Deciphering Elapsed Time and Predicting Action Timing from Neuronal Population Signals

The proper timing of actions is necessary for the survival of animals, whether in hunting prey or escaping predators. Researchers in the field of neuroscience have begun to explore neuronal signals correlated to behavioral interval timing. Here, we attempt to decode the lapse of time from neuronal population signals recorded from the frontal cortex of monkeys performing a multiple-interval timing task. We designed a Bayesian algorithm that deciphers temporal information hidden in noisy signals dispersed within the activity of individual neurons recorded from monkeys trained to determine the passage of time before initiating an action. With this decoder, we succeeded in estimating the elapsed time with a precision of approximately 1 s throughout the relevant behavioral period from firing rates of 25 neurons in the pre-supplementary motor area. Further, an extended algorithm makes it possible to determine the total length of the time-interval required to wait in each trial. This enables observers to predict the moment at which the subject will take action from the neuronal activity in the brain. A separate population analysis reveals that the neuronal ensemble represents the lapse of time in a manner scaled relative to the scheduled interval, rather than representing it as the real physical time

Outstanding in vivo mechanical integrity of additively manufactured spinal cages with a novel “honeycomb tree structure” design via guiding bone matrix orientation

BACKGROUND CONTEXT: Therapeutic devices for spinal disorders, such as spinal fusion cages, must be able to facilitate the maintenance and rapid recovery of spinal function. Therefore, it would be advantageous that future spinal fusion cages facilitate rapid recovery of spinal function without secondary surgery to harvest autologous bone. PURPOSE: This study investigated a novel spinal cage configuration that achieves in vivo mechanical integrity as a devise/bone complex by inducing bone that mimicked the sound trabecular bone, hierarchically and anisotropically structured trabeculae strengthened with a preferentially oriented extracellular matrix. STUDY DESIGN/SETTINGS: In vivo animal study. METHODS: A cage possessing an anisotropic through-pore with a grooved substrate, that we termed “honeycomb tree structure,” was designed for guiding bone matrix orientation; it was manufactured using a laser beam powder bed fusion method through an additive manufacturing processes. The newly designed cages were implanted into sheep vertebral bodies for 8 and 16 weeks. An autologous bone was not installed in the newly designed cage. A pull-out test was performed to evaluate the mechanical integrity of the cage/bone interface. Additionally, the preferential orientation of bone matrix consisting of collagen and apatite was determined. RESULTS: The cage/host bone interface strength assessed by the maximum pull-out load for the novel cage without an autologous bone graft (3360±411 N) was significantly higher than that for the conventional cage using autologous bone (903±188 N) after only 8 weeks post-implantation. CONCLUSIONS: These results highlight the potential of this novel cage to achieve functional fusion between the cage and host bone. Our study provides insight into the design of highly functional spinal devices based on the anisotropic nature of bone. CLINICAL SIGNIFICANCE: The sheep spine is similar to the human spine in its stress condition and trabecular bone architecture and is widely recognized as a useful model for the human spine. The present design may be useful as a new spinal device for humans.Ishimoto T., Kobayashi Y., Takahata M., et al. Outstanding in vivo mechanical integrity of additively manufactured spinal cages with a novel “honeycomb tree structure” design via guiding bone matrix orientation. Spine Journal, 22, 10, 1742. https://doi.org/10.1016/j.spinee.2022.05.006

Innovative design of bone quality-targeted intervertebral spacer: accelerated functional fusion guiding oriented collagen and apatite microstructure without autologous bone graft

BACKGROUND CONTEXT: Although autologous bone grafting is widely considered as an ideal source for interbody fusion, it still carries a risk of nonunion. The influence of the intervertebral device should not be overlooked. Requirements for artificial spinal devices are to join the vertebrae together and recover the original function of the spine rapidly. Ordered mineralization of apatite crystals on collagen accelerates bone functionalization during the healing process. Particularly, the stable spinal function requires the ingrowth of an ordered collagen and apatite matrix which mimics the intact intervertebral microstructure. This collagen and apatite ordering is imperative for functional bone regeneration, which has not been achieved using classical autologous grafting. PURPOSE: We developed an intervertebral body device to achieve high stability between the host bone and synthesized bone by controlling the ordered collagen and apatite microstructure. STUDY DESIGN: This was an in vivo animal study. METHODS: Intervertebral spacers with a through-pore grooved surface structure, referred to as a honeycomb tree structure, were produced using metal 3D printing. These spacers were implanted into normal sheep at the L2–L3 or L4–L5 disc levels. As a control group, grafting autologous bone was embedded. The mechanical integrity of the spacer/bone interface was evaluated through push-out tests. RESULTS: The spacer with honeycomb tree structure induced anisotropic trabecular bone growth with textured collagen and apatite orientation in the through-pore and groove directions. The push-out load of the spacer was significantly higher than that of the conventional autologous graft spacer. Moreover, the load was significantly correlated with the anisotropic texture of the newly formed bone matrix. CONCLUSIONS: The developed intervertebral spacer guided the regenerated bone matrix orientation of collagen and apatite, resulting in greater strength at the spacer/host bone interface than that obtained using a conventional gold-standard autologous bone graft. CLINICAL SIGNIFICANCE: Our results provide a foundation for designing future spacers for interbody fusion in human.Matsugaki A., Ito M., Kobayashi Y., et al. Innovative design of bone quality-targeted intervertebral spacer: accelerated functional fusion guiding oriented collagen and apatite microstructure without autologous bone graft. Spine Journal 23, 609 (2023); https://doi.org/10.1016/j.spinee.2022.12.011

Opto-Current-Clamp Actuation of Cortical Neurons Using a Strategically Designed Channelrhodopsin

BACKGROUND: Optogenetic manipulation of a neuronal network enables one to reveal how high-order functions emerge in the central nervous system. One of the Chlamydomonas rhodopsins, channelrhodopsin-1 (ChR1), has several advantages over channelrhodopsin-2 (ChR2) in terms of the photocurrent kinetics. Improved temporal resolution would be expected by the optogenetics using the ChR1 variants with enhanced photocurrents. METHODOLOGY/PRINCIPAL FINDINGS: The photocurrent retardation of ChR1 was overcome by exchanging the sixth helix domain with its counterpart in ChR2 producing Channelrhodopsin-green receiver (ChRGR) with further reform of the molecule. When the ChRGR photocurrent was measured from the expressing HEK293 cells under whole-cell patch clamp, it was preferentially activated by green light and has fast kinetics with minimal desensitization. With its kinetic advantages the use of ChRGR would enable one to inject a current into a neuron by the time course as predicted by the intensity of the shedding light (opto-current clamp). The ChRGR was also expressed in the motor cortical neurons of a mouse using Sindbis pseudovirion vectors. When an oscillatory LED light signal was applied sweeping through frequencies, it robustly evoked action potentials synchronized to the oscillatory light at 5-10 Hz in layer 5 pyramidal cells in the cortical slice. The ChRGR-expressing neurons were also driven in vivo with monitoring local field potentials (LFPs) and the time-frequency energy distribution of the light-evoked response was investigated using wavelet analysis. The oscillatory light enhanced both the in-phase and out-phase responses of LFP at the preferential frequencies of 5-10 Hz. The spread of activity was evidenced by the fact that there were many c-Fos-immunoreactive neurons that were negative for ChRGR in a region of the motor cortex. CONCLUSIONS/SIGNIFICANCE: The opto-current-clamp study suggests that the depolarization of a small number of neurons wakes up the motor cortical network over some critical point to the activated state

Non-additive activity modulation during a decision making task involving tactic selection

Human brain imaging has revealed that stimulus-induced activity does generally not simply add to the pre-stimulus activity, but rather builds in a non-additive way on this activity. Here we investigate this subject at the single neuron level and address the question whether and to what extent a strong form of non-additivity where activity drops post-cue is present in different areas of monkey cortex, including prefrontal and agranular frontal areas, during a perceptual decision making task involving action and tactic selection. Specifically we analyze spike train data recorded in vivo from the posterior dorsomedial prefrontal cortex (pmPFC), the supplementary motor area (SMA) and the presupplementary motor area (pre-SMA). For each neuron, we compute the ratio of the trial-averaged pre-stimulus spike count to the trial-averaged post-stimulus count. We also perform the ratio and averaging procedures in reverse order. We find that the statistics of these quantities behave differently across areas. pmPFC involved in tactic selection shows stronger non-additivity compared to the two other areas which more generically just increase their firing rate pos-stimulus. pmPFC behaved more similarly to pre-SMA, a likely consequence of the reciprocal connections between these areas. The trial-averaged ratio statistic was reproduced by a surrogate inhomogeneous Poisson process in which the measured trial-averaged firing rate for a given neuron is used as its time-dependent rate. Principal component analysis (PCA) of the trial-averaged firing rates of neuronal ensembles further reveals area-specific time courses of response to the stimulus, including latency to peak neural response, for the typical population activity. Our work demonstrates subtle forms of area-specific non-additivity based on the fine variability structure of pre- and post-stimulus spiking activity on the single neuron level. It also reveals significant differences between areas for PCA and surrogate analysis, complementing previous observations of regional differences based solely on post-stimulus responses. Moreover, we observe regional differences in non-additivity which are related to the monkey's successful tactic selection and decision making.!##!Supplementary information!#!The online version contains supplementary material available at 10.1007/s11571-021-09702-0

Non-centralized and functionally localized nervous system of ophiuroids: evidence from topical anesthetic experiments

Ophiuroids locomote along the seafloor by coordinated rhythmic movements of multi-segmented arms. The mechanisms by which such coordinated movements are achieved are a focus of interest from the standpoints of neurobiology and robotics, because ophiuroids appear to lack a central nervous system that could exert centralized control over five arms. To explore the underlying mechanism of arm coordination, we examined the effects of selective anesthesia to various parts of the body of ophiuroids on locomotion. We observed the following: (1) anesthesia of the circumoral nerve ring completely blocked the initiation of locomotion; however, initiation of single arm movement, such as occurs during the retrieval of food, was unaffected, indicating that the inability to initiate locomotion was not due to the spread of the anesthetic agent. (2) During locomotion, the midsegments of the arms periodically made contact with the floor to elevate the disc. In contrast, the distal segments of the arms were pointed aborally and did not make contact with the floor. (3) When the midsegments of all arms were anesthetized, arm movements were rendered completely uncoordinated. In contrast, even when only one arm was left intact, inter-arm coordination was preserved. (4) Locomotion was unaffected by anesthesia of the distal arms. (5) A radial nerve block to the proximal region of an arm abolished coordination among the segments of that arm, rendering it motionless. These findings indicate that the circumoral nerve ring and radial nerves play different roles in intra- and inter-arm coordination in ophiuroids

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

05 septembre 19271927/09/05 (A28,N9760)

Detecting Causality by Combined Use of Multiple Methods: Climate and Brain Examples

<div><p>Identifying causal relations from time series is the first step to understanding the behavior of complex systems. Although many methods have been proposed, few papers have applied multiple methods together to detect causal relations based on time series generated from coupled nonlinear systems with some unobserved parts. Here we propose the combined use of three methods and a majority vote to infer causality under such circumstances. Two of these methods are proposed here for the first time, and all of the three methods can be applied even if the underlying dynamics is nonlinear and there are hidden common causes. We test our methods with coupled logistic maps, coupled Rössler models, and coupled Lorenz models. In addition, we show from ice core data how the causal relations among the temperature, the CH₄ level, and the CO₂ level in the atmosphere changed in the last 800,000 years, a conclusion also supported by irregularly sampled data analysis. Moreover, these methods show how three regions of the brain interact with each other during the visually cued, two-choice arm reaching task. Especially, we demonstrate that this is due to bottom up influences at the beginning of the task, while there exist mutual influences between the posterior medial prefrontal cortex and the presupplementary motor area. Based on our results, we conclude that identifying causality with an appropriate ensemble of multiple methods ensures the validity of the obtained results more firmly.</p></div

video S4 from A brittle star-like robot capable of immediately adapting to unexpected physical damage

Robot experiments for various configuration