 the American Physiological Society.

  3. Synchronization across sensory cortical areas by electrical microstimulation is sufficient for behavioral discrimination.

    PubMed

    Manzur, Hachi E; Alvarez, Joel; Babul, Cecilia; Maldonado, Pedro E

    2013-12-01

    The temporal correlation hypothesis proposes that cortical neurons engage in synchronized activity, thus configuring a general mechanism to account for a range of cognitive processes from perceptual binding to consciousness. However, most studies supporting this hypothesis have only provided correlational, but not causal evidence. Here, we used electrical microstimulation of the visual and somatosensory cortices of the rat in both hemispheres, to test whether rats could discriminate synchronous versus asynchronous patterns of stimulation applied to the same cortical sites. To disambiguate synchrony from other related parameters, our experiments independently manipulated the rate and intensity of stimulation, the spatial locations of stimulation, the exact temporal sequence of stimulation patterns, and the degree of synchrony across stimulation sites. We found that rats reliably distinguished between 2 microstimulation patterns, differing in the spatial arrangement of cortical sites stimulated synchronously. Also, their performance was proportional to the level of synchrony in the microstimulation patterns. We demonstrated that rats can recognize artificial current patterns containing precise synchronization features, thus providing the first direct evidence that artificial synchronous activity can guide behavior. Such precise temporal information can be used as feedback signals in machine interface arrangements.

  4. Modulation of the Contrast Response Function by Electrical Microstimulation of the Macaque Frontal Eye Field

    PubMed Central

    Ekstrom, Leeland B.; Roelfsema, Pieter R.; Arsenault, John T.; Kolster, Hauke; Vanduffel, Wim

    2009-01-01

    Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, while others a response or activity gain when attention is directed to a contrast varying stimulus. Recent evidence has indicated that microstimulating the Frontal Eye Field (FEF) can produce modulations of V4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging activity throughout the visual system. Here, we used fMRI in awake, fixating monkeys to first measure the response in twelve visual cortical areas to stimuli of varying luminance contrast. Next, we simultaneously microstimulated sub-regions of the FEF with movement fields that overlapped the stimulus locations and measured how microstimulation modulated these contrast response functions (CRFs) throughout visual cortex. In general, we found evidence for a non-proportional scaling of the CRF under these conditions, resembling a contrast gain effect. Representations of low contrast stimuli were enhanced by stimulation of the FEF below the threshold needed to evoke saccades, while high contrast stimuli were unaffected or in some areas even suppressed. Further, we measured a characteristic spatial pattern of enhancement and suppression across the cortical surface, from which we propose a simple schematic of this contrast-dependent fMRI response. PMID:19710320

  5. Relationship between intracortical electrode design and chronic recording function.

    PubMed

    Karumbaiah, Lohitash; Saxena, Tarun; Carlson, David; Patil, Ketki; Patkar, Radhika; Gaupp, Eric A; Betancur, Martha; Stanley, Garrett B; Carin, Lawrence; Bellamkonda, Ravi V

    2013-11-01

    Intracortical electrodes record neural signals directly from local populations of neurons in the brain, and conduct them to external electronics that control prosthetics. However, the relationship between electrode design, defined by shape, size and tethering; and long-term (chronic) stability of the neuron-electrode interface is poorly understood. Here, we studied the effects of various commercially available intracortical electrode designs that vary in shape (cylindrical, planar), size (15 μm, 50 μm and 75 μm), and tethering [electrode connections to connector with (tethered) and without tethering cable (untethered)] using histological, transcriptomic, and electrophysiological analyses over acute (3 day) and chronic (12 week) timepoints. Quantitative analysis of histological sections indicated that Michigan 50 μm (M50) and Michigan tethered (MT) electrodes induced significantly (p < 0.01) higher glial scarring, and lesser survival of neurons in regions of blood-brain barrier (BBB) breach when compared to microwire (MW) and Michigan 15 μm (M15) electrodes acutely and chronically. Gene expression analysis of the neurotoxic cytokines interleukin (Il)1 (Il1α, Il1β), Il6, Il17 (Il17a, Il17b, Il17f), and tumor necrosis factor alpha (Tnf) indicated that MW electrodes induced significantly (p < 0.05) reduced expression of these transcripts when compared to M15, M50 and FMAA electrodes chronically. Finally, electrophysiological assessment of electrode function indicated that MW electrodes performed significantly (p < 0.05) better than all other electrodes over a period of 12 weeks. These studies reveal that intracortical electrodes with smaller size, cylindrical shape, and without tethering cables produce significantly diminished inflammatory responses when compared to large, planar and tethered electrodes. These studies provide a platform for the rational design and assessment of chronically functional intracortical electrode implants in the future. © 2013

  6. 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

  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. Equilibrium-based movement endpoints elicited from primary motor cortex using repetitive microstimulation.

    PubMed

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

    2014-11-19

    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. Copyright © 2014 the authors 0270-6474/14/3415722-13$15.00/0.

  9. 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

  10. Optimal parameters for microstimulation derived forelimb movement thresholds and motor maps in rats and mice.

    PubMed

    Young, Nicole A; Vuong, Jennifer; Flynn, Corey; Teskey, G Campbell

    2011-03-15

    Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representations (motor maps) of the motor cortex, and was originally used in cats and the capuchin monkey. In more modern experiments, ICMS has been used in rats and mice to assess and interpret plasticity of motor maps in response to experimental manipulation; however, a systematic determination of the optimal ICMS parameters necessary to derive baseline motor maps in rats and mice has not been published. In the present manuscript, we describe two experiments. We first determined the optimal stimulation frequency, pulse number, neocortical depth, and current polarity to achieve the minimum current intensity (movement threshold) to elicit forelimb movements in rats and mice. We show that experimentally naïve rats and mice differ on several of these ICMS parameters. In the second experiment, we measured movement thresholds and map size in states of enhanced neocortical inhibition by the administration of diazepam, as well as neocortical sensitization as the result of repeated seizures. We conclude that movement thresholds are inversely related to motor map size, and that treatments result in a widespread shift the balance between excitation and inhibition in motor neocortical layer 5 influences both movement thresholds and map size. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. 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

  12. 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

  13. Neuronix enables continuous, simultaneous neural recording and electrical microstimulation.

    PubMed

    Zhi Yang; Jian Xu; Anh Tuan Nguyen; Tong Wu; Wenfeng Zhao; Wing-Kin Tam

    2016-08-01

    This paper reports a novel neurotechnology (Neuronix) and its validation through experiments. It is a miniature system-on-chip (SoC) that allows recording with simultaneous electrical microstimulation. This function has not been demonstrated before and enables precise, closed-loop neuromodulation. Neuronix represents recent advancement in brain technology and applies to both animal research and clinical applications.

  14. Review: Human Intracortical recording and neural decoding for brain-computer interfaces.

    PubMed

    Brandman, David M; Cash, Sydney S; Hochberg, Leigh R

    2017-03-02

    Brain Computer Interfaces (BCIs) use neural information recorded from the brain for voluntary control of external devices. The development of BCI systems has largely focused on improving functional independence for individuals with severe motor impairments, including providing tools for communication and mobility. In this review, we describe recent advances in intracortical BCI technology and provide potential directions for further research.

  15. 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

  16. 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.

  17. Associative plasticity in intracortical inhibitory circuits in human motor cortex.

    PubMed

    Russmann, Heike; Lamy, Jean-Charles; Shamim, Ejaz A; Meunier, Sabine; Hallett, Mark

    2009-06-01

    Paired associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far. In 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABA(A) and GABA(B) interneurons, respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs. After PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 min after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS. PAS influences inhibitory circuits in M1. PAS paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks.

  18. Associative plasticity in intracortical inhibitory circuits in human motor cortex

    PubMed Central

    Russmann, Heike; Lamy, Jean-Charles; Shamim, Ejaz; Meunier, Sabine; Hallett, Mark

    2009-01-01

    Objective Paired-associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far. Method In 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABAA and GABAB interneurons respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs. Results After PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 minutes after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS. Conclusions PAS influences inhibitory circuits in M1. Significance PAS paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks. PMID:19435676

  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. 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.

  1. Microstimulation of the Human Substantia Nigra Alters Reinforcement Learning

    PubMed Central

    Ramayya, Ashwin G.; Misra, Amrit

    2014-01-01

    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

  2. Sensors and decoding for intracortical brain computer interfaces.

    PubMed

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

    2013-01-01

    Intracortical brain computer interfaces (iBCIs) are being developed to enable people 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 that decodes the user's intended movement from those signals. Here, we focus on recent advances in these two areas, placing special attention 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.

  3. 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

  4. Muscle afferent excitability testing in spinal root-intact rats: dissociating peripheral afferent and efferent volleys generated by intraspinal microstimulation.

    PubMed

    Tomatsu, Saeka; Kim, Geehee; Confais, Joachim; Seki, Kazuhiko

    2017-02-01

    Presynaptic inhibition of the sensory input from the periphery to the spinal cord can be evaluated directly by intra-axonal recording of primary afferent depolarization (PAD) or indirectly by intraspinal microstimulation (excitability testing). Excitability testing is superior for use in normal behaving animals, because this methodology bypasses the technically challenging intra-axonal recording. However, use of excitability testing on the muscle or joint afferent in intact animals presents its own technical challenges. Because these afferents, in many cases, are mixed with motor axons in the peripheral nervous system, it is crucial to dissociate antidromic volleys in the primary afferents from orthodromic volleys in the motor axon, both of which are evoked by intraspinal microstimulation. We have demonstrated in rats that application of a paired stimulation protocol with a short interstimulus interval (ISI) successfully dissociated the antidromic volley in the nerve innervating the medial gastrocnemius muscle. By using a 2-ms ISI, the amplitude of the volleys evoked by the second stimulation was decreased in dorsal root-sectioned rats, but the amplitude did not change or was slightly increased in ventral root-sectioned rats. Excitability testing in rats with intact spinal roots indicated that the putative antidromic volleys exhibited dominant primary afferent depolarization, which was reasonably induced from the more dorsal side of the spinal cord. We concluded that excitability testing with a paired-pulse protocol can be used for studying presynaptic inhibition of somatosensory afferents in animals with intact spinal roots.NEW & NOTEWORTHY Excitability testing of primary afferents has been used to evaluate presynaptic modulation of synaptic transmission in experiments conducted in vivo. However, to apply this method to muscle afferents of animals with intact spinal roots, it is crucial to dissociate antidromic and orthodromic volleys induced by spinal

  5. Intracortical modulation, and not spinal inhibition, mediates placebo analgesia.

    PubMed

    Martini, M; Lee, M C H; Valentini, E; Iannetti, G D

    2015-02-01

    Suppression of spinal responses to noxious stimulation has been detected using spinal fMRI during placebo analgesia, which is therefore increasingly considered a phenomenon caused by descending inhibition of spinal activity. However, spinal fMRI is technically challenging and prone to false-positive results. Here we recorded laser-evoked potentials (LEPs) during placebo analgesia in humans. LEPs allow neural activity to be measured directly and with high enough temporal resolution to capture the sequence of cortical areas activated by nociceptive stimuli. If placebo analgesia is mediated by inhibition at spinal level, this would result in a general suppression of LEPs rather than in a selective reduction of their late components. LEPs and subjective pain ratings were obtained in two groups of healthy volunteers - one was conditioned for placebo analgesia while the other served as unconditioned control. Laser stimuli at three suprathreshold energies were delivered to the right hand dorsum. Placebo analgesia was associated with a significant reduction of the amplitude of the late P2 component. In contrast, the early N1 component, reflecting the arrival of the nociceptive input to the primary somatosensory cortex (SI), was only affected by stimulus energy. This selective suppression of late LEPs indicates that placebo analgesia is mediated by direct intracortical modulation rather than inhibition of the nociceptive input at spinal level. The observed cortical modulation occurs after the responses elicited by the nociceptive stimulus in the SI, suggesting that higher order sensory processes are modulated during placebo analgesia.

  6. Theoretical analysis of intracortical microelectrode recordings

    NASA Astrophysics Data System (ADS)

    Lempka, Scott F.; Johnson, Matthew D.; Moffitt, Michael A.; Otto, Kevin J.; Kipke, Daryl R.; McIntyre, Cameron C.

    2011-08-01

    Advanced fabrication techniques have now made it possible to produce microelectrode arrays for recording the electrical activity of a large number of neurons in the intact brain for both clinical and basic science applications. However, the long-term recording performance desired for these applications is hindered by a number of factors that lead to device failure or a poor signal-to-noise ratio (SNR). The goal of this study was to identify factors that can affect recording quality using theoretical analysis of intracortical microelectrode recordings of single-unit activity. Extracellular microelectrode recordings were simulated with a detailed multi-compartment cable model of a pyramidal neuron coupled to a finite-element volume conductor head model containing an implanted recording microelectrode. Recording noise sources were also incorporated into the overall modeling infrastructure. The analyses of this study would be very difficult to perform experimentally; however, our model-based approach enabled a systematic investigation of the effects of a large number of variables on recording quality. Our results demonstrate that recording amplitude and noise are relatively independent of microelectrode size, but instead are primarily affected by the selected recording bandwidth, impedance of the electrode-tissue interface and the density and firing rates of neurons surrounding the recording electrode. This study provides the theoretical groundwork that allows for the design of the microelectrode and recording electronics such that the SNR is maximized. Such advances could help enable the long-term functionality required for chronic neural recording applications.

  7. 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.

  8. Theoretical analysis of intracortical microelectrode recordings

    PubMed Central

    Lempka, Scott F; Johnson, Matthew D; Moffitt, Michael A; Otto, Kevin J; Kipke, Daryl R; McIntyre, Cameron C

    2011-01-01

    Advanced fabrication techniques have now made it possible to produce microelectrode arrays for recording the electrical activity of a large number of neurons in the intact brain for both clinical and basic science applications. However, the long-term recording performance desired for these applications is hindered by a number of factors that lead to device failure or a poor signal-to-noise ratio (SNR). The goal of this study was to identify factors that can affect recording quality using theoretical analysis of intracortical microelectrode recordings of single-unit activity. Extracellular microelectrode recordings were simulated with a detailed multi-compartment cable model of a pyramidal neuron coupled to a finite element volume conductor head model containing an implanted recording microelectrode. Recording noise sources were also incorporated into the overall modeling infrastructure. The analyses of this study would be very difficult to perform experimentally; however, our model-based approach enabled a systematic investigation of the effects of a large number of variables on recording quality. Our results demonstrate that recording amplitude and noise are relatively independent of microelectrode size, but instead are primarily affected by the selected recording bandwidth, impedance of the electrode-tissue interface, and the density and firing rates of neurons surrounding the recording electrode. This study provides the theoretical groundwork that allows for the design of the microelectrode and recording electronics such that the SNR is maximized. Such advances could help enable the long-term functionality required for chronic neural recording applications. PMID:21775783

  9. Finite Element Analysis of a Floating Microstimulator

    PubMed Central

    Sahin, Mesut; Ur-Rahman, Syed S.

    2011-01-01

    Analytical solutions for voltage fields in a volume conductor are available only for ideal electrodes with radially symmetric contacts and infinitely extending substrates. Practical electrodes for neural stimulation may have asymmetric contacts and finite substrate dimensions and hence deviate from the ideal geometries. For instance, it needs to be determined if the analytical solutions are adequate for simulations of narrow shank electrodes where the substrate width is comparable to the size of the contacts. As an extension to this problem, a “floating” stimulator can be envisioned where the substrate would be finite in all directions. The question then becomes how small this floating stimulator can be made before its stimulation strength is compromised by the decrease in the medium impedance between the contacts as the contacts are approaching each other. We used finite element modeling to solve the voltage and current profiles generated by these radially asymmetric electrode geometries in a volume conductor. The simulation results suggest that both the substrate size and the bipolar contact separation influence the voltage field when these parameters are as small as a few times the contact size. Both of these effects are larger for increasing elevations from the contact surface, and even stronger for floating electrodes (finite substrate in all directions) than the shank-type electrodes. Location of the contacts on the floating electrode also plays a role in determining the voltage field. The voltage field for any device size and current, and any specific resistance of the volume conductor can be predicted from these results so long as the aspect ratios are preserved. PMID:17601192

  10. Development of ceramic-to-metal package for BION microstimulator

    NASA Astrophysics Data System (ADS)

    Jiang, Guangqiang

    2005-11-01

    The goal of the present research work is to develop a bonding method to produce quality ceramic-to-metal joints suitable for long term implantable biomedical devices, such as BIONRTM microstimulator where ceramic provides a transparent window for AC magnetic. A series of zirconia (3Y-TZP) ceramic to Ti-6Al-4V alloy braze runs have been carried out in vacuum using Tini-50RTM (50 wt.% Titanium/50 wt. % Nickel), and pure nickel filler metals. The evolution of microstructures was studied using Scanning Electron Microscopy (SEM) and Energy Dispersive Microanalysis (EDS). Reaction products, such as Ti2Ni and Ni 2Ti4O, were found on the fracture surfaces, as determined by X-Ray Diffraction (XRD) analysis. The interfacial reaction product Ni 2Ti4O is responsible for bond development. Temperature and holding time strongly influenced joint strength. Three fracture models were identified and the exact failure model is a function of the brazing parameter. The biocompatibility of the bond has been evaluated by means of electrochemical testing, immersion testing and gross pathology. Results demonstrated good corrosion resistance and safe biocompatibility of Tini-50RTM brazed joints. The same results can be expected from implantation utilizing nickel-brazed ceramic-to-metal joints, because microstructures in nickel-brazed joints are identical to that of Tini-50RTM brazed joints. It has been learned that 3Y-TZP ceramic are subject to moisture-induced tetragonal-to-monoclinic (T-M) phase transformation at body temperature resulting in degradation of its mechanical properties. To ensure the integrity of the BIONRTM microstimulator package over the projected lifetime, in-vitro accelerated life tests (ALT) at various temperatures and in-vivo aging tests in sheep and rats have been conducted. A reliable method to predict the implantation lifetime of biomedical devices containing 3Y-TZP has been developed. The BIONRTM microstimulator package utilizing the current 3Y-TZP ceramic is

  11. The effect of face patch microstimulation on perception of faces and objects.

    PubMed

    Moeller, Sebastian; Crapse, Trinity; Chang, Le; Tsao, Doris Y

    2017-05-01

    What is the range of stimuli encoded by face-selective regions of the brain? We asked how electrical microstimulation of face patches in macaque inferotemporal cortex affects perception of faces and objects. We found that microstimulation strongly distorted face percepts and that this effect depended on precise targeting to the center of face patches. While microstimulation had no effect on the percept of many non-face objects, it did affect the percept of some, including non-face objects whose shape is consistent with a face (for example, apples) as well as somewhat facelike abstract images (for example, cartoon houses). Microstimulation even perturbed the percept of certain objects that did not activate the stimulated face patch at all. Overall, these results indicate that representation of facial identity is localized to face patches, but activity in these patches can also affect perception of face-compatible non-face objects, including objects normally represented in other parts of inferotemporal cortex.

  12. 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.

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

    PubMed

    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 microA (200 micros, 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 microA, with the lowest recorded threshold being 1.1 microA. 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.

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

    PubMed Central

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

    2014-01-01

    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 ~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. PMID:24503597

  15. Efficient microstimulation of the brain: A parametric approach.

    PubMed

    Watson, Meghan; Dancause, Numa; Sawan, Mohamad

    2015-08-01

    Microstimulation of brain tissue plays a key role in a variety of sensory prosthetics, clinical therapies and research applications. At present, tailoring the parameters of a stimulation signal to a specific goal relies heavily on parameters from literature. Optimization methods seek to improve tried and tested waveforms developed for specific purposes, however the fundamental understanding of how stimulation parameters interact and the effects these interactions have on brain tissue remains widely unknown. This study explores the interactions between parameters of the constant-current, biphasic square waveform with the intention of developing a stimulation efficient strategy. We find that, the traditional premise of a waveform's effectiveness being dominated by its amplitude does apply, however exceptions are noted which may be of essential importance to the development of electrical stimuli in restrictive paradigms.

  16. Intracortical bone remodeling variation shows strong genetic effects.

    PubMed

    Havill, L M; Allen, M R; Harris, J A K; Levine, S M; Coan, H B; Mahaney, M C; Nicolella, D P

    2013-11-01

    Intracortical microstructure influences crack propagation and arrest within bone cortex. Genetic variation in intracortical remodeling may contribute to mechanical integrity and, therefore, fracture risk. Our aim was to determine the degree to which normal population-level variation in intracortical microstructure is due to genetic variation. We examined right femurs from 101 baboons (74 females, 27 males; aged 7-33 years) from a single, extended pedigree to determine osteon number, osteon area (On.Ar), haversian canal area, osteon population density, percent osteonal bone (%On.B), wall thickness (W.Th), and cortical porosity (Ct.Po). Through evaluation of the covariance in intracortical properties between pairs of relatives, we quantified the contribution of additive genetic effects (heritability [h (2)]) to variation in these traits using a variance decomposition approach. Significant age and sex effects account for 9 % (Ct.Po) to 21 % (W.Th) of intracortical microstructural variation. After accounting for age and sex, significant genetic effects are evident for On.Ar (h (2) = 0.79, p = 0.002), %On.B (h (2) = 0.82, p = 0.003), and W.Th (h (2) = 0.61, p = 0.013), indicating that 61-82 % of the residual variation (after accounting for age and sex effects) is due to additive genetic effects. This corresponds to 48-75 % of the total phenotypic variance. Our results demonstrate that normal, population-level variation in cortical microstructure is significantly influenced by genes. As a critical mediator of crack behavior in bone cortex, intracortical microstructural variation provides another mechanism through which genetic variation may affect fracture risk.

  17. Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear.

    PubMed

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

    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 of conditioned fear to the tone. In the present study we used microstimulation to investigate the role of additional mPFC subregions: the prelimbic (PL), dorsal anterior cingulate (ACd), and medial precentral (PrCm) cortices in the expression and extinction of conditioned fear. These are tone-responsive areas that have been implicated in both acquisition and extinction of conditioned fear. In contrast to IL, microstimulation of PL increased the expression of conditioned fear and prevented extinction. Microstimulation of ACd and PrCm had no effect. Under low-footshock conditions (to avoid ceiling levels of freezing), microstimulation of PL and IL had opposite effects, respectively increasing and decreasing freezing to the conditioned tone. We suggest that PL excites amygdala output and IL inhibits amygdala output, providing a mechanism for bidirectional modulation of fear expression.

  18. Methods for microstimulation and recording of single neurons and evoked potentials in the human central nervous system.

    PubMed

    Lenz, F A; Dostrovsky, J O; Kwan, H C; Tasker, R R; Yamashiro, K; Murphy, J T

    1988-04-01

    An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system.

  19. 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.

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

    PubMed

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

    2015-10-01

    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? 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. 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. 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 suggested in previous animal work.

  2. 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

  3. Simultaneous recording of ECoG and intracortical neuronal activity using a flexible multichannel electrode-mesh in visual cortex.

    PubMed

    Toda, Haruo; Suzuki, Takafumi; Sawahata, Hirohito; Majima, Kei; Kamitani, Yukiyasu; Hasegawa, Isao

    2011-01-01

    Electrocorticogram (ECoG) is a well-balanced methodology for stably mapping brain surface local field potentials (LFPs) over a wide cortical region with high signal fidelity and minimal invasiveness to the brain tissue. To directly compare surface ECoG signals with intracortical neuronal activity immediately underneath, we fabricated a flexible multichannel electrode array with mesh-form structure using micro-electro-mechanical systems. A Parylene-C-based "electrode-mesh" for rats contained a 6×6 gold electrode array with 1-mm interval. Specifically, the probe had 800×800 μm(2) fenestrae in interelectrode spaces, through which simultaneous penetration of microelectrode was capable. This electrode-mesh was placed acutely or chronically on the dural/pial surface of the visual cortex of Long-Evans rats for up to 2 weeks. We obtained reliable trial-wise profiles of visually evoked ECoG signals through individual eye stimulation. Visually evoked ECoG signals from the electrode-mesh exhibited as well or larger signal amplitudes as intracortical LFPs and less across-trial variability than conventional silver-ball ECoG. Ocular selectivity of ECoG responses was correlated with that of intracortical spike/LFP activities. Moreover, single-trial ECoG signals carried sufficient information for predicting the stimulated eye with a correct performance approaching 90%, and the decoding was significantly generalized across sessions over 6 hours. Electrode impedance or signal quality did not obviously deteriorate for 2 weeks following implantation. These findings open up a methodology to directly explore ECoG signals with reference to intracortical neuronal sources and would provide a key to developing minimally invasive next-generation brain-machine interfaces.

  4. 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

  5. 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.

  6. 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

  7. 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

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

    PubMed

    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

    2015-11-11

    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.

  9. 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…

  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. Improved surgical procedure using intraoperative navigation for the implantation of the SPG microstimulator in patients with chronic cluster headache.

    PubMed

    Kohlmeier, Carsten; Behrens, Peter; Böger, Andreas; Ramachandran, Brinda; Caparso, Anthony; Schulze, Dirk; Stude, Philipp; Heiland, Max; Assaf, Alexandre T

    2017-01-12

    The ATI SPG microstimulator is designed to be fixed on the posterior maxilla, with the integrated lead extending into the pterygopalatine fossa to electrically stimulate the sphenopalatine ganglion (SPG) as a treatment for cluster headache. Preoperative surgical planning to ensure the placement of the microstimulator in close proximity (within 5 mm) to the SPG is critical for treatment efficacy. The aim of this study was to improve the surgical procedure by navigating the initial dissection prior to implantation using a passive optical navigation system and to match the post-operative CBCT images with the preoperative treatment plan to verify the accuracy of the intraoperative placement of the microstimulator. Custom methods and software were used that result in a 3D rotatable digitally reconstructed fluoroscopic image illustrating the patient-specific placement with the ATI SPG microstimulator. Those software tools were preoperatively integrated with the planning software of the navigation system to be used intraoperatively for navigated placement. Intraoperatively, the SPG microstimulator was implanted by completing the initial dissection with CT navigation, while the final position of the stimulator was verified by 3D CBCT. Those reconstructed images were then immediately matched with the preoperative CT scans with the digitally inserted SPG microstimulator. This method allowed for visual comparison of both CT scans and verified correct positioning of the SPG microstimulator. Twenty-four surgeries were performed using this new method of CT navigated assistance during SPG microstimulator implantation. Those results were compared to results of 21 patients previously implanted without the assistance of CT navigation. Using CT navigation during the initial dissection, an average distance reduction of 1.2 mm between the target point and electrode tip of the SPG microstimulator was achieved. Using the navigation software for navigated implantation and matching the

  13. 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.

    2014-01-01

    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. Conclusions Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs. PMID:25128256

  14. Non-causal spike filtering improves decoding of movement intention for intracortical BCIs.

    PubMed

    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

    2014-10-30

    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. 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 4ms lag between recording and filtering neural signals. 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. Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

    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. 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). 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. 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.

  16. Distinct Corticostriatal and Intracortical Pathways Mediate Bilateral Sensory Responses in the Striatum

    PubMed Central

    Reig, Ramon; Silberberg, Gilad

    2016-01-01

    Individual striatal neurons integrate somatosensory information from both sides of the body, however, the afferent pathways mediating these bilateral responses are unclear. Whereas ipsilateral corticostriatal projections are prevalent throughout the neocortex, contralateral projections provide sparse input from primary sensory cortices, in contrast to the dense innervation from motor and frontal regions. There is, therefore, an apparent discrepancy between the observed anatomical pathways and the recorded striatal responses. We used simultaneous in vivo whole-cell and extracellular recordings combined with focal cortical silencing, to dissect the afferent pathways underlying bilateral sensory integration in the mouse striatum. We show that unlike direct corticostriatal projections mediating responses to contralateral whisker deflection, responses to ipsilateral stimuli are mediated mainly by intracortical projections from the contralateral somatosensory cortex (S1). The dominant pathway is the callosal projection from contralateral to ipsilateral S1. Our results suggest a functional difference between the cortico-basal ganglia pathways underlying bilateral sensory and motor processes. PMID:27664965

  17. 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

  18. Voluntary control of intracortical oscillations for reconfiguration of network activity

    PubMed Central

    Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

    2016-01-01

    Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

  19. 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

  20. Development of a polymer based fully flexible electrode tip for neuronal micro-stimulation applications

    NASA Astrophysics Data System (ADS)

    David, Romain; Miki, Norihisa

    2017-06-01

    Neural stimulation systems design is highly impacted by the overall resolution and adaptability of the device to the targeted application and area to stimulate. In this paper, we report a novel design for neural micro-stimulation electrode presenting high resolution and adaptability to any targeted area via a high flexibility. We propose the use of liquid metal micro-channels encapsulated into a polymer volume, achieving micro-stimulation pads at the tip of the channels. It presents a high degree of patternability to match different possible targeted applications, and good flexibility and mechanic properties to make it insertable and adaptable into soft tissues. A stable fabrication process, including insertion of the liquid alloy into 50 µm half-channels, the necessity of the U-shape to produce functional conductive micro-channels and the mechanical integrity of the device are discussed.

  1. Eliciting naturalistic cortical responses with a sensory prosthesis via optimized microstimulation

    NASA Astrophysics Data System (ADS)

    Choi, John S.; Brockmeier, Austin J.; McNiel, David B.; von Kraus, Lee M.; Príncipe, José C.; Francis, Joseph T.

    2016-10-01

    Objective. Lost sensations, such as touch, could one day be restored by electrical stimulation along the sensory neural pathways. Such stimulation, when informed by electronic sensors, could provide naturalistic cutaneous and proprioceptive feedback to the user. Perceptually, microstimulation of somatosensory brain regions produces localized, modality-specific sensations, and several spatiotemporal parameters have been studied for their discernibility. However, systematic methods for encoding a wide array of naturally occurring stimuli into biomimetic percepts via multi-channel microstimulation are lacking. More specifically, generating spatiotemporal patterns for explicitly evoking naturalistic neural activation has not yet been explored. Approach. We address this problem by first modeling the dynamical input-output relationship between multichannel microstimulation and downstream neural responses, and then optimizing the input pattern to reproduce naturally occurring touch responses as closely as possible. Main results. Here we show that such optimization produces responses in the S1 cortex of the anesthetized rat that are highly similar to natural, tactile-stimulus-evoked counterparts. Furthermore, information on both pressure and location of the touch stimulus was found to be highly preserved. Significance. Our results suggest that the currently presented stimulus optimization approach holds great promise for restoring naturalistic levels of sensation.

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

    PubMed Central

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

    2013-01-01

    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 vs. 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. PMID:23838067

  3. 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.

  4. 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

  5. Electrical Microstimulation of the Pulvinar Biases Saccade Choices and Reaction Times in a Time-Dependent Manner

    PubMed Central

    2017-01-01

    role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar (dPul) are rare. Building on our previous studies that pharmacologically suppressed dPul activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision making. We show that stimulation effects depend on timing and behavioral state and that effects on choices can be dissociated from motor effects. PMID:28119401

  6. Electrical Microstimulation of the Pulvinar Biases Saccade Choices and Reaction Times in a Time-Dependent Manner.

    PubMed

    Dominguez-Vargas, Adan-Ulises; Schneider, Lukas; Wilke, Melanie; Kagan, Igor

    2017-02-22

    role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar (dPul) are rare. Building on our previous studies that pharmacologically suppressed dPul activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision making. We show that stimulation effects depend on timing and behavioral state and that effects on choices can be dissociated from motor effects. Copyright © 2017 Dominguez-Vargas, Schneider et al.

  7. 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

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

    PubMed

    Waldert, Stephan; Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2015-06-03

    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. Copyright © 2015 Waldert et al.

  9. 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

  10. 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

    2016-04-06

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Biological, mechanical, and technological considerations affecting the longevity of intracortical electrode recordings.

    PubMed

    Harris, James P; Tyler, Dustin J

    2013-01-01

    Intracortical electrodes are important tools, with applications ranging from fundamental laboratory studies to potential solutions to intractable clinical applications. However, the longevity and reliability of the interfaces remain their major limitation to the wider implementation and adoption of this technology, especially in broader translational work. Accordingly, this review summarizes the most significant biological and technical factors influencing the long-term performance of intracortical electrodes. In a laboratory setting, intracortical electrodes have been used to study the normal and abnormal function of the brain. This improved understanding has led to valuable insights regarding many neurological conditions. Likewise, clinical applications of intracortical brain-machine interfaces offer the ability to improve the quality of life of many patients afflicted with high-level paralysis from spinal cord injury, brain stem stroke, amyotrophic lateral sclerosis, or other conditions. It is widely hypothesized that the tissue response to the electrodes, including inflammation, limits their longevity. Many studies have examined and modified the tissue response to intracortical electrodes to improve future intracortical electrode technologies. Overall, the relationship between biological, mechanical, and technological considerations are crucial for the fidelity of chronic electrode recordings and represent a presently active area of investigation in the field of neural engineering.

  12. Ovariectomy Stimulates and Bisphosphonates Inhibit Intracortical Remodeling in the Mouse Mandible

    PubMed Central

    Kubek, Daniel J.; Burr, David B.; Allen, Matthew R.

    2010-01-01

    Objective The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. Aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. Material and Methods Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to cancer patients on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur were performed. Results Vehicle-treated OVX animals had significantly higher (8-fold) intracortical remodeling of the alveolar portion of the mandible compared to sham – this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate (BFR) was lower with ZOL treatment compared to the corresponding VEH group. Conclusions Under normal conditions the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition. PMID:21040464

  13. Sensations evoked by microstimulation of single mechanoreceptive afferents innervating the human face and mouth.

    PubMed

    Trulsson, M; Essick, G K

    2010-04-01

    Intraneural microneurography and microstimulation were performed on single afferent axons in the inferior alveolar and lingual nerves innervating the face, teeth, labial, or oral mucosa. Using natural mechanical stimuli, 35 single mechanoreceptive afferents were characterized with respect to unit type [fast adapting type I (FA I), FA hair, slowly adapting type I and II (SA I and SA II), periodontal, and deep tongue units] as well as size and shape of the receptive field. All afferents were subsequently microstimulated with pulse trains at 30 Hz lasting 1.0 s. Afferents recordings whose were stable thereafter were also tested with single pulses and pulse trains at 5 and 60 Hz. The results revealed that electrical stimulation of single FA I, FA hair, and SA I afferents from the orofacial region can evoke a percept that is spatially matched to the afferent's receptive field and consistent with the afferent's response properties as observed on natural mechanical stimulation. Stimulation of FA afferents typically evoked sensations that were vibratory in nature; whereas those of SA I afferents were felt as constant pressure. These afferents terminate superficially in the orofacial tissues and seem to have a particularly powerful access to perceptual levels. In contrast, microstimulation of single periodontal, SA II, and deep tongue afferents failed to evoke a sensation that matched the receptive field of the afferent. These afferents terminate more deeply in the tissues, are often active in the absence of external stimulation, and probably access perceptual levels only when multiple afferents are stimulated. It is suggested that the spontaneously active afferents that monitor tension in collagen fibers (SA II and periodontal afferents) may have the role to register the mechanical state of the soft tissues, which has been hypothesized to help maintain the body's representation in the central somatosensory system.

  14. Radiographically detectable intracortical porosity. The dimensions and frequencies of its components in hand bones of normal men and women.

    PubMed

    Meema, H E

    1986-01-01

    Since the measurement of intracortical resorptive spaces by histologic methods is difficult and very few data are available in normal humans, we have measured their lengths and widths and calculated the intracortical porosity in metacarpals and phalanges of 79 normal women and 69 normal men, using fine-detail radiographs of the hands and a computerized semi-automatic image analysis system (Zeiss MOP-3), this being the first study of this kind. Several methodological problems were solved satisfactorily, and the results of this study could serve as a data bank for further investigations concerned with intracortical resorption. Significant differences were found between age and sex versus several intracortical resorptive parameters; also significant correlations were found with age in some cases. Normal intracortical porosity was found to be about three times greater in the proximal phalanges than in the metacarpals. It is concluded that this methodology could be used for further studies of intracortical resorption in osteoporosis and other metabolic bone diseases.

  15. 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

  16. Anatomy of the Intracortical Canal System: Scanning Electron Microscopy Study in Rabbit Femur

    PubMed Central

    Congiu, Terenzio; Raspanti, Mario; Ranchetti, Federico; Quacci, Daniela

    2009-01-01

    The current model of compact bone is that of a system of longitudinal (Haversian) canals connected by transverse (Volkmann’s) canals. Models based on histology or microcomputed tomography lack the morphologic detail and sense of temporal development provided by direct observation. Using direct scanning electron microscopy observation, we studied the bone surface and structure of the intracortical canal system in paired fractured surfaces in rabbit femurs, examining density of canal openings on periosteal and endosteal surfaces, internal network nodes and canal sizes, and collagen lining of the inner canal system. The blood supply of the diaphyseal compact bone entered the cortex through the canal openings on the endosteal and periosteal surfaces, with different morphologic features in the midshaft and distal shaft; their density was higher on endosteal than on periosteal surfaces in the midshaft but with no major differences among subregions. The circumference measurements along Haversian canals documented a steady reduction behind the head of the cutting cone but rather random variations as the distance from the head increased. These observations suggested discontinuous development and variable lamellar apposition rate of osteons in different segments of their trajectory. The frequent branching and types of network nodes suggested substantial osteonal plasticity and supported the model of a network organization. The collagen fibers of the canal wall were organized in intertwined, longitudinally oriented bundles with 0.1- to 0.5-μm holes connecting the canal lumen with the osteocyte canalicular system. PMID:19330389

  17. Adaptive Offset Correction for Intracortical Brain Computer Interfaces

    PubMed Central

    Homer, Mark L.; Perge, János A.; Black, Michael J.; Harrison, Matthew T.; Cash, Sydney S.; Hochberg, Leigh R.

    2014-01-01

    Intracortical brain computer interfaces (iBCIs) decode intended movement from neural activity for the control of external devices such as a robotic arm. Standard approaches include a calibration phase to estimate decoding parameters. During iBCI operation, the statistical properties of the neural activity can depart from those observed during calibration, sometimes hindering a user’s ability to control the iBCI. To address this problem, we adaptively correct the offset terms within a Kalman filter decoder via penalized maximum likelihood estimation. The approach can handle rapid shifts in neural signal behavior (on the order of seconds) and requires no knowledge of the intended movement. The algorithm, called MOCA, was tested using simulated neural activity and evaluated retrospectively using data collected from two people with tetraplegia operating an iBCI. In 19 clinical research test cases, where a nonadaptive Kalman filter yielded relatively high decoding errors, MOCA significantly reduced these errors (10.6 ±10.1%; p<0.05, pairwise t-test). MOCA did not significantly change the error in the remaining 23 cases where a nonadaptive Kalman filter already performed well. These results suggest that MOCA provides more robust decoding than the standard Kalman filter for iBCIs. PMID:24196868

  18. Adaptive offset correction for intracortical brain-computer interfaces.

    PubMed

    Homer, Mark L; Perge, Janos A; Black, Michael J; Harrison, Matthew T; Cash, Sydney S; Hochberg, Leigh R

    2014-03-01

    Intracortical brain-computer interfaces (iBCIs) decode intended movement from neural activity for the control of external devices such as a robotic arm. Standard approaches include a calibration phase to estimate decoding parameters. During iBCI operation, the statistical properties of the neural activity can depart from those observed during calibration, sometimes hindering a user's ability to control the iBCI. To address this problem, we adaptively correct the offset terms within a Kalman filter decoder via penalized maximum likelihood estimation. The approach can handle rapid shifts in neural signal behavior (on the order of seconds) and requires no knowledge of the intended movement. The algorithm, called multiple offset correction algorithm (MOCA), was tested using simulated neural activity and evaluated retrospectively using data collected from two people with tetraplegia operating an iBCI. In 19 clinical research test cases, where a nonadaptive Kalman filter yielded relatively high decoding errors, MOCA significantly reduced these errors ( 10.6 ± 10.1% ; p < 0.05, pairwise t-test). MOCA did not significantly change the error in the remaining 23 cases where a nonadaptive Kalman filter already performed well. These results suggest that MOCA provides more robust decoding than the standard Kalman filter for iBCIs.

  19. Role of intracortical inhibition in selective hand muscle activation.

    PubMed

    Stinear, Cathy M; Byblow, Winston D

    2003-04-01

    Previous studies have shown that intracortical inhibition (ICI) plays an important role in shaping the output from primary motor cortex (M1). This study explored the muscle specificity and temporal modulation of ICI during the performance of a phasic index finger flexion task. Fifteen subjects were asked to rest their dominant hand on a computer mouse and depress the mouse button using their index finger in time with a 1-Hz auditory metronome, while keeping the rest of their hand as relaxed as possible. Responses to single- and paired-pulse transcranial magnetic stimulation were recorded from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles while subjects were at rest and during "on" and "off" phases of the task. For FDI during the on phase, motor evoked potential (MEP) amplitude and pretrigger EMG increased and ICI decreased, as expected. This pattern of modulation was also observed for APB in seven subjects. The remaining eight subjects demonstrated a decrease in MEP amplitude and increase in ICI for APB during the on phase. This was associated with significantly less APB activation during the on phase. These findings suggest that an increase in ICI and decrease in corticospinal excitability can prevent unwanted muscle activation in a muscle-specific, temporally modulated manner.

  20. Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1

    PubMed Central

    Dagnino, Bruno; Gariel-Mathis, Marie-Alice

    2014-01-01

    Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness. We investigated the interactions between the primary visual cortex (V1) and area V4 by applying microstimulation in both cortical areas at various delays. We report that the monkeys detected the phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation did not influence V1 phosphene detection thresholds. A second experiment examined the influence of V4 microstimulation on the monkeys' ability to detect the dimming of one of three peripheral visual stimuli. Again, microstimulation of a group of V4 neurons failed to modulate the monkeys' perception of a stimulus in their receptive field. We conclude that conditions exist where microstimulation of area V4 has only a limited influence on visual perception. PMID:25392172

  1. Asynchronous distributed multielectrode microstimulation reduces seizures in the dorsal tetanus toxin model of temporal lobe epilepsy

    PubMed Central

    Desai, Sharanya Arcot; Rolston, John D.; McCracken, Courtney E.; Potter, Steve M.; Gross, Robert E.

    2015-01-01

    Background Electrical brain stimulation has shown promise for reducing seizures in drug-resistant epilepsy, but the electrical stimulation parameter space remains largely unexplored. New stimulation parameters, electrode types, and stimulation targets may be more effective in controlling seizures compared to currently available options. Hypothesis We hypothesized that a novel electrical stimulation approach involving distributed multielectrode microstimulation at the epileptic focus would reduce seizure frequency in the tetanus toxin model of temporal lobe epilepsy. Methods We explored a distributed multielectrode microstimulation (DMM) approach in which electrical stimulation was delivered through 15 33-µm-diameter electrodes implanted at the epileptic focus (dorsal hippocampus) in the rat tetanus toxin model of temporal lobe epilepsy. Results We show that hippocampal theta (6–12 Hz brain oscillations) is decreased in this animal model during awake behaving conditions compared to control animals (p< 10−4). DMM with biphasic, theta-range (6–12 Hz/ electrode) pulses delivered asynchronously on the 15 microelectrodes was effective in reducing seizures by 46% (p<0.05). When theta pulses or sinusoidal stimulation was delivered synchronously and continuously on the 15 microelectrodes, or through a single macroelectrode, no effects on seizure frequency were observed. High frequency stimulation (>16.66 Hz/per electrode), in contrast, had a tendency to increase seizure frequency. Conclusions These results indicate that DMM could be new effective approach to therapeutic brain stimulation for reducing seizures in epilepsy. PMID:26607483

  2. 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.

  3. 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

  4. Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

    PubMed Central

    Di Lazzaro, V; Oliviero, A; Saturno, E; Dileone, M; Pilato, F; Nardone, R; Ranieri, F; Musumeci, G; Fiorilla, T; Tonali, P

    2005-01-01

    Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABAA receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABAA activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABAA activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F3,9 = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F3,9 = 9.39, P = 0.0002). Our findings demonstrate that GABAA activity enhancement determines a suppression of SAI and an increase of SICI. PMID:15718269

  5. Intracortical Network Effects Preserve Thalamocortical Input Efficacy in a Cortex Without Layers.

    PubMed

    Guy, Julien; Sachkova, Alexandra; Möck, Martin; Witte, Mirko; Wagener, Robin J; Staiger, Jochen F

    2017-10-01

    Layer IV (LIV) of the rodent somatosensory cortex contains the somatotopic barrel field. Barrels receive much of the sensory input to the cortex through innervation by thalamocortical axons from the ventral posteromedial nucleus. In the reeler mouse, the absence of cortical layers results in the formation of mispositioned barrel-equivalent clusters of LIV fated neurons. Although functional imaging suggests that sensory input activates the cortex, little is known about the cellular and synaptic properties of identified excitatory neurons of the reeler cortex. We examined the properties of thalamic input to spiny stellate (SpS) neurons in the reeler cortex with in vitro electrophysiology, optogenetics, and subcellular channelrhodopsin-2-assisted circuit mapping (sCRACM). Our results indicate that reeler SpS neurons receive direct but weakened input from the thalamus, with a dispersed spatial distribution along the somatodendritic arbor. These results further document subtle alterations in functional connectivity concomitant of absent layering in the reeler mutant. We suggest that intracortical amplification mechanisms compensate for this weakening in order to allow reliable sensory transmission to the mutant neocortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans.

    PubMed

    Di Lazzaro, V; Oliviero, A; Saturno, E; Dileone, M; Pilato, F; Nardone, R; Ranieri, F; Musumeci, G; Fiorilla, T; Tonali, P

    2005-04-15

    Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA(A) receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA(A) activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F(3,9) = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity enhancement determines a suppression of SAI and an increase of SICI.

  7. 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

  8. Impaired modulation of intracortical inhibition in focal hand dystonia.

    PubMed

    Stinear, Cathy M; Byblow, Winston D

    2004-05-01

    Previous studies have shown that intracortical inhibition (ICI) plays an important role in shaping the output from primary motor cortex, and that ICI may be impaired in people with Focal Hand Dystonia (FHD). This study explored the muscle-specificity and temporal modulation of ICI during the performance of a phasic index finger flexion task. Eight control subjects and seven with FHD were asked to rest their dominant hand upon a computer mouse, and depress the mouse button using their index finger in time with a 1 Hz auditory metronome, while keeping the rest of their hand as relaxed as possible. Responses to single and paired-pulse transcranial magnetic stimulation were recorded from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles while subjects were at rest and during 'on' and 'off' phases of the task. For control subjects during the movement (i). FDI motor evoked potential (MEP) amplitude and pretrigger EMG increased, and ICI decreased, as expected, and (ii). there was no significant facilitation of MEP amplitude or pretrigger EMG for APB, which was associated with a significant increase in ICI during the movement. This may have helped prevent the unwanted activation of this muscle. While FHD subjects demonstrated the same patterns of modulation of both MEP amplitude and pretrigger EMG for both FDI and APB, their levels of ICI were not modulated by task performance. This was despite no difference between subject groups in the level of ICI observed at rest. These findings suggest that FHD is associated with impaired modulation of ICI during performance of a precise manual task, which may contribute to a lack of specificity in the output from M1 and the development of dystonic symptoms.

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

    PubMed

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

    2014-10-01

    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 [R(2)  = 0.68, P < 0.004], total osteon area [R(2)  = 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 interindividual variation in remodeling differentially impacts skeletal aging and an individuals' potential response to prophylactic treatments.

  10. Long-interval intracortical inhibition in a human hand muscle.

    PubMed

    McNeil, Chris J; Martin, Peter G; Gandevia, Simon C; Taylor, Janet L

    2011-03-01

    When two motor cortical stimuli are delivered with an interstimulus interval of 50-200 ms, the response (motor evoked potential; MEP) to the second stimulus is typically suppressed. This phenomenon is termed long-interval intracortical inhibition (LICI), although data from one subject suggest that facilitation is possible. Moreover, we recently showed that suppression can be mediated at a spinal level. We characterized LICI more fully by exploring a broad range of contraction strengths and test stimulus intensities. MEPs were evoked in first dorsal interosseous by transcranial magnetic stimulation over the motor cortex. Single test and paired (conditioning-test interval of 100 ms) stimuli at intensities of 100-160% resting motor threshold were delivered at rest or during brief contractions of 10, 25, or 100% maximal voluntary force. Inhibition or facilitation was quantified with the standard ratio in which conditioned MEPs were expressed as a percentage of unconditioned MEPs. Inhibition was greatest at weak-moderate contraction strengths and least at rest and during maximal efforts. Both at rest and during maximal efforts, MEPs evoked by strong stimuli were facilitated. In a subset of subjects, cervicomedullary stimulation was used to activate the corticospinal tract to identify possible spinal influences on changes to MEPs. Contraction strength and test stimulus intensity each had different effects on unconditioned and conditioned MEP size, and hence, LICI is highly dependent on both factors. Further, because motoneurons are facilitated during contraction but disfacilitated after a strong conditioning stimulus, the standard ratio of LICI is of questionable validity during voluntary contractions.

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

    PubMed

    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

  12. 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

  13. Selective Modulation of the Pupil Light Reflex by Microstimulation of Prefrontal Cortex.

    PubMed

    Ebitz, R Becket; Moore, Tirin

    2017-05-10

    The prefrontal cortex (PFC) is thought to flexibly regulate sensorimotor responses, perhaps through modulating activity in other circuits. However, the scope of that control remains unknown: it remains unclear whether the PFC can modulate basic reflexes. One canonical example of a central reflex is the pupil light reflex (PLR): the automatic constriction of the pupil in response to luminance increments. Unlike pupil size, which depends on the interaction of multiple physiological and neuromodulatory influences, the PLR reflects the action of a simple brainstem circuit. However, emerging behavioral evidence suggests that the PLR may be modulated by cognitive processes. Although the neural basis of these modulations remains unknown, one possible source is the PFC, particularly the frontal eye field (FEF), an area of the PFC implicated in the control of attention. We show that microstimulation of the rhesus macaque FEF alters the magnitude of the PLR in a spatially specific manner. FEF microstimulation enhanced the PLR to probes presented within the stimulated visual field, but suppressed the PLR to probes at nonoverlapping locations. The spatial specificity of this effect parallels the effect of FEF stimulation on attention and suggests that FEF is capable of modulating visuomotor transformations performed at a lower level than was previously known. These results provide evidence of the selective regulation of a basic brainstem reflex by the PFC.SIGNIFICANCE STATEMENT The pupil light reflex (PLR) is our brain's first and most fundamental mechanism for light adaptation. Although it is often described in textbooks as being an immutable reflex, converging evidence suggests that the magnitude of the PLR is modulated by cognitive factors. The neural bases of these modulations are unknown. Here, we report that microstimulation in the prefrontal cortex (PFC) modulates the gain of the PLR, changing how a simple reflex circuit responds to physically identical stimuli. These

  14. Black bears with longer disuse (hibernation) periods have lower femoral osteon population density and greater mineralization and intracortical porosity.

    PubMed

    Wojda, Samantha J; Weyland, David R; Gray, Sarah K; McGee-Lawrence, Meghan E; Drummer, Thomas D; Donahue, Seth W

    2013-08-01

    Intracortical bone remodeling is persistent throughout life, leading to age related increases in osteon population density (OPD). Intracortical porosity also increases with age in many mammals including humans, contributing to bone fragility and fracture risk. Unbalanced bone resorption and formation during disuse (e.g., physical inactivity) also increases intracortical porosity. In contrast, hibernating bears are a naturally occurring model for the prevention of both age-related and disuse osteoporoses. Intracortical bone remodeling is decreased during hibernation, but resorption and formation remain balanced. Black bears spend 0.25-7 months in hibernation annually depending on climate and food availability. We found longer hibernating bears demonstrate lower OPD and higher cortical bone mineralization than bears with shorter hibernation durations, but we surprisingly found longer hibernating bears had higher intracortical porosity. However, bears from three different latitudes showed age-related decreases in intracortical porosity, indicating that regardless of hibernation duration, black bears do not show the disuse- or age-related increases in intracortical porosity which is typical of other animals. This ability to prevent increases in intracortical porosity likely contributes to their ability to maintain bone strength during prolonged periods of physical inactivity and throughout life. Improving our understanding of the unique bone metabolism in hibernating bears will potentially increase our ability to develop treatments for age- and disuse-related osteoporoses in humans.

  15. Ovariectomy stimulates and bisphosphonates inhibit intracortical remodeling in the mouse mandible.

    PubMed

    Kubek, D J; Burr, D B; Allen, M R

    2010-11-01

    The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. The aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to patients with cancer on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur was performed. Vehicle-treated OVX animals had significantly higher (eightfold) intracortical remodeling of the alveolar portion of the mandible compared to sham--this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate was lower with ZOL treatment compared to the corresponding VEH group. Under normal conditions, the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice it can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition. © 2010 John Wiley & Sons A/S.

  16. 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

  17. 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

  18. 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

    2016-05-07

    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.

  19. 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

    2016-08-11

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  1. 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. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  2. 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

  3. Sensations evoked by intraneural microstimulation of C nociceptor fibres in human skin nerves.

    PubMed Central

    Ochoa, J; Torebjörk, E

    1989-01-01

    1. Seventy-one C polymodal nociceptors supplying glabrous and hairy skin in limbs of awake human volunteers were identified on the basis of cutaneous stimulus-response characteristics recorded intraneurally by microneurography (MNG). The large majority of such units were primarily detected during intraneural microstimulation (INMS) on the basis of subjective quality and cutaneous localization of evoked painful sensation. Electrophysiological studies were supplemented with rigorous psychophysical testing during microstimulation delivered at intraneural C recording sites. 2. The conduction velocity of single C nociceptor units could be shown to become transiently slowed following repetitive INMS at threshold intensity for conscious sensation. Such 'marking' witnessed that particular C units, identified by recording, had been effectively activated during INMS and psychophysical testing. 3. Cognitive attributes of sensations evoked from C recording sites by INMS at threshold intensity for perception were estimated psychophysically for subjective quality, temporal attributes and localized projection. There was remarkable matching of physiological unit type (C polymodal nociceptor) with subjective quality of evoked sensation (dull or burning pain). Further, there was remarkable spatial matching of receptive field of given C nociceptors with projected field of the pain sensation evoked from the C recording site by INMS delivered at threshold intensity for conscious sensation. 4. Dissociated A nerve fibre blocks caused by compression-ischaemia did not abolish the sensation of burning pain projected to hairy skin, evoked by INMS delivered at C recording sites. 5. While the double matching of (a) subjective quality and spatial localization with (b) objective physiological unitary type and receptor location, coupled with the results of A blocks, provide evidence that C nociceptor fibres can be fairly selectively activated during INMS, the results also attest that C polymodal

  4. Wireless front-end with power management for an implantable cardiac microstimulator.

    PubMed

    Lee, Shuenn-Yuh; Hsieh, Cheng-Han; Yang, Chung-Min

    2012-02-01

    Inductive coupling is presented with the help of a high-efficiency Class-E power amplifier for an implantable cardiac microstimulator. The external coil inductively transmits power and data with a carrier frequency of 256 kHz into the internal coil of electronic devices inside the body. The detected cardiac signal is fed back to the external device with the same pair of coils to save on space in the telemetry device. To maintain the power reliability of the microstimulator for long-term use, two small rechargeable batteries are employed to supply voltage to the internal circuits. The power management unit, which includes radio frequency front-end circuits with battery charging and detection functions, is used for the supply control. For cardiac stimulation, a high-efficiency charge pump is also proposed in the present paper to generate a stimulated voltage of 3.2 V under a 1 V supply voltage. A phase-locked-loop (PLL)-based phase shift keying demodulator is implemented to efficiently extract the data and clock from an inductive AC signal. The circuits, with an area of 0.45 mm², are implemented in a TSMC 0.35 μm 2P4M standard CMOS process. Measurement results reveal that power can be extracted from the inductive coupling and stored in rechargeable batteries, which are controlled by the power management unit, when one of the batteries is drained. Moreover, the data and clock can be precisely recovered from the coil coupling, and a stimulated voltage of 3.2 V can be readily generated by the proposed charge-pump circuits to stimulate cardiac tissues.

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

    PubMed

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

    2013-06-01

    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. 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). 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. We anticipate that signal acquisition and

  6. Brief communication: Reevaluating osteoporosis in human ribs: the role of intracortical porosity.

    PubMed

    Agnew, Amanda M; Stout, Sam D

    2012-07-01

    Osteoporosis is a major health concern in modern society and is continually being evaluated in past populations by quantifying bone loss. Cortical area measures are commonly used in anthropological analyses to assess bone loss in the ribs, but these values are typically based on endosteal expansion and do not account for intracortical bone loss. The objective of this study is to evaluate the effectiveness of using absolute cortical area, compared to traditional cortical area measures to describe global bone loss in elderly ribs. Transverse sections were prepared from sixth ribs of ten elderly subjects, and bone area measurements were made from 100× magnification composites of each rib for calculation of cortical area (Ct.Ar) and percent cortical area (% C/T). In addition, all areas of intracortical porosity were measured and percent porosity area (% Po.Ar) calculated. Absolute cortical area (Ct.Ar(A)) was calculated by subtracting porosity area from cortical area, and a percent absolute cortical area (% C(A)/T) calculated. ANOVA results reveal significant interindividual variation in percent porosity area (% Po.Ar). Percent cortical area and percent absolute cortical area values were compared and results show a mean difference of 4.08% exists across all subjects, with a range of 1.19-11.73%. This suggests that intracortical porosity is variable and does play a role in age-associated bone loss in the rib. All future investigations of osteoporosis should account for intracortical porosity in bone loss.

  7. 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.

  8. 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

  9. Investigating TMS-EEG Indices of Long-Interval Intracortical Inhibition at Different Interstimulus Intervals.

    PubMed

    Opie, George M; Rogasch, Nigel C; Goldsworthy, Mitchell R; Ridding, Michael C; Semmler, John G

    Long-interval intracortical inhibition (LICI) is a transcranial magnetic stimulation (TMS) paradigm that uses paired magnetic stimuli separated by 100-200 ms to investigate the activity of cortical GABAergic interneurons. While commonly applied, the mechanisms contributing to LICI are not well understood, and growing evidence suggests that inhibition observed at different interstimulus intervals (ISI) may involve non-identical processes. This study aims to utilise combined TMS-EEG to more thoroughly characterise LICI at different ISIs, as the TMS-evoked EEG potential (TEP) can provide more direct insight into the cortical response to stimulation that is not subject to variations in spinal cord excitability that can confound the motor evoked potential (MEP). In 12 subjects (22.6 ± 0.9 years), LICI was applied using two ISIs of 100 ms (LICI100) and 150 ms (LICI150), while TEPs were recorded using simultaneous high-definition EEG. Analysis of EEG data within a region of interest (C3 electrode) showed that test alone stimulation produced three consistent TEP peaks (corresponding to P30, N100 and P180) that were all significantly inhibited following paired-pulse stimulation. However, for P30, inhibition varied between LICI conditions, with reduced amplitude following LICI100 (P = 0.03) but not LICI150 (P = 0.3). In contrast, the N100 and P180 were significantly reduced by LICI at both intervals (all P-values < 0.05). In addition, topographical analyses suggested that the global change in P30, N40 and P180 differed between LICI conditions. These findings suggest that LICI100 and LICI150 reflect complex measurements of cortical inhibition with differential contributions from comparable circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 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.

  11. 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.

  12. Excitability changes in intracortical neural circuits induced by differentially controlled walking patterns.

    PubMed

    Ito, Tomotaka; Tsubahara, Akio; Shinkoda, Koichi; Yoshimura, Yosuke; Kobara, Kenichi; Osaka, Hiroshi

    2015-01-01

    Our previous single-pulse transcranial magnetic stimulation (TMS) study revealed that excitability in the motor cortex can be altered by conscious control of walking relative to less conscious normal walking. However, substantial elements and underlying mechanisms for inducing walking-related cortical plasticity are still unknown. Hence, in this study we aimed to examine the characteristics of electromyographic (EMG) recordings obtained during different walking conditions, namely, symmetrical walking (SW), asymmetrical walking 1 (AW1), and asymmetrical walking 2 (AW2), with left to right stance duration ratios of 1:1, 1:2, and 2:1, respectively. Furthermore, we investigated the influence of three types of walking control on subsequent changes in the intracortical neural circuits. Prior to each type of 7-min walking task, EMG analyses of the left tibialis anterior (TA) and soleus (SOL) muscles during walking were performed following approximately 3 min of preparative walking. Paired-pulse TMS was used to measure short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the left TA and SOL at baseline, immediately after the 7-min walking task, and 30 min post-task. EMG activity in the TA was significantly increased during AW1 and AW2 compared to during SW, whereas a significant difference in EMG activity of the SOL was observed only between AW1 and AW2. As for intracortical excitability, there was a significant alteration in SICI in the TA between SW and AW1, but not between SW and AW2. For the same amount of walking exercise, we found that the different methods used to control walking patterns induced different excitability changes in SICI. Our research shows that activation patterns associated with controlled leg muscles can alter post-exercise excitability in intracortical circuits. Therefore, how leg muscles are activated in a clinical setting could influence the outcome of walking in patients with stroke.

  13. Long-interval intracortical inhibition is asymmetric in young but not older adults.

    PubMed

    Vallence, A-M; Smalley, E; Drummond, P D; Hammond, G R

    2017-09-01

    Aging is typically accompanied by a decline in manual dexterity and handedness; the dominant hand executes tasks of manual dexterity more quickly and accurately than the nondominant hand in younger adults, but this advantage typically declines with age. Age-related changes in intracortical inhibitory processes might play a role in the age-related decline in manual dexterity. Long-interval intracortical inhibition (LICI) is asymmetric in young adults, with more sensitive and more powerful LICI circuits in the dominant hemisphere than in the nondominant hemisphere. Here we investigated whether the hemispheric asymmetry in LICI in younger adults persists in healthy older adults. Paired-pulse transcranial magnetic stimulation was used to measure LICI in the dominant and nondominant hemispheres of younger and older adults; LICI stimulus-response curves were obtained by varying conditioning stimulus intensity at two different interstimulus intervals [100 ms (LICI100) and 150 ms]. We have replicated the finding that LICI100 circuits are more sensitive and more powerful in the dominant than the nondominant hemisphere of young adults and extend this finding to show that the hemispheric asymmetry in LICI100 is lost with age. In the context of behavioral observations showing that dominant hand movements in younger adults are more fluent than nondominant hand movements in younger adults and dominant hand movements in older adults, we speculate a role of LICI100 in the age-related decline in manual dexterity.NEW & NOTEWORTHY In younger adults, more sensitive and more powerful long-interval intracortical inhibitory circuits are evident in the hemisphere controlling the more dexterous hand; this is not the case in older adults, for whom long-interval intracortical inhibitory circuits are symmetric and more variable than in younger adults. We speculate that the highly sensitive and powerful long-interval intracortical inhibition circuits in the dominant hemisphere play a role in

  14. Excitability Changes in Intracortical Neural Circuits Induced by Differentially Controlled Walking Patterns

    PubMed Central

    Ito, Tomotaka; Tsubahara, Akio; Shinkoda, Koichi; Yoshimura, Yosuke; Kobara, Kenichi; Osaka, Hiroshi

    2015-01-01

    Our previous single-pulse transcranial magnetic stimulation (TMS) study revealed that excitability in the motor cortex can be altered by conscious control of walking relative to less conscious normal walking. However, substantial elements and underlying mechanisms for inducing walking-related cortical plasticity are still unknown. Hence, in this study we aimed to examine the characteristics of electromyographic (EMG) recordings obtained during different walking conditions, namely, symmetrical walking (SW), asymmetrical walking 1 (AW1), and asymmetrical walking 2 (AW2), with left to right stance duration ratios of 1:1, 1:2, and 2:1, respectively. Furthermore, we investigated the influence of three types of walking control on subsequent changes in the intracortical neural circuits. Prior to each type of 7-min walking task, EMG analyses of the left tibialis anterior (TA) and soleus (SOL) muscles during walking were performed following approximately 3 min of preparative walking. Paired-pulse TMS was used to measure short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the left TA and SOL at baseline, immediately after the 7-min walking task, and 30 min post-task. EMG activity in the TA was significantly increased during AW1 and AW2 compared to during SW, whereas a significant difference in EMG activity of the SOL was observed only between AW1 and AW2. As for intracortical excitability, there was a significant alteration in SICI in the TA between SW and AW1, but not between SW and AW2. For the same amount of walking exercise, we found that the different methods used to control walking patterns induced different excitability changes in SICI. Our research shows that activation patterns associated with controlled leg muscles can alter post-exercise excitability in intracortical circuits. Therefore, how leg muscles are activated in a clinical setting could influence the outcome of walking in patients with stroke. PMID:25688972

  15. High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Motor Intracortical Neurophysiology: A Sham-Controlled Investigation.

    PubMed

    Malcolm, Matt P; Paxton, Roger J

    2015-10-01

    The purpose of this study was to investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) versus sham stimulation on intracortical inhibition (ICI) and intracortical facilitation within the motor cortex. Such data are needed to better understand the presumed neurophysiologic effects of rTMS. The authors hypothesized that, compared with sham stimulation, 20 Hz rTMS will decrease ICI and increase intracortical facilitation in healthy volunteers. Using single-pulse and paired-pulse TMS, the authors evaluated prestimulation and poststimulation effects on motor cortex neurophysiology in neurologically healthy volunteers who received 2,000 stimuli of either 20 Hz rTMS (n = 11) or sham rTMS (n = 8). Primary outcomes were changes in ICI and intracortical facilitation and secondary outcomes were changes in motor threshold and motor evoked potential amplitude, and both were assessed using separate 2 × 2 (group × time) repeated-measures analysis of variance. For ICI, there were main effects of time (P = 0.002) and group (P < 0.001) with a significant group-by-time interaction (P < 0.01). Intracortical inhibition decreased after rTMS, but was unchanged by sham rTMS. Intracortical facilitation results revealed a main effect of group (P = 0.02) and a significant group-by-time interaction (P = 0.048). Intracortical facilitation increased after rTMS and was slightly reduced after sham rTMS. The group-by-time interactions for motor threshold and motor evoked potential amplitude were not significant. High-frequency rTMS significantly influences the excitatory and inhibitory outputs of motor intracortical networks, specifically increasing intracortical facilitation and reducing ICI as compared with sham stimulation. Such changes were observed despite no significant changes in broader measures of motor cortex activation, that is, motor threshold and motor evoked potential amplitude.

  16. 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

  17. On-line compensation of gaze shifts perturbed by micro-stimulation of the superior colliculus in the cat with unrestrained head.

    PubMed

    Pélisson, D; Guitton, D; Goffart, L

    1995-01-01

    Prior studies have led to the gaze feedback hypothesis, which states that quick orienting movements of the visual axis (gaze shifts) are controlled by a feedback system. We have previously provided evidence for this hypothesis by extending the original study of Mays and Sparks (1980) to the cat with unrestrained head (Pélisson et al. 1989). We showed that cats compensated for a stimulation-induced perturbation of initial gaze position by generating, in the dark, an accurate gaze shift towards the remembered location of a flashed target. In the present study, we investigate goal-directed gaze shifts perturbed "in flight" by a brief stimulation of the superior colliculus. The microstimulation parameters were tuned such that significant perturbations were induced without halting the movement. The ambient light was turned off at the onset of the gaze shift, suppressing any visual feedback. We observed that, following stimulation offset, the gaze shift showed temporal and spatial changes in its trajectory to compensate for the transient perturbation. Such compensations, which occurred "on-line" before gaze shift termination, involved both eye and head movements and had dynamic characteristics resembling those of unperturbed saccadic gaze shifts. These on-line compensations maintained gaze accuracy when the stimulation was applied during the early phase of large and medium (about 60 and 40 degrees) movements. These results are compatible with the notion of a gaze feedback loop providing a dynamic gaze error signal.

  18. 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

  19. 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

  20. Muscle Plasticity in Rat Following Spinal Transection and Chronic Intraspinal Microstimulation

    PubMed Central

    Bamford, Jeremy A.; Putman, Charles T.; Mushahwar, Vivian K.

    2011-01-01

    Intraspinal microstimulation (ISMS) employs electrical stimulation of the ventral grey matter to reactivate paralyzed skeletal muscle. This work evaluated the transformations in the quadriceps muscle that occurred following complete transection and chronic stimulation with ISMS or a standard nerve cuff (NCS). Stimulation was applied for 30 days, 4 hours/day. Both methods induced significant increases in time-to-peak tension (ISMS 35%, NCS 25%) and ½ rise-time (ISMS 39%, NCS 25%) compared to intact controls (IC). Corresponding increases in type-IIA myosin heavy chain (MHC) and decreases in type-IID MHC were noted compared to IC. These results were unexpected because ISMS recruits motor units in a near-normal physiological order while NCS recruits motor units in a reversed order. Spinal cord transection and 30 days of stimulation did not alter either recruitment profile. The slope of the force recruitment curves obtained through ISMS following transection and 30 days of stimulation was similar to that obtained in intact animals, and 3.4-fold shallower than that obtained through NCS. The transformations observed in the current work are best explained by the near maximal level of motor unit recruitment, the total daily time of activity and the tonic nature of the stimulation paradigm. PMID:20813653

  1. Muscle plasticity in rat following spinal transection and chronic intraspinal microstimulation.

    PubMed

    Bamford, Jeremy A; Putman, Charles T; Mushahwar, Vivian K

    2011-02-01

    Intraspinal microstimulation (ISMS) employs electrical stimulation of the ventral grey matter to reactivate paralyzed skeletal muscle. This work evaluated the transformations in the quadriceps muscle that occurred following complete transection and chronic stimulation with ISMS or a standard nerve cuff (NCS). Stimulation was applied for 30 days, 4 h/day. Both methods induced significant increases in time-to-peak tension (ISMS 35%, NCS 25%) and half rise-time (ISMS 39%, NCS 25%) compared to intact controls (IC). Corresponding increases in type-IIA myosin heavy chain (MHC) and decreases in type-IID MHC were noted compared to IC. These results were unexpected because ISMS recruits motor units in a near-normal physiological order while NCS recruits motor units in a reversed order. Spinal cord transection and 30 days of stimulation did not alter either recruitment profile. The slope of the force recruitment curves obtained through ISMS following transection and 30 days of stimulation was similar to that obtained in intact animals, and 3.4-fold shallower than that obtained through NCS. The transformations observed in the current work are best explained by the near maximal level of motor unit recruitment, the total daily time of activity and the tonic nature of the stimulation paradigm.

  2. Real-time adaptive microstimulation increases reliability of electrically evoked cortical potentials.

    PubMed

    Brugger, Dominik; Butovas, Sergejus; Bogdan, Martin; Schwarz, Cornelius

    2011-05-01

    Cortical neuroprostheses that employ repeated electrical stimulation of cortical areas with fixed stimulus parameters, are faced with the problem of large trial-by-trial variability of evoked potentials. This variability is caused by the ongoing cortical signal processing, but it is an unwanted phenomenon if one aims at imprinting neural activity as precisely as possible. Here, we use local field potentials measured by one microelectrode, located at a distance of 200 microns from the stimulation site, to drive the electrically evoked potential toward a desired target potential by real-time adaptation of the stimulus intensity. The functional relationship between ongoing cortical activity, evoked potential, and stimulus intensity was estimated by standard machine learning techniques (support vector regression with problem-specific kernel function) from a set of stimulation trials with randomly varied stimulus intensities. The smallest deviation from the target potential was achieved for low stimulus intensities. Further, the observed precision effect proved time sensitive, since it was abolished by introducing a delay between data acquisition and stimulation. These results indicate that local field potentials contain sufficient information about ongoing local signal processing to stabilize electrically evoked potentials. We anticipate that adaptive low intensity microstimulation will play an important role in future cortical prosthetic devices that aim at restoring lost sensory functions.

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

    PubMed Central

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

    2013-01-01

    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 Eighty-four percent of the recorded units showed a statistically significant change in apparent firing rate (3.8±8.71Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and seventy-four percent of the units showed a significant change in spike amplitude (3.7±6.5μV or 5.5% of mean spike amplitude). Forty percent 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 fifty-six percent of all performance assessments in participant cursor control (n=2 participants, 108 and 20 assessments over two years), resulting in

  4. 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

  5. Intracortical inhibition and facilitation with unilateral dominant, unilateral nondominant and bilateral movement tasks in left and right handed adults

    PubMed Central

    Waller, Sandy McCombe; Forrester, Larry; Villagra, Federico; Whitall, Jill

    2009-01-01

    Purpose To investigate intracortical inhibition and facilitation in response to unilateral dominant, nondominant and bilateral biceps activation and short-term upper extremity training in right and left-handed adults. Methods Paired-pulse transcranial magnetic stimulation was used to measure intracortical excitability in motor dominant and nondominant cortices of 26 nondisabled adults. Neural facilitation and inhibition were measured in each hemisphere during unilateral dominant, nondominant and bilateral arm activation and after training in each condition. Results No differences were seen between right and left- handed subjects. Intracortical facilitation and decreased inhibition were seen in each hemisphere with unilateral activation/training of contralateral muscles and bilateral muscle activation/training. Persistent intracortical inhibition was seen in each hemisphere with ipsilateral muscle activation/training. Inhibition was greater in the nondominant hemisphere during dominant hemisphere activation (dominant arm contraction). Conclusion Strongly dominant individuals show no difference in intracortical responses given handedness. Intracortical activity with unilateral and bilateral arm activation and short-term training differs based on hemispheric dominance, with the motor dominant hemisphere exerting a larger inhibitory influence over the nondominant hemisphere. Bilateral activation and training has a disinhibitory effect in both dominant and nondominant hemispheres. PMID:18336839

  6. Isolation of components due to intracortical processing in the visual evoked potential.

    PubMed Central

    Victor, J D

    1986-01-01

    A class of stochastic visual textures are used to analyze the components of the visual evoked potential (VEP). This procedure exploits the differential sensitivity of populations of visual neurons to aspects of contrast and pattern. A simple transformation of VEP responses elicited by these stimuli separates components that reflect complex aspects of visual processing from those that reflect elementary aspects. Simultaneous recordings of the VEP and cellular activity in the cat lateral geniculate nucleus are obtained. Responses to traditional VEP stimuli contain a mixture of intracortically generated and precortically generated components. A theoretical and experimental analysis demonstrates that the present approach cleanly separates intracortical generators of the VEP from precortical generators. Images PMID:3464015

  7. Effect of atropine on intracortical evoked potentials during classical aversive conditioning in cats.

    PubMed

    Molnár, M; Karmos, G; Csépe, V

    1988-12-01

    In this article, intracortical evoked potentials (EPs) were recorded simultaneously from six different depths of the auditory cortex of freely moving cats. The effect of (a) different states of vigilance and that of atropine, (b) classical aversive conditioning, and (c) the effect of atropine during conditioning was studied on the intracortical EP profiles. Atropine induced EP changes that were similar to those seen in slow wave sleep. During classical aversive conditioning signal stimuli elicited a middle-latency negative EP component which was localized to the superficial cortical layers. Atropine (2 mg/kg body weight) did not abolish the appearance of this component but only increased its latency. It is proposed that the cholinergic part of the ascending activating system did not play an essential role in its generation.

  8. 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

  9. 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.

  10. Preparation for the Implantation of an Intracortical Visual Prosthesis in a Human

    DTIC Science & Technology

    2014-10-01

    tasks when provided with the simulated prosthetic vision obtained by the overlaying the phosphene map on the visual imagery. Figure 9. Design of...optic nerve prostheses,” Disability and Rehabilitation : Assistive Technology : 1–9. (doi:10.3109/17483107.2014.961178) Posted online on 26 Nov 2014. 2...to the intracortical visual prosthesis: final themes from the analysis of focus group data” Disability and Rehabilitation : Assistive Technology, Vol

  11. Preparation for the Implantation of an Intracortical Visual Prosthesis in a Human

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-12-1-0394 TITLE: Preparation for the Implantation of an...REPORT DATE 201 2. REPORT TYPE Annual 3. DATES COVERED 4. TITLE AND SUBTITLE Preparation for the Implantation of an Intracortical Visual...work. Preparatory tasks include final maturation of the implantable hardware, pre FDA IDE testing of the ICVP in non-human primates, reliability and

  12. Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study.

    PubMed

    Nardone, Raffaele; De Blasi, Pierpaolo; Höller, Yvonne; Brigo, Francesco; Golaszewski, Stefan; Frey, Vanessa N; Orioli, Andrea; Trinka, Eugen

    2016-10-01

    Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits,  but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.

  13. Intracortical Circuits in Thalamorecipient Layers of Auditory Cortex Refine after Visual Deprivation

    PubMed Central

    Meng, Xiangying; Kao, Joseph P. Y.

    2017-01-01

    Sensory cortices do not work in isolation. The functional responses of neurons in primary sensory cortices can be affected by activity from other modalities. For example, short-term visual deprivations, or dark exposure (DE), leads to enhanced neuronal responses and frequency selectivity to sounds in layer 4 (L4) of primary auditory cortex (A1). Circuit changes within A1 likely underlie these changes. Prior studies revealed that DE enhanced thalamocortical transmission to L4 in A1. Because the frequency selectivity of L4 neurons is determined by both thalamocortical and intracortical inputs, changes in intralaminar circuits to L4 neurons might also contribute to improved sound responses. We thus investigated in mouse A1 whether intracortical circuits to L4 cells changed after DE. Using in vitro whole-cell patch recordings in thalamocortical slices from mouse auditory cortex, we show that DE can lead to refinement of interlaminar excitatory as well as inhibitory connections from L2/3 to L4 cells, manifested as a weakening of these connections. The circuit refinement is present along the tonotopic axis, indicating reduced integration along the tonotopic axis. Thus, cross-modal influences may alter the spectral and temporal processing of sensory stimuli in multiple cortical layers by refinement of thalamocortical and intracortical circuits. PMID:28396883

  14. Cortical neural excitations in rats in vivo with using a prototype of a wireless multi-channel microstimulation system.

    PubMed

    Hayashida, Yuki; Umehira, Yuichi; Takatani, Kouki; Futami, Shigetoshi; Kameda, Seiji; Kamata, Takatsugu; Khan, Arif Ullah; Takeuchi, Yoshinori; Imai, Masaharu; Yagi, Tetsuya

    2015-08-01

    Understanding neural responses to multi-site electrical stimuli would be of essential importance for developing cortical neural prostheses. In order to provide a tool for such studies in experimental animals, we recently constructed a prototype of a wireless multi-channel microstimulation system, consisting of a stimulator chip, wireless data/power transmitters and receivers, and microcomputers. The proper operations of the system in cortical neural excitations were examined in anesthetized rats in vivo, with utilizing the voltage-sensitive dye imaging technique.

  15. Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling.

    PubMed

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

    2015-02-01

    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 22h/d, 7 d/wk for 12months. Control monkeys (n=13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7±0.2g alcohol/kg/d (mean±SE) during the 12months of self-administration, resulting in a mean daily blood alcohol concentration of 77±9mg/dl from samples taken at 7h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250mg/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/mm(2)versus 0.04±0.01/mm(2), p<0.003) in alcohol-consuming monkeys compared to controls, indicating a reduced rate of intracortical bone remodeling. In concordance, plasma CTx

  16. 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

  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. 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.

  19. 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.

  20. An intra-neural microstimulation system for ultra-high field magnetic resonance imaging and magnetoencephalography.

    PubMed

    Glover, Paul M; Watkins, Roger H; O'Neill, George C; Ackerley, Rochelle; Sanchez-Panchuelo, Rosa; McGlone, Francis; Brookes, Matthew J; Wessberg, Johan; Francis, Susan T

    2017-10-01

    Intra-neural microstimulation (INMS) is a technique that allows the precise delivery of low-current electrical pulses into human peripheral nerves. Single unit INMS can be used to stimulate individual afferent nerve fibres during microneurography. Combining this with neuroimaging allows the unique monitoring of central nervous system activation in response to unitary, controlled tactile input, with functional magnetic resonance imaging (fMRI) providing exquisite spatial localisation of brain activity and magnetoencephalography (MEG) high temporal resolution. INMS systems suitable for use within electrophysiology laboratories have been available for many years. We describe an INMS system specifically designed to provide compatibility with both ultra-high field (7T) fMRI and MEG. Numerous technical and safety issues are addressed. The system is fully analogue, allowing for arbitrary frequency and amplitude INMS stimulation. Unitary recordings obtained within both the MRI and MEG screened-room environments are comparable with those obtained in 'clean' electrophysiology recording environments. Single unit INMS (current <7μA, 200μs pulses) of individual mechanoreceptive afferents produces appropriate and robust responses during fMRI and MEG. This custom-built MRI- and MEG-compatible stimulator overcomes issues with existing INMS approaches; it allows well-controlled switching between recording and stimulus mode, prevents electrical shocks because of long cable lengths, permits unlimited patterns of stimulation, and provides a system with improved work-flow and participant comfort. We demonstrate that the requirements for an INMS-integrated system, which can be used with both fMRI and MEG imaging systems, have been fully met. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  1. Intraspinal microstimulation preferentially recruits fatigue-resistant muscle fibres and generates gradual force in rat

    PubMed Central

    Bamford, JA; Putman, CT; Mushahwar, VK

    2005-01-01

    Intraspinal microstimulation (ISMS), a novel rehabilitative therapy consisting of stimulation through fine, hair-like microwires targeted at the ventral spinal cord, has been proposed for restoring standing and walking following spinal cord injury. This study compared muscle recruitment characteristics of ISMS with those produced by peripheral nerve cuff stimulation (NCS). Thirty-three minutes of either ISMS or NCS at 1, 20 or 50 s−1 and 1.2 × threshold (T) amplitude depleted glycogen from muscle fibres of vastus lateralis and rectus femoris. ISMS and NCS were also carried out at 20 s−1 and 3.0T. Muscle serial sections were stained for glycogen and for myosin heavy chain (MHC)-based fibre types using a panel of monoclonal antibodies. The results of this study show that ISMS recruited fatigue-resistant (FR) fibres at 2.9, 1.9, 1.7 and 2.5 times their relative MHC content at 1, 20 and 50 s−1 1.2T and 20 s−1 3.0T, respectively. In contrast, NCS recruited FR fibres at 1.2, 1.0, 2.1 and 0.0 times their MHC content at 1, 20 and 50 s−1 1.2T and 20 s−1 3.0T, respectively. The proportion of FR fibres recruited by ISMS and NCS was significantly different in the 20 s−1 3.0T condition (P < 0.0001). We also report that force recruitment curves were 4.9-fold less steep (P < 0.019) for ISMS than NCS. The findings of this study provide evidence for the efficacy of ISMS and further our understanding of muscle recruitment properties of this novel rehabilitative therapy. PMID:16239281

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. The use of XFEM to assess the influence of intra-cortical porosity on crack propagation.

    PubMed

    Rodriguez-Florez, Naiara; Carriero, Alessandra; Shefelbine, Sandra J

    2017-03-01

    This study aimed at using eXtended finite element method (XFEM) to characterize crack growth through bone's intra-cortical pores. Two techniques were compared using Abaqus: (1) void material properties were assigned to pores; (2) multiple enrichment regions with independent crack-growth possibilities were employed. Both were applied to 2D models of transverse images of mouse bone with differing porous structures. Results revealed that assigning multiple enrichment regions allows for multiple cracks to be initiated progressively, which cannot be captured when the voids are filled. Therefore, filling pores with one enrichment region in the model will not create realistic fracture patterns in Abaqus-XFEM.

  9. Sensations evoked by intraneural microstimulation of single mechanoreceptor units innervating the human hand.

    PubMed Central

    Ochoa, J; Torebjörk, E

    1983-01-01

    Intraneural microstimulation (i.n.m.s.) was performed in awake human volunteers, using tungsten micro-electrodes inserted into median and ulnar nerve fascicles supplying the skin of the hand. The same electrodes were used alternatively to record impulse activity from single nerve fibres at the i.n.m.s. sites. Monitoring occasionally, with a proximal electrode, the impulse traffic evoked by i.n.m.s. distally in the same fascicle, established that the stimulation procedure could be made selective enough to activate single myelinated fibres in isolation, while also permitting multifibre recruitment. Monitoring propagated impulses also established that i.n.m.s. of a single myelinated fibre supplying a low-threshold mechanoreceptor in the hand might evoke an elementary sensation. Such sensations were fully endowed with cognitive attributes amenable to psychophysical estimation: quality, magnitude and localized projection. Psychophysical tests were made during i.n.m.s. at intraneural sites where single-unit activity was recorded from classified RA, PC, SA I or SA II mechanoreceptors. Changes in excitability of the nerve fibre of an identified unit, induced by further i.n.m.s., certified that the recorded unit had been stimulated during psychophysical tests. Comparing physical location of the receptive field of a recorded unit and localization of the projected field of the corresponding elementary sensation, revealed that either predicted the other accurately. This further assisted identification of the unit activated by i.n.m.s. The type of a recorded unit and the quality of the elementary sensation evoked by its activation were also reciprocally predictive. RA units evoked intermittent tapping, PC units vibration or tickle and SA I units evoked pressure. SA II units evoked no sensation when activated in isolation. Afferent impulse frequency determined magnitude of pressure in the SA I system, and frequency of vibration in the PC system. In the RA system, stimulation

  10. 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

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

    PubMed

    Grahn, Peter J; Lee, Kendall H; 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

    2015-07-01

    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. 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. 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 between movements evoked

  12. Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

    PubMed Central

    Pilurzi, G; Hasan, A; Saifee, T A; Tolu, E; Rothwell, J C; Deriu, F

    2013-01-01

    Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5–200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation–TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system. PMID:23297305

  13. Disturbed intracortical excitability in early Parkinson's disease is l-DOPA dose related: a prospective 12-month paired TMS study.

    PubMed

    Bares, Martin; Kanovský, Petr; Rektor, Ivan

    2007-12-01

    We were interested to know if chronic l-DOPA treatment in Parkinson's disease (PD) patients could restore impairment of the intracortical excitability, when this difference could occur, and if it was related to the total daily dose of l-DOPA. Twelve patients with early PD were studied using paired transcranial magnetic stimulation before the administration of l-DOPA, and then after 3, 6, and 12 months of l-DOPA treatment. The level of disturbed intracortical excitability strongly correlated with the total daily dose of l-DOPA. The level of cortical excitability in PD patients seems to be indirectly related to the nigro-striatal functioning.

  14. Intracortical myelination in musicians with absolute pitch: Quantitative morphometry using 7‐T MRI

    PubMed Central

    Knösche, Thomas R.

    2016-01-01

    Abstract Absolute pitch (AP) is known as the ability to recognize and label the pitch chroma of a given tone without external reference. Known brain structures and functions related to AP are mainly of macroscopic aspects. To shed light on the underlying neural mechanism of AP, we investigated the intracortical myeloarchitecture in musicians with and without AP using the quantitative mapping of the longitudinal relaxation rates with ultra‐high‐field magnetic resonance imaging at 7 T. We found greater intracortical myelination for AP musicians in the anterior region of the supratemporal plane, particularly the medial region of the right planum polare (PP). In the same region of the right PP, we also found a positive correlation with a behavioral index of AP performance. In addition, we found a positive correlation with a frequency discrimination threshold in the anterolateral Heschl's gyrus in the right hemisphere, demonstrating distinctive neural processes of absolute recognition and relative discrimination of pitch. Regarding possible effects of local myelination in the cortex and the known importance of the anterior superior temporal gyrus/sulcus for the identification of auditory objects, we argue that pitch chroma may be processed as an identifiable object property in AP musicians. Hum Brain Mapp 37:3486–3501, 2016. © 2016 Wiley Periodicals, Inc. PMID:27160707

  15. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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

  18. 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.

  19. Binocular matching of thalamocortical and intracortical circuits in the mouse visual cortex

    PubMed Central

    Gu, Yu; Cang, Jianhua

    2016-01-01

    Visual cortical neurons are tuned to similar orientations through the two eyes. The binocularly-matched orientation preference is established during a critical period in early life, but the underlying circuit mechanisms remain unknown. Here, we optogenetically isolated the thalamocortical and intracortical excitatory inputs to individual layer 4 neurons and studied their binocular matching. In adult mice, the thalamic and cortical inputs representing the same eyes are similarly tuned and both are matched binocularly. In mice before the critical period, the thalamic input is already slightly matched, but the weak matching is not manifested due to random connections in the cortex, especially those serving the ipsilateral eye. Binocular matching is thus mediated by orientation-specific changes in intracortical connections and further improvement of thalamic matching. Together, our results suggest that the feed-forward thalamic input may play a key role in initiating and guiding the functional refinement of cortical circuits in critical period development. DOI: http://dx.doi.org/10.7554/eLife.22032.001 PMID:28033094

  20. 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.

  1. A Systematic Relationship Between Functional Connectivity and Intracortical Myelin in the Human Cerebral Cortex.

    PubMed

    Huntenburg, Julia M; Bazin, Pierre-Louis; Goulas, Alexandros; Tardif, Christine L; Villringer, Arno; Margulies, Daniel S

    2017-02-01

    Research in the macaque monkey suggests that cortical areas with similar microstructure are more likely to be connected. Here, we examine this link in the human cerebral cortex using 2 magnetic resonance imaging (MRI) measures: quantitative  T1 maps, which are sensitive to intracortical myelin content and provide an in vivo proxy for cortical microstructure, and resting-state functional connectivity. Using ultrahigh-resolution MRI at 7 T and dedicated image processing tools, we demonstrate a systematic relationship between T1-based intracortical myelin content and functional connectivity. This effect is independent of the proximity of areas. We employ nonlinear dimensionality reduction to characterize connectivity components and identify specific aspects of functional connectivity that are linked to myelin content. Our results reveal a consistent spatial pattern throughout different analytic approaches. While functional connectivity and myelin content are closely linked in unimodal areas, the correspondence is lower in transmodal areas, especially in posteromedial cortex and the angular gyrus. Our findings are in agreement with comprehensive reports linking histologically assessed microstructure and connectivity in different mammalian species and extend them to the human cerebral cortex in vivo. © The Author 2017. Published by Oxford University Press.

  2. 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

  3. Greater occipital nerve stimulation via the Bion microstimulator: implantation technique and stimulation parameters. Clinical trial: NCT00205894.

    PubMed

    Trentman, Terrence L; Rosenfeld, David M; Vargas, Bert B; Schwedt, Todd J; Zimmerman, Richard S; Dodick, David W

    2009-01-01

    Millions of patients suffer from medically refractory and disabling primary headache disorders. This problem has led to a search for new and innovative treatment modalities, including neuromodulation of the occipital nerves. The primary aim of this study is to describe an implantation technique for the Bion microstimulator and document stimulation parameters and stimulation maps after Bion placement adjacent to the greater occipital nerve. The secondary aim is to document outcome measures one year post-implant. Prospective, observational feasibility study. Nine patients with medically refractory primary headache disorders participated in this study. Approximately 6 months after Bion insertion, stimulation parameters and maps were documented for all patients. At one year, outcome measures were collected including the Migraine Disability Assessment Score. At 6 months, the mean perception threshold was 0.47 mA, while the mean discomfort threshold was 6.8 mA (stimulation range 0.47-6.8 mA). The mean paresthesia threshold was 1.64 mA and the mean usage range was 16.0. There were no major complications reported such as device migration, infection, or erosion. One patient stopped using her Bion before the 12-month follow-up visit. At one year, 7 of the 8 patients were judged as having obtained fair or better results in terms of reduction of disability; 5 patients had greater than a 90% reduction in disability. Small, heterogeneous patient population without control group. Not blinded or randomized. The Bion can be successfully inserted adjacent to the greater occipital nerve in an effort to treat refractory primary headache disorders. This microstimulator may provide effective occipital stimulation and headache control while minimizing the risks associated with percutaneous or paddle leads implanted subcutaneously in the occipital region.

  4. Parameters of phosphene-inducing electric stimulation of the cat visual cortex via implanted surface and intracortical electrodes.

    PubMed

    Baziyan, B K; Gordeev, S A; Ivanova, M E; Ortmann, V V

    2008-01-01

    Parameters of phosphene-evoking electrical stimulation of cat striatal cortex via electrodes of different types (surface and intracortical) were studied. Similar actions (paw raising) in response to the light pattern and to phosphene-inducing electric stimulation of the striatal cortex were demonstrated. It seems that the animals associated phosphene sensations with light patterns.

  5. Intracortical inhibition abnormality during the remission phase of multiple sclerosis is related to upper limb dexterity and lesions.

    PubMed

    Nantes, Julia C; Zhong, Jidan; Holmes, Scott A; Whatley, Benjamin; Narayanan, Sridar; Lapierre, Yves; Arnold, Douglas L; Koski, Lisa

    2016-02-01

    The impact of inhibitory cortical activity on motor impairment of people with relapsing-remitting multiple sclerosis (RRMS) has not been fully elucidated despite its relevance to neurorehabilitation. The present study assessed the extent to which transcranial magnetic stimulation (TMS)-based metrics of intracortical inhibition are related to motor disability and brain damage. Participants included forty-three persons with RRMS in the remitting phase and twenty-nine healthy controls. We stimulated the dominant hemisphere and recorded from the dominant hand to assess short-interval intracortical inhibition (SICI) and cortical silent period (CSP) duration. Disability was evaluated with the Multiple Sclerosis Functional Composite (MSFC). Regional cortical thickness and lesion volume were measured. RRMS participants with dominant upper limb dexterity impairments had prolonged CSP, but equivalent SICI, compared to participants with preserved function. CSP was not related to walking or cognitive performance. Higher normalized lesion volume correlated with longer CSP duration. When adjusting for normalized lesion volume, longer CSP significantly predicted worse dominant upper extremity impairment. High intracortical inhibition possibly contributes to (or prevents remission from) motor impairment. Lesions may be associated with intracortical inhibition shifts. CSP duration and lesion burden should be considered when developing interventions aiming to mitigate motor impairment. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. 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.

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

    PubMed Central

    Chrostowski, Michael; Salvi, Richard J.; Allman, Brian L.

    2012-01-01

    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

  8. An image processing approach for blind mobility facilitated through visual intracortical stimulation.

    PubMed

    Mohammadi, Hossein Mahvash; Ghafar-Zadeh, Ebrahim; Sawan, Mohamad

    2012-07-01

    This article presents an image processing approach dedicated for a blind mobility aid facilitated through visual intracortical electrical stimulation. The method examines a display framework based on the distances related to a scene. The distances of objects to the walker are measured using a size perspective method which uses only one camera without any occlusion effect. The method extracts the information of the closest object to the camera and transfers a sense of distance to a blind walker. The proposed image processing method can estimate the distances of objects within 7.5 m of the walker, and alert the presence of the closest object to the person. This new method offers the advantages of information reduction and scene understanding suitable for visual prosthesis. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  9. Efficacy of thalamocortical and intracortical synaptic connections: quanta, innervation, and reliability.

    PubMed

    Gil, Z; Connors, B W; Amitai, Y

    1999-06-01

    Thalamocortical (TC) synapses carry information into the neocortex, but they are far outnumbered by excitatory intracortical (IC) synapses. We measured the synaptic properties that determine the efficacy of TC and IC axons converging onto spiny neurons of layer 4 in the mouse somatosensory cortex. Quantal events from TC and IC synapses were indistinguishable. However, TC axons had, on average, about 3 times more release sites than IC axons, and the mean release probability at TC synapses was about 1.5 times higher than that at IC synapses. Differences of innervation ratio and release probability make the average TC connection several times more effective than the average IC connection, and may allow small numbers of TC axons to dominate the activity of cortical layer 4 cells during sensory inflow.

  10. 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.

  11. Intermediate Progenitors Facilitate Intracortical Progression of Thalamocortical Axons and Interneurons through CXCL12 Chemokine Signaling.

    PubMed

    Abe, Philipp; Molnár, Zoltán; Tzeng, Yi-Shiuan; Lai, Dar-Ming; Arnold, Sebastian J; Stumm, Ralf

    2015-09-23

    Glutamatergic principal neurons, GABAergic interneurons and thalamocortical axons (TCAs) are essential elements of the cerebrocortical network. Principal neurons originate locally from radial glia and intermediate progenitors (IPCs), whereas interneurons and TCAs are of extrinsic origin. Little is known how the assembly of these elements is coordinated. C-X-C motif chemokine 12 (CXCL12), which is known to guide axons outside the neural tube and interneurons in the cortex, is expressed in the meninges and IPCs. Using mouse genetics, we dissected the influence of IPC-derived CXCL12 on TCAs and interneurons by showing that Cxcl12 ablation in IPCs, leaving meningeal Cxcl12 intact, attenuates intracortical TCA growth and disrupts tangential interneuron migration in the subventricular zone. In accordance with strong CXCR4 expression in the forming thalamus and TCAs, we identified a CXCR4-dependent growth-promoting effect of CXCL12 on TCAs in thalamus explants. Together, our findings indicate a cell-autonomous role of CXCR4 in promoting TCA growth. We propose that CXCL12 signals from IPCs link cortical neurogenesis to the progression of TCAs and interneurons spatially and temporally. Significance statement: The cerebral cortex exerts higher brain functions including perceptual and emotional processing. Evolutionary expansion of the mammalian cortex is mediated by intermediate progenitors, transient amplifying cells generating cortical excitatory neurons. During the peak period of cortical neurogenesis, migrating precursors of inhibitory interneurons originating in subcortical areas and thalamic axons invade the cortex. Although defects in the assembly of cortical network elements cause neurological and mental disorders, little is known how neurogenesis, interneuron recruitment, and axonal ingrowth are coordinated. We demonstrate that intermediate progenitors release the chemotactic cytokine CXCL12 to promote intracortical interneuron migration and growth of thalamic axons

  12. Scalp VEPs and intra-cortical responses to chromatic and achromatic stimuli in primates.

    PubMed

    Kulikowski, J J; Robson, A G; Murray, I J

    2002-09-01

    We propose asimple method of monitoring separate visual pathways inlightly sedated monkeys using chromatic and achromatic gratings of low contrast, which are known to activate predominantly either parvo- or magno-systems. The scalp Visual Evoked Potentials (VEPs) are compared with simultaneously recorded intra-cortical VEPs which in turn are compared with multi-unit and single-unit responses. At isoluminance, the onset of low contrast, coarse chromatic square wave spatial profile gratings generates negative scalp VEPs which exhibit properties consistent with the activation of sustained, parvocellular-chromatic mechanisms (e.g. low-pass spatio-temporal characteristics). In monkeys, most components of chromatic onset VEPs have latencies comparable to neuronal activity within the supragranular layers of V1. Corresponding coarse achromatic gratings elicit positive VEPs which exhibit properties consistent with the activation of transient-type magnocellular mechanisms (e.g. temporal tuning to higher temporal frequencies) and which have a more complex morphology. Achromatic onset VEPs may contain early components of similar timing to activity recorded in monkey V1, but later components cannot be related to V1 generators; other sources are not known. Achromatic reversal VEPs are similar to achromatic onset, chromatic reversal and both chromatic and achromatic offset VEPs and all differ from chromatic onset VEPs. It is observed that early components of scalp-recorded chromatic-onset VEPs are related in time to some intra-cortical potentials. These VEPs are generated by low spatial frequencies and have low pass temporal characteristics. Other scalp potentials, apparently unrelated to V1 field potential activity must be generated by other sources such as extra-striate areas.

  13. Age-related differences in short- and long-interval intracortical inhibition in a human hand muscle.

    PubMed

    Opie, George M; Semmler, John G

    2014-01-01

    Effects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) amplitude. To investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP amplitudes. In 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%-150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the amplitude of the MEP produced by the test alone TMS. When pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP amplitude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle. Advancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP amplitude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. 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

  15. Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes

    NASA Astrophysics Data System (ADS)

    Hara, Seth A.; Kim, Brian J.; Kuo, Jonathan T. W.; Lee, Curtis D.; Meng, Ellis; Pikov, Victor

    2016-12-01

    Objective. Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results. Approach. The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation. Main results. 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting. Significance. The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording

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

    PubMed

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

    2016-04-01

    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. 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. 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. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years

  17. Regional Heterogeneity in the Configuration of the Intracortical Canals of the Femoral Shaft.

    PubMed

    Perilli, Egon; Bala, Yohann; Zebaze, Roger; Reynolds, Karen J; Seeman, Ego

    2015-10-01

    Three-dimensional (3D) characterization of cortical porosity, most of which is under 100 µm in diameter, is usually confined to measurements made in 3-4 mm diameter cylinders of bone. We used micro-computed tomography (micro-CT) scanning of entire transaxial cross sections of human proximal femoral shafts (30-35 mm diameter) to quantify regional variation in porosity within the same scan. Complete, up to 10-mm-thick, transaxial slices of femoral upper shafts from 8 female cadavers were studied (n = 3 aged 29-37 years, n = 5 aged 72-90 years). Scanning was performed using high-resolution micro-CT (8.65 µm/voxel). Micro-CT volumes (10 × 10 × 5 mm) were selected via software in the anterior, medial and lateral regions. Images were segmented with voids appearing as 3D-interconnected canals. The percent void-to-tissue volume (Vo.V/TV) and the corresponding void surface area/TV were 86-309% higher in older than younger subjects in anterior (p = 0.034), medial (p = 0.077), and lateral aspects (p = 0.034). Although not significant, void separation was reciprocally lower by 19-39%, and void diameter was 65% larger in older than younger subjects; void number tended to be 24-25% higher medially and laterally but not anteriorly. For all specimens combined, medially there was higher Vo.V/TV and void surface area/TV than anteriorly (+48%, p = 0.018; +33%, p = 0.018) and laterally (+56%, p = 0.062; +36%, p = 0.043). There is regional heterogeneity in the 3D microarchitecture of the intracortical canals of the femoral shaft. The higher void volume in advanced age appears to be due to larger, rather than more, pores. However, creation of new canals from existing canals may contribute, depending on the location. High-resolution micro-computed tomography scanning of entire bone segments enables quantification of the 3D microanatomy of the intracortical void network at multiple locations.

  18. 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

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

    PubMed

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

    2013-12-01

    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. 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. 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 systematic early increases, which did

  20. 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

  1. Understanding how the brain changes its mind: microstimulation in the macaque frontal eye field reveals how saccade plans are changed.

    PubMed

    Ramakrishnan, Arjun; Sureshbabu, Ramakrishnan; Murthy, Aditya

    2012-03-28

    Accumulator models that integrate incoming sensory information into motor plans provide a robust framework to understand decision making. However, their applicability to situations that demand a change of plan raises an interesting problem for the brain. This is because interruption of the current motor plan must occur by a competing motor plan, which is necessarily weaker in strength. To understand how changes of mind get expressed in behavior, we used a version of the double-step task called the redirect task, in which monkeys were trained to modify a saccade plan. We microstimulated the frontal eye fields during redirect behavior and systematically measured the deviation of the evoked saccade from the response field to causally track the changing saccade plan. Further, to identify the underlying mechanisms, eight different computational models of redirect behavior were assessed. It was observed that the model that included an independent, spatially specific inhibitory process, in addition to the two accumulators representing the preparatory processes of initial and final motor plans, best predicted the performance and the pattern of saccade deviation profile in the task. Such an inhibitory process suppressed the preparation of the initial motor plan, allowing the final motor plan to proceed unhindered. Thus, changes of mind are consistent with the notion of a spatially specific, inhibitory process that inhibits the current inappropriate plan, allowing expression of the new plan.

  2. A Programmable Implantable Microstimulator SoC With Wireless Telemetry: Application in Closed-Loop Endocardial Stimulation for Cardiac Pacemaker.

    PubMed

    Shuenn-Yuh Lee; Su, M Y; Ming-Chun Liang; You-Yin Chen; Cheng-Han Hsieh; Chung-Min Yang; Hsin-Yi Lai; Jou-Wei Lin; Qiang Fang

    2011-12-01

    A low-power, wireless, and implantable microstimulator system on chip with smart powering management, immediate neural signal acquisition, and wireless rechargeable system is proposed. A system controller with parity checking handles the adjustable stimulus parameters for the stimulated objective. In the current paper, the rat's intra-cardiac electrogram is employed as the stimulated model in the animal study, and it is sensed by a low-voltage and low-power monitoring analog front end. The power management unit, which includes a rectifier, battery charging and detection, and a regulator, is used for the power control of the internal circuits. The stimulation data and required clock are extracted by a phase-locked-loop-based phase shift keying demodulator from an inductive AC signal. The full chip, which consumes 48 μW only, is fabricated in a TSMC 0.35 μm 2P4M standard CMOS process to perform the monitoring and pacing functions with inductively powered communication in the in vivo study.

  3. Prolonged intracortical delay of long-latency reflexes: electrophysiological evidence for a cortical dysfunction in multiple sclerosis.

    PubMed

    Bonfiglio, Luca; Rossi, Bruno; Sartucci, Ferdinando

    2006-05-31

    Convincing evidence suggests that long-latency reflexes (LLRs) are capable of testing the transcortical sensorimotor reflex arch. By subtracting the sum of the latencies of N20 (afferent branch) and transcranially elicited motor evoked potentials (MEP; efferent branch) from the LLR II latency, the cortical relay time (CRT) can also be obtained, which is alleged to represent the time required for the cortical sensorimotor integration. The aim of the present study was to investigate if a cortical dysfunction occurs in multiple sclerosis (MS). Median nerve somatosensory evoked potentials (SEPs), MEPs and LLRs were recorded from the upper limbs of 23, not severely disabled MS patients in acute phases of the disease. Eighteen age and sex matched healthy volunteers served as controls. N20, MEP, LLR II latencies were measured, and the CRT was calculated for each limb. The statistical comparison between patients and controls was only weakly significant by taking into account conduction times along either the afferent (N20) or the efferent (MEP) pathways. On the contrary, it turned out to be considerably significant if both branches of the transcortical sensorimotor reflex arch, together with the intracortical pathway, were simultaneously tested by means of the LLRs. Moreover, the patients showed a significantly higher CRT compared with that found in the control subjects. These findings are consistent with a prolonged intracortical delay of LLRs in the MS group and suggest the occurrence of conduction velocity slowing and/or synaptic transmission impairment along the sensorimotor intracortical pathway in MS.

  4. 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. Published by Elsevier Ltd.

  5. 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

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

    PubMed Central

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

    2015-01-01

    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 (FDS) 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

  7. Comparison of power spectrum predictors in computing coherence functions for intracortical EEG signals.

    PubMed

    Aydin, Serap

    2009-01-01

    The present study compares two Auto-Regressive (AR) model based (Burg Method (BM) and Yule Walker Method) and two subspace based (Eigen Method and Multiple Signal Classification Method) power spectral density predictors in computing the Coherence Function (CF) to observe EEG synchronization between right and left hemispheres. For this purpose, two channels intracortical EEG series recorded from WAG/Rij rats (a genetic model for human absence epilepsy) are analyzed. In tests, AR model-based predictors result the close performance such that the CF estimations are sensitive to the AR model order. Dealing with the subspace-based predictors; certain peaks in CF estimations can also be detected in case of low noise subspace dimension. Besides, they are more computational complexity. In conclusion, high order BM is proposed in EEG synchronization. The results support that each EEG sequence probably meets a high order AR model where the dimension of the related noise subspace is relatively low in comparison to the model order.

  8. 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.

  9. 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

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

    PubMed

    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.

  11. The influence of a single bout of aerobic exercise on short-interval intracortical excitability.

    PubMed

    Smith, Ashleigh E; Goldsworthy, Mitchell R; Garside, Tessa; Wood, Fiona M; Ridding, Michael C

    2014-06-01

    Regular physical activity can have positive effects on brain function and plasticity. Indeed, there is some limited evidence that even a single bout of exercise may promote plasticity within the cortex. However, the mechanisms by which exercise acutely promotes plasticity are not clear. To further explore the effects of acute exercise on cortical function, we examined whether a single bout of exercise was associated with changes in cortical excitability and inhibition. Using standard techniques, cortical stimulus-response curves [90% resting motor threshold (RMT)-150% RMT] were investigated in nine subjects (four females, 31.1 ± 11.7 years) and short-interval intracortical inhibition (SICI) [interstimulus interval 2 ms and 3 ms, conditioning intensities of 80% active motor threshold (AMT) and 90% AMT] in 13 subjects (six females, 28.4 ± 5.1 years) before and at 0 and 15 min following 30 min of ergometer cycling at low-moderate or moderate-high intensity. There were no changes in cortical excitability following exercise but less SICI at both 0 and 15 min post-exercise (F [2, 24] = 7.7, P = 0.003). These findings show that a short period of exercise can transiently reduce SICI. Such a change in inhibition after exercise may contribute to the development of a cortical environment that would be more optimal for plasticity and may partially explain previous findings of enhanced neuroplasticity following low-intensity exercise.

  12. 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

  13. Influence of position and stimulation parameters on intracortical inhibition and facilitation in human tongue motor cortex.

    PubMed

    Kothari, Mohit; Svensson, Peter; Nielsen, Jørgen Feldbæk; Baad-Hansen, Lene

    2014-04-04

    Paired-pulse transcranial magnetic stimulation (ppTMS) can be used to assess short-interval intracortical inhibitory (SICI) and facilitatory (ICF) networks. Many methodological parameters may however influence the outcome. The aim of the study was to examine the influence of body positions (recline and supine), inter-stimulus intervals (ISI) between the test stimulus (TS) and conditioning stimulus (CS) and intensities of the TS and CS on the degree of SICI and ICF. In studies 1 and 2, fourteen and seventeen healthy volunteers participated respectively. ppTMS was applied over the "hot-spot" of the tongue motor cortex and motor evoked potentials (MEPs) were recorded from contralateral tongue muscles. In study 1, single pulse and three ppTMS ISIs, 2, 10, and 15ms, were applied 8 times each in three blocks (TS: 120%, 140% and 160% of resting motor threshold (rMT); CS: 80% of rMT) in two different body positions (recline and supine) randomly. In study 2, single pulse and four ppTMS ISIs, 2, 2.5, 3, and 3.5ms, were applied 8 times each in randomized order in two blocks (CS: 70% and 80% of rMT; TS: 120% of rMT). There was a significant effect of body position (P=0.049), TS intensities (P<0.001) and ISIs (P<0.001) and interaction between intensity and ISIs (P=0.042) in study 1. In study 2, there was a significant effect of ISI (P<0.001) but not CS intensity (P=0.984) on MEP amplitude. These results may be applied in future studies on the mechanisms of cortical plasticity in the tongue motor pathways using ppTMS and SICI and ICF.

  14. High performance communication by people with paralysis using an intracortical brain-computer interface

    PubMed Central

    Pandarinath, Chethan; Nuyujukian, Paul; Blabe, Christine H; Sorice, Brittany L; Saab, Jad; Willett, Francis R; Hochberg, Leigh R

    2017-01-01

    Brain-computer interfaces (BCIs) have the potential to restore communication for people with tetraplegia and anarthria by translating neural activity into control signals for assistive communication devices. While previous pre-clinical and clinical studies have demonstrated promising proofs-of-concept (Serruya et al., 2002; Simeral et al., 2011; Bacher et al., 2015; Nuyujukian et al., 2015; Aflalo et al., 2015; Gilja et al., 2015; Jarosiewicz et al., 2015; Wolpaw et al., 1998; Hwang et al., 2012; Spüler et al., 2012; Leuthardt et al., 2004; Taylor et al., 2002; Schalk et al., 2008; Moran, 2010; Brunner et al., 2011; Wang et al., 2013; Townsend and Platsko, 2016; Vansteensel et al., 2016; Nuyujukian et al., 2016; Carmena et al., 2003; Musallam et al., 2004; Santhanam et al., 2006; Hochberg et al., 2006; Ganguly et al., 2011; O’Doherty et al., 2011; Gilja et al., 2012), the performance of human clinical BCI systems is not yet high enough to support widespread adoption by people with physical limitations of speech. Here we report a high-performance intracortical BCI (iBCI) for communication, which was tested by three clinical trial participants with paralysis. The system leveraged advances in decoder design developed in prior pre-clinical and clinical studies (Gilja et al., 2015; Kao et al., 2016; Gilja et al., 2012). For all three participants, performance exceeded previous iBCIs (Bacher et al., 2015; Jarosiewicz et al., 2015) as measured by typing rate (by a factor of 1.4–4.2) and information throughput (by a factor of 2.2–4.0). This high level of performance demonstrates the potential utility of iBCIs as powerful assistive communication devices for people with limited motor function. Clinical Trial No: NCT00912041 DOI: http://dx.doi.org/10.7554/eLife.18554.001 PMID:28220753

  15. Proactive modulation of long-interval intracortical inhibition during response inhibition

    PubMed Central

    Cowie, Matthew J.; MacDonald, Hayley J.; Cirillo, John

    2016-01-01

    Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a “default” nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective “brake” is applied. PMID:27281744

  16. High performance communication by people with paralysis using an intracortical brain-computer interface.

    PubMed

    Pandarinath, Chethan; Nuyujukian, Paul; Blabe, Christine H; Sorice, Brittany L; Saab, Jad; Willett, Francis R; Hochberg, Leigh R; Shenoy, Krishna V; Henderson, Jaimie M

    2017-02-21

    Brain-computer interfaces (BCIs) have the potential to restore communication for people with tetraplegia and anarthria by translating neural activity into control signals for assistive communication devices. While previous pre-clinical and clinical studies have demonstrated promising proofs-of-concept (Serruya et al., 2002; Simeral et al., 2011; Bacher et al., 2015; Nuyujukian et al., 2015; Aflalo et al., 2015; Gilja et al., 2015; Jarosiewicz et al., 2015; Wolpaw et al., 1998; Hwang et al., 2012; Spüler et al., 2012; Leuthardt et al., 2004; Taylor et al., 2002; Schalk et al., 2008; Moran, 2010; Brunner et al., 2011; Wang et al., 2013; Townsend and Platsko, 2016; Vansteensel et al., 2016; Nuyujukian et al., 2016; Carmena et al., 2003; Musallam et al., 2004; Santhanam et al., 2006; Hochberg et al., 2006; Ganguly et al., 2011; O'Doherty et al., 2011; Gilja et al., 2012), the performance of human clinical BCI systems is not yet high enough to support widespread adoption by people with physical limitations of speech. Here we report a high-performance intracortical BCI (iBCI) for communication, which was tested by three clinical trial participants with paralysis. The system leveraged advances in decoder design developed in prior pre-clinical and clinical studies (Gilja et al., 2015; Kao et al., 2016; Gilja et al., 2012). For all three participants, performance exceeded previous iBCIs (Bacher et al., 2015; Jarosiewicz et al., 2015) as measured by typing rate (by a factor of 1.4-4.2) and information throughput (by a factor of 2.2-4.0). This high level of performance demonstrates the potential utility of iBCIs as powerful assistive communication devices for people with limited motor function.Clinical Trial No: NCT00912041.

  17. Feedback control policies employed by people using intracortical brain-computer interfaces

    NASA Astrophysics Data System (ADS)

    Willett, Francis R.; Pandarinath, Chethan; Jarosiewicz, Beata; Murphy, Brian A.; Memberg, William D.; Blabe, Christine H.; Saab, Jad; Walter, Benjamin L.; Sweet, Jennifer A.; Miller, Jonathan P.; Henderson, Jaimie M.; Shenoy, Krishna V.; Simeral, John D.; Hochberg, Leigh R.; Kirsch, Robert F.; Bolu Ajiboye, A.

    2017-02-01

    Objective. When using an intracortical BCI (iBCI), users modulate their neural population activity to move an effector towards a target, stop accurately, and correct for movement errors. We call the rules that govern this modulation a ‘feedback control policy’. A better understanding of these policies may inform the design of higher-performing neural decoders. Approach. We studied how three participants in the BrainGate2 pilot clinical trial used an iBCI to control a cursor in a 2D target acquisition task. Participants used a velocity decoder with exponential smoothing dynamics. Through offline analyses, we characterized the users’ feedback control policies by modeling their neural activity as a function of cursor state and target position. We also tested whether users could adapt their policy to different decoder dynamics by varying the gain (speed scaling) and temporal smoothing parameters of the iBCI. Main results. We demonstrate that control policy assumptions made in previous studies do not fully describe the policies of our participants. To account for these discrepancies, we propose a new model that captures (1) how the user’s neural population activity gradually declines as the cursor approaches the target from afar, then decreases more sharply as the cursor comes into contact with the target, (2) how the user makes constant feedback corrections even when the cursor is on top of the target, and (3) how the user actively accounts for the cursor’s current velocity to avoid overshooting the target. Further, we show that users can adapt their control policy to decoder dynamics by attenuating neural modulation when the cursor gain is high and by damping the cursor velocity more strongly when the smoothing dynamics are high. Significance. Our control policy model may help to build better decoders, understand how neural activity varies during active iBCI control, and produce better simulations of closed-loop iBCI movements.

  18. Association of anxiety with intracortical inhibition and descending pain modulation in chronic myofascial pain syndrome

    PubMed Central

    2014-01-01

    Background This study aimed to answer three questions related to chronic myofascial pain syndrome (MPS): 1) Is the motor cortex excitability, as assessed by transcranial magnetic stimulation parameters (TMS), related to state-trait anxiety? 2) Does anxiety modulate corticospinal excitability changes after evoked pain by Quantitative Sensory Testing (QST)? 3) Does the state-trait anxiety predict the response to pain evoked by QST if simultaneously receiving a heterotopic stimulus [Conditional Pain Modulation (CPM)]? We included females with chronic MPS (n = 47) and healthy controls (n = 11), aged 19 to 65 years. Motor cortex excitability was assessed by TMS, and anxiety was assessed based on the State-Trait Anxiety Inventory. The disability related to pain (DRP) was assessed by the Profile of Chronic Pain scale for the Brazilian population (B:PCP:S), and the psychophysical pain measurements were measured by the QST and CPM. Results In patients, trait-anxiety was positively correlated to intracortical facilitation (ICF) at baseline and after QST evoked pain (β = 0.05 and β = 0.04, respectively) and negatively correlated to the cortical silent period (CSP) (β = -1.17 and β = -1.23, respectively) (P <0.05 for all comparisons). After QST evoked pain, the DRP was positively correlated to ICF (β = 0.02) (P < 0.05). Pain scores during CPM were positively correlated with trait-anxiety when it was concurrently with high DRP (β = 0.39; P = 0.02). Controls’ cortical excitability remained unchanged after QST. Conclusions These findings suggest that, in chronic MPS, the imbalance between excitatory and inhibitory descending systems of the corticospinal tract is associated with higher trait-anxiety concurrent with higher DRP. PMID:24645677

  19. Reduced short-interval intracortical inhibition after eccentric muscle damage in human elbow flexor muscles.

    PubMed

    Pitman, Bradley M; Semmler, John G

    2012-09-01

    The purpose of this study was to use paired-pulse transcranial magnetic stimulation (TMS) to examine the effect of eccentric exercise on short-interval intracortical inhibition (SICI) after damage to elbow flexor muscles. Nine young (22.5 ± 0.6 yr; mean ± SD) male subjects performed maximal eccentric exercise of the elbow flexor muscles until maximal voluntary contraction (MVC) force was reduced by ∼40%. TMS was performed before, 2 h after, and 2 days after exercise under Rest and Active (5% MVC) conditions with motor-evoked potentials (MEPs) recorded from the biceps brachii (BB) muscle. Peripheral electrical stimulation of the brachial plexus was used to assess maximal M-waves, and paired-pulse TMS with a 3-ms interstimulus interval was used to assess changes in SICI at each time point. The eccentric exercise resulted in a 34% decline in strength (P < 0.001), a 41% decline in resting M-wave (P = 0.01), changes in resting elbow joint angle (10°, P < 0.001), and a shift in the optimal elbow joint angle for force production (18°, P < 0.05) 2 h after exercise. This was accompanied by impaired muscle strength (27%, P < 0.001) and increased muscle soreness (P < 0.001) 2 days after exercise, which is indicative of muscle damage. When the test MEP amplitudes were matched between sessions, we found that SICI was reduced by 27% in resting and 23% in active BB muscle 2 h after exercise. SICI recovered 2 days after exercise when muscle pain and soreness were present, suggesting that delayed onset muscle soreness from eccentric exercise does not influence SICI. The change in SICI observed 2 h after exercise suggests that eccentric muscle damage has widespread effects throughout the motor system that likely includes changes in motor cortex.

  20. 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

  1. 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

  2. Task-related changes in intracortical inhibition assessed with paired- and triple-pulse transcranial magnetic stimulation.

    PubMed

    Opie, George M; Ridding, Michael C; Semmler, John G

    2015-03-01

    Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI; 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process. Copyright © 2015 The American Physiological Society.

  3. 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

  4. Eliciting Naturalistic Cortical Responses with a Sensory Prosthesis via Optimized Microstimulation

    DTIC Science & Technology

    2016-08-12

    in colour only in the online journal) 1. Introduction Loss of somatosensation could one day be treated by direct electrical stimulation of the central...error and correlation as metrics amenable to highly efficient convex optimization. This study concentrates on characterizing the neural responses to both...spiking signal. For LFP, distance measures such as the traditional mean-squared error and cross- correlation can be used, whereas distances between spike

  5. Homeostatic metaplasticity of corticospinal excitatory and intracortical inhibitory neural circuits in human motor cortex

    PubMed Central

    Murakami, Takenobu; Müller-Dahlhaus, Florian; Lu, Ming-Kuei; Ziemann, Ulf

    2012-01-01

    Homeostatic metaplasticity, a fundamental principle for maintaining overall synaptic weight in the physiological range in neuronal networks, was demonstrated at the cellular and systems level predominantly for excitatory synaptic neurotransmission. Although inhibitory networks are crucial for regulating excitability, it is largely unknown to what extent homeostatic metaplasticity of inhibition also exists. Here, we employed intermittent and continuous transcranial magnetic theta burst stimulation (iTBS, cTBS) of the primary motor cortex in healthy subjects for induction of long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity. We studied metaplasticity by testing the interactions of priming TBS with LTP/LTD-like plasticity induced by subsequent test TBS. Changes in excitatory neurotransmission were measured by the input–output curve of motor-evoked potentials (IO-MEP), and changes in GABAAergic inhibitory neurotransmission by the IO of short-interval intracortical inhibition (IO-SICI, four conditioning stimulus intensities of 70–100% active motor threshold, interstimulus interval 2.0 ms). Non-primed iTBS increased IO-MEP, while non-primed cTBS decreased IO-MEP. Pairing of identical protocols (iTBS→iTBS, cTBS→cTBS) resulted in suppression of the non-primed TBS effects on IO-MEP, and pairing of different protocols (cTBS→iTBS, iTBS→cTBS) enhanced the test TBS effects on IO-MEP. While non-primed TBS did not result in significant changes of IO-SICI, iTBS→iTBS resulted in IO-SICI decrease, and cTBS→cTBS in IO-SICI increase compared with the non-primed conditions. The changes in SICI induced by priming TBS correlated with the changes in MEP induced by subsequent test TBS. Findings demonstrate that plasticity in both excitatory and inhibitory circuits in the human motor cortex are regulated by homeostatic metaplasticity, and that priming effects on inhibition contribute to the homeostatic regulation of metaplasticity in excitatory

  6. 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.

  7. MRI of bilateral sensorimotor network activation in response to direct intracortical stimulation in rats after unilateral stroke

    PubMed Central

    van Meer, Maurits PA; van der Marel, Kajo; van der Sprenkel, Jan Willem Berkelbach; Dijkhuizen, Rick M

    2011-01-01

    Reinstatement of perilesional activation and connectivity may underlie functional recovery after stroke. To measure activation responsiveness in perilesional cortex in relation to white matter integrity, we performed functional functional magnetic resonance imaging during stimulation of the contralesional cortex, together with diffusion tensor imaging, 3 and 28 days after stroke in rats. Despite disturbed sensorimotor function and abnormal callosal appearance at day 3, activation amplitudes were preserved in the perilesional sensorimotor cortex, although time-to-peak was significantly delayed. This indicates that in spite of dysfunction, perilesional cortical tissue can be activated subacutely after stroke, while delay of the hemodynamic activation response suggests impaired neurovascular coupling. PMID:21522166

  8. 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

  9. Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat.

    PubMed

    Belayev, Ludmila; Saul, Isabel; Busto, Raul; Danielyan, Kristine; Vigdorchik, Alexey; Khoutorova, Larissa; Ginsberg, Myron D

    2005-02-01

    Acute intracerebral hemorrhage (ICH) is a common and severe form of stroke. To date, medical management of ICH has had scant impact on morbidity and mortality. Because albumin therapy is markedly neuroprotective in preclinical models of ischemic stroke, and because ischemic and hemorrhagic stroke share several common injury mechanisms, we hypothesized that albumin therapy might also benefit ICH. Acute intracortical hematoma was produced in anesthetized, normothermic rats by the single stereotaxic injection of 50 muL of autologous, nonheparinized whole blood over 5 minutes. Separate animal groups were treated either with 25% human albumin, 1.25 g/kg, or with intravenous saline vehicle at 60 minutes after ICH. Neurobehavior was quantified sequentially over the next 2 to 7 days. Damage to the blood-brain barrier was assessed at 2 days after ICH by fluorometric measurement of Evans blue extravasation in dissected brain regions. High-grade neurological deficits were present in all rats at 50 minutes after ICH (score 10.3+/-0.2, mean+/-SEM [maximal score 12]). Albumin-treated rats showed improved neuroscores relative to saline-treated animals beginning within hours of treatment and persisting throughout the 7-day survival period. At 3 and 7 days, mean total neuroscores of the albumin group were 38% to 43% lower than in saline-treated animals. Perihematomal Evans blue discoloration was readily evident in saline-treated ICH rats but was reduced by albumin treatment. Hemispheric Evans blue content ipsilateral to the hematoma was reduced by 49% by albumin treatment (albumin 93.9+/-13.3 versus saline 184.7+/-33.7 mg/g, P<0.05). Hematoma volume and brain swelling were not affected by albumin treatment. Prompt albumin therapy improves neurological function and blood-brain barrier integrity after acute intracortical hematoma. These observations have important potential clinical implications.

  10. 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

  11. 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

  12. 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

  13. Triggering slow waves during NREM sleep in the rat by intracortical electrical stimulation: effects of sleep/wake history and background activity.

    PubMed

    Vyazovskiy, Vladyslav V; Faraguna, Ugo; Cirelli, Chiara; Tononi, Giulio

    2009-04-01

    In humans, non-rapid eye movement (NREM) sleep slow waves occur not only spontaneously but can also be induced by transcranial magnetic stimulation. Here we investigated whether slow waves can also be induced by intracortical electrical stimulation during sleep in rats. Intracortical local field potential (LFP) recordings were obtained from several cortical locations while the frontal or the parietal area was stimulated intracortically with brief (0.1 ms) electrical pulses. Recordings were performed in early sleep (1st 2-3 h after light onset) and late sleep (6-8 h after light onset). The stimuli reliably triggered LFP potentials that were visually indistinguishable from naturally occurring slow waves. The induced slow waves shared the following features with spontaneous slow waves: they were followed by spindling activity in the same frequency range ( approximately 15 Hz) as spontaneously occurring sleep spindles; they propagated through the neocortex from the area of the stimulation; and compared with late sleep, waves triggered during early sleep were larger, had steeper slopes and fewer multipeaks. Peristimulus background spontaneous activity had a profound influence on the amplitude of the induced slow waves: they were virtually absent if the stimulus was delivered immediately after the spontaneous slow wave. These results show that in the rat a volley of electrical activity that is sufficiently strong to excite and recruit a large cortical neuronal population is capable of inducing slow waves during natural sleep.

  14. Modulation of short- and long-interval intracortical inhibition with increasing motor evoked potential amplitude in a human hand muscle.

    PubMed

    Opie, George M; Semmler, John G

    2014-07-01

    The aim of the current study was to investigate the effect of increasing test motor evoked potential (MEP) amplitude on short- (SICI) and long-interval intracortical inhibition (LICI) at rest and during activation of the first dorsal interosseous (FDI) muscle. In 22 young subjects, a conditioning-test transcranial magnetic stimulation (TMS) paradigm was used to assess SICI and LICI at 5 different test TMS intensities (110-150% motor threshold) in resting and active FDI. In 9 additional subjects, SICI and LICI data were quantified when the test MEP amplitude represented specific proportions of the maximal compound muscle action potential (Mmax) in each subject. Test TMS intensity influenced SICI and LICI in rest and active FDI muscle. The normalised test MEP amplitude (%Mmax) did not influence SICI at rest, whereas there was a decrease in LICI at rest and an increase in SICI in active FDI with an increased normalised test MEP amplitude (%Mmax). Our results demonstrate differential effects of normalised test MEP amplitude (%Mmax) on SICI and LICI in resting and active FDI muscle. Estimation of SICI and LICI under some circumstances may be influenced by the normalised test MEP amplitude in subject populations with different Mmax characteristics. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. 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

  16. Changes in Corticomotor Excitability and Intracortical Inhibition of the Primary Motor Cortex Forearm Area Induced by Anodal tDCS

    PubMed Central

    Zhang, Xue; Woolley, Daniel G.; Swinnen, Stephan P.; Feys, Hilde; Meesen, Raf; Wenderoth, Nicole

    2014-01-01

    Objective Previous studies have investigated how tDCS over the primary motor cortex modulates excitability in the intrinsic hand muscles. Here, we tested if tDCS changes corticomotor excitability and/or cortical inhibition when measured in the extensor carpi radialis (ECR) and if these aftereffects can be successfully assessed during controlled muscle contraction. Methods We implemented a double blind cross-over design in which participants (n = 16) completed two sessions where the aftereffects of 20 min of 1 mA (0.04 mA/cm2) anodal vs sham tDCS were tested in a resting muscle, and two more sessions where the aftereffects of anodal vs sham tDCS were tested in an active muscle. Results Anodal tDCS increased corticomotor excitability in ECR when aftereffects were measured with a low-level controlled muscle contraction. Furthermore, anodal tDCS decreased short interval intracortical inhibition but only when measured at rest and after non-responders (n = 2) were removed. We found no changes in the cortical silent period. Conclusion These findings suggest that targeting more proximal muscles in the upper limb with anodal tDCS is achievable and corticomotor excitability can be assessed in the presence of a low-level controlled contraction of the target muscle. PMID:24999827

  17. Sex Differences Distinguish Intracortical Glutamate Receptor-Mediated Regulation of Extracellular Dopamine Levels in the Prefrontal Cortex of Adult Rats

    PubMed Central

    Locklear, M. N.; Cohen, A. B.; Jone, A.; Kritzer, M. F.

    2016-01-01

    Executive functions of the prefrontal cortex (PFC) are sensitive to local dopamine (DA) levels. Although sex differences distinguish these functions and their dysfunction in disease, the basis for this is unknown. We asked whether sex differences might result from dimorphisms in the glutamatergic mechanisms that regulate PFC DA levels. Using antagonists selective for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, we compared drug effects on in vivo microdialysis DA measurements in the PFC of adult male and female rats. We found that baseline DA levels were similar across sex, AMPA antagonism decreased PFC DA in both sexes, and NMDA antagonism increased DA in males but decreased DA in females. We also found that, at subseizure-producing drug levels, γ-aminobutyric acid (GABA)-A antagonism did not affect DA in either sex but that GABA-B antagonism transiently increased PFC DA in both sexes, albeit more so in females. Finally, when NMDA antagonism was coincident with GABA-B antagonism, PFC DA levels in males responded as if to GABA-B antagonism alone, whereas in females, DA effects mirrored those induced by NMDA antagonism. Taken together, these data suggest commonalities and fundamental differences in the intracortical amino acid transmitter mechanisms that regulate DA homeostasis in the male and female rat PFCs. PMID:25260707

  18. Reconstruction of movement-related intracortical activity from micro-electrocorticogram array signals in monkey primary motor cortex

    NASA Astrophysics Data System (ADS)

    Watanabe, Hidenori; Sato, Masa-aki; Suzuki, Takafumi; Nambu, Atsushi; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi

    2012-06-01

    Subdural electrode arrays provide stable, less invasive electrocorticogram (ECoG) recordings of neural signals than multichannel needle electrodes. Accurate reconstruction of intracortical local field potentials (LFPs) from ECoG signals would provide a critical step for the development of a less invasive, high-performance brain-machine interface; however, neural signals from individual ECoG channels are generally coarse and have limitations in estimating deep layer LFPs. Here, we developed a high-density, 32-channel, micro-ECoG array and applied a sparse linear regression algorithm to reconstruct the LFPs at various depths of primary motor cortex (M1) in a monkey performing a reach-and-grasp task. At 0.2 mm beneath the cortical surface, the real and estimated LFPs were significantly correlated (correlation coefficient (r); 0.66 ± 0.11), and the r at 3.2 mm was still as high as 0.55 ± 0.04. A time-frequency analysis of the reconstructed LFP showed clear transition between resting and movements by the monkey. These methods would be a powerful tool with wide-ranging applicability in neuroscience studies.

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

    PubMed

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

    2015-05-15

    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 to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease.

  20. Microstimulation of single human motor axons in the toe extensors: force production during long-lasting trains of irregular and regular stimuli.

    PubMed

    Leitch, Michael; Macefield, Vaughan G

    2017-02-01

    Human motoneurones are known to discharge with a physiological variability of ~25% during voluntary contractions. Using microstimulation of single human motor axons, we have previously shown that delivering brief trains (10 pulses) of irregular stimuli, which incorporate discharge variability, generates greater contractile responses than trains of regular stimuli with identical mean frequency but zero variability. We tested the hypothesis that longer irregular (physiological) trains would produce greater contractile responses than regular (nonphysiological) trains of the same mean frequency (18 Hz) and duration (45 sec). Tungsten microelectrodes were inserted into the common peroneal nerve of human subjects, and single motor axons supplying the toe extensors (n = 14) were isolated. Irregular trains of stimuli showed greater contractile responses over identical mean frequencies in both fatigue-resistant and fatigable motor units, but because the forces were higher the rate of decline was higher. Nevertheless, forces produced by the irregular trains were significantly higher than those produced by the regular trains. We conclude that discharge irregularity augments force production during long as well as short trains of stimulation.

  1. Lateral Spread of Orientation Selectivity in V1 is Controlled by Intracortical Cooperativity

    PubMed Central

    Chavane, Frédéric; Sharon, Dahlia; Jancke, Dirk; Marre, Olivier; Frégnac, Yves; Grinvald, Amiram

    2011-01-01

    Neurons in the primary visual cortex receive subliminal information originating from the periphery of their receptive fields (RF) through a variety of cortical connections. In the cat primary visual cortex, long-range horizontal axons have been reported to preferentially bind to distant columns of similar orientation preferences, whereas feedback connections from higher visual areas provide a more diverse functional input. To understand the role of these lateral interactions, it is crucial to characterize their effective functional connectivity and tuning properties. However, the overall functional impact of cortical lateral connections, whatever their anatomical origin, is unknown since it has never been directly characterized. Using direct measurements of postsynaptic integration in cat areas 17 and 18, we performed multi-scale assessments of the functional impact of visually driven lateral networks. Voltage-sensitive dye imaging showed that local oriented stimuli evoke an orientation-selective activity that remains confined to the cortical feedforward imprint of the stimulus. Beyond a distance of one hypercolumn, the lateral spread of cortical activity gradually lost its orientation preference approximated as an exponential with a space constant of about 1 mm. Intracellular recordings showed that this loss of orientation selectivity arises from the diversity of converging synaptic input patterns originating from outside the classical RF. In contrast, when the stimulus size was increased, we observed orientation-selective spread of activation beyond the feedforward imprint. We conclude that stimulus-induced cooperativity enhances the long-range orientation-selective spread. PMID:21629708

  2. The Time-Course of Acute Changes in Corticospinal Excitability, Intra-Cortical Inhibition and Facilitation Following a Single-Session Heavy Strength Training of the Biceps Brachii.

    PubMed

    Latella, Christopher; Hendy, Ashlee M; Pearce, Alan J; VanderWesthuizen, Dan; Teo, Wei-Peng

    2016-01-01

    Objective: The current understanding of acute neurophysiological responses to resistance training remains unclear. Therefore, we aimed to compare the time-course of acute corticospinal responses following a single-session heavy strength training (HST) of the biceps brachii (BB) muscle and provide quantifiable evidence based on the super-compensation model in an applied setting. Methods: Fourteen participants completed a counter-balanced, cross-over study that consisted of a single HST session (5 sets × 3 repetition maximum [RM]) of the BB and a control session (CON). Single- and paired-pulse transcranial magnetic stimulation (TMS) was used to measure changes in motor-evoked potential (MEP) amplitude, intra-cortical facilitation (ICF), short-interval intra-cortical inhibition (SICI) and long-interval intra-cortical inhibition (LICI). Additionally, maximal muscle compound wave (MMAX) and maximal voluntary isometric contraction (MVIC) of the BB were taken. All measures were taken at baseline, immediately post and at 10, 20, 30 min and 1, 2, 6, 24, 48 and 72 h post-training. Results: A significant reduction in MEP amplitude was observed immediately post training (P = 0.001), while MVIC (P < 0.001) and MMAX (P = 0.047) were reduced for up to 30 min post-training. An increase in MVIC (p < 0.001) and MMAX (p = 0.047) was observed at 6 h, while an increase in MEP amplitude (p = 0.014) was only observed at 48 and 72 h. No changes in SICI, ICF and LICI were observed. Conclusion: Our results suggest that: (1) acute changes in corticospinal measures returned to baseline in a shorter timeframe than the current super-compensation model (24-48 h) and (2) changes in corticospinal excitability post-HST may be modulated "downstream" of the primary motor cortex (M1).

  3. The Time-Course of Acute Changes in Corticospinal Excitability, Intra-Cortical Inhibition and Facilitation Following a Single-Session Heavy Strength Training of the Biceps Brachii

    PubMed Central

    Latella, Christopher; Hendy, Ashlee M.; Pearce, Alan J.; VanderWesthuizen, Dan; Teo, Wei-Peng

    2016-01-01

    Objective: The current understanding of acute neurophysiological responses to resistance training remains unclear. Therefore, we aimed to compare the time-course of acute corticospinal responses following a single-session heavy strength training (HST) of the biceps brachii (BB) muscle and provide quantifiable evidence based on the super-compensation model in an applied setting. Methods: Fourteen participants completed a counter-balanced, cross-over study that consisted of a single HST session (5 sets × 3 repetition maximum [RM]) of the BB and a control session (CON). Single- and paired-pulse transcranial magnetic stimulation (TMS) was used to measure changes in motor-evoked potential (MEP) amplitude, intra-cortical facilitation (ICF), short-interval intra-cortical inhibition (SICI) and long-interval intra-cortical inhibition (LICI). Additionally, maximal muscle compound wave (MMAX) and maximal voluntary isometric contraction (MVIC) of the BB were taken. All measures were taken at baseline, immediately post and at 10, 20, 30 min and 1, 2, 6, 24, 48 and 72 h post-training. Results: A significant reduction in MEP amplitude was observed immediately post training (P = 0.001), while MVIC (P < 0.001) and MMAX (P = 0.047) were reduced for up to 30 min post-training. An increase in MVIC (p < 0.001) and MMAX (p = 0.047) was observed at 6 h, while an increase in MEP amplitude (p = 0.014) was only observed at 48 and 72 h. No changes in SICI, ICF and LICI were observed. Conclusion: Our results suggest that: (1) acute changes in corticospinal measures returned to baseline in a shorter timeframe than the current super-compensation model (24–48 h) and (2) changes in corticospinal excitability post-HST may be modulated “downstream” of the primary motor cortex (M1). PMID:27990108

  4. 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

  5. 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

  6. High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

    PubMed

    Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

    2016-05-18

    of the motor affordance while working memory load was varied. We observed a typical motor affordance signature when working memory load was low; however, it was abolished when load was high. Further, there was increased intracortical inhibition in primary motor cortex under high working memory load. This suggests that being in a state of high cognitive load "sets" the motor system to be imperturbable to distracting motor influences. This makes a novel link between working memory load and the balance of excitatory/inhibitory activity in the motor cortex and potentially has implications for disorders of impulsivity. Copyright © 2016 the authors 0270-6474/16/365544-12$15.00/0.

  7. Differential Modulation of Intracortical Inhibition in Human Motor Cortex during Selective Activation of an Intrinsic Hand Muscle

    PubMed Central

    Zoghi, Maryam; Pearce, Sophie L; Nordstrom, Michael A

    2003-01-01

    Paired-pulse transcranial magnetic stimulation (TMS) was used to assess the effectiveness of intracortical inhibition (ICI) acting on corticospinal neurons controlling three intrinsic hand muscles in humans. We hypothesised that the suppression of ICI with selective activation of a muscle would be restricted to corticospinal neurons controlling the muscle targeted for activation. Surface EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the left hand. Subjects were tested at rest and during weak selective activation of APB or ADM, while they attempted to keep the other muscles relaxed using visual feedback. Paired-pulse TMS was applied with a circular coil oriented to produce antero-posterior (AP) current flow in the right motor cortex (to preferentially evoke I3 waves in corticospinal neurons) and with postero-anterior (PA) currents (to preferentially evoke I1 waves). Paired-pulse TMS was less effective in suppressing the muscle evoked potential (MEP) when the muscle was targeted for selective activation, with both AP and PA stimulation. The mechanism for this includes effects on late I waves, as it was evident with a weak AP test TMS pulse that elicited negligible I1 waves in corticospinal neurons. ICI circuits activated by TMS, which exert their effects on late I waves but do not affect I1 waves, are strongly implicated in this modulation. With AP stimulation, paired-pulse inhibition was not significantly altered for corticospinal neurons controlling other muscles of the same hand which were required to be inactive during the selective activation task. This differential modulation was not seen with PA stimulation, which preferentially activates I1 waves and evokes a MEP that is less influenced by ICI. The observations with AP stimulation suggest that selective activation of a hand muscle is accompanied by a selective suppression of ICI effects on the corticospinal neurons controlling

  8. Signal-independent noise in intracortical brain-computer interfaces causes movement time properties inconsistent with Fitts’ law

    NASA Astrophysics Data System (ADS)

    Willett, Francis R.; Murphy, Brian A.; Memberg, William D.; Blabe, Christine H.; Pandarinath, Chethan; Walter, Benjamin L.; Sweet, Jennifer A.; Miller, Jonathan P.; Henderson, Jaimie M.; Shenoy, Krishna V.; Hochberg, Leigh R.; Kirsch, Robert F.; Bolu Ajiboye, A.

    2017-04-01

    Objective. Do movements made with an intracortical BCI (iBCI) have the same movement time properties as able-bodied movements? Able-bodied movement times typically obey Fitts’ law: \\text{MT}=a+b{{log}2}(D/R) (where MT is movement time, D is target distance, R is target radius, and a,~b are parameters). Fitts’ law expresses two properties of natural movement that would be ideal for iBCIs to restore: (1) that movement times are insensitive to the absolute scale of the task (since movement time depends only on the ratio D/R ) and (2) that movements have a large dynamic range of accuracy (since movement time is logarithmically proportional to D/R ). Approach. Two participants in the BrainGate2 pilot clinical trial made cortically controlled cursor movements with a linear velocity decoder and acquired targets by dwelling on them. We investigated whether the movement times were well described by Fitts’ law. Main results. We found that movement times were better described by the equation \\text{MT}=a+bD+c{{R}-2} , which captures how movement time increases sharply as the target radius becomes smaller, independently of distance. In contrast to able-bodied movements, the iBCI movements we studied had a low dynamic range of accuracy (absence of logarithmic proportionality) and were sensitive to the absolute scale of the task (small targets had long movement times regardless of the D/R ratio). We argue that this relationship emerges due to noise in the decoder output whose magnitude is largely independent of the user’s motor command (signal-independent noise). Signal-independent noise creates a baseline level of variability that cannot be decreased by trying to move slowly or hold still, making targets below a certain size very hard to acquire with a standard decoder. Significance. The results give new insight into how iBCI movements currently differ from able-bodied movements and suggest that restoring a Fitts’ law-like relationship to iBCI movements may require

  9. Signal-independent noise in intracortical brain-computer interfaces causes movement time properties inconsistent with Fitts' law.

    PubMed

    Willett, Francis R; Murphy, Brian A; Memberg, William D; Blabe, Christine H; Pandarinath, Chethan; Walter, Benjamin L; Sweet, Jennifer A; Miller, Jonathan P; Henderson, Jaimie M; Shenoy, Krishna V; Hochberg, Leigh R; Kirsch, Robert F; Ajiboye, A Bolu

    2017-04-01

    Do movements made with an intracortical BCI (iBCI) have the same movement time properties as able-bodied movements? Able-bodied movement times typically obey Fitts' law: [Formula: see text] (where MT is movement time, D is target distance, R is target radius, and [Formula: see text] are parameters). Fitts' law expresses two properties of natural movement that would be ideal for iBCIs to restore: (1) that movement times are insensitive to the absolute scale of the task (since movement time depends only on the ratio [Formula: see text]) and (2) that movements have a large dynamic range of accuracy (since movement time is logarithmically proportional to [Formula: see text]). Two participants in the BrainGate2 pilot clinical trial made cortically controlled cursor movements with a linear velocity decoder and acquired targets by dwelling on them. We investigated whether the movement times were well described by Fitts' law. We found that movement times were better described by the equation [Formula: see text], which captures how movement time increases sharply as the target radius becomes smaller, independently of distance. In contrast to able-bodied movements, the iBCI movements we studied had a low dynamic range of accuracy (absence of logarithmic proportionality) and were sensitive to the absolute scale of the task (small targets had long movement times regardless of the [Formula: see text] ratio). We argue that this relationship emerges due to noise in the decoder output whose magnitude is largely independent of the user's motor command (signal-independent noise). Signal-independent noise creates a baseline level of variability that cannot be decreased by trying to move slowly or hold still, making targets below a certain size very hard to acquire with a standard decoder. The results give new insight into how iBCI movements currently differ from able-bodied movements and suggest that restoring a Fitts' law-like relationship to iBCI movements may require non

  10. A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid.

    PubMed

    Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

    2012-02-01

    This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury", which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed.

  11. 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

    2016-09-07

    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. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. 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

  13. Extracellular Neural Microstimulation May Activate Much Larger Regions than Expected by Simulations: A Combined Experimental and Modeling Study

    PubMed Central

    Joucla, Sébastien; Branchereau, Pascal; Cattaert, Daniel; Yvert, Blaise

    2012-01-01

    Electrical stimulation of the central nervous system has been widely used for decades for either fundamental research purposes or clinical treatment applications. Yet, very little is known regarding the spatial extent of an electrical stimulation. If pioneering experimental studies reported that activation threshold currents (TCs) increase with the square of the neuron-to-electrode distance over a few hundreds of microns, there is no evidence that this quadratic law remains valid for larger distances. Moreover, nowadays, numerical simulation approaches have supplanted experimental studies for estimating TCs. However, model predictions have not yet been validated directly with experiments within a common paradigm. Here, we present a direct comparison between experimental determination and modeling prediction of TCs up to distances of several millimeters. First, we combined patch-clamp recording and microelectrode array stimulation in whole embryonic mouse spinal cords to determine TCs. Experimental thresholds did not follow a quadratic law beyond 1 millimeter, but rather tended to remain constant for distances larger than 1 millimeter. We next built a combined finite element – compartment model of the same experimental paradigm to predict TCs. While theoretical TCs closely matched experimental TCs for distances <250 microns, they were highly overestimated for larger distances. This discrepancy remained even after modifications of the finite element model of the potential field, taking into account anisotropic, heterogeneous or dielectric properties of the tissue. In conclusion, these results show that quadratic evolution of TCs does not always hold for large distances between the electrode and the neuron and that classical models may underestimate volumes of tissue activated by electrical stimulation. PMID:22879886

  14. Mechanisms of Direction Selectivity in Cat Primary Visual Cortex as Revealed by Visual Adaptation

    PubMed Central

    Lampl, Ilan; Ferster, David

    2010-01-01

    In contrast to neurons of the lateral geniculate nucleus (LGN), neurons in the primary visual cortex (V1) are selective for the direction of visual motion. Cortical direction selectivity could emerge from the spatiotemporal configuration of inputs from thalamic cells, from intracortical inhibitory interactions, or from a combination of thalamic and intracortical interactions. To distinguish between these possibilities, we studied the effect of adaptation (prolonged visual stimulation) on the direction selectivity of intracellularly recorded cortical neurons. It is known that adaptation selectively reduces the responses of cortical neurons, while largely sparing the afferent LGN input. Adaptation can therefore be used as a tool to dissect the relative contribution of afferent and intracortical interactions to the generation of direction selectivity. In both simple and complex cells, adaptation caused a hyperpolarization of the resting membrane potential (−2.5 mV, simple cells, −0.95 mV complex cells). In simple cells, adaptation in either direction only slightly reduced the visually evoked depolarization; this reduction was similar for preferred and null directions. In complex cells, adaptation strongly reduced visual responses in a direction-dependent manner: the reduction was largest when the stimulus direction matched that of the adapting motion. As a result, adaptation caused changes in the direction selectivity of complex cells: direction selectivity was reduced after preferred direction adaptation and increased after null direction adaptation. Because adaptation in the null direction enhanced direction selectivity rather than reduced it, it seems unlikely that inhibition from the null direction is the primary mechanism for creating direction selectivity. PMID:20739595

  15. A study on the effect of multisensory stimulation in behaving rats.

    PubMed

    Semprini, Marianna; Boi, Fabio; Tucci, Valter; Vato, Alessandro

    2016-08-01

    This study explored the psychophysical effects of intracortical microstimulation (ICMS) coupled to auditory stimulation during a behavioral detection task in rats. ICMS directed to the sensory areas of the cortex can be instrumental in facilitating operant conditioning behavior. Moreover, multisensory stimulation promotes learning by enabling the subject to access multiple information channels. However, the extent to which multisensory information can be used as a cue to make decisions has not been fully understood. This study addressed the exploration of the parameters of multisensory stimulation delivered to behaving rats in an operant conditioning task. Preliminary data indicate that animal decisions can be shaped by online changing the stimulation parameters.

  16. 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

  17. 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

  18. Determining in vivo sternoclavicular, acromioclavicular and glenohumeral joint centre locations from skin markers, CT-scans and intracortical pins: A comparison study.

    PubMed

    Michaud, B; Jackson, M; Arndt, A; Lundberg, A; Begon, M

    2016-03-01

    To describe shoulder motion the sternoclavicular, acromioclavicular and glenohumeral joint centres must be accurately located. Within the literature various methods to estimate joint centres of rotation location are proposed, with no agreement of the method best suited to the shoulder. The objective of this study was to determine the most reliable non-invasive method for locating joint centre locations of the shoulder complex. Functional methods using pin mounted markers were compared to anatomical methods, functional methods using skin mounted markers, imaging-based methods using CT-scan data, and regression equations. Three participants took part in the study, that involved insertion of intracortical pins into the clavicle, scapula and humerus, a CT-scan of the shoulder, and finally data collection using a motion analysis system. The various methods to estimate joint centre location did not all agree, however suggestions about the most reliable non-invasive methods could be made. For the sternoclavicular joint, the authors suggest the anatomical method using the most ventral landmark on the sternoclavicular joint, as recommended by the International Society of Biomechanics. For the acromioclavicular joint, the authors suggest the anatomical method using the landmark defined as the most dorsal point on the acromioclavicular joint, as proposed by van der Helm. For the glenohumeral joint, the simple regression equation of Rab is recommended.

  19. Time-frequency analysis of short-lasting modulation of EEG induced by intracortical and transcallosal paired TMS over motor areas.

    PubMed

    Manganotti, Paolo; Formaggio, Emanuela; Storti, Silvia Francesca; De Massari, Daniele; Zamboni, Alessandro; Bertoldo, Alessandra; Fiaschi, Antonio; Toffolo, Gianna Maria

    2012-05-01

    Dynamic changes in spontaneous electroencephalogram (EEG) rhythms can be seen to occur with a high rate of variability. An innovative method to study brain function is by triggering oscillatory brain activity with transcranial magnetic stimulation (TMS). EEG-TMS coregistration was performed on five healthy subjects during a 1-day experimental session that involved four steps: baseline acquisition, unconditioned single-pulse TMS, intracortical inhibition (ICI, 3 ms) paired-pulse TMS, and transcallosal stimulation over left and right primary motor cortex (M1). A time-frequency analysis based on the wavelet method was used to characterize rapid modifications of oscillatory EEG rhythms induced by TMS. Single, paired, and transcallosal TMS applied on the sensorimotor areas induced rapid desynchronization over the frontal and central-parietal electrodes mainly in the alpha and beta bands, followed by a rebound of synchronization, and rapid synchronization of delta and theta activity. Wavelet analysis after a perturbation approach is a novel way to investigate modulation of oscillatory brain activity. The main findings are consistent with the concept that the human motor system may be based on networklike oscillatory cortical activity and might be modulated by single, paired, and transcallosal magnetic pulses applied to M1, suggesting a phenomenon of fast brain activity resetting and triggering of slow activity.

  20. The Effect of Bilateral Isometric Forces in Different Directions on Motor Cortical Function in Humans

    PubMed Central

    Yedimenko, Juliette A.

    2010-01-01

    The activity in the primary motor cortex (M1) reflects the direction of movements, but little is known about physiological changes in the M1 during generation of bilateral isometric forces in different directions. Here, we used transcranial magnetic stimulation to examine motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI) in the left first dorsal interosseous (FDI) during isometric index finger abduction while the right index finger remained at rest or performed isometric forces in different directions (abduction or adduction) and in different postures (prone and supine). Left FDI MEPs were suppressed during bilateral compared with unilateral forces, with a stronger suppression when the right index finger force was exerted in the adduction direction regardless of hand posture. IHI targeting the left FDI increased during bilateral compared with unilateral forces and this increase was stronger during right index finger adduction despite the posture of the right hand. SICI decreased to a similar extent during both bilateral forces in both hand postures. Thus generation of index finger isometric forces away from the body midline (adduction direction), regardless of the muscle engaged in the task, down-regulates corticospinal output in the contralateral active hand to a greater extent than forces exerted toward the body midline (abduction direction). Transcallosal inhibition, but not GABAergic intracortical circuits, was modulated by the direction of the force. These findings suggest that during generation of bimanual isometric forces the M1 is driven by “extrinsic” parameters related to the hand action. PMID:20668276

  1. New approaches to eliminating common-noise artifacts in recordings from intracortical microelectrode arrays: inter-electrode correlation and virtual referencing

    PubMed Central

    Paralikar, Kunal J; Rao, Chinmay R; Clement, Ryan S

    2009-01-01

    Intracortical microelectrode arrays record multi-unit extracellular activity for neurophysiology studies and for brain-machine interface applications. The common first step is neural spike detection; a process complicated by common-noise signals from motion artifacts, electromyographic activity, and electric field pickup, especially in awake/behaving subjects. Often common-noise spikes are very similar to neural spikes in their magnitude, spectral, and temporal features. Provided sufficient spacing exists between electrodes of the array, a local neural spike is rarely recorded on multiple electrodes simultaneously. This is not true for distant common-noise sources. Two new techniques compatible with standard spike detection schemes are introduced and evaluated. The first method, virtual referencing (VR), takes the average recording from all functional electrodes in the array (represents the signal from a virtual electrode at the array's center) and subtracts it from the test electrode signal. The second method, inter-electrode correlation (IEC), computes a correlation coefficient between threshold exceeding candidate spike segments on the test electrode and concurrent segments from remaining electrodes. When sufficient correlation is detected, the candidate spike is rejected as originating from a distant common-noise source. The performance of these algorithms was compared with standard thresholding and differential referencing approaches using neural recordings from unanaesthetized rats. By evaluating characteristics of mean-spike waveforms generated by each method under different levels of common-noise, it was found that IEC consistently offered the most robust means of neural spike-detection. Furthermore, IEC's rejection of supra-threshold events not likely originating from local neurons significantly reduces data handling for downstream spike sorting and processing operations. PMID:19394363

  2. New approaches to eliminating common-noise artifacts in recordings from intracortical microelectrode arrays: inter-electrode correlation and virtual referencing.

    PubMed

    Paralikar, Kunal J; Rao, Chinmay R; Clement, Ryan S

    2009-06-30

    Intracortical microelectrode arrays record multi-unit extracellular activity for neurophysiology studies and for brain-machine interface applications. The common first step is neural spike-detection; a process complicated by common-noise signals from motion artifacts, electromyographic activity, and electric field pickup, especially in awake/behaving subjects. Often common-noise spikes are very similar to neural spikes in their magnitude, spectral, and temporal features. Provided sufficient spacing exists between electrodes of the array, a local neural spike is rarely recorded on multiple electrodes simultaneously. This is not true for distant common-noise sources. Two new techniques compatible with standard spike-detection schemes are introduced and evaluated. The first method, virtual referencing (VR), takes the average recording from all functional electrodes in the array (represents the signal from a virtual-electrode at the array's center) and subtracts it from the test electrode signal. The second method, inter-electrode correlation (IEC), computes a correlation coefficient between threshold exceeding candidate spike segments on the test electrode and concurrent segments from remaining electrodes. When sufficient correlation is detected, the candidate spike is rejected as originating from a distant common-noise source. The performance of these algorithms was compared with standard thresholding and differential referencing approaches using neural recordings from un-anaesthetized rats. By evaluating characteristics of mean-spike waveforms generated by each method under different levels of common-noise, it was found that IEC consistently offered the most robust means of neural spike-detection. Furthermore, IEC's rejection of supra-threshold events not likely originating from local neurons significantly reduces data handling for downstream spike sorting and processing operations.

  3. 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

  4. Decoding of intended saccade direction in an oculomotor brain-computer interface

    NASA Astrophysics Data System (ADS)

    Jia, Nan; Brincat, Scott L.; Salazar-Gómez, Andrés F.; Panko, Mikhail; Guenther, Frank H.; Miller, Earl K.

    2017-08-01

    Objective. To date, invasive brain-computer interface (BCI) research has largely focused on replacing lost limb functions using signals from the hand/arm areas of motor cortex. However, the oculomotor system may be better suited to BCI applications involving rapid serial selection from spatial targets, such as choosing from a set of possible words displayed on a computer screen in an augmentative and alternative communication (AAC) application. Here we aimed to demonstrate the feasibility of a BCI utilizing the oculomotor system. Approach. We developed a chronic intracortical BCI in monkeys to decode intended saccadic eye movement direction using activity from multiple frontal cortical areas. Main results. Intended saccade direction could be decoded in real time with high accuracy, particularly at contralateral locations. Accurate decoding was evident even at the beginning of the BCI session; no extensive BCI experience was necessary. High-frequency (80-500 Hz) local field potential magnitude provided the best performance, even over spiking activity, thus simplifying future BCI applications. Most of the information came from the frontal and supplementary eye fields, with relatively little contribution from dorsolateral prefrontal cortex. Significance. Our results support the feasibility of high-accuracy intracortical oculomotor BCIs that require little or no practice to operate and may be ideally suited for ‘point and click’ computer operation as used in most current AAC systems.

  5. Representations of the temporal envelope of sounds in human auditory cortex: can the results from invasive intracortical "depth" electrode recordings be replicated using non-invasive MEG "virtual electrodes"?

    PubMed

    Millman, Rebecca E; Prendergast, Garreth; Hymers, Mark; Green, Gary G R

    2013-01-01

    Magnetoencephalography (MEG) beamformer analyses use spatial filters to estimate neuronal activity underlying the magnetic fields measured by the MEG sensors. MEG "virtual electrodes" are the outputs of beamformer spatial filters. The present study aimed to test the hypothesis that MEG virtual electrodes can replicate the findings from intracortical "depth" electrode studies relevant to the processing of the temporal envelopes of sounds [e.g. Nourski et al. (2009) "Temporal envelope of time-compressed speech represented in the human auditory cortex," J. Neurosci. 29:15564-15574]. Specifically we aimed to determine whether it is possible to use non-invasive MEG virtual electrodes to characterise the representation of temporal envelopes of 6-Hz sinusoidal amplitude modulation (SAM) and speech using both auditory evoked fields (AEFs) and patterns of power changes in high-frequency (>70 Hz) bands. MEG signals were analysed using a location of interest (LOI) approach by seeding virtual electrodes in the left and right posteromedial Heschl's gyri. AEFs showed phase-locking to the temporal envelope of SAM and speech stimuli. Time-frequency analyses revealed no clear differences in high gamma power between the pre-stimulus baseline and the post-stimulus presentation periods. Nevertheless the patterns of changes in high gamma power were significantly correlated with the temporal envelopes of 6-Hz SAM and speech in the majority of participants. The present study reveals difficulties in replicating clear augmentations in high gamma power changes using MEG virtual electrodes cf. intracortical "depth" electrode studies (Nourski et al., 2009). Copyright © 2012 Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  7. 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

  8. 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

  9. Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity.

    PubMed

    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.

  10. Do Advance Directives Direct?

    PubMed

    Shapiro, Susan P

    2015-06-01

    Resolution of long-standing debates about the role and impact of advance directives - living wills and powers of attorney for health care - has been hampered by a dearth of appropriate data, in particular data that compare the process and outcomes of end-of-life decision making on behalf of patients with and without advance directives. Drawing on a large ethnographic study of patients in two intensive care units in a large urban teaching hospital, this article compares aspects of the medical decision-making process and outcomes by advance-directive status. Controlling for demographic characteristics and severity of illness, the study finds few significant differences between patients without advance directives and those who claim to have them. Surprisingly, these few differences hold only for those whose directives are in their hospital chart. There are no significant differences between those with no directive and those claiming to have a copy at home or elsewhere. The article considers the implications if directives seemingly must be in hand to show even modest effects. Do advance directives direct? The intensive care unit data provide far more support for the growing body of literature that casts doubt on their impact than studies that promote the use of them.

  11. An oculomotor representation area within the ventral premotor cortex

    PubMed Central

    Fujii, Naotaka; Mushiake, Hajime; Tanji, Jun

    1998-01-01

    We explored the ventral part of the premotor cortex (PMV) with intracortical microstimulation (ICMS) while monkeys performed a visual fixation task, to see whether the PMV is involved in oculomotor control. ICMS evoked saccades from a small-restricted region in the PMV, without evoking movements in the limbs, neck, or body. We found the saccade-evoking site in the PMV in a total of three hemispheres in two monkeys. Quantitative analysis of the effects of eye position on saccades evoked by microstimulation of the PMV characterized the evoked saccades as goal directed. The nature of the saccades evoked in the PMV contrasted with the fixed vector nature of saccades evoked by ICMS of the frontal eye field. We also found that neurons in this restricted area of the PMV were active while the animals were performing a saccade task that required them to make saccades toward targets without arm movements. These data provide evidence for the presence of an oculomotor-specific subregion within the PMV. This subregion and the surrounding skeletomotor-representing regions of the PMV seem to coordinate oculomotor and skeletomotor control in performing goal-directed motor tasks. PMID:9751785

  12. Treadmill Walking Combined With Anodal Transcranial Direct Current Stimulation in Parkinson Disease: A Pilot Study of Kinematic and Neurophysiological Effects.

    PubMed

    Fernández-Lago, Helena; Bello, Olalla; Mora-Cerdá, Francina; Montero-Cámara, Jorge; Fernández-Del-Olmo, Miguel Ángel

    2017-04-08

    We tested the hypothesis that combining treadmill walking with transcranial direct current stimulation (tDCS) enhances the gait improvements associated with treadmill walking in Parkinson disease. We explored the effects of these combined methodologies on corticospinal parameters. Eighteen participants with Parkinson disease were evaluated under the following three conditions: treadmill walking alone (treadmill), treadmill walking combined with anodal tDCS (AtDCS+treadmill) delivered over the motor cortex, and treadmill walking combined with sham stimulation (StDCS+treadmill). Overground walking performance, soleus H-reflex, reciprocal Ia inhibition from the tibialis anterior to the soleus muscle, intracortical facilitation, and short intracortical inhibition of the tibialis anterior muscle, were measured before and after each treadmill condition. The soleus H-reflex and walking performance on the treadmill were also evaluated. All treadmill conditions improved walking performance and modulated spinal and corticospinal parameters in a similar way. However, AtDCS+treadmill lead to a different modulation of reciprocal Ia inhibition in comparison with the other treadmill conditions. A single session combining treadmill walking and anodal tDCS delivered over the motor cortex resulted in a specific modulation of the reciprocal Ia inhibition from the tibialis anterior to the soleus muscle. However, this acute effect did not result in improvements of gait parameters associated with treadmill walking in Parkinson disease.

  13. 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.

  14. Constant RMS versus constant peak modulation for the perceptual equivalence of sinusoidal amplitude modulated signals.

    PubMed

    Regele, Oliver B; Koivuniemi, Andrew S; Otto, Kevin J

    2013-01-01

    Neuroprosthetics using intracortical microstimulation can potentially alleviate sensory deprivation due to injury or disease. However the information bandwidth of a single microstimulation channel remains largely unanswered. This paper presents three experiments that examine the importance of Peak Power/Charge and RMS Power/Charge for detection of acoustic and electrical Sinusoidal Amplitude Modulated stimuli by the auditory system. While the peripheral auditory system is sensitive to RMS power cues for the detection of acoustic stimuli, here we provide results that suggest that the auditory cortex is sensitive to peak charge cues for electrical stimuli. Varying the modulation frequency and depth do not change this effect for detection of modulated electrical stimuli.

  15. Parietal transcranial direct current stimulation modulates primary motor cortex excitability.

    PubMed

    Rivera-Urbina, Guadalupe Nathzidy; Batsikadze, Giorgi; Molero-Chamizo, Andrés; Paulus, Walter; Kuo, Min-Fang; Nitsche, Michael A

    2015-03-01

    The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto-motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto-motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto-motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short-interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto-motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity-dependent M1 excitability alterations primarily after P3 tDCS. Single-pulse TMS-elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto-motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse-TMS-elicited MEPs, and parieto-motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex-motor cortex connections suggest a relevant connectivity-driven effect.

  16. 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

  17. fNIRS exhibits weak tuning to hand movement direction.

    PubMed

    Waldert, Stephan; Tüshaus, Laura; Kaller, Christoph P; Aertsen, Ad; Mehring, Carsten

    2012-01-01

    Functional near-infrared spectroscopy (fNIRS) has become an established tool to investigate brain function and is, due to its portability and resistance to electromagnetic noise, an interesting modality for brain-machine interfaces (BMIs). BMIs have been successfully realized using the decoding of movement kinematics from intra-cortical recordings in monkey and human. Recently, it has been shown that hemodynamic brain responses as measured by fMRI are modulated by the direction of hand movements. However, quantitative data on the decoding of movement direction from hemodynamic responses is still lacking and it remains unclear whether this can be achieved with fNIRS, which records signals at a lower spatial resolution but with the advantage of being portable. Here, we recorded brain activity with fNIRS above different cortical areas while subjects performed hand movements in two different directions. We found that hemodynamic signals in contralateral sensorimotor areas vary with the direction of movements, though only weakly. Using these signals, movement direction could be inferred on a single-trial basis with an accuracy of ∼65% on average across subjects. The temporal evolution of decoding accuracy resembled that of typical hemodynamic responses observed in motor experiments. Simultaneous recordings with a head tracking system showed that head movements, at least up to some extent, do not influence the decoding of fNIRS signals. Due to the low accuracy, fNIRS is not a viable alternative for BMIs utilizing decoding of movement direction. However, due to its relative resistance to head movements, it is promising for studies investigating brain activity during motor experiments.

  18. fNIRS Exhibits Weak Tuning to Hand Movement Direction

    PubMed Central

    Waldert, Stephan; Tüshaus, Laura; Kaller, Christoph P.; Aertsen, Ad; Mehring, Carsten

    2012-01-01

    Functional near-infrared spectroscopy (fNIRS) has become an established tool to investigate brain function and is, due to its portability and resistance to electromagnetic noise, an interesting modality for brain-machine interfaces (BMIs). BMIs have been successfully realized using the decoding of movement kinematics from intra-cortical recordings in monkey and human. Recently, it has been shown that hemodynamic brain responses as measured by fMRI are modulated by the direction of hand movements. However, quantitative data on the decoding of movement direction from hemodynamic responses is still lacking and it remains unclear whether this can be achieved with fNIRS, which records signals at a lower spatial resolution but with the advantage of being portable. Here, we recorded brain activity with fNIRS above different cortical areas while subjects performed hand movements in two different directions. We found that hemodynamic signals in contralateral sensorimotor areas vary with the direction of movements, though only weakly. Using these signals, movement direction could be inferred on a single-trial basis with an accuracy of ∼65% on average across subjects. The temporal evolution of decoding accuracy resembled that of typical hemodynamic responses observed in motor experiments. Simultaneous recordings with a head tracking system showed that head movements, at least up to some extent, do not influence the decoding of fNIRS signals. Due to the low accuracy, fNIRS is not a viable alternative for BMIs utilizing decoding of movement direction. However, due to its relative resistance to head movements, it is promising for studies investigating brain activity during motor experiments. PMID:23145138

  19. Intracortical cartography in an agranular area.

    PubMed

    Shepherd, Gordon M G

    2009-01-01

    A well-defined granular layer 4 is a defining cytoarchitectonic feature associated with sensory areas of mammalian cerebral cortex, and one with hodological significance: the local axons ascending from cells in thalamorecipient layer 4 and connecting to layer 2/3 pyramidal neurons form a major feedforward excitatory interlaminar projection. Conversely, agranular cortical areas, lacking a distinct layer 4, pose a hodological conundrum: without a laminar basis for the canonical layer 4-->2/3 pathway, what is the basic circuit organization? This review highlights current challenges and prospects for local-circuit electroanatomy and electrophysiology in agranular cortex, focusing on the mouse. Different lines of evidence, drawn primarily from studies of motor areas in frontal cortex in rodents, support the view that synaptic circuits in agranular cortex are organized around prominent descending excitatory layer 2/3-->5 pathways targeting multiple classes of projection neurons.

  20. Implantable microcoils for intracortical magnetic stimulation

    PubMed Central

    Lee, Seung Woo; Fallegger, Florian; Casse, Bernard D. F.; Fried, Shelley I.

    2016-01-01

    Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome. Magnetic stimulation can address many of these limitations, but coils small enough to be implanted into the cortex were not thought strong enough to activate neurons. We describe a new microcoil design and demonstrate its effectiveness for both activating cortical neurons and driving behavioral responses. The stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 μm). The spatially asymmetric fields arising from the coil helped to avoid the simultaneous activation of passing axons. In vivo implantation was safe and resulted in consistent and predictable behavioral responses. The high permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes. These findings suggest that a coil-based implant might be a useful alternative to existing electrode-based devices. The enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex. PMID:27957537

  1. Synchronous intracortical adamantinomas with keratin cyst formation.

    PubMed

    Park, Yong-Koo; Ryu, Kyung Nam; Han, Chung Soo

    2006-03-01

    Adamantinoma of the long bones is a rare primary bone tumor of uncertain embryogenesis. It tends to involve the tibia almost exclusively. We report on adamantinomas occurring in a 16-year-old male patient, with synchronous tibial and fibular lesions. Histologically, there were characteristic clusters of epithelial cells in a fibrous background, forming a keratin cyst. Immunohistochemically, these cells were strongly positive for cytokeratin. This keratin cyst formation is quite an unusual finding in classic adamantinoma.

  2. 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.

  3. 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…

  4. 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…

  5. Direct seeding

    Treesearch

    Richard M. Godman; G. A. Mattson

    1992-01-01

    At present, direct seeding of hardwoods in the Lake States is more of a supplemental than a primary means of artificial regeneration. Direct seeding may be used to augment a poor seed crop or increase the proportion of a preferred species. In the future, it will no doubt play a bigger role-in anticipation of this we need to collect and store the amounts of seed needed...

  6. Direct Instruction.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    This paper provides an overview of Direct Instruction, an intensive instructional method for grades K-6 based on the theory that learning can be greatly accelerated if instructional presentations are clear, rule out likely misinterpretations and facilitate generalizations. Over 50 instructional programs have been developed based on this…

  7. 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.

  8. 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)

  9. 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.

  10. Late emergence of the vibrissa direction selectivity map in the rat barrel cortex.

    PubMed

    Kremer, Yves; Léger, Jean-François; Goodman, Dan; Brette, Romain; Bourdieu, Laurent

    2011-07-20

    In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

  11. 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. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. 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.

  13. How confident do you feel?

    PubMed

    de Lafuente, Victor; Romo, Ranulfo

    2014-08-20

    In this issue of Neuron, Fetsch et al. (2014) show that microstimulation of motion-sensitive neurons in the visual cortex (MT/MST) of primates mimics the addition of sensory information for which the stimulated neurons are selective. Such microstimulation increases the confidence that monkeys have in their decisions about motion direction.

  14. Future directions.

    PubMed

    Erickson, David L; Kress, W John

    2012-01-01

    It is a risky task to attempt to predict the direction that DNA barcoding and its applications may take in the future. In a very short time, the endeavor of DNA barcoding has gone from being a tool to facilitate taxonomy in difficult to identify species, to an ambitious, global initiative that seeks to tackle such pertinent and challenging issues as quantifying global biodiversity, revolutionizing the forensic identifications of species, advancing the study of interactions among species, and promoting the reconstruction of evolutionary relationships within communities. The core element of DNA barcoding will always remain the same: the generation of a set of well-identified samples collected and genotyped at one or more genetic barcode markers and assembled into a properly curated database. But the application of this body of data will depend on the creativity and need of the research community in using a "gold standard" of annotated DNA sequence data at the species level. We foresee several areas where the application of DNA barcode data is likely to yield important evolutionary, ecological, and societal insights, and while far from exclusive, provide examples of how DNA barcode data will continue to empower scientists to address hypothesis-driven research. Three areas of immediate and obvious concern are (1) biodiversity inventories, (2) phylogenetic applications, and (3) species interactions.

  15. 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

  16. Direction selectivity of neurons in visual cortex is non-linear and laminar dependent

    PubMed Central

    Kim, Taekjun; Freeman, Ralph D.

    2016-01-01

    Neurons in the visual cortex are generally selective to direction of movement of a stimulus. Although models of this direction selectivity (DS) assume linearity, experimental data show stronger degrees of DS than those predicted by linear models. Our current study is intended to determine the degree of non-linearity of the DS mechanism for cells within different lamina of the cat’s primary visual cortex. To do this, we analyzed cells in our database using neurophysiological and histological approaches to quantify non-linear components of DS in four principal cortical laminae (layers 2/3, 4, 5, and 6). We use a direction selectivity index (DSI) to quantify degrees of DS in our sample. Our results show laminar differences. In layer 4, the main thalamic input region, most neurons are simple type and exhibit high DSI values. For complex cells in layer 4, there is a broad distribution of DSI values. Similar features are observed in layer 2/3, but complex cells are dominant. In deeper layers (5 and 6), DSI distributions are characterized by clear peaks at high values. Independent of specific lamina, high DSI values are accompanied by narrow orientation tuning widths. Differences of orientation tuning for non-preferred versus preferred directions are smallest in layer 4 and largest in layer 6. These results are consistent with a non-linear process of intra-cortical inhibition which enhances DS by selective suppression of neuronal firing for non-preferred directions of stimulus motion in a laminar dependent manner. Other potential mechanisms are also considered. PMID:26929101

  17. Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

    PubMed

    Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

    2013-04-01

    Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI

  18. 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

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

    PubMed

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

    2015-01-01

    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. 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. 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. 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). 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Beyond intuitive anthropomorphic control: recent achievements using brain computer interface technologies

    NASA Astrophysics Data System (ADS)

    Pohlmeyer, Eric A.; Fifer, Matthew; Rich, Matthew; Pino, Johnathan; Wester, Brock; Johannes, Matthew; Dohopolski, Chris; Helder, John; D'Angelo, Denise; Beaty, James; Bensmaia, Sliman; McLoughlin, Michael; Tenore, Francesco

    2017-05-01

    Brain-computer interface (BCI) research has progressed rapidly, with BCIs shifting from animal tests to human demonstrations of controlling computer cursors and even advanced prosthetic limbs, the latter having been the goal of the Revolutionizing Prosthetics (RP) program. These achievements now include direct electrical intracortical microstimulation (ICMS) of the brain to provide human BCI users feedback information from the sensors of prosthetic limbs. These successes raise the question of how well people would be able to use BCIs to interact with systems that are not based directly on the body (e.g., prosthetic arms), and how well BCI users could interpret ICMS information from such devices. If paralyzed individuals could use BCIs to effectively interact with such non-anthropomorphic systems, it would offer them numerous new opportunities to control novel assistive devices. Here we explore how well a participant with tetraplegia can detect infrared (IR) sources in the environment using a prosthetic arm mounted camera that encodes IR information via ICMS. We also investigate how well a BCI user could transition from controlling a BCI based on prosthetic arm movements to controlling a flight simulator, a system with different physical dynamics than the arm. In that test, the BCI participant used environmental information encoded via ICMS to identify which of several upcoming flight routes was the best option. For both tasks, the BCI user was able to quickly learn how to interpret the ICMSprovided information to achieve the task goals.

  1. Linear summation of cat motor cortex outputs.

    PubMed

    Ethier, Christian; Brizzi, Laurent; Darling, Warren G; Capaday, Charles

    2006-05-17

    Recruitment of movement-related muscle synergies involves the functional linking of motor cortical points. We asked how the outputs of two simultaneously stimulated motor cortical points would interact. To this end, experiments were done in ketamine-anesthetized cats. When prolonged (e.g., 500 ms) trains of intracortical microstimulation were applied in the primary motor cortex, stimulus currents as low as 10-20 microA evoked coordinated movements of the contralateral forelimb. Paw kinematics in three dimensions and the electromyographic (EMG) activity of eight muscles were simultaneously recorded. We show that the EMG outputs of two cortical points simultaneously stimulated are additive. The movements were represented as displacement vectors pointing from initial to final paw position. The displacement vectors resulting from simultaneous stimulation of two cortical points pointed in nearly the same direction as the algebraic resultant vector. Linear summation of outputs was also found when inhibition at one of the cortical points was reduced by GABAA receptor antagonists. A simple principle emerges from these results. Notwithstanding the underlying complex neuronal circuitry, motor cortex outputs combine nearly linearly in terms of movement direction and muscle activation patterns. Importantly, simultaneous activation does not change the nature of the output at each point. An additional implication is that not all possible movements need be explicitly represented in the motor cortex; a large number of different movements may be synthesized from a smaller repertoire.

  2. Deep Brain Stimulation of the Lateral Cerebellar Nucleus Produces Frequency-Specific Alterations in Motor Evoked Potentials in the Rat In Vivo

    PubMed Central

    Baker, Kenneth B.; Schuster, Daniel; Cooperrider, Jessica; Machado, Andre G.

    2010-01-01

    The cerebral cortex is tightly and reciprocally linked to the cerebellum and the ascending dentato-thalalmo-cortical pathway influences widespread cortical regions. Using a rodent model of middle cerebral artery stroke, we showed previously that chronic, 20 Hz stimulation of the contralateral lateral cerebellar nucleus (LCN) improved motor recovery, while 50 Hz stimulation did not. Using motor evoked potentials (MEP) elicited by intracortical microstimulation, we now show the effect of LCN stimulation on motor cortex excitability as a function of pulse frequency in propofol-anesthetized rats. MEPs were recorded serially, at 15-second intervals, with cerebellar stimulation delivered in 10-minute blocks at rates of 20, 30, 40, 50 or 100 Hz. Stimulation at 20, 30, 40 or 50 Hz enhanced the average MEP response across the block, with the maximal overall increase observed during 30 Hz stimulation. However, the effect varied as a function of both repeated trials within the block and LCN stimulation frequency, such that 40 Hz and 50 Hz stimulation showed a reduced effect over time. Stimulation at 100 Hz produced a transient increase in MEP amplitude in some animals; however the overall effect across the block was a trend towards reduced cortical excitability. These results suggest that direct stimulation of the LCN can yield frequency-dependent changes in cortical excitability and may provide a therapeutic approach to modulating cortical activity for the treatment of strokes or other focal cortical lesions, movement disorders and epilepsy. PMID:20816822

  3. 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.

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

    PubMed

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

    2015-07-09

    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.

  5. 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

    2011-10-05

    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.

  6. Optical imaging in galagos reveals parietal-frontal circuits underlying motor behavior.

    PubMed

    Stepniewska, Iwona; Friedman, Robert M; Gharbawie, Omar A; Cerkevich, Christina M; Roe, Anna W; Kaas, Jon H

    2011-09-13

    The posterior parietal cortex (PPC) of monkeys and prosimian galagos contains a number of subregions where complex, behaviorally meaningful movements, such as reaching, grasping, and body defense, can be evoked by electrical stimulation with long trains of electrical pulses through microelectrodes. Shorter trains of pulses evoke no or simple movements. One possibility for the difference in effectiveness of intracortical microstimulation is that long trains activate much larger regions of the brain. Here, we show that long-train stimulation of PPC does not activate widespread regions of frontal motor and premotor cortex but instead, produces focal, somatotopically appropriate activations of frontal motor and premotor cortex. Shorter stimulation trains activate the same frontal foci but less strongly, showing that longer stimulus trains do not produce less specification. Because the activated sites in frontal cortex correspond to the locations of direct parietal-frontal anatomical connections from the stimulated PPC subregions, the results show the usefulness of optical imaging in conjunction with electrical stimulation in showing functional pathways between nodes in behavior-specific cortical networks. Thus, long-train stimulation is effective in evoking ethologically relevant sequences of movements by activating nodes in a cortical network for a behaviorally relevant period rather than spreading activation in a nonspecific manner.

  7. 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

  8. Predicting link directions using local directed path

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Zhang, Xue; Zhao, Chengli; Xie, Zheng; Zhang, Shengjun; Yi, Dongyun

    2015-02-01

    Link prediction in directed network is attracting growing interest among many network scientists. Compared with predicting the existence of a link, determining its direction is more complicated. In this paper, we propose an efficient solution named Local Directed Path to predict link direction. By adding an extra ground node to the network, we solve the information loss problem in sparse network, which makes our method effective and robust. As a quasi-local method, our method can deal with large-scale networks in a reasonable time. Empirical analysis on real networks shows that our method can correctly predict link directions, which outperforms some local and global methods.

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

    PubMed

    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.

  10. 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

  11. Origin of facilitation of motor-evoked potentials after paired magnetic stimulation: direct recording of epidural activity in conscious humans.

    PubMed

    Di Lazzaro, V; Pilato, F; Oliviero, A; Dileone, M; Saturno, E; Mazzone, P; Insola, A; Profice, P; Ranieri, F; Capone, F; Tonali, P A; Rothwell, J C

    2006-10-01

    A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below active threshold for obtaining motor-evoked potentials (MEPs) facilitates EMG responses evoked at rest in hand muscles by a suprathreshold magnetic stimulus given 10-25 ms later. This is known as intracortical facilitation (ICF). We recorded descending volleys produced by single and paired magnetic motor cortex stimulation through high cervical epidural electrodes implanted for pain relief in six conscious patients. At interstimulus intervals (ISIs) of 10 and 15 ms, although MEP was facilitated, there was no change in the amplitude or number of descending volleys. An additional I wave sometimes was observed at 25 ms ISI. In one subject, we also evaluated the effects of reversing the direction of the induced current in the brain. At 10 ms ISI, the facilitation of the MEPs disappeared and was replaced by slight suppression; at 2 ms ISI, there was a pronounced facilitation of epidural volleys. Subsequent experiments on healthy subjects showed that a conditioning stimulus capable of producing ICF of MEPs had no effect on the EMG response evoked by transmastoidal electrical stimulation of corticospinal tract. We conclude that ICF occurs because either 1) the conditioning stimulus has a (thus far undetected) effect on spinal cord excitability that increases its response to the same amplitude test volley or 2) that it can alter the composition (but not the amplitude) of the descending volleys set up by the test stimulus such that a larger proportion of the activity is destined for the target muscle.

  12. On directed interacting animals and directed percolation

    NASA Astrophysics Data System (ADS)

    Knezevic, Milan; Vannimenus, Jean

    2002-03-01

    We study the phase diagram of fully directed lattice animals with nearest-neighbour interactions on the square lattice. This model comprises several interesting ensembles (directed site and bond trees, bond animals, strongly embeddable animals) as special cases and its collapse transition is equivalent to a directed bond percolation threshold. Precise estimates for the animal size exponents in the different phases and for the critical fugacities of these special ensembles are obtained from a phenomenological renormalization group analysis of the correlation lengths for strips of width up to n = 17. The crossover region in the vicinity of the collapse transition is analysed in detail and the crossover exponent φ is determined directly from the singular part of the free energy. We show using scaling arguments and an exact relation due to Dhar that φ is equal to the Fisher exponent σ governing the size distribution of large directed percolation clusters.

  13. Integrated circuit amplifiers for multi-electrode intracortical recording.

    PubMed

    Jochum, Thomas; Denison, Timothy; Wolf, Patrick

    2009-02-01

    Significant progress has been made in systems that interpret the electrical signals of the brain in order to control an actuator. One version of these systems senses neuronal extracellular action potentials with an array of up to 100 miniature probes inserted into the cortex. The impedance of each probe is high, so environmental electrical noise is readily coupled to the neuronal signal. To minimize this noise, an amplifier is placed close to each probe. Thus, the need has arisen for many amplifiers to be placed near the cortex. Commercially available integrated circuits do not satisfy the area, power and noise requirements of this application, so researchers have designed custom integrated-circuit amplifiers. This paper presents a comprehensive survey of the neural amplifiers described in publications prior to 2008. Methods to achieve high input impedance, low noise and a large time-constant high-pass filter are reviewed. A tutorial on the biological, electrochemical, mechanical and electromagnetic phenomena that influence amplifier design is provided. Areas for additional research, including sub-nanoampere electrolysis and chronic cortical heating, are discussed. Unresolved design concerns, including teraohm circuitry, electrical overstress and component failure, are identified.

  14. Intracortical BCIs: A Brief History of Neural Timing

    NASA Astrophysics Data System (ADS)

    Taylor, Dawn M.; Stetner, Michael E.

    In this chapter, we will explore the option of using neural activity recorded from tiny arrays of hair-thin microelectrodes inserted a few millimeters into the brain itself. These tiny electrodes are small and sensitive enough to detect the firing activity of individual neurons. The ability to record individual neurons is unique to recording technologies that penetrate the brain. These microelectrodes are also small enough that many hundreds of them can be implanted in the brain at one time without displacing much tissue. Therefore, the activity patterns of hundreds or even thousands of individual neurons could potentially be detected and used for brain-computer interfacing (BCI) applications.

  15. μ-Foil Polymer Electrode Array for Intracortical Neural Recordings.

    PubMed

    Ejserholm, Fredrik; Köhler, Per; Granmo, Marcus; Schouenborg, Jens; Bengtsson, Martin; Wallman, Lars

    2014-01-01

    We have developed a multichannel electrode array-termed [Formula: see text]-foil-that comprises ultrathin and flexible electrodes protruding from a thin foil at fixed distances. In addition to allowing some of the active sites to reach less compromised tissue, the barb-like protrusions that also serves the purpose of anchoring the electrode array into the tissue. This paper is an early evaluation of technical aspects and performance of this electrode array in acute in vitro/in vivo experiments. The interface impedance was reduced by up to two decades by electroplating the active sites with platinum black. The platinum black also allowed for a reduced phase lag for higher frequency components. The distance between the protrusions of the electrode array was tailored to match the architecture of the rat cerebral cortex. In vivo acute measurements confirmed a high signal-to-noise ratio for the neural recordings, and no significant crosstalk between recording channels.

  16. Homeland Security Presidential Directives

    EPA Pesticide Factsheets

    Three of these directives directly affect EPA's role in the national emergency response system: HSPD-5 Management of Domestic Incidents; HSPD-7 Critical Infrastructure Identification, Prioritization, and Protection; and HSPD-8 National Preparedness.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT.

    PubMed

    Burghardt, Andrew J; Buie, Helen R; Laib, Andres; Majumdar, Sharmila; Boyd, Steven K

    2010-09-01

    Quantitative cortical microarchitectural end points are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and microarchitecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia and detect intracortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled data set of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%, p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23 microm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume but not for density or microarchitecture. This study indicates that HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality.

  19. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.

    PubMed

    Fricke, K; Seeber, A A; Thirugnanasambandam, N; Paulus, W; Nitsche, M A; Rothwell, J C

    2011-03-01

    Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

  20. A form of motor cortical plasticity that correlates with recovery of function after brain injury

    PubMed Central

    Ramanathan, Dhakshin; Conner, James M.; H. Tuszynski, Mark

    2006-01-01

    To investigate functional mechanisms underlying cortical motor plasticity in the intact and injured brain, we used “behaviorally relevant,” long-duration intracortical microstimulation. We now report the existence of complex, multijoint movements revealed with a 500-msec duration intracortical stimulation in rat motor cortex. A consistent topographic distribution of these complex motor patterns is present across the motor cortex in naïve rats. We further document the plasticity of these complex movement patterns after focal cortical injury, with a significant expansion of specific complex movement representations in response to rehabilitative training after injury. Notably, the degree of functional recovery attained after cortical injury and rehabilitation correlates significantly with a specific feature of map reorganization, the ability to reexpress movement patterns disrupted by the initial injury. This evidence suggests the existence of complex movement representations in the rat motor cortex that exhibit plasticity after injury and rehabilitation, serving as a relevant predictor of functional recovery. PMID:16837575

  1. Rubber friction directional asymmetry

    NASA Astrophysics Data System (ADS)

    Tiwari, A.; Dorogin, L.; Steenwyk, B.; Warhadpande, A.; Motamedi, M.; Fortunato, G.; Ciaravola, V.; Persson, B. N. J.

    2016-12-01

    In rubber friction studies it is usually assumed that the friction force does not depend on the sliding direction, unless the substrate has anisotropic properties, like a steel surface grinded in one direction. Here we will present experimental results for rubber friction, where we observe a strong asymmetry between forward and backward sliding, where forward and backward refer to the run-in direction of the rubber block. The observed effect could be very important in tire applications, where directional properties of the rubber friction could be induced during braking.

  2. Directional radiation detectors

    DOEpatents

    Dowell, Jonathan L.

    2017-09-12

    Directional radiation detectors and systems, methods, and computer-readable media for using directional radiation detectors to locate a radiation source are provided herein. A directional radiation detector includes a radiation sensor. A radiation attenuator partially surrounds the radiation sensor and defines an aperture through which incident radiation is received by the radiation sensor. The aperture is positioned such that when incident radiation is received directly through the aperture and by the radiation sensor, a source of the incident radiation is located within a solid angle defined by the aperture. The radiation sensor senses at least one of alpha particles, beta particles, gamma particles, or neutrons.

  3. Colposcopy - directed biopsy

    MedlinePlus

    ... squamous cells - colposcopy; Pap smear - colposcopy; HPV - colposcopy; Human papilloma virus - colposcopy; Cervix - colposcopy; Colposcopy Images Female reproductive anatomy Colposcopy-directed biopsy Uterus References American College of ...

  4. Direct current transformer

    NASA Technical Reports Server (NTRS)

    Khanna, S. M.; Urban, E. W. (Inventor)

    1979-01-01

    A direct current transformer in which the primary consists of an elongated strip of superconductive material, across the ends of which is direct current potential is described. Parallel and closely spaced to the primary is positioned a transformer secondary consisting of a thin strip of magnetoresistive material.

  5. Decisions Concerning Directional Dependence

    ERIC Educational Resources Information Center

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

  6. Modelling directional solidification

    NASA Technical Reports Server (NTRS)

    Wilcox, William R.

    1991-01-01

    The long range goal of this program is to develop an improved understanding of phenomena of importance to directional solidification and to enable explanation and prediction of differences in behavior between solidification on Earth and in space. Current emphasis is on determining the influence of perturbations on directional solidification.

  7. Direct Instruction News, 2001.

    ERIC Educational Resources Information Center

    Tarver, Sara, Ed.

    2001-01-01

    These three issues of a newsletter offer diverse kinds of information deemed to be of interest to Association for Direct Instruction (ADI) members--stories of successful implementations in different settings, write-ups of ADI awards, tips on "how to" deliver direct instruction (DI) more effectively, topical articles focused on particular…

  8. Direct Conversion of Energy.

    ERIC Educational Resources Information Center

    Corliss, William R.

    This publication is one of a series of information booklets for the general public published by the United States Atomic Energy Commission. Direct energy conversion involves energy transformation without moving parts. The concepts of direct and dynamic energy conversion plus the laws governing energy conversion are investigated. Among the topics…

  9. Direct Support Workforce Development.

    ERIC Educational Resources Information Center

    Impact, 1998

    1998-01-01

    The fourteen brief articles in this theme issue all examine challenges in the development of direct support staff working with people who have developmental disabilities. The articles also include the views of direct support providers and people with developmental disabilities themselves, as well as examples of strategies used by provider agencies…

  10. Direct Electron Detectors.

    PubMed

    McMullan, G; Faruqi, A R; Henderson, R

    2016-01-01

    Direct electron detectors have played a key role in the recent increase in the power of single-particle electron cryomicroscopy (cryoEM). In this chapter, we summarize the background to these recent developments, give a practical guide to their optimal use, and discuss future directions. © 2016 Elsevier Inc. All rights reserved.

  11. Modelling Directional Solidification

    NASA Technical Reports Server (NTRS)

    Wilcox, William R.; Regel, Liya L.; Zhou, Jian; Yuan, Weijun

    1992-01-01

    The long range goal of this program has been to develop an improved understanding of phenomena of importance to directional solidification, in order to enable explanation and prediction of differences in behavior between solidification on Earth and in space. Current emphasis is on determining the influence of perturbations on directional solidification.

  12. Decisions Concerning Directional Dependence

    ERIC Educational Resources Information Center

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

  13. Highly directional acoustic receivers

    NASA Astrophysics Data System (ADS)

    Cray, Benjamin A.; Evora, Victor M.; Nuttall, Albert H.

    2003-03-01

    The theoretical directivity of a single combined acoustic receiver, a device that can measure many quantities of an acoustic field at a collocated point, is presented here. The formulation is developed using a Taylor series expansion of acoustic pressure about the origin of a Cartesian coordinate system. For example, the quantities measured by a second-order combined receiver, denoted a dyadic sensor, are acoustic pressure, the three orthogonal components of acoustic particle velocity, and the nine spatial gradients of the velocity vector. The power series expansion, which can be of any order, is cast into an expression that defines the directivity of a single receiving element. It is shown that a single highly directional dyadic sensor can have a directivity index of up to 9.5 dB. However, there is a price to pay with highly directive sensors; these sensors can be significantly more sensitive to nonacoustic noise sources.

  14. Direct peroral cholangioscopy

    PubMed Central

    Parsi, Mansour A

    2014-01-01

    Peroral cholangioscopy is an important tool for diagnosis and treatment of various biliary disorders. Peroral cholangioscopy can be performed by using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope, or by direct insertion of a small-diameter endoscope into the bile duct. Direct peroral cholangioscopy refers to insertion of an ultraslim endoscope directly into the bile duct for visualization of the biliary mucosa and lumen. This approach provides a valuable and economic solution for diagnostic and therapeutic applications in the biliary tree. Compared to ductoscopy using a dedicated cholangioscope, the direct approach has several advantages and disadvantages. In this editorial, I discuss the advantages, disadvantages, and possible future developments pertaining to direct peroral cholangioscopy. PMID:24527174

  15. Multimode Directional Coupler

    NASA Technical Reports Server (NTRS)

    Simons, Rainee N. (Inventor); Wintucky, Edwin G. (Inventor)

    2016-01-01

    A multimode directional coupler is provided. In some embodiments, the multimode directional coupler is configured to receive a primary signal and a secondary signal at a first port of a primary waveguide. The primary signal is configured to propagate through the primary waveguide and be outputted at a second port of the primary waveguide. The multimode directional coupler also includes a secondary waveguide configured to couple the secondary signal from the primary waveguide with no coupling of the primary signal into the secondary waveguide. The secondary signal is configured to propagate through the secondary waveguide and be outputted from a port of the secondary waveguide.

  16. Directionality of dog vocalizations

    NASA Astrophysics Data System (ADS)

    Frommolt, Karl-Heinz; Gebler, Alban

    2004-07-01

    The directionality patterns of sound emission in domestic dogs were measured in an anechoic environment using a microphone array. Mainly long-distance signals from four dogs were investigated. The radiation pattern of the signals differed clearly from an omnidirectional one with average differences in sound-pressure level between the frontal and rear position of 3-7 dB depending from the individual. Frequency dependence of directionality was shown for the range from 250 to 3200 Hz. The results indicate that when studying acoustic communication in mammals, more attention should be paid to the directionality pattern of sound emission.

  17. AISI direct steelmaking program

    SciTech Connect

    Aukrust, E.

    1991-01-09

    AISI with co-funding from DOE has initiated a research and development program aimed at the development of a new process for direct steelmaking, and the program is discussed in this document. The project is expected to cost about $30 million over a three-year period, with the government providing approximately 77 percent of the funds and AISI the balance. In contrast to current steelmaking processes which are largely open and batch, the direct steelmaking process would be closed and continuous. Further, it would use coal directly, thereby avoiding the need for coke ovens. The second year of the Direct Steelmaking Program (November 29, 1989, through November 28, 1990) was a year of significant accomplishment. The various research programs proceeded essentially on schedule and the pilot plant, the centerpiece of the program, was completed about three months behind schedule but began operation in almost a picture-perfect manner. This report presents the last years accomplishments.

  18. Advanced care directives

    MedlinePlus

    ... you want no matter how ill you are. Writing an advance care directive may be hard. You ... wishes usually replace those you made previously in writing. Additional Information Write your living will or health ...

  19. Direct nuclear pumped laser

    DOEpatents

    Miley, George H.; Wells, William E.; DeYoung, Russell J.

    1978-01-01

    There is provided a direct nuclear pumped gas laser in which the lasing mechanism is collisional radiated recombination of ions. The gas laser active medium is a mixture of the gases, with one example being neon and nitrogen.

  20. Direct interval volume visualization.

    PubMed

    Ament, Marco; Weiskopf, Daniel; Carr, Hamish

    2010-01-01

    We extend direct volume rendering with a unified model for generalized isosurfaces, also called interval volumes, allowing a wider spectrum of visual classification. We generalize the concept of scale-invariant opacity—typical for isosurface rendering—to semi-transparent interval volumes. Scale-invariant rendering is independent of physical space dimensions and therefore directly facilitates the analysis of data characteristics. Our model represents sharp isosurfaces as limits of interval volumes and combines them with features of direct volume rendering. Our objective is accurate rendering, guaranteeing that all isosurfaces and interval volumes are visualized in a crack-free way with correct spatial ordering. We achieve simultaneous direct and interval volume rendering by extending preintegration and explicit peak finding with data-driven splitting of ray integration and hybrid computation in physical and data domains. Our algorithm is suitable for efficient parallel processing for interactive applications as demonstrated by our CUDA implementation.

  1. Tevatron direct photon results.

    SciTech Connect

    Kuhlmann, S.

    1999-09-21

    Tevatron direct photon results since DIS98 are reviewed. Two new CDF measurements are discussed, the Run Ib inclusive photon cross section and the photon + Muon cross section. Comparisons with the latest NLO QCD calculations are presented.

  2. Advance Directives - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Advance Directives URL of this page: https://medlineplus.gov/languages/advancedirectives.html Other topics A-Z Expand Section ...

  3. Refrigerant directly cooled capacitors

    DOEpatents

    Hsu, John S.; Seiber, Larry E.; Marlino, Laura D.; Ayers, Curtis W.

    2007-09-11

    The invention is a direct contact refrigerant cooling system using a refrigerant floating loop having a refrigerant and refrigeration devices. The cooling system has at least one hermetic container disposed in the refrigerant floating loop. The hermetic container has at least one electronic component selected from the group consisting of capacitors, power electronic switches and gating signal module. The refrigerant is in direct contact with the electronic component.

  4. Directed Energy Weapons

    DTIC Science & Technology

    2007-12-01

    negative side is a reduction in serious competition for defense contracts and a large number of 2nd and 3r’ tier companies out of work or turning to...the USD (I) staff to be afocalpointfor advocating improvement in all dimensions of directed energy intelligence. - The Director, Defense Inteligence ...staff to be afocalpoint for advocating iprovement in all dimensions of directed energy intelligence. The Director, Defense Inteligence Ageng7 should

  5. Directivity of Antenna Arrays

    NASA Astrophysics Data System (ADS)

    Bulgakova, A. A.; Gorobets, N. N.; Katrich, V. A.; Lyashchenko, V. A.

    2016-12-01

    Purpose: Theoretical investigation of directive gains of linear and planar antenna arrays depending on the distance between radiators and wavelength. Design/methodology/approach: Computing methods in applied mathematics in MathCad were used to calculate the twofold integrals of the radiation pattern over power throughout the whole space observed, defining the directivity in the most general terms. Patterns of radiators, i. e. elements of antenna arrays, are specified by mathematical models. The calculation accounts for the subintegral fast oscillating function. Findings: Calculations and analysis of a directive gain according to the number of radiators and distances between them in fractions of wavelength are made. It is shown that at the ratio of distance between radiators to wave-length being d/λ =0.5 the directivity of array of isotropic radiators is 1.5N², N – number of radiators. When increasing the d/λ to 0.65÷0.97 the directivity increases according to the law close to the linear one up to the maximum possible value for the specified number of radiators. With the increase of d/λ to the values greater than one, the directivity is significantly reduced (the “blinding” effect of non-phased antenna arrays) and its dependence with the growth of d/λ is decaying and oscillating in character. By that, the transfer function of antenna arrays has some vital difference from the transfer function of continuous antennas. Conclusions: Antenna arrays distort the waveform and spectrum of radiated and received signals as a result of irregular changes of their directivity depending on wavelength. The detected “blinding” effect of non-phased antenna arrays of large electrical dimensions must be taken into account in wideband and superwideband radio-electronics systems, especially in radio astronomy, telecommunications systems and superwideband radar.

  6. Electrohydrodynamic direct-writing

    NASA Astrophysics Data System (ADS)

    Huang, Yongan; Bu, Ningbin; Duan, Yongqing; Pan, Yanqiao; Liu, Huimin; Yin, Zhouping; Xiong, Youlun

    2013-11-01

    The electrohydrodynamic (EHD) direct-writing technique can be used to print solid/liquid straight/serpentine nanofibers onto a large-area substrate, in a direct, continuous, and controllable manner. It is a high-efficiency and cost-effective solution-processable technique to satisfy increasing demands of large-area micro/nano-manufacturing. It is ground-breaking to direct-write sub-100 nm fibers on a rigid/flexible substrate using organic materials. A comprehensive review is presented on the research and developments related to the EHD direct-writing technique and print heads. Many developments have been presented to improve the controllability of the electrospun fibers to form high-resolution patterns and devices. EHD direct-writing is characterized by its non-contact, additive and reproducible processing, high resolution, and compatibility with organic materials. It combines dip-pen, inkjet, and electrospinning by providing the feasibility of controllable electrospinning for sub-100 nm nanofabrication, and overcomes the drawbacks of conventional electron-beam lithography, which is relatively slow, complicated and expensive.

  7. Direct Photons at RHIC

    SciTech Connect

    Gabor,D.

    2008-07-29

    Direct photons are ideal tools to investigate kinematical and thermodynamical conditions of heavy ion collisions since they are emitted from all stages of the collision and once produced they leave the interaction region without further modification by the medium. The PHENIX experiment at RHIC has measured direct photon production in p+p and Au+Au collisions at 200 GeV over a wide transverse momentum (p{sub T}) range. The p+p measurements allow a fundamental test of QCD, and serve as a baseline when we try to disentangle more complex mechanisms producing high p{sub T} direct photons in Au+Au. As for thermal photons in Au+Au we overcome the difficulties due to the large background from hadronic decays by measuring 'almost real' virtual photons which appear as low invariant mass e{sup +}e{sup -} pairs: a significant excess of direct photons is measured above the above next-to-leading order perturbative quantum chromodynamics calculations. Additional insights on the origin of direct photons can be gained with the study of the azimuthal anisotropy which benefits from the increased statistics and reaction plane resolution achieved in RHIC Year-7 data.

  8. Directivity of singers

    NASA Astrophysics Data System (ADS)

    Jers, Harald

    2005-09-01

    Studies of acoustical balance between singers within a choir by means of room acoustical measurements have shown that the directional sound propagation of the source is important. For this reason the directivity of female and male singers for different vowels has been measured in this investigation. Measurements of a pilot study and some first measurements in 1998 have been supplemented with new measurements and an enhanced setup. A special measurement setup with reference and recording microphones was used to collect the directivity data. A resolution of 10 deg for azimuth and elevation angle was obtained. The results will be shown in 3D spherical plots with frequency adjustments in semitones from 80 to 8000 Hz. The measurements are compared to an artificial singer's directivity, and the influence of a sheet music binder in front of a singer will be shown. The results give information on the directivity of singers and are relevant for the prediction of self-to-other-ratios that result from placement and formation aspects within a choir.

  9. Electrohydrodynamic direct-writing.

    PubMed

    Huang, YongAn; Bu, Ningbin; Duan, Yongqing; Pan, Yanqiao; Liu, Huimin; Yin, Zhouping; Xiong, Youlun

    2013-12-21

    The electrohydrodynamic (EHD) direct-writing technique can be used to print solid/liquid straight/serpentine nanofibers onto a large-area substrate, in a direct, continuous, and controllable manner. It is a high-efficiency and cost-effective solution-processable technique to satisfy increasing demands of large-area micro/nano-manufacturing. It is ground-breaking to direct-write sub-100 nm fibers on a rigid/flexible substrate using organic materials. A comprehensive review is presented on the research and developments related to the EHD direct-writing technique and print heads. Many developments have been presented to improve the controllability of the electrospun fibers to form high-resolution patterns and devices. EHD direct-writing is characterized by its non-contact, additive and reproducible processing, high resolution, and compatibility with organic materials. It combines dip-pen, inkjet, and electrospinning by providing the feasibility of controllable electrospinning for sub-100 nm nanofabrication, and overcomes the drawbacks of conventional electron-beam lithography, which is relatively slow, complicated and expensive.

  10. Estimating directional epistasis

    PubMed Central

    Le Rouzic, Arnaud

    2014-01-01

    Epistasis, i.e., the fact that gene effects depend on the genetic background, is a direct consequence of the complexity of genetic architectures. Despite this, most of the models used in evolutionary and quantitative genetics pay scant attention to genetic interactions. For instance, the traditional decomposition of genetic effects models epistasis as noise around the evolutionarily-relevant additive effects. Such an approach is only valid if it is assumed that there is no general pattern among interactions—a highly speculative scenario. Systematic interactions generate directional epistasis, which has major evolutionary consequences. In spite of its importance, directional epistasis is rarely measured or reported by quantitative geneticists, not only because its relevance is generally ignored, but also due to the lack of simple, operational, and accessible methods for its estimation. This paper describes conceptual and statistical tools that can be used to estimate directional epistasis from various kinds of data, including QTL mapping results, phenotype measurements in mutants, and artificial selection responses. As an illustration, I measured directional epistasis from a real-life example. I then discuss the interpretation of the estimates, showing how they can be used to draw meaningful biological inferences. PMID:25071828

  11. Direct conversion technology

    SciTech Connect

    Massier, P.F.; Back, L.H.; Ryan, M.A.; Fabris, G.

    1992-01-07

    The overall objective of the Direct Conversion Technology task is to develop an experimentally verified technology base for promising direct conversion systems that have potential application for energy conservation in the end-use sectors. This report contains progress of research on the Alkali Metal Thermal-to-Electric Converter (AMTEC) and on the Two-Phase Liquid-Metal MHD Electrical Generator (LMMHD) for the period January 1, 1991 through December 31, 1991. Research on AMTEC and on LMMHD was initiated during October 1987. Reports prepared on previous occasions (Refs. 1--5) contain descriptive and performance discussions of the following direct conversion concepts: thermoelectric, pyroelectric, thermionic, thermophotovoltaic, thermoacoustic, thermomagnetic, thermoelastic (Nitionol heat engine); and also, more complete descriptive discussions of AMTEC and LMMHD systems.

  12. Highly directional thermal emitter

    DOEpatents

    Ribaudo, Troy; Shaner, Eric A; Davids, Paul; Peters, David W

    2015-03-24

    A highly directional thermal emitter device comprises a two-dimensional periodic array of heavily doped semiconductor structures on a surface of a substrate. The array provides a highly directional thermal emission at a peak wavelength between 3 and 15 microns when the array is heated. For example, highly doped silicon (HDSi) with a plasma frequency in the mid-wave infrared was used to fabricate nearly perfect absorbing two-dimensional gratings structures that function as highly directional thermal radiators. The absorption and emission characteristics of the HDSi devices possessed a high degree of angular dependence for infrared absorption in the 10-12 micron range, while maintaining high reflectivity of solar radiation (.about.64%) at large incidence angles.

  13. Direct conversion technology

    NASA Technical Reports Server (NTRS)

    Massier, Paul F.; Bankston, C. P.; Williams, R.; Underwood, M.; Jeffries-Nakamura, B.; Fabris, G.

    1989-01-01

    The overall objective of the Direct Conversion Technology task is to develop an experimentally verified technology base for promising direct conversion systems that have potential application for energy conservation in the end-use sectors. This report contains progress of research on the Alkali Metal Thermal-to-Electric Converter (AMTEC), and on the Two-Phase Liquid-Metal Magnetohydrodynamic Electrical Generator (LMMHD) for the period January 1, 1989 through December 31, 1989. Research on these concepts was initiated during October 1987. Reports prepared on previous occasions contain discussions on the following other direct conversion concepts: thermoelectric, pyroelectric, thermionic, thermophotovoltaic, thermoacoustic, thermomagnetic, thermoelastic (nitinol heat engines); and also, more complete discussions of AMTEC and LMMHD systems.

  14. The direction of acceleration

    NASA Astrophysics Data System (ADS)

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  15. Microsegregation during directional solidification

    NASA Technical Reports Server (NTRS)

    Coriell, S. R.; Mcfadden, G. B.

    1984-01-01

    During the directional solidification of alloys, solute inhomogeneities transverse to the growth direction arise due to morphological instabilities (leading to cellular or dendritic growth) and/or due to convection in the melt. In the absence of convection, the conditions for the onset of morphological instability are given by the linear stability analysis of Mullins and Sekerka. For ordinary solidification rates, the predictions of linear stability analysis are similar to the constitutional supercooling criterion. However, at very rapid solidification rates, linear stability analysis predicts a vast increase in stabilization in comparison to constitutional supercooling.

  16. Directed flux motor

    NASA Technical Reports Server (NTRS)

    Wilson, Andrew (Inventor); Punnoose, Andrew (Inventor); Strausser, Katherine (Inventor); Parikh, Neil (Inventor)

    2011-01-01

    A directed flux motor described utilizes the directed magnetic flux of at least one magnet through ferrous material to drive different planetary gear sets to achieve capabilities in six actuated shafts that are grouped three to a side of the motor. The flux motor also utilizes an interwoven magnet configuration which reduces the overall size of the motor. The motor allows for simple changes to modify the torque to speed ratio of the gearing contained within the motor as well as simple configurations for any number of output shafts up to six. The changes allow for improved manufacturability and reliability within the design.

  17. Directed flux motor

    NASA Technical Reports Server (NTRS)

    Wilson, Andrew (Inventor); Punnoose, Andrew (Inventor); Strausser, Katherine (Inventor); Parikh, Neil (Inventor)

    2011-01-01

    A directed flux motor described utilizes the directed magnetic flux of at least one magnet through ferrous material to drive different planetary gear sets to achieve capabilities in six actuated shafts that are grouped three to a side of the motor. The flux motor also utilizes an interwoven magnet configuration which reduces the overall size of the motor. The motor allows for simple changes to modify the torque to speed ratio of the gearing contained within the motor as well as simple configurations for any number of output shafts up to six. The changes allow for improved manufacturability and reliability within the design.

  18. Optically switchable directional invisibility.

    PubMed

    Hurwitz, Elisa; Gbur, Greg

    2017-04-01

    It is shown that a scatterer can be designed to be directionally invisible for an incident field composed of a given sum of plane waves. These scatterers are invisible only when all plane waves are present with the given amplitudes and directions of incidence, which suggests a new type of "switchable" invisibility. Such objects could find application in optical devices such as couplers, switches, and optical position sensors. It is also demonstrated that the designed scatterers have balanced gain-loss profiles that are more general than most PT-symmetric objects considered so far.

  19. [New direct restorative materials].

    PubMed

    Hickel, R; Dasch, W; Janda, R; Tyas, M; Anusavice, K

    1999-04-01

    People worldwide have become increasingly aware of the potential adverse effects on the environment, of pollution control and of toxic effects of food, drugs and biomaterials. Amalgam and its potential toxic side effects (still scientifically unproven) continue to be discussed with increasing controversy by the media in some countries. Consequently, new direct restorative materials are now being explored by dentists, materials scientists and patients who are searching for the so-called 'amalgam substitute' or 'amalgam alternative'. From a critical point of view some of the new direct restorative materials are good with respect in aesthetics, but all material characteristics must be considered, such as mechanical properties, biological effects, and longterm clinical behaviour.

  20. Fermilab Library directions

    SciTech Connect

    Garrett, P.; Ritchie, D.

    1990-05-04

    In this document, we indicate our current thinking about the directions of the Fermilab Library. The ideas relate to the preprint management issue in a number of ways. The ideas are subject to revision as we come to understand what is possible as well as what is needed by the Laboratory community. This document should therefore be regarded as our personal view--the availability of off-the-shelf technology, of funding as well as feedback from the laboratory community about their needs will all affect how far we actually proceed in any of these directions.

  1. Directly Executed Languages.

    DTIC Science & Technology

    2014-09-26

    Architecture 2 1.1 An Evaluation of Adept-A Pascal Based Architecture 2 1.2 A Microprocessor Implementation of a DCA 2 1.3 The Instruction Bandwidth of...Direct Correspondence Architectures 3 1.4 Memory Hierarchies for Directly Executed Language Microprocessors 3 2 Architectural Analysis 4 3 Concurrent...reduction: 3.46 I data read reduction (in bytes): 5.42 "-data write reduction (in bytes): 14.72 A microprocessor based implementation of a Pascal-based DCA

  2. Direct Conversion Technology

    SciTech Connect

    Back, L.H.; Fabris, G.; Ryan, M.A.

    1992-07-01

    The overall objective of the Direct Conversion Technology task is to develop an experimentally verified technology base for promising direct conversion systems that have potential application for energy conservation in the end-use sectors. Initially, two systems were selected for exploratory research and advanced development. These are Alkali Metal Thermal-to-Electric Converter (AMTEC) and Two-Phase Liquid Metal MD Generator (LMMHD). This report describes progress that has been made during the first six months of 1992 on research activities associated with these two systems. (GHH)

  3. Serotonin 1A receptors alter expression of movement representations.

    PubMed

    Scullion, Kathleen; Boychuk, Jeffery A; Yamakawa, Glenn R; Rodych, Justin T G; Nakanishi, Stan T; Seto, Angela; Smith, Victoria M; McCarthy, Ryan W; Whelan, Patrick J; Antle, Michael C; Pittman, Quentin J; Teskey, G Campbell

    2013-03-13

    Serotonin has a myriad of central functions involving mood, appetite, sleep, and memory and while its release within the spinal cord is particularly important for generating movement, the corresponding role on cortical movement representations (motor maps) is unknown. Using adult rats we determined that pharmacological depletion of serotonin (5-HT) via intracerebroventricular administration of 5,7 dihydroxytryptamine resulted in altered movements of the forelimb in a skilled reaching task as well as higher movement thresholds and smaller maps derived using high-resolution intracortical microstimulation (ICMS). We ruled out the possibility that reduced spinal cord excitability could account for the serotonin depletion-induced changes as we observed an enhanced Hoffman reflex (H-reflex), indicating a hyperexcitable spinal cord. Motor maps derived in 5-HT1A receptor knock-out mice also showed higher movement thresholds and smaller maps compared with wild-type controls. Direct cortical application of the 5-HT1A/7 agonist 8-OH-DPAT lowered movement thresholds in vivo and increased map size in 5-HT-depleted rats. In rats, electrical stimulation of the dorsal raphe lowered movement thresholds and this effect could be blocked by direct cortical application of the 5-HT1A antagonist WAY-100135, indicating that serotonin is primarily acting through the 5-HT1A receptor. Next we developed a novel in vitro ICMS preparation that allowed us to track layer V pyramidal cell excitability. Bath application of WAY-100135 raised the ICMS current intensity to induce action potential firing whereas the agonist 8-OH-DPAT had the opposite effect. Together our results demonstrate that serotonin, acting through 5-HT1A receptors, plays an excitatory role in forelimb motor map expression.

  4. Direct fired heat exchanger

    DOEpatents

    Reimann, Robert C.; Root, Richard A.

    1986-01-01

    A gas-to-liquid heat exchanger system which transfers heat from a gas, generally the combustion gas of a direct-fired generator of an absorption machine, to a liquid, generally an absorbent solution. The heat exchanger system is in a counterflow fluid arrangement which creates a more efficient heat transfer.

  5. Optimizing WIMP directional detectors

    NASA Astrophysics Data System (ADS)

    Green, Anne M.; Morgan, Ben

    2007-03-01

    We study the dependence of the exposure required to directly detect a WIMP directional recoil signal on the capabilities of a directional detector. Specifically we consider variations in the nuclear recoil energy threshold, the background rate, whether the detector measures the recoil momentum vector in two or three dimensions and whether or not the sense of the momentum vector can be determined. We find that the property with the biggest effect on the required exposure is the measurement of the momentum vector sense. If the detector cannot determine the recoil sense, the exposure required is increased by an order of magnitude for 3-d read-out and two orders of magnitude for 2-d read-out. For 2-d read-out the required exposure, in particular if the senses cannot be measured, can be significantly reduced by analyzing the reduced angles with the, time dependent, projected direction of solar motion subtracted. The background rate effectively places a lower limit on the WIMP cross-section to which the detector is sensitive; it will be very difficult to detect WIMPs with a signal rate more than an order of magnitude below the background rate. Lowering the energy threshold also reduces the required exposure, but only for thresholds above 20 keV.

  6. Optimizing WIMP Directional Detectors

    NASA Astrophysics Data System (ADS)

    Green, A. M.; Morgan, B.

    2007-08-01

    We study the dependence of the number of events required to directly detect a WIMP directional recoil signal on the capabilities of a directional detector. We consider variations in the nuclear recoil energy threshold, the background rate, whether the detector measures the recoil momentum vector in 2 or 3 dimensions and whether or not the sense of the momentum vector can be determined. The property with the biggest effect on the required exposure is the measurement of the momentum vector sense. If the detector cannot determine the recoil sense, the exposure required is increased by an order of magnitude for 3-d read-out and two orders of magnitude for 2-d read-out. For 2-d read-out the required exposure, in particular if the senses can not be measured, can be significantly reduced by analyzing the reduced angles with the, time dependent, projected direction of solar motion subtracted. The background rate effectively places a lower limit on the WIMP cross-section to which the detector is sensitive; it will be very difficult to detect WIMPs with a signal rate more than an order of magnitude below the background rate. Lowering the energy threshold also reduces the required exposure, but only for thresholds above 20 keV.

  7. The Directed Case Method.

    ERIC Educational Resources Information Center

    Cliff, William H.; Curtin, Leslie Nesbitt

    2000-01-01

    Provides an example of a directed case on human anatomy and physiology. Uses brief real life newspaper articles and clinical descriptions of medical reference texts to describe an actual, fictitious, or composite event. Includes interrelated human anatomy and physiology topics in the scenario. (YDS)

  8. The Direct Relationship.

    ERIC Educational Resources Information Center

    Sokol, William

    This autoinstructional program deals with experiences that will aid chemistry students at the secondary school level to determine the slope of the straight line graph relating the variables in a given set of data involving a direct relationship. Prerequisites set for this activity include three Del Mod System packets (SE 018 018, SE 018 020, and…

  9. Directional gamma detector

    DOEpatents

    LeVert, Francis E.; Cox, Samson A.

    1981-01-01

    An improved directional gamma radiation detector has a collector sandwiched etween two layers of insulation of varying thicknesses. The collector and insulation layers are contained within an evacuated casing, or emitter, which releases electrons upon exposure to gamma radiation. Delayed electrons and electrons entering the collector at oblique angles are attenuated as they pass through the insulation layers on route to the collector.

  10. Summary and future directions

    Treesearch

    Janaki R.R. Alavalapati; D. Evan Mercer

    2004-01-01

    This chapter summarizes the main results from the preceding chapters, identifies gaps, and provides direction for fbture economics research on agroforestry systems. Although a common theme throughout the 1990s was that economic research on agroforestry continued to lag the advances made in the bio-physical sciences, the wide range of systems, regions, and techniques...

  11. Developing Ethical Direction

    ERIC Educational Resources Information Center

    Ribble, Mike S.; Bailey,Gerald D.

    2005-01-01

    When you read or hear an unethical suggestion, such as "Steal this article and sell it to another magazine," we're guessing that your internal compass indicates "wrong direction." In other words, your internal voice says, "No, that would be wrong!" Your internal compass tells you when something is right and something is wrong. In our example, your…

  12. Direct seeding for forestation

    Treesearch

    Walter H. Davidson

    1980-01-01

    Direct seeding, an attractive alternative to planting, is not a simple method of forestation. Past experiences show far more failures than successes. Well documented procedures must be followed to insure any degree of success. In general, conifers have given the best results. Black walnut and black locust are notable exceptions. Current research suggests that other...

  13. Statewide Direct Writing Assessment.

    ERIC Educational Resources Information Center

    Peckham, Irvin

    1987-01-01

    Criticizes the California Assessment Program (CAP) prior to l987 for testing writing skills objectively. Describes the specific improvements in the new CAP Directed Writing Assessment which focuses on the most important characteristics necessary to a particular type of writing rather than those that are common to all types.(NH)

  14. Core Directions in HRD.

    ERIC Educational Resources Information Center

    1996

    This document consists of four papers presented at a symposium on core directions in human resource development (HRD) moderated by Verna Willis at the 1996 conference of the Academy of Human Resource Development. "Reengineering the Organizational HRD Function: Two Case Studies" (Neal Chalofsky) reports an action research study in which…

  15. Conclusions and Future Directions

    ERIC Educational Resources Information Center

    Lillibridge, Fred

    2012-01-01

    Benchmarking, when done properly, offers a lot of promise for higher education units that want to improve how they do business. It is clear that much is known, but still more needs to be learned before it reaches its full potential as a useful tool. Readers of this issue of "New Directions for Institutional Research" have been treated to useful…

  16. Audio direct broadcast satellites

    NASA Technical Reports Server (NTRS)

    Miller, J. E.

    1983-01-01

    Satellite sound broadcasting is, as the name implies, the use of satellite techniques and technology to broadcast directly from space to low-cost, consumer-quality receivers the types of sound programs commonly received in the AM and FM broadcast bands. It would be a ubiquitous service available to the general public in the home, in the car, and out in the open.

  17. Conclusions and Future Directions

    ERIC Educational Resources Information Center

    Lillibridge, Fred

    2012-01-01

    Benchmarking, when done properly, offers a lot of promise for higher education units that want to improve how they do business. It is clear that much is known, but still more needs to be learned before it reaches its full potential as a useful tool. Readers of this issue of "New Directions for Institutional Research" have been treated to useful…

  18. The Directed Case Method.

    ERIC Educational Resources Information Center

    Cliff, William H.; Curtin, Leslie Nesbitt

    2000-01-01

    Provides an example of a directed case on human anatomy and physiology. Uses brief real life newspaper articles and clinical descriptions of medical reference texts to describe an actual, fictitious, or composite event. Includes interrelated human anatomy and physiology topics in the scenario. (YDS)

  19. Directed and diode percolation

    NASA Astrophysics Data System (ADS)

    Redner, S.

    1982-03-01

    We study the novel percolation phenomena that occur in random-lattice networks consisting of resistor-like and diode-like bonds. Resistor bonds connect or "transmit information" in either direction along their length, while diodes connect in one direction only. We first treat the special case of directed bond percolation, in which the diodes are aligned along a preferred axis. Mean-field theory shows that clusters become extremely anisotropic near the percolation transition and that their shapes are characterized by two correlation lengths, one parallel and one transverse to the preferred axis. These lengths diverge with exponents ν∥=1 and ν⊥=12, respectively, from which we can show that the upper critical dimension for this system must be five. We also treat a more general random network on the square lattice containing resistors and diodes of arbitrary orientation. Duality arguments are applied to obtain exact results for the location of phase transitions in this system. We then use a position-space renormalization-group approach to map out the phase diagram and calculate critical exponents. This system has an isotropic percolating phase, and phases which percolate in only one direction. Novel types of transitions occur between these phases, in which the diode orientation plays a fundamental role. These percolating phases meet with the nonpercolating phase along a line of multicritical points, where concentration and orientational fluctuations are simultaneously critical.

  20. Direct Multizone System.

    ERIC Educational Resources Information Center

    Lennox Industries, Inc., Marshalltown, IA.

    Describes Lennox indoor direct multizone equipment and controls. The following areas are covered--(1) unit features, (2) controls and operations, (3) approvals, (4) air patterns, (5) typical applications, (6) specifications and ratings, (7) dimensioned drawings of a typical unit, (8) mixing boxes, (9) blower data, (10) water valve selection and…

  1. Direct Multizone System.

    ERIC Educational Resources Information Center

    Lennox Industries, Inc., Marshalltown, IA.

    Describes Lennox indoor direct multizone equipment and controls. The following areas are covered--(1) unit features, (2) controls and operations, (3) approvals, (4) air patterns, (5) typical applications, (6) specifications and ratings, (7) dimensioned drawings of a typical unit, (8) mixing boxes, (9) blower data, (10) water valve selection and…

  2. Restoring the sense of touch with a prosthetic hand through a brain interface.

    PubMed

    Tabot, Gregg A; Dammann, John F; Berg, Joshua A; Tenore, Francesco V; Boback, Jessica L; Vogelstein, R Jacob; Bensmaia, Sliman J

    2013-11-05

    Our ability to manipulate objects dexterously relies fundamentally on sensory signals originating from the hand. To restore motor function with upper-limb neuroprostheses requires that somatosensory feedback be provided to the tetraplegic patient or amputee. Given the complexity of state-of-the-art prosthetic limbs and, thus, the huge state space they can traverse, it is desirable to minimize the need for the patient to learn associations between events impinging on the limb and arbitrary sensations. Accordingly, we have developed approaches to intuitively convey sensory information that is critical for object manipulation--information about contact location, pressure, and timing--through intracortical microstimulation of primary somatosensory cortex. In experiments with nonhuman primates, we show that we can elicit percepts that are projected to a localized patch of skin and that track the pressure exerted on the skin. In a real-time application, we demonstrate that animals can perform a tactile discrimination task equally well whether mechanical stimuli are delivered to their native fingers or to a prosthetic one. Finally, we propose that the timing of contact events can be signaled through phasic intracortical microstimulation at the onset and offset of object contact that mimics the ubiquitous on and off responses observed in primary somatosensory cortex to complement slowly varying pressure-related feedback. We anticipate that the proposed biomimetic feedback will considerably increase the dexterity and embodiment of upper-limb neuroprostheses and will constitute an important step in restoring touch to individuals who have lost it.

  3. Restoring the sense of touch with a prosthetic hand through a brain interface

    PubMed Central

    Tabot, Gregg A.; Dammann, John F.; Berg, Joshua A.; Tenore, Francesco V.; Boback, Jessica L.; Vogelstein, R. Jacob; Bensmaia, Sliman J.

    2013-01-01

    Our ability to manipulate objects dexterously relies fundamentally on sensory signals originating from the hand. To restore motor function with upper-limb neuroprostheses requires that somatosensory feedback be provided to the tetraplegic patient or amputee. Given the complexity of state-of-the-art prosthetic limbs and, thus, the huge state space they can traverse, it is desirable to minimize the need for the patient to learn associations between events impinging on the limb and arbitrary sensations. Accordingly, we have developed approaches to intuitively convey sensory information that is critical for object manipulation—information about contact location, pressure, and timing—through intracortical microstimulation of primary somatosensory cortex. In experiments with nonhuman primates, we show that we can elicit percepts that are projected to a localized patch of skin and that track the pressure exerted on the skin. In a real-time application, we demonstrate that animals can perform a tactile discrimination task equally well whether mechanical stimuli are delivered to their native fingers or to a prosthetic one. Finally, we propose that the timing of contact events can be signaled through phasic intracortical microstimulation at the onset and offset of object contact that mimics the ubiquitous on and off responses observed in primary somatosensory cortex to complement slowly varying pressure-related feedback. We anticipate that the proposed biomimetic feedback will considerably increase the dexterity and embodiment of upper-limb neuroprostheses and will constitute an important step in restoring touch to individuals who have lost it. PMID:24127595

  4. Reproducibility of Direct Quantitative Measures of Cortical Bone Micro-architecture of the Distal Radius and Tibia by HR-pQCT

    PubMed Central

    Burghardt, Andrew J.; Buie, Helen R.; Laib, Andres; Majumdar, Sharmila; Boyd, Steven K.

    2010-01-01

    Quantitative cortical micro-architectural endpoints are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and micro-architecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia, and detect intra-cortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled dataset of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which, the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%; p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23μm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume, but not density nor microarchitecture. This study indicates HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality. PMID:20561906

  5. Polar Direct Drive

    NASA Astrophysics Data System (ADS)

    Skupsky, S.

    2003-10-01

    Direct drive offers the potential of higher target gain on the National Ignition Facility (NIF) than x-ray drive: The initial direct-drive target design had a 1-D gain of 45 and consisted primarily of a pure cryogenic DT shell. Using the expected levels of target and laser nonuniformities for the NIF, two-dimensional (2-D) hydrodynamic simulations predicted target gains around 30.(P.W. McKenty et al.), Phys. Plasmas 8, 2315 (2001). More-recent designs have shown that higher target gains could be obtained by replacing a portion of the DT shell with ``wetted'' CH foam and by using adiabat shaping: (1) Higher-Z material (C) in the foam increases laser absorption by about 40% (from 60% absorption to 85%).(S. Skupsky et al.), in Inertial Fusion Sciences and Applications 2001, edited by K. Tanaka et al. (Elsevier, Paris, 2002), p. 240. (2) Adiabat shaping allows the main portion of the fuel to be placed on a lower adiabat without compromising target stability.(V.N. Goncharov et al.), Phys. Plasmas 10, 1906 (2003). These direct-drive concepts can be tested on the NIF, long before that facility is converted to a direct-drive (spherically symmetric) irradiation configuration. Using the NIF x-ray-drive beam configuration, some of the near-polar beams could be pointed to better illuminate the target's equator. These more-oblique, equatorial beams will have lower absorption and reduced drive efficiency than the polar beams. One strategy to compensate for the difference in polar and equatorial drive is to reduce the irradiation at the poles and employ different pulse shapes to accommodate the time-dependent variations in drive and absorption. This concept of polar direct drive (PDD) has been studied using the 2-D hydrocode DRACO to determine the requirements for achieving ignition and moderate target gain for the NIF. Experiments on the OMEGA laser will examine the effects of oblique irradiation on target drive. Results of simulations for different direct-drive target designs

  6. Measures to Predict The Individual Variability of Corticospinal Responses Following Transcranial Direct Current Stimulation

    PubMed Central

    Nuzum, Nathan D.; Hendy, Ashlee M.; Russell, Aaron P.; Teo, Wei-Peng

    2016-01-01

    Individual responses to transcranial direct current stimulation (tDCS) are varied and therefore potentially limit its application. There is evidence that this variability is related to the contributions of Indirect waves (I-waves) recruited in the cortex. The latency of motor-evoked potentials (MEPs) can be measured through transcranial magnetic stimulation (TMS), allowing an individual’s responsiveness to tDCS to be determined. However, this single-pulse method requires several different orientations of the TMS coil, potentially affecting its reliability. Instead, we propose a paired-pulse TMS paradigm targeting I-waves as an alternative method. This method uses one orientation that reduces inter- and intra-trial variability. It was hypothesized that the paired-pulse method would correlate more highly to tDCS responses than the single-pulse method. In a randomized, double blinded, cross-over design, 30 healthy participants completed two sessions, receiving 20 min of either anodal (2 mA) or sham tDCS. TMS was used to quantify Short interval intracortical facilitation (SICF) at Inter stimulus intervals (ISIs) of 1.5, 3.5 and 4.5 ms. Latency was determined in the posterior-anterior (PA), anterior-posterior (AP) and latero-medial (LM) coil orientations. The relationship between latency, SICF measures and the change in suprathreshold MEP amplitude size following tDCS were determined with Pearson’s correlations. TMS measures, SICI and SICF were also used to determine responses to Anodal-tDCS (a-tDCS). Neither of the latency differences nor the SICF measures correlated to the change in MEP amplitude from pre-post tDCS (all P > 0.05). Overall, there was no significant response to tDCS in this cohort. This study highlights the need for testing the effects of various tDCS protocols on the different I-waves. Further research into SICF and whether it is a viable measure of I-wave facilitation is warranted. PMID:27766075

  7. [Direct biosynthesis of ethylene].

    PubMed

    Sun, Zhilan; Chen, Yifeng

    2013-10-01

    Ethylene is the most widely used petrochemical feedstock globally. The development of bio-ethylene is essential due to limited fossil fuels and rising oil prices. Bio-ethylene is produced primarily by the dehydration of ethanol, but can alternatively be directly produced from ethylene biosynthesis pathways in plants, algae, or microorganisms by using cheap and renewable substrates. This review addressed the biosynthesis of ethylene in plants and microorganisms, the characterization of key enzymes, genetic engineering strategies for ethylene biosynthesis in microorganisms, and evaluated its perspective and successful cases toward the industrial application. The direct production of bio-ethylene from a biological process in situ is promising to supplement and even replace the petrochemical ethylene production.

  8. Direct insolation models

    SciTech Connect

    Bird, R.; Hulstrom, R.L.

    1980-01-01

    Several recently published models of the direct component of the broadband insolation are compared for clear sky conditions. The comparison includes seven simple models and one rigorous model that is used as a basis for determining accuracy. Where possible, the comparison is made between the results of each model for each atmospheric constituent (H/sub 2/O, CO/sub 2/, O/sub 3/, O/sub 2/, aerosol and molecular scattering) separately as well as for the combined effect of all of the constituents. Two optimum simple models of varying degrees of complexity are developed as a result of this comparison. The study indicates: aerosols dominate the attenuation of the direct beam for reasonable atmospheric conditions; molecular scattering is next in importance; water vapor is an important absorber; and carbon dioxide and oxygen are relatively unimportant as attenuators of the broadband solar energy.

  9. Direction sensitive neutron detector

    DOEpatents

    Ahlen, Steven; Fisher, Peter; Dujmic, Denis; Wellenstein, Hermann F.; Inglis, Andrew

    2017-01-31

    A neutron detector includes a pressure vessel, an electrically conductive field cage assembly within the pressure vessel and an imaging subsystem. A pressurized gas mixture of CF.sub.4, .sup.3He and .sup.4He at respective partial pressures is used. The field cage establishes a relatively large drift region of low field strength, in which ionization electrons generated by neutron-He interactions are directed toward a substantially smaller amplification region of substantially higher field strength in which the ionization electrons undergo avalanche multiplication resulting in scintillation of the CF.sub.4 along scintillation tracks. The imaging system generates two-dimensional images of the scintillation patterns and employs track-finding to identify tracks and deduce the rate and direction of incident neutrons. One or more photo-multiplier tubes record the time-profile of the scintillation tracks permitting the determination of the third coordinate.

  10. Modelling directional solidification

    NASA Technical Reports Server (NTRS)

    Wilcox, William R.

    1987-01-01

    An improved understanding of the phenomena of importance to directional solidification is attempted to enable explanation and prediction of differences in behavior between solidification on Earth and in space. Emphasis is now on experimentally determining the influence of convection and freezing rate fluctuations on compositional homogeneity and crystalline perfection. A correlation is sought between heater temperature profiles, buoyancy-driven convection, and doping inhomogeneities using naphthalene doped with anthracene. The influence of spin-up/spin-down is determined on compositional homogeneity and microstructure of indium gallium antimonide. The effect is determined of imposed melting - freezing cycles on indium gallium antimonide. The mechanism behind the increase of grain size caused by using spin-up/spin-down in directional solidification of mercury cadimum telluride is sought.

  11. Propulsion by directional adhesion

    NASA Astrophysics Data System (ADS)

    Bush, John; Prakash, Manu

    2008-03-01

    The rough, hairy integument of water-walking arthropods is well known to be responsible for their water-repellency; we here consider its additional propulsive role. We demonstrate that the tilted flexible leg hairs of water-walking arthropods render the leg cuticle directionally anisotropic: contact lines advance most readily towards the leg tips. The dynamical role of the resulting unidirectional adhesion is explored, and yields new insight into the manner in which water-walking arthropods generate thrust, glide and leap from the free surface. We thus provide new rationale for the fundamental topological difference in the roughness on plants and insects, and suggest novel directions for biomimetic design of smart, hydrophobic surfaces.

  12. Directional Hearing Aid

    NASA Technical Reports Server (NTRS)

    Jhabvala, M.; Lin, H. C.

    1989-01-01

    Hearing-aid device indicates visually whether sound is coming from left, right, back, or front. Device intended to assist individuals who are deaf in at least one ear and unable to discern naturally directions to sources of sound. Device promotes safety in street traffic, on loading docks, and in presence of sirens, alarms, and other warning sounds. Quadraphonic version of device built into pair of eyeglasses and binaural version built into visor.

  13. Directional Ocean Wave Spectra

    DTIC Science & Technology

    1991-01-01

    of Ocean Waves: Some Observations from R. K. Raney and LIMEX/LEWEX 󈨛 P. W, Vachon 104 Directional Spectra from the CCRS C-Band SAR during LEWEX P...11. Vachon , A. S. Bhogal, and i%’. G. Freeman I10 SAR Scattering Mechanisms as Inferred from LEWEX D. G, Tiller Spectral Intercomparisons 117...Duiring her stay. Michelle Champagne- on time scales usually recommended to define the mean. Philippe explored some of the aspects ofthe ’sind %aniahilits

  14. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Jesse, Stowell; Costin, Daniel

    2006-10-10

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  15. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Jesse, Stowell; Costin, Daniel

    2007-02-27

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  16. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

    2006-07-11

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  17. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett Lee; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

    2006-09-19

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  18. Directional Hearing Aid

    NASA Technical Reports Server (NTRS)

    Jhabvala, M.; Lin, H. C.

    1989-01-01

    Hearing-aid device indicates visually whether sound is coming from left, right, back, or front. Device intended to assist individuals who are deaf in at least one ear and unable to discern naturally directions to sources of sound. Device promotes safety in street traffic, on loading docks, and in presence of sirens, alarms, and other warning sounds. Quadraphonic version of device built into pair of eyeglasses and binaural version built into visor.

  19. Directionally Solidified Multifunctional Ceramics

    DTIC Science & Technology

    2006-12-01

    properties (creep, high temperature strength and toughness) and formulate in-situ composite mechanics for multiphase structures. The research efforts on...naturally occurring in-situ composite. The mechanical properties of two phase eutectic are superior to that of either constituent alone due to the strong...directional solidification and can produce strong and stable reinforcing phase/matrix bonding [5]. The phases compromising a eutectic are thermodynamically

  20. Directional Spherical Cherenkov Detector

    NASA Technical Reports Server (NTRS)

    Wrbanek, John D.; Fralick, Gustave C.; Wrbanek, Susan Y.

    2010-01-01

    A proposed radiation-detecting apparatus would provide information on the kinetic energies, directions, and electric charges of highly energetic incident subatomic particles. The apparatus was originally intended for use in measuring properties of cosmic rays in outer space, but could also be adapted to terrestrial uses -- for example, radiation dosimetry aboard high-altitude aircraft and in proton radiation therapy for treatment of tumors.

  1. Direct hydrocarbon fuel cells

    DOEpatents

    Barnett, Scott A.; Lai, Tammy; Liu, Jiang

    2010-05-04

    The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

  2. Portable direct reading instruments

    NASA Astrophysics Data System (ADS)

    Hermon-Cruz, Ivette Z.

    1991-09-01

    Direct reading instruments are those instruments in which the analysis of the contaminant is carried out within the instrument itself. When selecting equipment, the industrial hygienist must consider the physical characteristics of the instruments as well as their performance characteristics and price. Some of the methods of detection that are used in instruments with multi-gas detection capabilities are: photoionization, Flame ionization, infrared, gas chromatography, infrared photoacoustic, and electrochemical.

  3. Future directions for QCD

    SciTech Connect

    Bjorken, J.D.

    1996-10-01

    New directions for exploring QCD at future high-energy colliders are sketched. These include jets within jets. BFKL dynamics, soft and hard diffraction, searches for disoriented chiral condensate, and doing a better job on minimum bias physics. The new experimental opportunities include electron-ion collisions at HERA, a new collider detector at the C0 region of the TeVatron, and the FELIX initiative at the LHC.

  4. Modelling direction solidification

    NASA Technical Reports Server (NTRS)

    Wilcox, W. R.

    1986-01-01

    The overall objective of this program is to develop an improved understanding of some phenomena of importance to directional solidification. The aim of this research is also to help predict differences in behavior between solidification on Earth and solidification in space. In this report, the validity of the Burton-Primslichter equation is explored. The influence of operating variables on grain and twin generation and propagation in single crystals of In sub (x) Ga sub (1-x) Sb is also investigated.

  5. Topologies on directed graphs

    NASA Technical Reports Server (NTRS)

    Lieberman, R. N.

    1972-01-01

    Given a directed graph, a natural topology is defined and relationships between standard topological properties and graph theoretical concepts are studied. In particular, the properties of connectivity and separatedness are investigated. A metric is introduced which is shown to be related to separatedness. The topological notions of continuity and homeomorphism. A class of maps is studied which preserve both graph and topological properties. Applications involving strong maps and contractions are also presented.

  6. Direct somatic lineage conversion

    PubMed Central

    Tanabe, Koji; Haag, Daniel; Wernig, Marius

    2015-01-01

    The predominant view of embryonic development and cell differentiation has been that rigid and even irreversible epigenetic marks are laid down along the path of cell specialization ensuring the proper silencing of unrelated lineage programmes. This model made the prediction that specialized cell types are stable and cannot be redirected into other lineages. Accordingly, early attempts to change the identity of somatic cells had little success and was limited to conversions between closely related cell types. Nuclear transplantation experiments demonstrated, however, that specialized cells even from adult mammals can be reprogrammed into a totipotent state. The discovery that a small combination of transcription factors can reprogramme cells to pluripotency without the need of oocytes further supported the view that these epigenetic barriers can be overcome much easier than assumed, but the extent of this flexibility was still unclear. When we showed that a differentiated mesodermal cell can be directly converted to a differentiated ectodermal cell without a pluripotent intermediate, it was suggested that in principle any cell type could be converted into any other cell type. Indeed, the work of several groups in recent years has provided many more examples of direct somatic lineage conversions. Today, the question is not anymore whether a specific cell type can be generated by direct reprogramming but how it can be induced. PMID:26416679

  7. Direct conversion technology

    NASA Technical Reports Server (NTRS)

    Massier, P. F.; Bankston, C. P.; Fabris, G.; Kirol, L. D.

    1988-01-01

    The overall objective of the Direct Conversion Technology task is to develop an experimentally verified technology base for promising direct thermal-to-electric energy conversion systems that have potential application for energy conservation in the end-use sectors. This report contains progress of research on the Alkali Metal Thermal-to-Electric Converter (AMTEC), and on the Two-Phase Liquid-Metal MHD Electrical Generator (LMMHD) for the period January 1988 through December 1988. Research on these concepts was initiated during October 1987. In addition, status reviews and assessments are presented for thermomagnetic converter concepts and for thermoelastic converters (Nitinol heat engines). Reports prepared on previous occasions contain discussions on the following other direct conversion concepts: thermoelectric, pyroelectric, thermionic thermophotovoltaic and thermoacoustic; and also, more complete discussions of AMTEC and LMMHD systems. A tabulated summary of the various systems which have been reviewed thus far has been prepared. Some of the important technical research needs are listed and a schematic of each system is shown.

  8. Direct observation detonator operation

    NASA Astrophysics Data System (ADS)

    Hall, Charles R.

    2001-11-01

    The analysis of detonator-timing performance has involved the use of rotating-mirror cameras (RMC) used in the streak mode and high-speed film. Fiducial timing marks are applied to the film to provide temporal references. The use of a RMC for detonator analysis requires aligning the camera, performing an exposure test, capturing light from the detonation and then processing the film. This procedure can take up to an hour for two technicians. After the film is possessed another technician compares each light streak on the film with the fiducial timing marks also recorded on the film. Capturing light from a detonator and recording it directly to a digitizer can improve detonator-timing measurement in several ways. The digitized signals can then be directly analyzed with software. The direct recording method reduces the need for expensive rotating mirror cameras, film processing and subjective optical measurement comparison. Furthermore, an extensive support facility requiring several specialized technicians is reduced to a single technician in a modest laboratory. This technician is then capable of performing several tests an hour. Tests were preformed to measure light intensity at detonation. An optical method of capturing the light was designed using a remote microscope coupled to optical fiber to bring the light to an optical/electrical converter and a digitizer then records the signal. This system is presently used in parallel with a RMC. The results are compared for accuracy.

  9. Direct conversion technology

    NASA Astrophysics Data System (ADS)

    Massier, P. F.; Bankston, C. P.; Fabris, G.; Kirol, L. D.

    1988-12-01

    The overall objective of the Direct Conversion Technology task is to develop an experimentally verified technology base for promising direct thermal-to-electric energy conversion systems that have potential application for energy conservation in the end-use sectors. This report contains progress of research on the Alkali Metal Thermal-to-Electric Converter (AMTEC), and on the Two-Phase Liquid-Metal MHD Electrical Generator (LMMHD) for the period January 1988 through December 1988. Research on these concepts was initiated during October 1987. In addition, status reviews and assessments are presented for thermomagnetic converter concepts and for thermoelastic converters (Nitinol heat engines). Reports prepared on previous occasions contain discussions on the following other direct conversion concepts: thermoelectric, pyroelectric, thermionic thermophotovoltaic and thermoacoustic; and also, more complete discussions of AMTEC and LMMHD systems. A tabulated summary of the various systems which have been reviewed thus far has been prepared. Some of the important technical research needs are listed and a schematic of each system is shown.

  10. Direct imaging of exoplanets.

    PubMed

    Lagrange, Anne-Marie

    2014-04-28

    Most of the exoplanets known today have been discovered by indirect techniques, based on the study of the host star radial velocity or photometric temporal variations. These detections allowed the study of the planet populations in the first 5-8 AU from the central stars and have provided precious information on the way planets form and evolve at such separations. Direct imaging on 8-10 m class telescopes allows the detection of giant planets at larger separations (currently typically more than 5-10 AU) complementing the indirect techniques. So far, only a few planets have been imaged around young stars, but each of them provides an opportunity for unique dedicated studies of their orbital, physical and atmospheric properties and sometimes also on the interaction with the 'second-generation', debris discs. These few detections already challenge formation theories. In this paper, I present the results of direct imaging surveys obtained so far, and what they already tell us about giant planet (GP) formation and evolution. Individual and emblematic cases are detailed; they illustrate what future instruments will routinely deliver for a much larger number of stars. I also point out the limitations of this approach, as well as the needs for further work in terms of planet formation modelling. I finally present the progress expected in direct imaging in the near future, thanks in particular to forthcoming planet imagers on 8-10 m class telescopes.

  11. Directional control of radiant heat

    NASA Technical Reports Server (NTRS)

    Howell, J. R.; Perlmutter, M.

    1970-01-01

    Surface with grooves having flat bases gives directional emissivities and absorptivities that can be made to approximate a perfect directional surface. Radiant energy can then be transferred in desired directions.

  12. Improved VHF direction finding system

    NASA Technical Reports Server (NTRS)

    Graf, E. R.; Neff, H.

    1969-01-01

    Direction finding device operating at very high frequencies requires a loop antenna, mechanical rotation, and large structures. The system is applicable to an unmanned configuration. Direction information is extracted in the form of a direction cosine analog.

  13. Visual direction finding by fishes

    NASA Technical Reports Server (NTRS)

    Waterman, T. H.

    1972-01-01

    The use of visual orientation, in the absence of landmarks, for underwater direction finding exercises by fishes is reviewed. Celestial directional clues observed directly near the water surface or indirectly at an asymptatic depth are suggested as possible orientation aids.

  14. Directional Antineutrino Detection

    NASA Astrophysics Data System (ADS)

    Safdi, B. R.; Suerfu, J.

    2014-12-01

    We propose the first truly directional antineutrino detector for antineutrinos near the threshold for the inverse beta decay (IBD) of hydrogen, with potential applications including the spatial mapping of geo-neutrinos, searches for stellar antineutrinos, and the monitoring of nuclear reactors. The detector consists of adjacent and separated target and neutron-capture layers. The IBD events, which result in a neutron and a positron, take place in the target layers. These layers are thin enough so that the neutrons escape without scattering elastically. The neutrons are detected in the thicker neutron-capture layers. The location of the IBD event is determined from the energy deposited by the positron as it slows in the medium and from the two gamma rays that come from the positron annihilation. Since the neutron recoils in the direction of the antineutrino's motion, a line may then be drawn between the IBD event location and the neutron-capture location to approximate the antineutrino's velocity. In some events, we may even measure the positron's velocity, which further increases our ability to reconstruct the antineutrino's direction of motion. Our method significantly improves upon previous methods by allowing the neutron to freely travel a long distance before diffusing and being captured. Moreover, our design is a straightforward modification of existing antineutrino detectors; a prototype could easily be built with existing technology. We verify our design through Monte Carlo simulations in Geant4, using commercially-available boron-loaded plastic scintillators for the target and neutron-capture layer materials. We are able to discriminate from background using multiple coincidence signatures within a short, ~microsecond time interval. We conclude that the detector could likely operate above ground with minimal shielding.

  15. Directed energy planetary defense

    NASA Astrophysics Data System (ADS)

    Lubin, Philip; Hughes, Gary B.; Bible, Johanna; Bublitz, Jesse; Arriola, Josh; Motta, Caio; Suen, Jon; Johansson, Isabella; Riley, Jordan; Sarvian, Nilou; Clayton-Warwick, Deborah; Wu, Jane; Milich, Andrew; Oleson, Mitch; Pryor, Mark; Krogen, Peter; Kangas, Miikka

    2013-09-01

    Asteroids and comets that cross Earth's orbit pose a credible risk of impact, with potentially severe disturbances to Earth and society. Numerous risk mitigation strategies have been described, most involving dedicated missions to a threatening object. We propose an orbital planetary defense system capable of heating the surface of potentially hazardous objects to the vaporization point as a feasible approach to impact risk mitigation. We call the system DE-STAR for Directed Energy System for Targeting of Asteroids and exploRation. DE-STAR is a modular phased array of kilowatt class lasers powered by photovoltaic's. Modular design allows for incremental development, test, and initial deployment, lowering cost, minimizing risk, and allowing for technological co-development, leading eventually to an orbiting structure that would be developed in stages with both technological and target milestones. The main objective of DE-STAR is to use the focused directed energy to raise the surface spot temperature to ~3,000K, allowing direct vaporization of all known substances. In the process of heating the surface ejecting evaporated material a large reaction force would alter the asteroid's orbit. The baseline system is a DE-STAR 3 or 4 (1-10km array) depending on the degree of protection desired. A DE-STAR 4 allows for asteroid engagement starting beyond 1AU with a spot temperature sufficient to completely evaporate up to 500-m diameter asteroids in one year. Small asteroids and comets can be diverted/evaporated with a DESTAR 2 (100m) while space debris is vaporized with a DE-STAR 1 (10m).

  16. Investigating the Efficacy of Novel TrkB Agonists to Augment Stroke Recovery

    NASA Astrophysics Data System (ADS)

    Warraich, Zuha

    Stroke remains the leading cause of adult disability in developed countries. Most survivors live with residual motor impairments that severely diminish independence and quality of life. After stroke, the only accepted treatment for these patients is motor rehabilitation. However, the amount and kind of rehabilitation required to induce clinically significant improvements in motor function is rarely given due to the constraints of our current health care system. Research reported in this dissertation contributes towards developing adjuvant therapies that may augment the impact of motor rehabilitation and improve functional outcome. These studies have demonstrated reorganization of maps within motor cortex as a function of experience in both healthy and brain-injured animals by using intracortical microstimulation technique. Furthermore, synaptic plasticity has been identified as a key neural mechanism in directing motor map plasticity, evidenced by restoration of movement representations within the spared cortical tissue accompanied by increase in synapse number translating into motor improvement after stroke. There is increasing evidence that brain-derived neurotrophic factor (BDNF) modulates synaptic and morphological plasticity in the developing and mature nervous system. Unfortunately, BDNF itself is a poor candidate because of its short half-life, low penetration through the blood brain barrier, and activating multiple receptor units, p75 and TrkB on the neuronal membrane. In order to circumvent this problem efficacy of two recently developed novel TrkB agonists, LM22A-4 and 7,8-dihydroxyflavone, that actively penetrate the blood brain barrier and enhance functional recovery. Findings from these dissertation studies indicate that administration of these pharmacological compounds, accompanied by motor rehabilitation provide a powerful therapeutic tool for stroke recovery.

  17. Development of motor maps in rats and their modulation by experience.

    PubMed

    Young, Nicole A; Vuong, Jennifer; Teskey, G Campbell

    2012-09-01

    While a substantial literature demonstrates the effect of differential experience on development of mammalian sensory cortices and plasticity of adult motor cortex, characterization of differential experience on the functional development of motor cortex is meager. We first determined when forelimb movement representations (motor maps) could be detected in rats during postnatal development and then whether their motor map expression could be altered with rearing in an enriched environment consisting of group housing and novel toys or skilled learning by training on the single pellet reaching task. All offspring had high-resolution intracortical microstimulation (ICMS)-derived motor maps using methodologies previously optimized for the adult rat. First, cortical GABA-mediated inhibition was depressed by bicuculline infusion directly into layer V of motor cortex and ICMS-responsive points were first reliably detected on postnatal day (PND) 13. Without relying on bicuculline disinhibition of cortex, motor maps emerged on PND 35 and then increased in size until PND 60 and had progressively lower movement thresholds. Second, environmental enrichment did not affect initial detection of responsive points and motor maps in non-bicuculline-treated pups on PND 35. However, motor maps were larger on PND 45 in enriched rat pups relative to pups in the standard housing condition. Rats in both conditions had similar map sizes on PNDs 60, 75, and 90. Third, reach training in rat pups resulted in an internal reorganization of the map in the hemisphere contralateral, but not ipsilateral, to the trained forelimb. The map reorganization was expressed as proportionately more distal (digit and wrist) representations on PND 45. Our data indicate that both environmental enrichment and skilled reach training experience can differentially modify expression of motor maps during development.

  18. Direct to Digital Holography

    SciTech Connect

    Bingham, P.R.; Tobin, K.W.

    2003-06-15

    In this CRADA, Oak Ridge National Laboratory (ORNL) assisted nLine Corporation of Austin, TX in the development of prototype semiconductor wafer inspection tools based on the direct-to-digital holographic (DDH) techniques invented at ORNL. Key components of this work included, development of the first prototype named the Visible Alpha Tool (VAT) that uses visible spectrum illumination of 532 nm, assist in design of second prototype tool named the DUV Alpha Tool (DAT) using deep UV (266 nm) illumination, and continuing support of nLine in the development of higher throughput commercial tools.

  19. Direct to Digital Holography

    SciTech Connect

    Bingham, P.R.; Tobin, K.W.

    2002-06-15

    In this CRADA, Oak Ridge National Laboratory (ORNL) assisted nLine Corporation of Austin, TX in the development of prototype semiconductor wafer inspection tools based on the direct-to-digital holographic (DDH) techniques invented at ORNL. Key components of this work included, testing of DDH for detection of defects in High Aspect Ratio (HAR) structures, development of image processing techniques to enhance detection capabilities through the use of both phase and intensity, and development of methods for autofocus on the DDH tools.

  20. Goal directed fluid therapy.

    PubMed

    Marik, Paul E; Desai, Himanshu

    2012-01-01

    The cornerstone of treating patients with shock remains as it has for decades, intravenous fluids. Surprisingly, dosing intravenous fluid during resuscitation of shock remains largely empirical. Recent data suggests that early aggressive resuscitation of critically ill patients may limit and/or reverse tissue hypoxia, progression to organ failure and improve outcome. However, overzealous fluid resuscitation has been associated with increased complications, increased length of intensive care unit (ICU) and hospital stay and increased mortality. This review focuses on methods to assess fluid responsiveness and the application of these methods for goal directed fluid therapy in critically ill and peri-operative patients.

  1. Omni-directional railguns

    SciTech Connect

    Shahinpoor, M.

    1994-12-31

    This invention is comprised of a device for electromagetically accelerating projectiles. The invention features two parallel conducting circular plates, a plurality of electrode connections to both upper and lower plates, a support base, and a projectile magazine. A projectile is spring-loaded into a firing position concentrically located between the parallel plates. A voltage source is applied to the plates to cause current to flow in directions defined by selectable, discrete electrode connections on both upper and lower plates. Repulsive Lorentz forces are generated to eject the projectile in a 360 degree range of fire.

  2. Reciprocity in directed networks

    NASA Astrophysics Data System (ADS)

    Yin, Mei; Zhu, Lingjiong

    2016-04-01

    Reciprocity is an important characteristic of directed networks and has been widely used in the modeling of World Wide Web, email, social, and other complex networks. In this paper, we take a statistical physics point of view and study the limiting entropy and free energy densities from the microcanonical ensemble, the canonical ensemble, and the grand canonical ensemble whose sufficient statistics are given by edge and reciprocal densities. The sparse case is also studied for the grand canonical ensemble. Extensions to more general reciprocal models including reciprocal triangle and star densities will likewise be discussed.

  3. On Direct Social Perception.

    PubMed

    Spaulding, Shannon

    2015-11-01

    Direct Social Perception (DSP) is the idea that we can non-inferentially perceive others' mental states. In this paper, I argue that the standard way of framing DSP leaves the debate at an impasse. I suggest two alternative interpretations of the idea that we see others' mental states: others' mental states are represented in the content of our perception, and we have basic perceptual beliefs about others' mental states. I argue that the latter interpretation of DSP is more promising and examine the kinds of mental states that plausibly could satisfy this version of DSP. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Direct reading inductance meter

    NASA Technical Reports Server (NTRS)

    Kolby, R. B. (Inventor)

    1977-01-01

    A direct reading inductance meter comprised of a crystal oscillator and an LC tuned oscillator is presented. The oscillators function respectively to generate a reference frequency, f(r), and to generate an initial frequency, f(0), which when mixed produce a difference equal to zero. Upon connecting an inductor of small unknown value in the LC circuit to change its resonant frequency to f(x), a difference frequency (f(r)-f(x)) is produced that is very nearly a linear function of the inductance of the inductor. The difference frequency is measured and displayed on a linear scale in units of inductance.

  5. Direct to Digital Holography

    SciTech Connect

    Bingham, P.R.; Tobin, K.W.

    2007-09-30

    In this Cooperative Research and Development Agreement (CRADA), Oak Ridge National Laboratory (ORNL) assisted nLine Corporation of Austin, TX in the development of prototype semiconductor wafer inspection tools based on the direct-to-digital holographic (DDH) techniques invented at ORNL. Key components of this work included, testing of DDH for detection of defects in High Aspect Ratio (HAR) structures, development of image processing techniques to enhance detection capabilities through the use of both phase and intensity, and development of methods for autofocus on the DDH tools.

  6. Direct effects protection

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Protection of an aircraft and each of its various systems against the direct effects of lightning were analyzed. Components located in different sections of the aircraft were individually examined since they are likely to experience different degrees of susceptibility to lightning, and may be vulnerable to different components of the lightning flash. The basic steps to be followed in establishing lightning protection were presented by discussing the varieties of arc entry and current flow-through damage. The lightning-strike zones and lightning current environments are established, since environmental conditions in the zones are those under which specific protective measures must perform. Airworthiness regulations which apply to lightning protection are cited.

  7. DISE: directed sphere exclusion.

    PubMed

    Gobbi, Alberto; Lee, Man-Ling

    2003-01-01

    The Sphere Exclusion algorithm is a well-known algorithm used to select diverse subsets from chemical-compound libraries or collections. It can be applied with any given distance measure between two structures. It is popular because of the intuitive geometrical interpretation of the method and its good performance on large data sets. This paper describes Directed Sphere Exclusion (DISE), a modification of the Sphere Exclusion algorithm, which retains all positive properties of the Sphere Exclusion algorithm but generates a more even distribution of the selected compounds in the chemical space. In addition, the computational requirement is significantly reduced, thus it can be applied to very large data sets.

  8. Omni-directional railguns

    DOEpatents

    Shahinpoor, M.

    1995-07-25

    A device is disclosed for electromagnetically accelerating projectiles. The invention features two parallel conducting circular plates, a plurality of electrode connections to both upper and lower plates, a support base, and a projectile magazine. A projectile is spring-loaded into a firing position concentrically located between the parallel plates. A voltage source is applied to the plates to cause current to flow in directions defined by selectable, discrete electrode connections on both upper and lower plates. Repulsive Lorentz forces are generated to eject the projectile in a 360 degree range of fire. 4 figs.

  9. Omni-directional railguns

    DOEpatents

    Shahinpoor, Mohsen

    1995-01-01

    A device for electromagnetically accelerating projectiles. The invention features two parallel conducting circular plates, a plurality of electrode connections to both upper and lower plates, a support base, and a projectile magazine. A projectile is spring-loaded into a firing position concentrically located between the parallel plates. A voltage source is applied to the plates to cause current to flow in directions defined by selectable, discrete electrode connections on both upper and lower plates. Repulsive Lorentz forces are generated to eject the projectile in a 360 degree range of fire.

  10. Psychiatric Advance Directives: Getting Started

    MedlinePlus

    ... More... Home Getting Started National Resource Center on Psychiatric Advance Directives - Getting Started Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments ...

  11. Remote direct memory access

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.

    2012-12-11

    Methods, parallel computers, and computer program products are disclosed for remote direct memory access. Embodiments include transmitting, from an origin DMA engine on an origin compute node to a plurality target DMA engines on target compute nodes, a request to send message, the request to send message specifying a data to be transferred from the origin DMA engine to data storage on each target compute node; receiving, by each target DMA engine on each target compute node, the request to send message; preparing, by each target DMA engine, to store data according to the data storage reference and the data length, including assigning a base storage address for the data storage reference; sending, by one or more of the target DMA engines, an acknowledgment message acknowledging that all the target DMA engines are prepared to receive a data transmission from the origin DMA engine; receiving, by the origin DMA engine, the acknowledgement message from the one or more of the target DMA engines; and transferring, by the origin DMA engine, data to data storage on each of the target compute nodes according to the data storage reference using a single direct put operation.

  12. Direct Aerosol Forcing Uncertainty

    DOE Data Explorer

    Mccomiskey, Allison

    2008-01-15

    Understanding sources of uncertainty in aerosol direct radiative forcing (DRF), the difference in a given radiative flux component with and without aerosol, is essential to quantifying changes in Earth's radiation budget. We examine the uncertainty in DRF due to measurement uncertainty in the quantities on which it depends: aerosol optical depth, single scattering albedo, asymmetry parameter, solar geometry, and surface albedo. Direct radiative forcing at the top of the atmosphere and at the surface as well as sensitivities, the changes in DRF in response to unit changes in individual aerosol or surface properties, are calculated at three locations representing distinct aerosol types and radiative environments. The uncertainty in DRF associated with a given property is computed as the product of the sensitivity and typical measurement uncertainty in the respective aerosol or surface property. Sensitivity and uncertainty values permit estimation of total uncertainty in calculated DRF and identification of properties that most limit accuracy in estimating forcing. Total uncertainties in modeled local diurnally averaged forcing range from 0.2 to 1.3 W m-2 (42 to 20%) depending on location (from tropical to polar sites), solar zenith angle, surface reflectance, aerosol type, and aerosol optical depth. The largest contributor to total uncertainty in DRF is usually single scattering albedo; however decreasing measurement uncertainties for any property would increase accuracy in DRF. Comparison of two radiative transfer models suggests the contribution of modeling error is small compared to the total uncertainty although comparable to uncertainty arising from some individual properties.

  13. Direct neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Weinheimer, Christian

    2013-03-01

    Direct neutrino mass experiments are complementary to searches for neutrinoless double β-decay and to analyses of cosmological data. The previous tritium beta decay experiments at Mainz and at Troitsk have achieved upper limits on the neutrino mass of about 2 eV/c2 . The KATRIN experiment under construction will improve the neutrino mass sensitivity down to 200 meV/c2 by increasing strongly the statistics and—at the same time—reducing the systematic uncertainties. Huge improvements have been made to operate the system extremely stably and at very low background rate. The latter comprises new methods to reject secondary electrons from the walls as well as to avoid and to eject electrons stored in traps. As an alternative to tritium β-decay experiments cryo-bolometers investigating the endpoint region of 187Re β-decay or the electron capture of 163Ho are being developed. This article briefly reviews the current status of the direct neutrino mass measurements.

  14. Direct thermal dyes

    NASA Astrophysics Data System (ADS)

    Ehlinger, Edward

    1990-07-01

    Direct thermal dyes are members of a class of compounds referred to in the imaging industry as color formers or leuco dyes. The oldest members of that class have simple triarylmethane structures, and have been employed for years in various dyeing applications. More complex triarylmethane compounds, such as phthalides and fluorans, are now used in various imaging systems to produce color. Color is derived from all of these compounds via the same mechanism, on a molecular level. That is, an event of activation produces a highly resonating cationic system whose interaction with incident light produces reflected light of a specific color. The activation event in the case of a direct thermal system is the creation of a melt on the paper involving dye and an acidic developer. The three major performance parameters in a thermal system are background color, image density, and image stability. The three major dye physical parameters affecting thermal performance are chemical constituency, purity, and particle size. Those dyes having the best combination of characteristics which can also be manufactured economically dominate the marketplace. Manufacturing high performance dyes for the thermal market involves multi-step, convergent reaction sequences performed on large scale. Intermediates must be manufactured at the right time, and at the right quality to be useful.

  15. Detecting Extrasolar Planets Directly

    NASA Astrophysics Data System (ADS)

    Guenther, E. W.; Neuhäuser, R.; Huélamo, N.; Ott, T.; Brandner, W.; Alves, J.; Comerón, F.; Eckart, A.; Hatzes, A.

    Up to now, all extrasolar planets have been found by means of indirect methods. Direct detection of planets orbiting even the nearest stars seems at first glance to be impossible with present day equipment, because of the enormous difference in brightness between the star and the planet, and the small angular separation between them. However, young planets which are still in the contraction phase of evolution are comparatively bright in the infrared, and since many of the extrasolar planets detected have excentric orbits, where they are most of the time at a relatively large distance from the stars, the prospect of detecting young planets directly is much better. In fact, it is principle be possible to detect an extrasolar giant planet, if the planet is younger than 100 millon years, and if the distance is less than 100 pc. Three years ago we thus have embarked on a survey to observe more than one-hundred young, nearby stars in the near infrared. In this talk, we will review the status of the survey. In order to find out whether these stars have additionally a planet at a small distance from the star, we also carried out sensitive radial velocity observation of a subsample using an iodine-cell and the Echelle spectrograph of the Alfred-Jensch Telescope in Tautenburg.

  16. NON-DIRECTIVE PSYCHOTHERAPY

    PubMed Central

    Smith, Lloyd F.

    1950-01-01

    Psychotherapy is a word to describe an age-old process. It would be better not to speak of psychotherapy, but of psychotherapies. Specialists are not the only ones who act as psychotherapists, since every human being fills this role at one time or another. Besides this, no two persons follow an identical approach. Finally, all therapists change technique constantly. The kinds of psychotherapy must therefore approach infinity. Some physicians appear to assume that only one type of psychotherapy may claim a scientific basis. Although Freud first put psychotherapy on a scientific path, there is no reason to say that Freud must be the last in this field. Over the past few years a new trend has started in psychotherapy which deserves close study. This new trend challenges some old beliefs and gives a new tool to help patients of some types. It is called non-directive or client-centered psychotherapy. This therapy does not try to solve the patient's problems for him, but rather establishes the conditions under which a patient can work out his own salvation. Each year non-directive psychotherapy grows in importance. Much can be learned from the method. PMID:14778014

  17. Task directed sensing

    NASA Technical Reports Server (NTRS)

    Firby, R. James

    1990-01-01

    High-level robot control research must confront the limitations imposed by real sensors if robots are to be controlled effectively in the real world. In particular, sensor limitations make it impossible to maintain a complete, detailed world model of the situation surrounding the robot. To address the problems involved in planning with the resulting incomplete and uncertain world models, traditional robot control architectures must be altered significantly. Task-directed sensing and control is suggested as a way of coping with world model limitations by focusing sensing and analysis resources on only those parts of the world relevant to the robot's active goals. The RAP adaptive execution system is used as an example of a control architecture designed to deploy sensing resources in this way to accomplish both action and knowledge goals.

  18. Direct temperature measurement.

    PubMed

    Fessenden, P; Lee, E R; Samulski, T V

    1984-10-01

    Hyperthermia has little hope of progressing as a clinical modality without accurate assessment of the temperature distributions obtained. At the present time only direct, invasive temperature-measuring techniques are possible, posing severe limitations. Established techniques for clinical temperature measurement have developed over the past few years, and for both ultrasound and electromagnetic hyperthermia it is possible to get temperature-time profiles at a large number of spatial points. Position uncertainty, thermal conduction smearing, and artifactual heating limit the accuracy to about 0.2 degrees (electromagnetic) or 0.5 degrees (ultrasound), but this is probably less of a hindrance than the inadequate percentage of tumor and normal tissue volume for which achieved temperatures can be documented.

  19. Site directed recombination

    DOEpatents

    Jurka, Jerzy W.

    1997-01-01

    Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

  20. Direct Field Acoustic Testing

    NASA Technical Reports Server (NTRS)

    Larkin, Paul; Goldstein, Bob

    2008-01-01

    This paper presents an update to the methods and procedures used in Direct Field Acoustic Testing (DFAT). The paper will discuss some of the recent techniques and developments that are currently being used and the future publication of a reference standard. Acoustic testing using commercial sound system components is becoming a popular and cost effective way of generating a required acoustic test environment both in and out of a reverberant chamber. This paper will present the DFAT test method, the usual setup and procedure and the development and use of a closed-loop, narrow-band control system. Narrow-band control of the acoustic PSD allows all standard techniques and procedures currently used in random control to be applied to acoustics and some examples are given. The paper will conclude with a summary of the development of a standard practice guideline that is hoped to be available in the first quarter of next year.

  1. Magnetostrictive direct drive motors

    NASA Technical Reports Server (NTRS)

    Naik, Dipak; Dehoff, P. H.

    1990-01-01

    Developing magnetostrictive direct drive research motors to power robot joints is discussed. These type motors are expected to produce extraordinary torque density, to be able to perform microradian incremental steps and to be self-braking and safe with the power off. Several types of motor designs have been attempted using magnetostrictive materials. One of the candidate approaches (the magnetostrictive roller drive) is described. The method in which the design will function is described as is the reason why this approach is inherently superior to the other approaches. Following this, the design will be modelled and its expected performance predicted. This particular candidate design is currently undergoing detailed engineering with prototype construction and testing scheduled for mid 1991.

  2. Task directed sensing

    NASA Technical Reports Server (NTRS)

    Firby, R. James

    1990-01-01

    High-level robot control research must confront the limitations imposed by real sensors if robots are to be controlled effectively in the real world. In particular, sensor limitations make it impossible to maintain a complete, detailed world model of the situation surrounding the robot. To address the problems involved in planning with the resulting incomplete and uncertain world models, traditional robot control architectures must be altered significantly. Task-directed sensing and control is suggested as a way of coping with world model limitations by focusing sensing and analysis resources on only those parts of the world relevant to the robot's active goals. The RAP adaptive execution system is used as an example of a control architecture designed to deploy sensing resources in this way to accomplish both action and knowledge goals.

  3. Direct Field Acoustic Testing

    NASA Technical Reports Server (NTRS)

    Larkin, Paul; Goldstein, Bob

    2008-01-01

    This paper presents an update to the methods and procedures used in Direct Field Acoustic Testing (DFAT). The paper will discuss some of the recent techniques and developments that are currently being used and the future publication of a reference standard. Acoustic testing using commercial sound system components is becoming a popular and cost effective way of generating a required acoustic test environment both in and out of a reverberant chamber. This paper will present the DFAT test method, the usual setup and procedure and the development and use of a closed-loop, narrow-band control system. Narrow-band control of the acoustic PSD allows all standard techniques and procedures currently used in random control to be applied to acoustics and some examples are given. The paper will conclude with a summary of the development of a standard practice guideline that is hoped to be available in the first quarter of next year.

  4. Mutanome directed cancer immunotherapy.

    PubMed

    Vormehr, Mathias; Diken, Mustafa; Boegel, Sebastian; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2016-04-01

    Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the repertoire of mutations ('the mutanome') in every patient's tumor. This review highlights insights into immune recognition of neo-epitopes and novel concepts for comprehensive identification and immunotherapeutic exploitation of individual mutations.

  5. Directed light fabrication

    SciTech Connect

    Lewis, G.K.; Nemec, R.; Milewski, J.; Thoma, D.J.; Cremers, D.; Barbe, M.

    1994-09-01

    Directed Light Fabrication (DLF) is a rapid prototyping process being developed at Los Alamos National Laboratory to fabricate metal components. This is done by fusing gas delivered metal powder particles in the focal zone of a laser beam that is, programmed to move along or across the part cross section. Fully dense metal is built up a layer at a time to form the desired part represented by a 3 dimensional solid model from CAD software. Machine ``tool paths`` are created from the solid model that command the movement and processing parameters specific to the DLF process so that the part can be built one layer at a time. The result is a fully dense, near net shape metal part that solidifies under rapid solidification conditions.

  6. Modelling directional solidification

    NASA Technical Reports Server (NTRS)

    Wilcox, William R.

    1990-01-01

    The long range goal is to develop an improved understanding of phenomena of importance to directional solidification, to enable explanation and prediction of differences in behavior between solidification on Earth and in space. Emphasis during the period of this grant was on experimentally determining the influence of convection and freezing rate fluctuations on compositional homogeneity and crystalline perfection in the vertical Bridgman-Stockbarger technique. Heater temperature profiles, buoyancy-driven convection, and doping inhomogeneties were correlated using naphthalene doped with azulene. In addition the influence of spin-up/spin-down on compositional homogeneity and microstructure of indium gallium antimonide and the effect of imposed melting-freezing cycles on indium gallium antimonide are discussed.

  7. DIRECT CURRENT ELECTROMAGNETIC PUMP

    DOEpatents

    Barnes, A.H.

    1957-11-01

    An improved d-c electromagnetic pump is presented in which the poles, and consequently the magetic gap at the poles, are tapered to be wider at the upstream end. In addition, the cross section of the tube carryiQ the liquid metal is tapered so that the velocity of the pumped liquid increases in the downstream direction at a rate such that the counter-induced voltage in the liquid metal remains constant as it traverses the region between the poles. This configuration compensates for the distortion of the magnetic field caused by the induced voltage that would otherwise result in the lowering of the pumping capacity. This improved electromagnetic pump as practical application in the pumping of liquid metal coolants for nuclear reactors where conventional positive displacement pumps have proved unsatisfactory due to the high temperatures and the corrosive properties of the liquid metals involved.

  8. Nanoparticles and direct immunosuppression

    PubMed Central

    Ngobili, Terrika A

    2016-01-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  9. Speech research directions

    SciTech Connect

    Atal, B.S.; Rabiner, L.R.

    1986-09-01

    This paper presents an overview of the current activities in speech research. The authors discuss the state of the art in speech coding, text-to-speech synthesis, speech recognition, and speaker recognition. In the speech coding area, current algorithms perform well at bit rates down to 9.6 kb/s, and the research is directed at bringing the rate for high-quality speech coding down to 2.4 kb/s. In text-to-speech synthesis, what we currently are able to produce is very intelligible but not yet completely natural. Current research aims at providing higher quality and intelligibility to the synthetic speech that these systems produce. Finally, today's systems for speech and speaker recognition provide excellent performance on limited tasks; i.e., limited vocabulary, modest syntax, small talker populations, constrained inputs, etc.

  10. Comprehension of Navigation Directions

    NASA Technical Reports Server (NTRS)

    Healy, Alice F.; Schneider, Vivian I.

    2002-01-01

    Subjects were shown navigation instructions varying in length directing them to move in a space represented by grids on a computer screen. They followed the instructions by clicking on the grids in the locations specified. Some subjects repeated back the instructions before following them, some did not, and others repeated back the instructions in reduced form, including only the critical words. The commands in each message were presented simultaneously for half of the subjects and sequentially for the others. For the longest messages, performance was better on the initial commands and worse on the final commands with simultaneous than with sequential presentation. Instruction repetition depressed performance, but reduced repetition removed this disadvantage. Effects of presentation format were attributed to visual scanning strategies. The advantage for reduced repetition was attributable either to enhanced visual scanning or to reduced output interference. A follow-up study with auditory presentation supported the visual scanning explanation.

  11. Directed light fabrication

    NASA Astrophysics Data System (ADS)

    Lewis, G. K.; Nemec, R.; Milewski, J.; Thoma, D. J.; Cremers, D.; Barbe, M.

    1994-09-01

    Directed Light Fabrication (DLF) is a rapid prototyping process being developed at Los Alamos National Laboratory to fabricate metal components. This is done by fusing gas delivered metal powder particles in the focal zone of a laser beam that is programmed to move along or across the part cross section. Fully dense metal is built up a layer at a time to form the desired part represented by a 3 dimensional solid model from CAD software. Machine 'tool paths' are created from the solid model that command the movement and processing parameters specific to the DLF process so that the part can be built one layer at a time. The result is a fully dense, near net shape metal part that solidifies under rapid solidification conditions.

  12. Fiber optic TV direct

    NASA Technical Reports Server (NTRS)

    Kassak, John E.

    1991-01-01

    The objective of the operational television (OTV) technology was to develop a multiple camera system (up to 256 cameras) for NASA Kennedy installations where camera video, synchronization, control, and status data are transmitted bidirectionally via a single fiber cable at distances in excess of five miles. It is shown that the benefits (such as improved video performance, immunity from electromagnetic interference and radio frequency interference, elimination of repeater stations, and more system configuration flexibility) can be realized if application of the proven fiber optic transmission concept is used. The control system will marry the lens, pan and tilt, and camera control functions into a modular based Local Area Network (LAN) control network. Such a system does not exist commercially at present since the Television Broadcast Industry's current practice is to divorce the positional controls from the camera control system. The application software developed for this system will have direct applicability to similar systems in industry using LAN based control systems.

  13. Directed Polymerase Evolution

    PubMed Central

    Chen, Tingjian; Romesberg, Floyd E.

    2014-01-01

    Polymerases evolved in nature to synthesize DNA and RNA, and they underlie the storage and flow of genetic information in all cells. The availability of these enzymes for use at the bench has driven a revolution in biotechnology and medicinal research; however, polymerases did not evolve to function efficiently under the conditions required for some applications and their high substrate fidelity precludes their use for most applications that involve modified substrates. To circumvent these limitations, researchers have turned to directed evolution to tailor the properties and/or substrate repertoire of polymerases for different applications, and several systems have been developed for this purpose. These systems draw on different methods of creating a pool of randomly mutated polymerases and are differentiated by the process used to isolate the most fit members. A variety of polymerases have been evolved, providing new or improved functionality, as well as interesting new insight into the factors governing activity. PMID:24211837

  14. Direct neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Drexlin, G.

    2008-11-01

    Direct neutrino mass measurements are based on high precision spectroscopy studies close to the kinematic end-point of low-energy β-emitters such as 3H and 187Re. Relying only on energy-momentum conservation in β-decay, they offer the only model-independent method to measure the absolute ν-mass scale with sub-eV sensitivity. The two most sensitive detection principles, electrostatic retarding spectrometers and microbolometers, are complementary to each other, and two experiments are currently being prepared to explore ν-masses down to m(ν) = 200 meV. β-spectroscopy will thus allow to constrain the role of neutrino hot dark matter in structure formation, as well as to explore the parameter region of ν-mass scenarios with quasi-degenerate pattern. The MARE project will investigate the β-decay of 187Re with bolometers based on metallic Re and AgReO4 in a two-staged approach: in a phase-I set-up a sensitivity of m(ν) = 2 eV is expected, forming the basis for a later sub-eV phase-II. The Karlsruhe Tritium Neutrino (KATRIN) experiment is currently being set-up on the site of Tritium Laboratory at KIT. The experiment will combine an ultra-luminous windowless gaseous tritium source with a high resolution electrostatic spectrometer and offer an unprecedented precision in β-decay studies, pushing this technique to its technological limits. First KATRIN measurements with 3H after successful system integration are expected for mid-2011. This contribution gives a status report and outlook for both experiments and discusses the impact of direct ν-mass experiments on astroparticle physics.

  15. Directionally Solidified Ceramics Produced

    NASA Technical Reports Server (NTRS)

    Farmer, Serene C.; Sayir, Ali

    2000-01-01

    Produced Multiphase, interpenetrating structures are an alternative route to obtaining structural ceramic materials with adequate strength, toughness, and stability for high-temperature aerospace applications. The eutectic architecture, a continuous-reinforcing phase within a higher volume phase or matrix, can be described as a naturally occurring, in situ composite. The phases of a eutectic are thermodynamically compatible at high homologous temperatures. Strong and stable materials have been produced. Toughness, however, remains a technical obstacle. The potential for producing materials with enhanced toughness along with adequate strength and stability was demonstrated using the laser-heated float zone (LHFZ) growth method at the NASA Glenn Research Center at Lewis Field. LHFZ growth at Glenn provides a means to efficiently produce and record the underlying growth phenomena associated with two-phase structures. To initiate directional solidification, a seed of single-crystal sapphire (<0001> direction) was lowered onto the molten liquid until wetting occurred and then withdrawn at a constant rate. Neither the crystal nor the source rod was rotated. The materials produced were tested mechanically in tension, and the resulting microstructure was examined with a scanning electron microscope. Both the inherent properties of the constituent phases and the properties of the interface between them affect the mechanical behavior and the fracture surfaces. The following scanning electron micrographs show the microstructures of two different materials that were tested to failure in tension. In the left micrograph, the flat fracture surface is typical of a material that is strong but has low toughness. In the right micrograph, the crack is effectively deflected at the interface between the two phases, achieving higher toughness at moderately lower strength levels. Conducting mechanical tests to determine the high temperature properties of these materials is the next step

  16. Conclusions and Policy Directions,

    SciTech Connect

    Wilbanks, Thomas J; Romero-Lankao, Paty; Gnatz, P

    2011-01-01

    This chapter briefly revisits the constraints and opportunities of mitigation and adaptation, and highlights and the multiple linkages, synergies and trade-offs between mitigation, adaptation and urban development. The chapter then presents future policy directions, focusing on local, national and international principles and policies for supporting and enhancing urban responses to climate change. In summary, policy directions for linking climate change responses with urban development offer abundant opportunities; but they call for new philosophies about how to think about the future and how to connect different roles of different levels of government and different parts of the urban community. In many cases, this implies changes in how urban areas operate - fostering closer coordination between local governments and local economic institutions, and building new connections between central power structures and parts of the population who have often been kept outside of the circle of consultation and discourse. The difficulties involved in changing deeply set patterns of interaction and decision-making in urban areas should not be underestimated. Because it is so difficult, successful experiences need to be identified, described and widely publicized as models for others. However, where this challenge is met, it is likely not only to increase opportunities and reduce threats to urban development in profoundly important ways, but to make the urban area a more effective socio-political entity, in general - a better city in how it works day to day and how it solves a myriad of problems as they emerge - far beyond climate change connections alone. It is in this sense that climate change responses can be catalysts for socially inclusive, economically productive and environmentally friendly urban development, helping to pioneer new patterns of stakeholder communication and participation.

  17. New directions in mechanics

    SciTech Connect

    Kassner, Michael E.; Nemat-Nasser, Sia; Suo, Zhigang; Bao, Gang; Barbour, J. Charles; Brinson, L. Catherine; Espinosa, Horacio; Gao, Huajian; Granick, Steve; Gumbsch, Peter; Kim, Kyung -Suk; Knauss, Wolfgang; Kubin, Ladislas; Larson, Ben C.; Mahadevan, L.; Majumdar, Arun; Torquato, Salvatore; van Swol, Frank

    2004-09-15

    The Division of Materials Sciences and Engineering of the US Department of Energy (DOE) sponsored a workshop to identify cutting-edge research needs and opportunities, enabled by the application of theoretical and applied mechanics. The workshop also included input from biochemical, surface science, and computational disciplines, on approaching scientific issues at the nanoscale, and the linkage of atomistic-scale with nano-, meso-, and continuum-scale mechanics. This paper is a summary of the outcome of the workshop, consisting of three main sections, each put together by a team of workshop participants. Section 1 addresses research opportunities that can be realized by the application of mechanics fundamentals to the general area of self-assembly, directed self-assembly, and fluidics. Section 2 examines the role of mechanics in biological, bioinspired, and biohybrid material systems, closely relating to and complementing the material covered in Section 1. In this manner, it was made clear that mechanics plays a fundamental role in understanding the biological functions at all scales, in seeking to utilize biology and biological techniques to develop new materials and devices, and in the general area of bionanotechnology. While direct observational investigations are an essential ingredient of new discoveries and will continue to open new exciting research doors, it is the basic need for controlled experimentation and fundamentally- based modeling and computational simulations that will be truly empowered by a systematic use of the fundamentals of mechanics. Section 3 brings into focus new challenging issues in inelastic deformation and fracturing of materials that have emerged as a result of the development of nanodevices, biopolymers, and hybrid bio–abio systems. As a result, each section begins with some introductory overview comments, and then provides illustrative examples that were presented at the workshop and which are believed to highlight the enabling

  18. New directions in mechanics

    DOE PAGES

    Kassner, Michael E.; Nemat-Nasser, Sia; Suo, Zhigang; ...

    2004-09-15

    The Division of Materials Sciences and Engineering of the US Department of Energy (DOE) sponsored a workshop to identify cutting-edge research needs and opportunities, enabled by the application of theoretical and applied mechanics. The workshop also included input from biochemical, surface science, and computational disciplines, on approaching scientific issues at the nanoscale, and the linkage of atomistic-scale with nano-, meso-, and continuum-scale mechanics. This paper is a summary of the outcome of the workshop, consisting of three main sections, each put together by a team of workshop participants. Section 1 addresses research opportunities that can be realized by the applicationmore » of mechanics fundamentals to the general area of self-assembly, directed self-assembly, and fluidics. Section 2 examines the role of mechanics in biological, bioinspired, and biohybrid material systems, closely relating to and complementing the material covered in Section 1. In this manner, it was made clear that mechanics plays a fundamental role in understanding the biological functions at all scales, in seeking to utilize biology and biological techniques to develop new materials and devices, and in the general area of bionanotechnology. While direct observational investigations are an essential ingredient of new discoveries and will continue to open new exciting research doors, it is the basic need for controlled experimentation and fundamentally- based modeling and computational simulations that will be truly empowered by a systematic use of the fundamentals of mechanics. Section 3 brings into focus new challenging issues in inelastic deformation and fracturing of materials that have emerged as a result of the development of nanodevices, biopolymers, and hybrid bio–abio systems. As a result, each section begins with some introductory overview comments, and then provides illustrative examples that were presented at the workshop and which are believed to highlight the

  19. Growth directions of microstructures in directional solidification of crystalline materials.

    PubMed

    Deschamps, J; Georgelin, M; Pocheau, A

    2008-07-01

    In directional solidification, as the solidification velocity increases, the growth direction of cells or dendrites rotates from the direction of the thermal gradient to that of a preferred cristalline orientation. Meanwhile, their morphology varies with important implications for microsegregation. Here, we experimentally document the growth directions of these microstructures in a succinonitrile alloy in the whole accessible range of directions, velocities, and spacings. For this, we use a thin sample made of a single crystal on which the direction of the thermal gradient can be changed. This allows a fine monitoring of the misorientation angle between thermal gradient and preferred crystalline orientation. Data analysis shows evidence of an internal symmetry which traces back to a scale invariance of growth directions with respect to a Péclet number. This enables the identification of the relationship between growth directions and relevant variables, in fair agreement with experiment. Noticeable variations of growth directions with misorientation angles are evidenced and linked to a single parameter.

  20. Modulation of Training by Single-Session Transcranial Direct Current Stimulation to the Intact Motor Cortex Enhances Motor Skill Acquisition of the Paretic Hand

    PubMed Central

    Zimerman, Máximo; Heise, Kirstin F.; Hoppe, Julia; Cohen, Leonardo G.; Gerloff, Christian; Hummel, Friedhelm C.

    2016-01-01

    Background and Purpose Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand. Method Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation. Results tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R2=0.63). Conclusions These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke. PMID:22618381

  1. Link direction for link prediction

    NASA Astrophysics Data System (ADS)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-03-01

    Almost all previous studies on link prediction have focused on using the properties of the network to predict the existence of links between pairs of nodes. Unfortunately, previous methods rarely consider the role of link direction for link prediction. In fact, many real-world complex networks are directed and ignoring the link direction will mean overlooking important information. In this study, we propose a phase-dynamic algorithm of the directed network nodes to analyse the role of link directions and demonstrate that the bi-directional links and the one-directional links have different roles in link prediction and network structure formation. From this, we propose new directional prediction methods and use six real networks to test our algorithms. In real networks, we find that compared to a pair of nodes which are connected by a one-directional link, a pair of nodes which are connected by a bi-directional link always have higher probabilities to connect to the common neighbours with only bi-directional links (or conversely by one-directional links). We suggest that, in the real networks, the bi-directional links will generally be more informative for link prediction and network structure formation. In addition, we propose a new directional randomized algorithm to demonstrate that the direction of the links plays a significant role in link prediction and network structure formation.

  2. Multiple direction vibration fixture

    DOEpatents

    Cericola, Fred; Doggett, James W.; Ernest, Terry L.; Priddy, Tommy G.

    1991-01-01

    An apparatus for simulating a rocket launch environment on a test item undergoing centrifuge testing by subjecting the item simultaneously or separately to vibration along an axis of centripetal force and along an axis perpendicular to the centripetal force axis. The apparatus includes a shaker motor supported by centrifuge arms and a right angle fixture pivotally connected to one of the shaker motor mounts. When the shaker motor vibrates along the centripetal force axis, the vibrations are imparted to a first side of the right angle fixture. The vibrations are transmitted 90 degrees around the pivot and are directed to a second side of the right angle fixture which imparts vibrations perpendicular to the centripetal force axis. The test item is in contact with a third side of the right angle fixture and receives both centripetal-force-axis vibrations and perpendicular axis vibrations simultaneously. A test item can be attached to the third side near the flexible coupling or near the air bag to obtain vibrations along the centripetal force axis or transverse to the centripetal force axis.

  3. Directed Incremental Symbolic Execution

    NASA Technical Reports Server (NTRS)

    Person, Suzette; Yang, Guowei; Rungta, Neha; Khurshid, Sarfraz

    2011-01-01

    The last few years have seen a resurgence of interest in the use of symbolic execution -- a program analysis technique developed more than three decades ago to analyze program execution paths. Scaling symbolic execution and other path-sensitive analysis techniques to large systems remains challenging despite recent algorithmic and technological advances. An alternative to solving the problem of scalability is to reduce the scope of the analysis. One approach that is widely studied in the context of regression analysis is to analyze the differences between two related program versions. While such an approach is intuitive in theory, finding efficient and precise ways to identify program differences, and characterize their effects on how the program executes has proved challenging in practice. In this paper, we present Directed Incremental Symbolic Execution (DiSE), a novel technique for detecting and characterizing the effects of program changes. The novelty of DiSE is to combine the efficiencies of static analysis techniques to compute program difference information with the precision of symbolic execution to explore program execution paths and generate path conditions affected by the differences. DiSE is a complementary technique to other reduction or bounding techniques developed to improve symbolic execution. Furthermore, DiSE does not require analysis results to be carried forward as the software evolves -- only the source code for two related program versions is required. A case-study of our implementation of DiSE illustrates its effectiveness at detecting and characterizing the effects of program changes.

  4. Microfluidic Compartmentalized Directed Evolution

    PubMed Central

    Paegel, Brian M.; Joyce, Gerald F.

    2010-01-01

    Summary Directed evolution studies often make use of water-in-oil compartments, which conventionally are prepared by bulk emulsification, a crude process that generates non-uniform droplets and can damage biochemical reagents. A microfluidic emulsification circuit was devised that generates uniform water-in-oil droplets (21.9 ± 0.8 μm radius) with high throughput (107–108 droplets per hour). The circuit contains a radial array of aqueous flow nozzles that intersect a surrou