Comparative connectomics of dauer reveals developmental plasticity.

A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the chemical connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode has evolved to respond to harsh environments by developing a quantitatively and qualitatively differentiated connectome.

Caenorhabditis elegans Connectomes of both Sexes as Image Classifiers.

Connectome, the complete wiring diagram of the nervous system of an organism, is the biological substrate of the mind. While biological neural networks are crucial to the understanding of neural computation mechanisms, recent artificial neural networks (ANNs) have been developed independently from the study of real neural networks. Computational scientists are searching for various ANN architectures to improve machine learning since the architectures are associated with the accuracy of ANNs. A recent study used the hermaphrodite Caenorhabditis elegans (C. elegans) connectome for image classification tasks, where the edge directions were changed to construct a directed acyclic graph (DAG). In this study, we used the whole-animal connectomes of C. elegans hermaphrodite and male to construct a DAG that preserves the chief information flow in the connectomes and trained them for image classification of MNIST and fashion-MNIST datasets. The connectome-inspired neural networks exhibited over 99.5% and 92.6% of accuracy for MNIST and fashion-MNIST datasets, respectively, which increased from the previous study. Together, we conclude that realistic biological neural networks provide the basis of a plausible ANN architecture. This study suggests that biological networks can provide new inspiration to improve artificial intelligences (AIs).

A leaky integrate-and-fire computational model based on the connectome of the entire adult Drosophila brain reveals insights into sensorimotor processing.

The forthcoming assembly of the adult Drosophila melanogaster central brain connectome, containing over 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain. Here, we create a leaky integrate-and-fire computational model of the entire Drosophila brain, based on neural connectivity and neurotransmitter identity, to study circuit properties of feeding and grooming behaviors. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation. Computational activation of neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing, a testable hypothesis that we validate by optogenetic activation and behavioral studies. Moreover, computational activation of different classes of gustatory neurons makes accurate predictions of how multiple taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. Our computational model predicts that the sugar and water pathways form a partially shared appetitive feeding initiation pathway, which our calcium imaging and behavioral experiments confirm. Additionally, we applied this model to mechanosensory circuits and found that computational activation of mechanosensory neurons predicts activation of a small set of neurons comprising the antennal grooming circuit that do not overlap with gustatory circuits, and accurately describes the circuit response upon activation of different mechanosensory subtypes. Our results demonstrate that modeling brain circuits purely from connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can accurately describe complete sensorimotor transformations.

Influence of the Hawthorne effect on spatiotemporal parameters, kinematics, ground reaction force, and the symmetry of the dominant and nondominant lower limbs during gait.

The Hawthorne effect is a change in behavior resulting from awareness of being observed or evaluated. This study aimed to determine whether awareness of being evaluated or presence of an observer influence gait. Twenty-one young women were asked to walk in three conditions. In the first condition (unawareness of evaluation; UE), participants were aware that it was a practice trial, and there was no observer. In the second condition (awareness of evaluation; AE), participants were aware that their gait was being evaluated. The third condition (AE + researcher observation; RO) was similar to the second condition except that an additional researcher observed the participant' gait. The spatiotemporal, kinematic, ground reaction forces, and ratio index (symmetry of both lower limbs) were compared among the three conditions. A higher ratio index indicated a relative increase in the value on left versus right. Gait speed (P = 0.012) and stride length (right and left; P = 0.006 and 0.007, respectively) were significantly increased in the AE + RO than in UE. Range of motion of the right hip and left ankle was significantly greater in AE than in UE (P = 0.039 and 0.012, respectively). The ratio index of ground reaction force during push-off was significantly higher in AE and AE + RO conditions than in UE (P < 0.001 and P = 0.004, respectively). The Hawthorne effect (awareness of being evaluated or presence of an observer) potentially influences gait. Thus, factors that influence gait analysis should be considered when evaluating normal gait.

Comparing the Impact of Upper Body Control and Core Muscle Stabilization Training on Landing Biomechanics in Individuals with Functional Ankle Instability: A Randomized Controlled Trial.

Functional ankle instability (FAI), which is characterized by recurrent ankle sprains and perceived joint instability, arises from various factors contributing to compromised biomechanical control during activities, particularly those involving landing tasks. While current research predominantly addresses lower-extremity and core stabilization interventions for FAI, the contribution of upper body control to landing biomechanics in this population remains insufficiently explored. In this study, 42 participants (19 males, 23 females) with FAI were randomly assigned to either the upper-body control training group (UBCTG) or the core muscle stabilization training group (CMSTG). The groups underwent six-week interventions, with the UBCTG receiving a dynamic core exercise program including upper body control and the CMSTG receiving static core muscle training. Pre- and post-intervention assessments encompassed electromyography of the gastrocnemius, tibialis anterior, and peroneus longus, motion analysis of the lower extremities, and ground reaction force (GRF) readings during a single-leg-jump task. Additionally, dynamic balance was assessed using the Y balance test and self-reported measurements of ankle instability were performed. The results showed similar increases in muscle activation, joint movement, and self-reported ankle instability scores within both groups. However, significant between-group differences were observed in terms of knee flexion angle, dynamic balance, and ankle instability scores, favoring the UBCTG. Although the peak vertical GRF significantly decreased and the time to peak vertical GRF increased in both groups, more changes were noted in the UBCTG. Our results demonstrated that dynamic core exercises with additional upper body control training enhance landing biomechanics, dynamic balance, and stability in individuals with FAI. Consequently, we recommend incorporating shoulder girdle exercises, proprioceptive drills, and balance exercises into dynamic core training.

Effects of Augmented Reality Game-Based Cognitive-Motor Training on Restricted and Repetitive Behaviors and Executive Function in Patients with Autism Spectrum Disorder.

Restricted and repetitive behaviors (RRBs) and executive dysfunction are widely acknowledged as core features and hallmarks in patients with autism spectrum disorder (ASD). This study aimed to investigate the effects of augmented reality (AR) using motivational games with cognitive-motor exercises on RRBs, executive function (EF), attention, and reaction time in patients with ASD. Twenty-four patients (range from 6 to 18 years) diagnosed with ASD were recruited from local social welfare centers and randomly allocated to the AR game-based cognitive-motor training group (study group) or the conventional cognitive training group (control group). Both groups completed 30 min training sessions, twice a week for four weeks. Outcome measures were conducted before and after the intervention. As a result, improvements were observed in all the subscales of the RRBs in the study group except for self-injurious and ritualistic behavior. Significant improvements were observed in EF and reaction time in the study group, which was significantly higher compared to the control group. With the present findings, we can suggest that cognitive-motor training using AR game-based content generates positive effects on improving executive function reaction time and accuracy of responses and has a limited effect on RRBs in patients with ASD. This can be proposed as a complementary intervention associated with individualized daily management.

Effects of Augmented Reality-Based Dual-Task Program on Physical Ability by Cognitive Stage with Developmental Disabilities.

People diagnosed with developmental disabilities are less likely to participate in physical activities even if they are provided opportunities. This study aimed to examine the effects of dual-task exercise-based augmented reality (AR) on muscle strength, muscle endurance, balance ability, and flexibility among people with developmental disabilities. Twenty-seven patients with developmental disabilities were included in the study. The intervention was based on an AR-based rehabilitation program and lasted for 8 weeks. The results showed a statistically significant improvement in muscle strength, muscle endurance, balance ability, and flexibility after the intervention (p < 0.05). The AR-based dual-task program increased interest and motivation in the high-cognitive-stage groups, while less interest and motivation were observed in the low-cognitive-stage groups. Our results suggest that an AR-based dual-task program can be an effective method to improve physical ability in patients with high cognitive levels.

The Effect of Augmented Reality-Based Proprioceptive Training Program on Balance, Positioning Sensation and Flexibility in Healthy Young Adults: A Randomized Controlled Trial.

This study investigates whether Augmented Reality (AR)-based interventions can be as effective as physical therapists (PT) regarding balance, positioning sensation, and flexibility. A sample of 39 regular people who voluntarily participated in this study were randomly distributed into two groups. Then AR was applied in the experimental group and PT was applied in the control group. Variables were measured by Tetrax (static balance), Y-balance test (dynamic balance), CSMI (proprioception), and sit and reach test (flexibility). All measurements were analyzed using paired t-test and independent t-test. The exercise program of this study improved the stability index (ST) of the static balance in both groups after the intervention, and there was a significant difference (p < 0.05) at normal eye close (NC) and Pillow with eye close (PC) positions. Moreover, regarding the case of dynamic balance, there were significant differences in AR and PT groups to reach in all directions (p < 0.05). In the case of positioning sensation, there was no significant difference in both groups (p > 0.05), and there was a significant difference in flexibility (p < 0.05). When comparing the two groups, there was no significant difference in all categories (p > 0.05). As a result, AR can be considered an effective form of therapy and can be selected according to individual conditions.

Comparison of screw-home movement between patients with knee osteoarthritis and normal adults.

BACKGROUND: Tibial rotation accompanying sagittal movement contains the phenomenon of screw-home movement (SHM) of the knee, which plays an important role in knee stability during extension. OBJECTIVE: This study aimed to investigate the change of SHM in patients with knee osteoarthritis (OA). METHODS: Thirty-one sex-matched patients with knee OA and 31 normal subjects were recruited. The total tibial rotation was obtained during knee sagittal movement (extension and flexion) using an inertial measurement unit. The acquired angle of tibial rotation was divided into eight periods. The total tibial rotation and the variation of each period were compared between the OA and control groups. The difference in tibial rotation according to Kellgren-Lawrence (KL) grade was compared. RESULTS: The total tibial rotation of the OA group decreased compared with the control group during knee extension and flexion (P< 0.001). Variations of tibial rotation were significantly different between groups in all periods (P< 0.001) except for knee extension at 70∘ to 45∘ (P= 0.081). There was no significant difference in tibial rotations among the KA grades of OA patients. CONCLUSION: We found a reduction in the total tibial rotation and loss of the SHM in the unloaded OA knee. It could be predicted that reduced SHM appeared early in knee OA.

Automated Synapse Detection Method for Cerebellar Connectomics.

The connectomic analyses of large-scale volumetric electron microscope (EM) images enable the discovery of hidden neural connectivity. While the technologies for neuronal reconstruction of EM images are under rapid progress, the technologies for synapse detection are lagging behind. Here, we propose a method that automatically detects the synapses in the 3D EM images, specifically for the mouse cerebellar molecular layer (CML). The method aims to accurately detect the synapses between the reconstructed neuronal fragments whose types can be identified. It extracts the contacts between the reconstructed neuronal fragments and classifies them as synaptic or non-synaptic with the help of type information and two deep learning artificial intelligences (AIs). The method can also assign the pre- and postsynaptic sides of a synapse and determine excitatory and inhibitory synapse types. The accuracy of this method is estimated to be 0.955 in F1-score for a test volume of CML containing 508 synapses. To demonstrate the usability, we measured the size and number of the synapses in the volume and investigated the subcellular connectivity between the CML neuronal fragments. The basic idea of the method to exploit tissue-specific properties can be extended to other brain regions.

Effects of Caffeine Intake on Cardiopulmonary Variables and QT Interval after a Moderate-Intensity Aerobic Exercise in Healthy Adults: A Randomized Controlled Trial.

Caffeine is considered a widely consumed natural and legal psychoactive stimulant with several effects on the body. The present study attempted to investigate the effects of caffeine consumed before and after a physical exercise on cardiovascular and cardiorespiratory functions in healthy adults. 36 healthy adult males were recruited and randomly allocated to one of the three (3) groups: group I (exercise without caffeine consumption), group II (caffeine beverage intake before exercise), and group III (caffeine beverage intake immediately after exercise). The heart rate (HR), QTc interval, blood pressure (BP), respiratory rate (RR), oxygen consumption (VO2), and carbon dioxide emission (VCO2) were measured at 0, 5, 10, and 15 min after the exercise. We observed a significant difference in all measured outcomes during the different recovery times in all the groups (p < 0.05). HR, RR, SBP, VO2, and VCO2 gradually decreased with time, DBP contrarily increased with time, and the QTc showed an irregular pattern. We can affirm that ingestion of caffeine before and after moderate aerobic exercise slows down the parasympathetic stimulation, heart rate recovery, and the recovery of HR and QTc with no major effects on BP, RR, VO2, and VCO2 in healthy adult men.

Synapses from the Motor Cortex and a High-Order Thalamic Nucleus are Spatially Clustered in Proximity to Each Other in the Distal Tuft Dendrites of Mouse Somatosensory Cortex.

The posterior medial nucleus of the thalamus (POm) and vibrissal primary motor cortex (vM1) convey essential information to the barrel cortex (S1BF) regarding whisker position and movement. Therefore, understanding the relative spatial relationship of these two inputs is a critical prerequisite for acquiring insights into how S1BF synthesizes information to interpret the location of an object. Using array tomography, we identified the locations of synapses from vM1 and POm on distal tuft dendrites of L5 pyramidal neurons where the two inputs are combined. Synapses from vM1 and POm did not show a significant branchlet preference and impinged on the same set of dendritic branchlets. Within dendritic branches, on the other hand, the two inputs formed robust spatial clusters of their own type. Furthermore, we also observed POm clusters in proximity to vM1 clusters. This work constitutes the first detailed description of the relative distribution of synapses from POm and vM1, which is crucial to elucidate the synaptic integration of whisker-based sensory information.

Correlation of eccentric strength of the knee extensors and knee proprioception with dynamic postural control.

BACKGROUND: It is important for clinicians and researchers to perform dynamic postural control evaluation for predicting musculoskeletal conditions, injury prevention, and rehabilitation. OBJECTIVE: The purpose of this study was to investigate the relationship (1) between the eccentric strength of the knee extensors and star excursion balance test (SEBT), and (2) between the knee proprioception and SEBT. METHODS: Forty healthy young adults participated in this study. The eccentric peak torque (EPT) of the knee extensors, joint position sense, and force sense were measured. The participants also performed SEBT. Pearson's product-moment correlation and multiple linear regression analysis were used to determine the relationship between the variables and SEBT. RESULTS: The posteromedial direction of the SEBT was positively and strongly correlated with EPT (r= 0.74, P< 0.01). The anterior and posterolateral directions were positively and moderately correlated with EPT (r= 0.46, P< 0.01, and r= 0.69, P< 0.01, respectively.). However, knee proprioception was not correlated with all the directions of SEBT (P> 0.05). According to the results of multiple linear regression analysis, EPT of the knee extensors significantly predicted SEBT reach distances. CONCLUSION: The eccentric strength of the knee extensors seems to be an essential factor in dynamic postural control. However, the knee proprioception did not show a significant correlation with SEBT.

Efficient and Accurate Synapse Detection With Selective Structured Illumination Microscopy on the Putative Regions of Interest of Ultrathin Serial Sections.

Critical determinants of synaptic functions include subcellular locations, input sources, and specific molecular characteristics. However, there is not yet a reliable and efficient method that can detect synapses. Electron microscopy is a gold-standard method to detect synapses due to its exceedingly high spatial resolution. However, it requires laborious and time-consuming sample preparation and lengthy imaging time with limited labeling methods. Recent advances in various fluorescence microscopy methods have highlighted fluorescence microscopy as a substitute for electron microscopy in reliable synapse detection in a large volume of neural circuits. In particular, array tomography has been verified as a useful tool for neural circuit reconstruction. To further improve array tomography, we developed a novel imaging method, called "structured illumination microscopy on the putative region of interest on ultrathin sections", which enables efficient and accurate detection of synapses-of-interest. Briefly, based on low-magnification conventional fluorescence microscopy images, synapse candidacy was determined. Subsequently, the coordinates of the regions with candidate synapses were imaged using super-resolution structured illumination microscopy. Using this system, synapses from the high-order thalamic nucleus, the posterior medial nucleus in the barrel cortex were rapidly and accurately imaged.

Effect of trunk stabilization exercise on abdominal muscle thickness, balance and gait abilities of patients with hemiplegic stroke: A randomized controlled trial.

BACKGROUND: Trunk stability has been identified as an important prerequisite of functional movement. OBJECTIVE: To investigate the effectiveness of core muscle contraction training on abdominal muscle thickness, balance, and gait ability in stroke patients. METHODS: Thirty patients with stroke were randomly assigned to two experimental groups and a control group. All groups received conventional therapeutic exercise program for six weeks. The experimental groups additionally trained trunk stability exercise with abdominal hollowing or bracing maneuvers within training time. Primary outcome measures were evaluated abdominal muscle thickness using the sonography. Secondary outcome measures were evaluated by the Functional Reach Test (FRT), Berg Balance Scale (BBS), 10-meter walk test (10MWT), and Timed Up and Go test (TUG). RESULTS: Compared with the control group, the effect of trunk stability training for the experimental groups on the abdominal muscles thickness change was observed (p < 0.05). The values in balance and gait measures, BBS, FRT, 10MWT, and TUG, showed significant improvement after the intervention periods (p < 0.05), although no significant differences were found in scores of gait and balance scales among groups. CONCLUSIONS: Trunk stability training with selective abdominal muscles activation has beneficial effects on abdominal muscles, balance, and mobility in stroke patients. Our findings might provide support for introducing stroke rehabilitation.

Use of real-time visual feedback during overground walking training on gait symmetry and velocity in patients with post-stroke hemiparesis: randomized controlled, single-blind study.

This study aimed to determine the efficacy of using real-time visual feedback during overground walking training to improve walking function in patients with post-stroke hemiparesis. Twenty-four patients with post-stroke hemiparesis who were able to walk independently under less impact of synergy pattern on the affected lower limbs (Brunnstrom stage IV or V) were randomly assigned to either the experimental group or the control group. All subjects performed overground walking for 30 min, three times a week for 6 weeks, with real-time visual feedback (weight load to the affected lower limb) provided during training for subjects in the experimental group. Outcome measures comprised the timed up-and-go test and gait parameters (step length, stride length, single and double support times, step and stride length ratios, and single support time ratio). In between-group comparison, the changes between pre-test and post-test scores in all parameters were significantly greater in the experimental group than in the control group (P < 0.05), except for double support time and step length ratio. Furthermore, post-test values of all parameters were significantly more improved in the experimental group than in the control group (P < 0.05). Our findings suggest that real-time visual feedback may be an advantageous therapeutic adjunct to reinforce the effects of overground walking training in patients with post-stroke hemiparesis.

Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology.

When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system.

Analogous Convergence of Sustained and Transient Inputs in Parallel On and Off Pathways for Retinal Motion Computation.

Visual motion information is computed by parallel On and Off pathways in the retina, which lead to On and Off types of starburst amacrine cells (SACs). The approximate mirror symmetry between this pair of cell types suggests that On and Off pathways might compute motion using analogous mechanisms. To test this idea, we reconstructed On SACs and On bipolar cells (BCs) from serial electron microscopic images of a mouse retina. We defined a new On BC type in the course of classifying On BCs. Through quantitative contact analysis, we found evidence that sustained and transient On BC types are wired to On SAC dendrites at different distances from the SAC soma, mirroring our previous wiring diagram for the Off BC-SAC circuit. Our finding is consistent with the hypothesis that On and Off pathways contain parallel correlation-type motion detectors.

Effects of fast and slow squat exercises on the muscle activity of the paretic lower extremity in patients with chronic stroke.

[Purpose] The purpose of this study was to investigate the effects of the speed of squat exercises on paretic lower extremity muscle activity in patients with hemiplegia following a stroke. [Subjects and Methods] Ten stroke patients performed fast and slow squat exercises for 2 seconds and 8 seconds, respectively. The muscle activities of the paretic and non-paretic sides of the rectus femoris muscle, the biceps femoris muscle, and the tibialis anterior muscle were assessed and compared using surface electromyography. [Results] The paretic side of the rectus femoris muscle showed statistically significant differences in the fast squat exercise group, which demonstrated the highest muscle activity during the rapid return to the upright position. [Conclusion] The rectus femoris muscle showed the highest muscle activity during the return to the upright position during the fast squat exercise, which indicates that the rectus femoris muscle is highly active during the fast squat exercise.

Effects of visibility and types of the ground surface on the muscle activities of the vastus medialis oblique and vastus lateralis.

[Purpose] The purpose of this study was to compare the effects of visibility and types of ground surface (stable and unstable) during the performance of squats on the muscle activities of the vastus medialis oblique (VMO) and vastus lateralis (VL). [Subjects and Methods] The subjects were 25 healthy adults in their 20s. They performed squats under four conditions: stable ground surface (SGS) with vision-allowed; unstable ground surface (UGS) with vision-allowed; SGS with vision-blocked; and UGS with vision-blocked. The different conditions were performed on different days. Surface electromyogram (EMG) values were recorded. [Results] The most significant difference in the activity of the VMO and VL was observed when the subjects performed squats on the UGS, with their vision blocked. [Conclusion] For the selective activation of the VMO, performing squats on an UGS was effective, and it was more effective when subjects' vision was blocked.