Complementary roles of primate dorsal premotor and pre-supplementary motor areas to the control of motor sequences.

We are able to temporally organize multiple movements in a purposeful manner in everyday life. Both the dorsal premotor (PMd) and pre-supplementary motor areas (pre-SMA) are known to be involved in the performance of motor sequences. However, it is unclear how each area differentially contributes to controlling multiple motor sequences. To address this issue, we recorded single-unit activity in both areas while monkeys (one male, one female) performed sixteen motor sequences. Each sequence comprised either a series of two identical movements (repetitive) or two different movements (non-repetitive). The sequence was initially instructed with visual signals but had to be remembered thereafter. Here we showed that the activity of single neurons in both areas transitioned from reactive- to predictive encoding while motor sequences were memorized. In the memory-guided trials, in particular, the activity of PMd cells preferentially represented the second movement in the sequence leading to a reward generally irrespective of the first movement. Such activity frequently began even before the first movement in a prospective manner, and was enhanced in non-repetitive sequences. Behaviorally, a lack of the activity enhancement often resulted in premature execution of the second movement. In contrast, cells in pre-SMA instantiated particular sequences of actions by coordinating switching or non-switching movements in sequence. Our findings suggest that PMd and pre-SMA play complementary roles within behavioral contexts: PMd preferentially controls the movement that leads to a reward rather than the sequence per se, whereas pre-SMA coordinates all elements in a sequence by integrating temporal orders of multiple movements.Significance statement:Although both PMd and pre-SMA are involved in the control of motor sequences, it is not clear how these two areas contribute to coordination of sequential movements differently. To address this issue, we directly compared neuronal activity in the two areas recorded while monkeys memorized and performed multiple motor sequences. Our findings suggest that PMd preferentially represents the final action that ultimately leads to a reward in a prospective manner, whereas the pre-SMA coordinates switching among multiple actions within the context of the sequence. Our findings are of significance to understand the distinct roles for motor-related areas in the planning and executing motor sequences and the pathophysiology of apraxia and/or Parkinson's diseases that disables skilled motor actions.

Perceptions About Nursing Practice Based on the Internet of Things: A Survey of Nursing Managers.

The purpose of this study was to investigate the perceptions of nursing managers about adopting nursing practices based on the Internet of Things and to examine related ethical issues. Questionnaires were sent to 538 nursing managers in Japan, with 131 responses. Of these, 87% and 33% agreed that a system using radio frequency identifiers would be useful for locating patients and nurses, respectively, 58%-81% recognized the value for patient safety of various camera systems for nursing observation, such as cameras linked to biometric alarms, 73% agreed the usefulness of automatically prioritizing alarms, but only around 39% were in favor of using facial recognition to help nursing observation. Many nursing managers expressed concerns about privacy. Data storage for at least 6 months was supported by 53% for location data and 41% for ceiling camera videos. Thus, nursing practice based on the Internet of Things is widely accepted in Japan.

Theta Dynamics Contribute to Retrieving Motor Plans after Interruptions in the Primate Premotor Area.

To achieve a behavioral goal, we often need to maintain an internal action plan against external interruption and thereafter retrieve the action plan. We recently found that the maintenance and updating of motor plans are reflected by reciprocal changes in the beta and gamma power of the local field potential (LFP) of the primate medial motor areas. In particular, the maintenance of the immediate motor plan is supported by enhanced beta oscillations. However, it is unclear how the brain manages to maintain and retrieve the internal action plan against interruptions. Here, we show that dynamic theta changes contribute to the maintenance of the action plan. Specifically, the power of the theta frequency band (4-10 Hz) of LFPs increased before and during the interruption in the dorsal premotor areas in two monkeys. Without theta enhancement before the interruption, retrieval of the internal action plan was impaired. Theta and beta oscillations showed distinct changes depending on the behavioral context. Our results demonstrate that immediate and suspended motor plans are supported by the beta and theta oscillatory components of LFPs. Motor cortical theta oscillations may contribute to bridging motor plans across behavioral interruptions in a prospective manner.

Multimodal Functional Analysis Platform: 4. Optogenetics-Induced Oscillatory Activation to Explore Neural Circuits.

To elucidate neural mechanisms underlying oscillatory phenomena in brain function, we have developed optogenetic tools and statistical methods. Specifically, opto-current-clamp induced oscillation reveals intrinsic frequency preferences in the neural circuits by oscillatory resonance. Furthermore, resonance or entrainment to intrinsic frequency is state-dependent. When resonance phenomena go beyond a certain range, it could even induce epileptic seizure in highly reproducible manner. We are able to study how seizures start, develop, and stop in neural circuits. Therefore, the optogenetics-induced oscillatory activation is a powerful tool in neuroscience research.

[Monotherapy using a direct oral anticoagulant (apixaban) for catheter thrombosis and pulmonary thromboembolism in a patient with ulcerative colitis: a case report].

A 20-year-old woman with ulcerative colitis flare was admitted to Fukui Red Cross Hospital. During treatment with granulocyte and monocyte apheresis (GMA), the patient complained of chest discomfort and was diagnosed with pulmonary thromboembolism with central intravenous catheter thrombosis. Apixaban, a direct oral anticoagulant (DOAC), was used as monotherapy for anticoagulation, and thromboembolism was resolved without complication. Among extraintestinal complications in patients with ulcerative colitis, pulmonary thromboembolism can be a life-threatening condition and requires prompt anticoagulant therapy. Although the effectiveness of conventional pharmacological anticoagulation using warfarin and heparin has been reported, the efficacy of DOAC monotherapy remains controversial. DOAC monotherapy may be considered and innovative therapeutic strategy for a thromboembolic condition in patients with ulcerative colitis.

Intended arm use influences interhemispheric correlation of ß-oscillations in primate medial motor areas.

To investigate the role of interhemispheric ß-synchronization in the selection of motor effectors, we trained two monkeys to memorize and perform multiple two-movement sequences that included unimanual repetition and bimanual switching. We recorded local field potentials simultaneously in the bilateral supplementary motor area (SMA) and pre-SMA to examine how the ß-power in both hemispheres and the interhemispheric relationship of ß-oscillations depend on the prepared sequence of arm use. We found a significant ipsilateral enhancement of ß-power for bimanual switching trials in the left hemisphere and an enhancement of ß-power in the right SMA while preparing for unimanual repetition. Furthermore, interhemispheric synchrony in the SMA was significantly more enhanced while preparing unimanual repetition than while preparing bimanual switching. This enhancement of synchrony was detected in terms of ß-phase but not in terms of modulation of ß-power. Furthermore, the assessment of the interhemispheric phase difference revealed that the ß-oscillation in the hemisphere contralateral to the instructed arm use significantly advanced its phase relative to that in the ipsilateral hemisphere. There was no arm use-dependent shift in phase difference in the pairwise recordings within each hemisphere. Both neurons with and without arm use-selective activity were phase-locked to the ß-oscillation. These results imply that the degree of interhemispheric phase synchronization as well as phase differences and oscillatory power in the ß-band may contribute to the selection of arm use depending on the behavioral conditions of sequential arm use.NEW & NOTEWORTHY We addressed interhemispheric relationships of ß-oscillations during bimanual coordination. While monkeys prepared to initiate movement of the instructed arm, ß-oscillations in the contralateral hemisphere showed a phase advance relative to the other hemisphere. Furthermore, the sequence of arm use influenced ß-power and the degree of interhemispheric phase synchronization. Thus the dynamics of interhemispheric phases and power in ß-oscillations may contribute to the specification of motor effectors in a given behavioral context.

The Suppression of Beta Oscillations in the Primate Supplementary Motor Complex Reflects a Volatile State During the Updating of Action Sequences.

The medial motor areas play crucial but flexible roles in the temporal organizations of multiple movements. The beta oscillation of local field potentials is the predominant oscillatory activity in the motor areas, but the manner in which increases and decreases in beta power contribute to updating of multiple action plans is not yet fully understood. In the present study, beta and high-gamma activities in the supplementary motor area (SMA) and pre-SMA of monkeys were analyzed during performance of a bimanual motor sequence task that required updating and maintenance of the memory of action sequences. Beta power was attenuated during early delay periods of updating trials but was increased during maintenance trials, while there was a reciprocal increase in high-gamma power during updating trials. Moreover, transient attenuation of beta power during maintenance trials resulted in the erroneous selection of an action sequence. Therefore, it was concluded that the suppression of beta power during the early delay period reflects volatility of neural representation of the action sequence. This neural representation would be properly updated to the appropriate instructed action sequence via increases in high-gamma power in updating trials whereas it would be erroneously updated without the appropriate updating signal in maintenance trials.

Anomalous neuronal responses to fluctuated inputs.

The irregular firing of a cortical neuron is thought to result from a highly fluctuating drive that is generated by the balance of excitatory and inhibitory synaptic inputs. A previous study reported anomalous responses of the Hodgkin-Huxley neuron to the fluctuated inputs where an irregularity of spike trains is inversely proportional to an input irregularity. In the current study, we investigated the origin of these anomalous responses with the Hindmarsh-Rose neuron model, map-based models, and a simple mixture of interspike interval distributions. First, we specified the parameter regions for the bifurcations in the Hindmarsh-Rose model, and we confirmed that the model reproduced the anomalous responses in the dynamics of the saddle-node and subcritical Hopf bifurcations. For both bifurcations, the Hindmarsh-Rose model shows bistability in the resting state and the repetitive firing state, which indicated that the bistability was the origin of the anomalous input-output relationship. Similarly, the map-based model that contained bistability reproduced the anomalous responses, while the model without bistability did not. These results were supported by additional findings that the anomalous responses were reproduced by mimicking the bistable firing with a mixture of two different interspike interval distributions. Decorrelation of spike trains is important for neural information processing. For such spike train decorrelation, irregular firing is key. Our results indicated that irregular firing can emerge from fluctuating drives, even weak ones, under conditions involving bistability. The anomalous responses, therefore, contribute to efficient processing in the brain.

Arm-use dependent lateralization of gamma and beta oscillations in primate medial motor areas.

The neurons in the motor cortex show lateralization depending on the arm to use. To investigate if local field potential (LFP) oscillations change with contralateral and ipsilateral arm use, we analyzed the power of LFP in supplementary motor areas (SMA) and pre-SMA while animals performed a delayed-response arm use task under visual guidance and memory-based. LFP power changed with the laterality of the arm use, but it was frequency dependent. Specifically, power in the gamma range increased during contralateral arm use, while beta power increased with ipsilateral arm use. Subsequently, we confirmed that the frequency-dependent laterality was true also for the memory-driven movements. Our data therefore suggest that gamma oscillation is linked to the local neuronal activities in the contralateral hemisphere, and beta oscillation is related to withholding undesired arm movements by suppression of the local neuronal activities of the ipsilateral hemisphere.

Two-dimensional representation of action and arm-use sequences in the presupplementary and supplementary motor areas.

The medial frontal cortex has been thought to be crucially involved in temporal structuring of behavior in monkeys and humans. We examined neuronal activity in the supplementary and presupplementary motor areas of monkeys to investigate how the nervous system deals with the coding of 16 motor sequences resulting from multiple actions involving bilateral use of the arms. We first found in both areas that this behavioral demand resulted in attribute-based representation of individual motor acts, reflecting functional (action) or anatomical (right/left arm) attributes. Actions were frequently represented according to a body-axis-centered reference frame (supination or pronation) regardless of the arm to be used. Moreover, behavioral sequences were primarily represented with respect to the action- or arm-use sequence rather than the sequence of individual movements. We propose that the two-dimensional attribute-based sequence representation provides a robust and efficient means of processing multiple behavioral sequences.

Redesigned computerized prescribing system to reduce physicians' workload and improve patient safety.

The aim of our study was to redesign and evaluate the Computerized Prescribing System (PRS) to reduce physicians' workload and improve patient safety. The study was conducted in 2 prefectures in Japan. 186 physicians were surveyed with regard to prescription by physicians and medical office assistants. As a result, it was found that physicians demanded support from medical office assistants with regard to entry of prescription orders but for limited types of medicines. Based on our findings, we developed recommendations for a redesigned outline for PRS for the following 4 scenarios: (1) Continue prescription; (2) narcotic medicines; (3) chemotherapeutic medicines; and (4) medicines used in medical procedures. The outline was evaluated for effectiveness and safety and was confirmed to be a useful future prescription system.

Optogenetically induced seizure and the longitudinal hippocampal network dynamics.

Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel in vivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamics during seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to the rodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local field potentials (LFPs). Seizure-like afterdischarges were successfully induced after the stimulation in both W-TChR2V4 transgenic (ChR2V-TG) rats and in wild type rats transfected with adeno-associated virus (AAV) vectors carrying ChR2. Pulse frequency at 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining after a single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded during seizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Granger causality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischarge phenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel in vivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along the ST hippocampus in the genesis and termination of epileptic seizures.

Covert representation of second-next movement in the pre-supplementary motor area of monkeys.

We attempted to analyze the nature of premovement activity of neurons in medial motor areas [supplementary motor area (SMA) and pre-SMA] from a perspective of coding multiple movements. Monkeys were trained to perform a series of two movements with an intervening delay: supination or pronation with either forearm. Movements were initially instructed with visual signals but had to be remembered thereafter. Although a well-known type of premovement activity representing the forthcoming movements was found in the two areas, we found an unexpected type of activity that represented a second-next movement before initiating the first of the two movements. Typically in the pre-SMA, such activity selective for the second-next movement peaked before the initiation of the first movement, decayed thereafter, and remained low in magnitude while initiating the second movement. This type of activity may tentatively hold information for the second movement while initiating the first. That information may be fed into another group of neurons that themselves build a preparatory activity required to plan the second movements. Alternatively, the activity could serve as a signal to inhibit a premature exertion of the motor command for the second movement.

STDP provides the substrate for igniting synfire chains by spatiotemporal input patterns.

Spike-timing-dependent synaptic plasticity (STDP), which depends on the temporal difference between pre- and postsynaptic action potentials, is observed in the cortices and hippocampus. Although several theoretical and experimental studies have revealed its fundamental aspects, its functional role remains unclear. To examine how an input spatiotemporal spike pattern is altered by STDP, we observed the output spike patterns of a spiking neural network model with an asymmetrical STDP rule when the input spatiotemporal pattern is repeatedly applied. The spiking neural network comprises excitatory and inhibitory neurons that exhibit local interactions. Numerical experiments show that the spiking neural network generates a single global synchrony whose relative timing depends on the input spatiotemporal pattern and the neural network structure. This result implies that the spiking neural network learns the transformation from spatiotemporal to temporal information. In the literature, the origin of the synfire chain has not been sufficiently focused on. Our results indicate that spiking neural networks with STDP can ignite synfire chains in the cortices.

An analysis for specifications of medical use RFID system as a wireless communication.

Most of medical accidents around patients are depended on misidentification of human or medical articles. The accidents can be reduced, if information about the human or medical articles are managed automatically. RFID(Radio Frequency IDentification) tag can be identified automatically, since the tag uses wireless communication for identification. However, a specification of medical use RFID system as a communication medium was not discussed. In this study, the problems and suitable specification of the system are discussed. Anti metal tag is useful for medical environment. Small identification distance of the tag can be improved by some ways. In the case of 125 kHz, confliction between another wireless communications can be reduced, since small number of communications are located in the band. The tag circuit can be made small in size to choice 2.45 GHz band. In Japan, 0.4mm square sized tag is realized. The tag can be included in each tablets or capsules. Automatically identification is recommended in most of medical environment. Most of RFID tags are small in size and weight, and will not disturb the daily life of the patient, even if it is attached to the wristband and so on. However, it is necessary to discuss the principal factors of RFID as wireless communication media. Medical use RFID system can not be effective and safety management system without the discussion.