Multiple Sessions of Entorhinal Cortex Deep Brain Stimulation in C57BL/6J Mice Increases Exploratory Behavior and Hippocampal Neurogenesis.

Deep brain stimulation (DBS) has been a medical intervention for a variety of nervous system diseases and mental diseases. The input of DBS in the entorhinal cortex (EC) regulates the neurophysiological activities in its downstream regions, such as the dentate gyrus (DG) area. EC DBS may play a role in the treatment of diseases through hippocampal neurogenesis. This study we examined the effect of multiple sessions of EC DBS on the regulation of hippocampal neurogenesis. 4-month-old male C57BL/6J mice received bilateral multiple sessions of EC DBS (130 Hz, 90 µs, 100 µA, 1 h/d, 21 days), and the DBS parameters used are close to the high-frequency DBS parameters in clinical studies. The open field test (OFT) was used to test the exploratory behavior of mice, and hippocampal neurogenesis was detected by immunofluorescence staining with anti-doublecortin (DCX). We found that multiple sessions of EC DBS were tolerated in C57BL/6J mice, significantly increased exploratory behavior and the number of DCX-positive neurons in the DG area.Clinical Relevance- Hippocampal neurogenesis may be part of the reason for DBS to improve memory, and the results of this study show that multiple sessions of EC DBS increases exploratory behavior and hippocampal neurogenesis, which is conducive to the application of DBS in nervous system diseases and mental diseases related to memory impairment.

Inter-Limb Muscle Synergies and Kinematic Analysis of Hands-and-Knees Crawling in Typically Developing Infants and Infants With Developmental Delay.

Hands-and-knees-crawling is an important motor developmental milestone and a unique window into the development of central nervous system (CNS). Mobility during crawling is regularly used in clinical assessments to identify delays in motor development. However, possible contribution from CNS impairments to motor development delay is still unknown. The aim of this study was to quantify and compare inter-limb muscle synergy and kinematics during crawling among infants at a similar developmental age, however, clinically determined to be typically developing (TD, N = 20) infants, infants at risk of developmental delay (ARDD, N = 33), or infants with confirmed developmental delay (CDD, N = 13). We hypothesized that even though all of the groups are at a similar developmental age, there would be differences in kinematic measures during crawling, and such differences would be associated with CNS impairment as measured by electromyography (EMG) features. Surface EMG of eight arm and leg muscles and the corresponding joint kinematic data were collected while participants crawled on hands and knees at their self-selected velocity. Temporal-spatial parameters and normalized Jerk-Cost (JC) function (i.e., smoothness of movement) were computed from the measured kinematics. The inter-limb muscle synergy and the number of co-activating muscles per synergy were measured using EMGs. We found that the infants with CDD demonstrated higher normalized JC values (less movement smoothness), fewer muscle synergies, and more co-activating muscles per synergy, compared to infants with TD (p < 0.05) and ARDD (p < 0.05). Furthermore, the normalized JC values were correlated (p < 0.05) with the number of co-activation muscles per synergy. Our results suggest a constrained neuromuscular control strategy due to neurological injury in infants with CDD, and such constrain may contribute to the reduced movement smoothness in infant crawling.

Inter-Limb Muscle Synergy of Hands-and-Knees Crawling in Typical Developing Infants and Infants with Developmental Delay.

The aim of this study was to quantify and compare the inter-limb muscle coordination during crawling between typically developing infants and infants with developmental delay. Typically developing (TD, $\text{N}=$20) infants and infants with at risk of developmental delay (ARDD, $\textbf{N}=$33) or confirmed developmental delayCDD, N=14) participated in this study. Surface electromyography of eight muscles from arms and legs and the corresponding joint kinematic data were collected while they were crawling on hands and knees at their self-selected velocity. The number of used inter-limb muscle synergies during crawling was identified by nonnegative matrix factorization algorithm. Our results showed that there was no significant difference in the number of used muscle synergies between ARDD and TD infants during crawling. However, a reduced number of synergies were identified in infants with CDD, as compared to that in TD and ARDD infants, indicating constrained neuromuscular control strategy during crawling in developmental delayed infants. The absence of inter-limb muscle synergies may be one of the mechanisms underlying the impairments of crawling in developmental delayed infants, who are at high risk of cerebral palsy. This result also suggests that the metrics of muscle synergy during infant crawling, such as the number of synergy, may be feasible as a biomarker for early diagnosis of infants with cerebral palsy.

Motor Skill Development Alters Kinematics and Co-Activation Between Flexors and Extensors of Limbs in Human Infant Crawling.

Hands and knees crawling is an important motor developmental milestone but the current clinical measures of motor function during crawling stage are relatively subjective. Objective metrics using kinematics and electromyography (EMG) in infant crawling may provide more stable and accurate measures of such developmental milestone, demonstrating changes in locomotion during age span. The purpose of this paper was to determine whether joint kinematics and the underlying co-activation between flexor and extensor in infant crawling are different for arms and legs across the infant age span. Surface EMG of two pairs of flexors and extensors from arms and legs and the corresponding joint kinematic data were collected in twenty health infants (11 males and 9 females, range 8-15 months), while they were crawling on hands and knees. Co-activation index of averaged EMG was used to quantify the simultaneous contractions between flexor and extensor muscles. Coefficient of variation of joint's maximum vertical acceleration from multiple cycles was used to quantify the repeatability of kinematics during crawling. Our results indicated that the arm exhibited significantly higher co-activation and higher repeatability of joint movement than the leg, suggesting earlier development of arm compared to leg. Moreover, elder age groups, who had stronger walking ability developed, showed increased co-activation of the leg and significant increase in repeatability of the knee movement. These results were consistent with the rapid reinforcement of the leg during motor development from quadrupeds to bipedal walking. Furthermore, the EMG and kinematic parameters were significantly correlated with clinical variables. These results suggest that the EMG and kinematic analysis of infant crawling are useful in building effective assessment of infant's motor function before independent walking.

The variability of co-activation pattern of antagonist muscles in human infant crawling.

Infant crawling is part of normal human gross motor development, and a 4-beat gait that involves rhythmical flexion and extension of limbs and the underlying muscle co-activation of antagonist muscle around the joint. However, detection the co-activation pattern of antagonist muscle are sparse due to the general difficulty of measuring locomotion in human infants. In this paper, sEMG of antagonist muscles and the corresponding kinematics data of limbs were collected when infants were crawling on hands and knees at their self-selected speed. The infant's gross motor developmental status was assessed by the global Gross Motor Function Measure Scale (GMFM-88) as well. The method based on EMG-EMG plots was used to quantify the variability of co-activation pattern of antagonist muscle. After that, we observed that antagonist muscles of upper limb (triceps brachii and biceps brachii) showed less variability of co-activation pattern of muscles than lower limb(quadriceps femoris and hamstrings) during crawling, and this variability was also varied in different crawling phases (stance and swing). Furthermore, we found some varied behaviors in the co-activation patterns of antagonist muscles when gross motor developmental level increased. The preliminary work suggests that such adaptive changes may be related to the adjustment of neuromuscular in the early stage of gross motor development.

Neural representation of different mandarin tones in the inferior colliculus of the guinea pig.

Mandarin speech has four different tones and the coding mechanism underlying tone identification still remain unclear. Here in the inferior colliculus (IC) of anesthetized guinea pigs, we recorded single neuron activities to one word with four tones using tungsten electrode. Peri-stimulus time histograms (PSTHs) and inter-spike-interval (ISI) were used to evaluate the neural response. The results showed that PSTHs grouped into frequency band reflected the spectrotemporal patterns of different tones; average population PSTHs matched envelops of different tones; and the peaks of histogram of ISIs in three time segments exhibited a displacement which reflected the profile of fundamental frequency (F0). These preliminary results suggested IC neurons could encode the spectrotemporal acoustic features of different Mandarin tones.

Antagonist muscle co-activation of limbs in human infant crawling: A pilot study.

Muscle Co-activation (MCo) is the simultaneous muscular activation of agonist and antagonist muscle groups, which provides adequate joint stability, movement accuracy during movement. Infant crawling is an important stage of motor function development that manifests non-synchronization growth and development of upper and lower limbs due to the well-known gross motor development principle of head to toe. However, the effect of MCo level for agonist and antagonist muscle groups on motor function development of limbs has not been previously reported. In this paper, sEMG signals were collected from triceps brachii (TB) and biceps brachii (BB), quadriceps femoris (QF) and hamstrings (HS) of limbs when fourteen infants were crawling at their self-selected speed. Antagonist muscle co-activation was evaluated by measuring two common indexes (co-activation index and Pearson's correlation coefficient).A significant difference was observed between upper limbs and lower limbs, but the relationship between MCo and speed of crawling was poor. This study is an opening for further investigation including a longitudinal study and compare against infant with CNS disorders.

Pulsed 808-nm infrared laser stimulation of the auditory nerve in guinea pig cochlea.

Pulsed near-infrared radiation has been proposed as an alternative stimulus for auditory nerve stimulation and could be potentially used in the design of cochlear implant. Although the infrared with high absorption coefficient of water (i.e., wavelength ranged from 1.8 to 2.2 µm) has been widely investigated, the lymph in the cochlea absorbs most of the infrared energies, and only a small part can arrive at the target auditory nerves. The present study is aimed to test whether the short-wavelength near-infrared irradiation with lower absorption coefficients can penetrate the lymph fluid to stimulate the auditory nerves. An 808-nm near-infrared laser was chosen to stimulate the auditory nerve in the guinea pig cochlea. The infrared pulse was delivered by an optical fiber that was surgically inserted near the round window membrane and oriented toward the spiral ganglion cells in the basal turn of the cochlea. The 2-Hz infrared pulses were used to stimulate the cochlea before and after the deafness with different pulse durations (100-1,000 µs). Optically evoked compound action potentials (oCAPs) were recorded during the infrared radiation. We successfully recorded oCAPs from both normal hearing animals and deafened animals. The oCAP amplitude increased with the infrared radiation energy. The preliminary experiment suggests that the near-infrared with lower absorption coefficients can effectively pass through the lymph filled in the cochlea and stimulate the auditory nerve. Further studies will optimize the deafness animal model and determine the optimal stimulation parameters.

Optical stimulation of primary motor cortex with 980nm infrared neural stimulation.

To explore the penetration depth with short-wavelength infrared light, 980 nm pulse infrared light was used to stimulate the primary motor cortex of rat. The heating model was created to simulate the temperature distribution for 1875 nm and 980 nm infrared neural stimulation. Post-stimulus time histogram was used to observe the neural response induced by Infrared neural stimulation on primary motor cortex. The model predicted the penetration depth of 980 nm was deep into 1.2 mm. Cortical neural located between 500 µm to 1000 µm were successfully activated by 980 nm INS. The preliminary results suggested that, 980 nm pulse INS could serve as a candidate for deep tissue stimulation.

Short-wavelength near infrared stimulation of the inner ear hair cells.

To explore whether the short wavelength near infrared laser can stimulate the functional hair cells, pulsed laser with wavelength of 808-nm was used to stimulate guinea pigs cochlea. Compound action potential (CAP) and auditory brainstem responses (ABR) were recorded during the experiments. We successfully recorded photomechanical responses from normal hearing animals and demonstrated the responses were not induced by optical acoustic events. Furthermore, we studied the effect of different stimulation parameters on neural response. The results show that cochlear activation can be modulated with different optical parameters.

Irradiation of 850-nm laser light changes the neural activities in rat primary visual cortex.

Although infrared laser was proven to be an alternative approach for neural stimulation, there is very little known about the neural response to infrared laser irradiation in visual cortex. This study is to investigate the effect of near-infrared laser irradiation on neural activities at the cortex level. A 850-nm pigtailed diode laser was applied to stimulate the rat primary visual cortex while the horizontal black and white stripe pattern was used as standard visual stimulation to evoke visual-evoked potential (VEP). Both amplitude and latency of VEP P100 was measured with or without infrared pulse stimulation applied in rat primary visual cortex. Paired t test and one-way analysis of variance were used to evaluate the impact of infrared irradiation and its pulse width on the amplitudes and latencies of P100, respectively. The results from our preliminary study revealed that, the pulsed near-infrared laser depressed the VEP amplitude and shortened the latency of P100; with the increment of pulse width of infrared irradiation, further decline of VEP amplitude and much shortened latency of P100 were observed. The present work suggests that near-infrared laser irradiation can alter the neural activities in primary visual cortex transiently, and could provide a novel contactless artificial neural stimulus to brain cortex with high spatial selectivity.

Optical stimulation of visual cortex with pulsed 620-nm red light.

To explore the optical neural stimulation with visible light, 620-nm red light pulse emitted by LED was used to stimulate the left primary visual cortex of adult rat. The neural response in right primary visual cortex was recorded with a flexible microelectrode. By synchronized averaging the raw signal, optical evoked potentials (OEPs) were observed a negative wave and positive wave after optical stimuli. Furthermore, the amplitude and occurrence of the negative and positive wave were modulated by the strength and pulse width of the optical stimulus. The preliminary experiment suggested that, beyond the infrared laser, the pulse of visible light (e.g. red light) can modulate the neural activity in central nervous system.