Respiratory entrainment of the locus coeruleus modulates arousal level to avoid physical risks from external vibration.

Slow rocking chairs can easily put people to sleep, while violent shaking, such as during earthquakes, may lead to rapid awakening. However, the influence of external body vibrations on arousal remains unclear. Herein, a computational model of a locus coeruleus (LC)-norepinephrine (NE) system and cardio-respiratory system were used to show that respiratory entrainment of the LC modulates arousal levels, which is an adaptation to avoid physical risks from external vibration. External vibrations of sinusoidal waves with different frequencies ranging from 0.1 to 20 [Hz] were applied to the LC based on the results of previous studies. We found that respiratory entrainment of the LC decreased the breathing rate (BR) and heart rate (HR) to maintain the HR within its normal range. Furthermore, 1:1 phase locking enhanced arousal level while phase-amplitude coupling decreased it for larger vibration stimuli. These findings suggest that respiratory entrainment of the LC might automatically modulate cardio-respiratory system homeostasis and arousal levels for performance readiness (fight/flight or freeze) to avoid physical risks from larger external vibrations.

Acute Effects of Combination Therapy by Triceps Surae Stretching and Electrical Stimulation to the Tibialis Anterior on Medial Forefoot Plantar Pressure During Gait in Patients With Diabetes Mellitus.

High plantar flexor moment and limited ankle mobility are known to cause high plantar pressure under the forefoot. Stretching is an effective physical therapy for the limited ankle range of motion (ROM), and electrical stimulation is used to regulate the activity of antagonistic muscle via the action of reciprocal inhibition. Additionally, stretching paired with electrical stimulation has been reported to improve the limited ROM significantly. This study aims to investigate the influences of stretching on triceps surae (STR), electrical stimulation to tibialis anterior (ES), and the combination (ES+STR) on the ROM, kinematic parameters, and plantar pressure distribution during gait in patients with diabetes mellitus. Planter pressure and other parameters were measured before and after the intervention of ES, STR, ES+STR, or the rest sitting on the bed (CON) for 10 min. Pressure time integral under the medial forefoot decreased in the ES+STR compared to CON (P< .05). Interestingly, ES+STR increased passive and dynamic ROM on ankle dorsiflexion during gait and increased the lateral center of pressure excursion (P < .05). Furthermore, these changes were followed by decreased contact duration under the medial forefoot (P < .05). The combined therapy improves ankle mobility during gait and reduces the contact duration and the plantar pressure under the medial forefoot in patients with diabetes mellitus.

Open-ended movements structure sensorimotor information in early human development.

Human behaviors, with whole-body coordination, involve large-scale sensorimotor interaction. Spontaneous bodily movements in the early developmental stage potentially lead toward acquisition of such coordinated behavior. These movements presumably contribute to the structuration of sensorimotor interaction, providing specific regularities in bidirectional information among muscle activities and proprioception. Whether and how spontaneous movements, despite being task-free, structure and organize sensorimotor interactions in the entire body during early development remain unknown. Herein, to address these issues, we gained insights into the structuration process of the sensorimotor interaction in neonates and 3-mo-old infants. By combining detailed motion capture and musculoskeletal simulation, sensorimotor information flows among muscle activities and proprioception throughout the body were obtained. Subsequently, we extracted spatial modules and temporal state in sensorimotor information flows. Our approach demonstrated that early spontaneous movements elicited body-dependent sensorimotor modules, revealing age-related changes in them, depending on the combination or direction. The sensorimotor interactions also displayed temporal non-random fluctuations analogous to those seen in spontaneous activities in the cerebral cortex and spinal cord. Furthermore, we found recurring state sequence patterns across multiple participants, characterized by a substantial increase in infants compared to the patterns in neonates. Therefore, early spontaneous movements induce the spatiotemporal structuration in sensorimotor interactions and subsequent developmental changes. These results implicated that early open-ended movements, emerging from a certain neural substrate, regulate the sensorimotor interactions through embodiment and contribute to subsequent coordinated behaviors. Our findings also provide a conceptual linkage between early spontaneous movements and spontaneous neuronal activity in terms of spatiotemporal characteristics.

Applying Multichannel Optogenetic System for Epidural Spinal Cord Stimulation in Rats.

This study reports on the technique of applying multichannel optogenetic system to spinal cord stimulation in rats. Epidural spinal cord stimulation has been shown to reactivate spinalized hind limb motion; however, the stimulating parameters and detailed mechanism remain unclear. In order to utilize the high spatial resolution and cell type selectivity of optogenetics for studying the mechanism behind epidural spinal cord stimulation, a multichannel optical fiber bundle was designed, composed of 720 optical fibers of 200 $\mu $m diameter arranged in a 48$\times $ textbf15 matrix cover the vertebral columns of rats from level T13 to L2. The stimulating location was controlled by changing the direction of projection of a laser diode, and the appropriate projecting angle to obtain the maximum optical power output of each fiber was determined by a hill-climbing algorithm. A spinal cord window was developed to fit the head of the optical fiber bundle onto the dorsal part of rat spinal cord. Preliminary test in a rat revealed different stimulating area distribution of the optogenetically induced tibialis anterior (TA) and medial gastrocnemius (MG) muscle reactions and demonstrated the capability of the system for in-vivo study.

Modulation of EMG-EMG Coherence in a Choice Stepping Task.

The voluntary step execution task is a popular measure for identifying fall risks among elderly individuals in the community setting because most falls have been reported to occur during movement. However, the neurophysiological functions during this movement are not entirely understood. Here, we used electromyography (EMG) to explore the relationship between EMG-EMG coherence, which reflects common oscillatory drive to motoneurons, and motor performance associated with stepping tasks: simple reaction time (SRT) and choice reaction time (CRT) tasks. Ten healthy elderly adults participated in the study. Participants took a single step forward in response to a visual imperative stimulus. EMG-EMG coherence was analyzed for 1000 ms before the presentation of the stimulus (stationary standing position) from proximal and distal tibialis anterior (TA) and soleus (SOL) muscles. The main result showed that all paired EMG-EMG coherences in the alpha and beta frequency bands were greater in the SRT than the CRT task. This finding suggests that the common oscillatory drive to the motoneurons during the SRT task occurred prior to taking a step, whereas the lower value of corticospinal activity during the CRT task prior to taking a step may indicate an involvement of inhibitory activity, which is consistent with observations from our previous study (Watanabe et al., 2016). Furthermore, the beta band coherence in intramuscular TA tended to positively correlate with the number of performance errors that are associated with fall risks in the CRT task, suggesting that a reduction in the inhibitory activity may result in a decrease of stepping performance. These findings could advance the understanding of the neurophysiological features of postural adjustments in elderly individuals.

Validity of spectral analysis based on heart rate variability from 1-minute or less ECG recordings.

BACKGROUND: To broaden the utility of heart rate variability (HRV) in clinical medicine and mass screening, results based on shorter electrocardiogram (ECG) recordings require validation with those based on standard 5-minute recordings. We investigated the association between HRV variables obtained from 5-minute ECGs with those obtained from ECGs shorter than 5 minutes. METHODS: Twenty-two participants aged 20-69 years underwent 5-minute resting ECG recordings in the supine position with natural breathing. Spectral analysis using MemCalc method was performed to calculate high-frequency (HF, which required at least 10 seconds) and low-frequency (LF, which required at least 30 seconds) components. Participants were not strictly preconditioned as in previous experimental studies in order to simulate a setting similar to that of a general health checkup. Associations of each variable between the 5-minute ECG recordings and those for shorter recordings were examined by Pearson's correlation coefficients and Bland-Altman plots. RESULTS: HF and LF components were log-transformed based on their distributions. Correlation coefficients between 5-minute data and shorter recordings in the supine position with natural breathing ranged from 0.80 to 0.91 (HF by 10-second recording, 0.80; LF by 30-second recording, 0.83, respectively). Bland-Altman plots showed that gaps between the values from both methods slightly increased as the HF and LF component values increased. CONCLUSIONS: Although slight proportional errors were possible, values from standard 5-minute and shorter recordings in the supine position were strongly correlated. Our findings suggest that shorter ECG data without strict preconditioning can be reliably used for spectral analysis.

An Embodied Brain Model of the Human Foetus.

Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system.

Screening for secondary hyperparathyroidism in preterm infants.

BACKGROUND: The major cause of osteopathy of prematurity is dietary phosphate deficiency, but secondary hyperparathyroidism caused by calcium deficiency or vitamin D deficiency is also important. Because parathyroid hormone (PTH) mobilizes calcium and phosphate from the bone, hyperparathyroidism worsens osteopathy of prematurity. In order to identify useful markers to screen for and diagnose hyperparathyroidism in preterm infants, we measured serum and urinary biochemical markers. METHODS: Several biomarkers, including serum intact PTH (iPTH), were measured in urine and serum samples obtained from 95 preterm infants, and the relationship between serum iPTH and the other parameters was analyzed. RESULTS: Mean gestation was 33.2 ± 2.9 weeks, and mean birthweight was 1705 ± 402 g. Samples were collected around postnatal day 17.3 ± 7.4. Fourteen infants (14.7%) had iPTH >65 pg/mL. Cut-offs for serum alkaline phosphatase (ALP) and percent tubular reabsorption rate of phosphate (%TRP) were fixed at 1300 IU/L and 93%, respectively using receiver operating characteristic curves with iPTH cut-off of 65 pg/mL. Serum ALP was proven to be a good marker: ALP had a sensitivity of 78.6% and a specificity of 86.4%, while %TRP itself was not: %TRP had a sensitivity of 64.3% and a specificity of 58.0%. Combined measurement of serum ALP (>1300 IU/L) and %TRP (≤93%), however, had a specificity of 93.8% for detecting elevated iPTH. CONCLUSION: Measurement of serum ALP (>1300 IU/L) is considered as an effective screening method to detect hyperparathyroidism. In addition, combined assessment of ALP(>1300 IU/L) and %TRP(≤93%) is a good indicator of elevated iPTH in preterm infants.

Cortical muscle control of spontaneous movements in human neonates.

Anatomical studies show the existence of corticomotor neuronal projections to the spinal cord before birth, but whether the primary motor cortex drives muscle activity in neonatal 'spontaneous' movements is unclear. To investigate this issue, we calculated corticomuscular coherence (CMC) and Granger causality in human neonates. CMC is widely used as an index of functional connectivity between the primary motor cortex and limb muscles, and Granger causality is used across many fields of science to detect the direction of coherence. To calculate CMC and Granger causality, we used electroencephalography (EEG) to measure activity over the cortical region that governs leg muscles, and surface electromyography (EMG) over the right and left tibialis anterior muscles, in 15 healthy term and preterm neonates, during spontaneous movements without any external stimulation. We found that 17 leg muscles (10 right, seven left) in 12 neonates showed significant CMC, whose magnitude significantly correlated with postnatal age only in the beta frequency band. Further analysis revealed Granger causal drive from EEG to EMG in 14 leg muscles. Our findings suggest that the primary motor cortex drives muscle activity when neonates move their limbs. Moreover, the positive correlation between CMC magnitude and postnatal age suggests that corticomuscular communication begins to develop during the neonatal stage. This process may facilitate sensory-motor integration and activity-dependent development.

High prevalence of severe circulatory complications with diazoxide in premature infants.

BACKGROUND: Since diazoxide was approved for clinical use in Japan in 2008, its prescription for the treatment of infants with hyperinsulinemic hypoglycemia (HIH) has rapidly expanded. Concomitantly, reports of complications associated with diazoxide are increasing. OBJECTIVES: To clarify the trends and problems associated with the treatment of infants with HIH, we planned a nationwide surveillance in Japan. METHODS: Questionnaires were sent to 255 institutions belonging to the Japanese Neonatologist Association inquiring about neonatal cases of HIH from 2009 to 2011. RESULTS: One hundred nineteen cases of neonates with transient HIH (THIH) related to perinatal problems and 15 cases with permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and the administration was completed within 3 months in 46 infants (71.9%). Fourteen of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had hypoglycemia persisting beyond a year. Circulatory complications were reported in 15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis revealed that a younger gestational age at birth and higher maximum doses of diazoxide were significant risk factors for circulatory complications. CONCLUSIONS: Diazoxide is widely prescribed for infants with HIH as a first-line medicine in Japan, but prophylactic diuretics are uncommon. Under these circumstances, a high prevalence of severe circulatory complications in very-low-birth-weight infants was reported.

Limited response to CRH stimulation tests at 2 weeks of age in preterm infants born at less than 30 weeks of gestational age.

BACKGROUND: The high incidence of glucocorticoid-responsive complications in extremely preterm infants suggests the immaturity of their adrenal function; however, knowledge of the hypothalamus-pituitary-adrenal (HPA) axis in extremely preterm infants is limited. METHODS: To clarify the characteristics of the HPA axis in preterm very low birthweight (VLBW) infants, we performed CRH tests repeatedly: at about 2 weeks of age and at term (37-41 weeks of postmenstrual age) for 21 VLBW infants with a gestational age (GA) <30 weeks at birth. RESULTS: Basal cortisol values at 2 weeks of age were significantly higher than those at term in VLBW infants < 30 weeks of gestation at birth (304·1 ± 146·3 nmol/l vs 184·7 ± 108·2 nmol/l). Response to corticotropin-releasing hormone (CRH) stimulation tests at 2 weeks of age was significantly lower than at term (delta cortisol 148·3 ± 90·7 nmol/l vs 271·8 ± 167·0 nmol/l, delta ACTH 3·9 ± 3·2 pmol/l vs 12·3 ± 9·2 pmol/l, respectively). We found that earlier GA contributed to the higher basal cortisol values, and antenatal glucocorticoid (AG) contributed to the lower response of cortisol to CRH tests at 2 weeks of age. CONCLUSIONS: VLBW infants showed a characteristic pattern in the HPA axis at 2 weeks of age: higher basal cortisol values and lower response to CRH tests. This study suggested that AG was related to the lower response to CRH tests, at least partly.

Hyperthyrotropinemia at 2 weeks of age indicates thyroid dysfunction and predicts the occurrence of delayed elevation of thyrotropin in very low birth weight infants.

BACKGROUND: For preterm infants, transient hypothyroxinemia of prematurity and transient primary hypothyroidism, especially with delayed elevation of serum thyrotropin (TSH), are important. METHODS: To address the above two issues, we performed thyrotropin-releasing hormone (TRH) stimulation tests at about 2 weeks of age for 31 preterm infants with a gestational age of 30 weeks or less. RESULTS: For basal TSH levels, 68% of infants (21 of 31) showed normal values (TSH < 10 mU/l) and 32% of infants (10 of 31) showed higher values (four infants: TSH 10-15 mU/l, six infants: TSH > 15 mU/l). Peak TSH values in response to TRH stimulation tests ranged from 9·76 to 114·8 mU/l. All infants showed a significant response to TRH stimulation tests. Only 9·5% of infants (two of 21) with normal basal TSH values showed a hyperresponse (peak TSH > 45 mU/l), whereas 80% of infants (eight of 10) who had higher basal TSH values showed a hyperresponse. All infants who showed mildly elevated basal TSH values (TSH 10-15 mU/l) and a hyperresponse to TRH stimulation tests showed delayed elevation of basal TSH values (TSH > 15 mU/l) later. CONCLUSIONS: Thyrotropin-releasing hormone stimulation tests at about 2 weeks of age suggested that the hypothalamic-pituitary-thyroid axis might be established even in extremely premature infants. Basal increased TSH levels (TSH > 10 mU/l) and a hyperresponse to TRH stimulation tests (peak TSH > 45 mU/l) suggested subclinical thyroid dysfunction. Serum TSH values at about 2 weeks of age could be useful for the prediction of delayed TSH elevation.