Revealing neural dynamical structure of C. elegans with deep learning.

Caenorhabditis elegans serves as a common model for investigating neural dynamics and functions of biological neural networks. Data-driven approaches have been employed in reconstructing neural dynamics. However, challenges remain regarding the curse of high-dimensionality and stochasticity in realistic systems. In this study, we develop a deep neural network (DNN) approach to reconstruct the neural dynamics of C. elegans and study neural mechanisms for locomotion. Our model identifies two limit cycles in the neural activity space: one underpins basic pirouette behavior, essential for navigation, and the other introduces extra Ω turns. The combination of two limit cycles elucidates predominant locomotion patterns in neural imaging data. The corresponding energy landscape explains the switching strategies between two limit cycles, quantitatively, and provides testable predictions on neural functions and circuit roles. Our work provides a general approach to study neural dynamics by combining imaging data and stochastic modeling.

In vivo neuropil density from anatomical MRI and machine learning.

Brain energy budgets specify metabolic costs emerging from underlying mechanisms of cellular and synaptic activities. While current bottom-up energy budgets use prototypical values of cellular density and synaptic density, predicting metabolism from a person's individualized neuropil density would be ideal. We hypothesize that in vivo neuropil density can be derived from magnetic resonance imaging (MRI) data, consisting of longitudinal relaxation (T1) MRI for gray/white matter distinction and diffusion MRI for tissue cellularity (apparent diffusion coefficient, ADC) and axon directionality (fractional anisotropy, FA). We present a machine learning algorithm that predicts neuropil density from in vivo MRI scans, where ex vivo Merker staining and in vivo synaptic vesicle glycoprotein 2A Positron Emission Tomography (SV2A-PET) images were reference standards for cellular and synaptic density, respectively. We used Gaussian-smoothed T1/ADC/FA data from 10 healthy subjects to train an artificial neural network, subsequently used to predict cellular and synaptic density for 54 test subjects. While excellent histogram overlaps were observed both for synaptic density (0.93) and cellular density (0.85) maps across all subjects, the lower spatial correlations both for synaptic density (0.89) and cellular density (0.58) maps are suggestive of individualized predictions. This proof-of-concept artificial neural network may pave the way for individualized energy atlas prediction, enabling microscopic interpretations of functional neuroimaging data.

Switching of brain networks across different cerebral perfusion states: insights from EEG dynamic microstate analyses.

The alteration of neural interactions across different cerebral perfusion states remains unclear. This study aimed to fulfill this gap by examining the longitudinal brain dynamic information interactions before and after cerebral reperfusion. Electroencephalogram in eyes-closed state at baseline and postoperative 7-d and 3-month follow-ups (moyamoya disease: 20, health controls: 23) were recorded. Dynamic network analyses were focused on the features and networks of electroencephalogram microstates across different microstates and perfusion states. Considering the microstate features, the parameters were disturbed of microstate B, C, and D but preserved of microstate A. The transition probabilities of microstates A-B and B-D were increased to play a complementary role across different perfusion states. Moreover, the microstate variability was decreased, but was significantly improved after cerebral reperfusion. Regarding microstate networks, the functional connectivity strengths were declined, mainly within frontal, parietal, and occipital lobes and between parietal and occipital lobes in different perfusion states, but were ameliorated after cerebral reperfusion. This study elucidates how dynamic interaction patterns of brain neurons change after cerebral reperfusion, which allows for the observation of brain network transitions across various perfusion states in a live clinical setting through direct intervention.

A 3D atlas of functional human brain energetic connectome based on neuropil distribution.

The human brain is energetically expensive, yet the key factors governing its heterogeneous energy distributions across cortical regions to support its diversity of functions remain unexplored. Here, we built up a 3D digital cortical energy atlas based on the energetic costs of all neuropil activities into a high-resolution stereological map of the human cortex with cellular and synaptic densities derived, respectively, from ex vivo histological staining and in vivo PET imaging. The atlas was validated with PET-measured glucose oxidation at the voxel level. A 3D cortical activity map was calculated to predict the heterogeneous activity rates across all cortical regions, which revealed that resting brain is indeed active with heterogeneous neuronal activity rates averaging around 1.2 Hz, comprising around 70% of the glucose oxidation of the cortex. Additionally, synaptic density dominates spatial patterns of energetics, suggesting that the cortical energetics rely heavily on the distribution of synaptic connections. Recent evidence from functional imaging studies suggests that some cortical areas act as hubs (i.e., interconnecting distinct and functionally active regions). An inverse allometric relationship was observed between hub metabolic rates versus hub volumes. Hubs with smaller volumes have higher synapse density, metabolic rate, and activity rates compared to nonhubs. The open-source BrainEnergyAtlas provides a granular framework for exploring revealing design principles in energy-constrained human cortical circuits across multiple spatial scales.

Visual-Based Spatial Coordinate Dominates Probabilistic Multisensory Inference in Macaque MST-d Disparity Encoding.

Numerous studies have demonstrated that animal brains accurately infer whether multisensory stimuli are from a common source or separate sources. Previous work proposed that the multisensory neurons in the dorsal medial superior temporal area (MST-d) serve as integration or separation encoders determined by the tuning-response ratio. However, it remains unclear whether MST-d neurons mainly take a sense input as a spatial coordinate reference for carrying out multisensory integration or separation. Our experimental analysis shows that the preferred tuning response to visual input is generally larger than vestibular according to the Macaque MST-d neuronal recordings. This may be crucial to serving as the base of coordinate reference when the subject perceives moving direction information from two senses. By constructing a flexible Monte-Carlo probabilistic sampling (fMCS) model, we validate this hypothesis that the visual and vestibular cues are more likely to be integrated into a visual-based coordinate rather than vestibular. Furthermore, the property of the tuning gradient also affects decision-making regarding whether the cues should be integrated or not. To a dominant modality, an effective decision is produced by a steep response-tuning gradient of the corresponding neurons, while to a subordinate modality a steep tuning gradient produces a rigid decision with a significant bias to either integration or separation. This work proposes that the tuning response amplitude and tuning gradient jointly modulate which modality serves as the base coordinate for the reference frame and the direction change with which modality is decoded effectively.

Unveiling Dynamic System Strategies for Multisensory Processing: From Neuronal Fixed-Criterion Integration to Population Bayesian Inference.

Multisensory processing is of vital importance for survival in the external world. Brain circuits can both integrate and separate visual and vestibular senses to infer self-motion and the motion of other objects. However, it is largely debated how multisensory brain regions process such multisensory information and whether they follow the Bayesian strategy in this process. Here, we combined macaque physiological recordings in the dorsal medial superior temporal area (MST-d) with modeling of synaptically coupled multilayer continuous attractor neural networks (CANNs) to study the underlying neuronal circuit mechanisms. In contrast to previous theoretical studies that focused on unisensory direction preference, our analysis showed that synaptic coupling induced cooperation and competition in the multisensory circuit and caused single MST-d neurons to switch between sensory integration or separation modes based on the fixed-criterion causal strategy, which is determined by the synaptic coupling strength. Furthermore, the prior of sensory reliability was represented by pooling diversified criteria at the MST-d population level, and the Bayesian strategy was achieved in downstream neurons whose causal inference flexibly changed with the prior. The CANN model also showed that synaptic input balance is the dynamic origin of neuronal direction preference formation and further explained the misalignment between direction preference and inference observed in previous studies. This work provides a computational framework for a new brain-inspired algorithm underlying multisensory computation.

A simultaneous electroencephalography and eye-tracking dataset in elite athletes during alertness and concentration tasks.

The dataset of simultaneous 64-channel electroencephalography (EEG) and high-speed eye-tracking (ET) recordings was collected from 31 professional athletes and 43 college students during alertness behavior task (ABT) and concentration cognitive task (CCT). The CCT experiment lasting 1-2 hours included five sessions for groups of the Shooting, Archery and Modern Pentathlon elite athletes and the controls. Concentration targets included shooting target and combination target with or without 24 different directions of visual distractors and 2 types of music distractors. Meditation and Schulte Grid trainings were done as interventions. Analysis of the dataset aimed to extract effective biological markers of eye movement and EEG that can assess the concentration level of talented athletes compared with same-aged controls. Moreover, this dataset is useful for the research of related visual brain-computer interfaces.

A dynamics model of neuron-astrocyte network accounting for febrile seizures.

Febrile seizure (FS) is a full-body convulsion caused by a high body temperature that affect young kids, however, how these most common of human seizures are generated by fever has not been known. One common observation is that cortical neurons become overexcited with abnormal running of sodium and potassium ions cross membrane in raised body temperature condition, Considering that astrocyte Kir4.1 channel play a critical role in maintaining extracellular homeostasis of ionic concentrations and electrochemical potentials of neurons by fast depletion of extracellular potassium ions, we examined here the potential role of temperature-dependent Kir4.1 channel in astrocytes in causing FS. We first built up a temperature-dependent computational model of the Kir4.1 channel in astrocytes and validated with experiments. We have then built up a neuron-astrocyte network and examine the role of the Kir4.1 channel in modulating neuronal firing dynamics as temperature increase. The numerical experiment demonstrated that the Kir4.1 channel function optimally in the body temperature around 37 °C in cleaning 'excessive' extracellular potassium ions during neuronal firing process, however, higher temperature deteriorates its cleaning function, while lower temperature slows down its cleaning efficiency. With the increase of temperature, neurons go through different stages of spiking dynamics from spontaneous slow oscillations, to tonic spiking, fast bursting oscillations, and eventually epileptic bursting. Thus, our study may provide a potential new mechanism that febrile seizures may be happened due to temperature-dependent functional disorders of Kir4.1 channel in astrocytes. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09706-w.

Changes in Brain Functional Network Connectivity in Adult Moyamoya Diseases.

Moyamoya disease (MMD) is a cerebrovascular disease that is characterized by progressive stenosis or occlusion of the internal carotid arteries and its main branches, which leads to the formation of abnormal small collateral vessels. However, little is known about how these special vascular structures affect cortical network connectivity and brain function. By applying EEG analysis and graphic network analyses undergoing EEG recording of subjects with eyes-closed (EC) and eyes-open (EO) resting states, and working memory (WM) tasks, we examined the brain network features of hemorrhagic (HMMD) and ischemic MMD (IMMD) brains. For the first time, we observed that IMMD had the much lower alpha-blocking rate during EO state than healthy controls while HMMD exhibited the relatively low EEG activity rate across all the behavior states. Further, IMMD showed strong network connections in the alpha-wave band in frontal and parietal regions during EO and WM states. EEG frequency and network topological maps during both resting and WM states indicated that the left frontal lobe and left parietal lobe in HMMD patients and the right parietal lobe and temporal lobe in IMMD patients have clear differences compared with controls, which provides a new insight to understand distinct electrophysiological features of MMD. However, due to the small sample size of recruited patient subjects, the result conclusion may be limited. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s11571-021-09666-1).

Sparsely Wiring Connectivity in the Upper Beta Band Characterizes the Brains of Top Swimming Athletes.

Human brains are extremely energy costly in neural connections and activities. However, it is unknown what is the difference in the brain connectivity between top athletes with long-term professional trainings and age-matched controls. Here we ask whether long-term training can lower brain-wiring cost while have better performance. Since elite swimming requires athletes to move their arms and legs at different tempos in time with high coordination skills, we selected an eye-hand-foot complex reaction (CR) task to examine the relations between the task performance and the brain connections and activities, as well as to explore the energy cost-efficiency of top athletes. Twenty-one master-level professional swimmers and 23 age-matched non-professional swimmers as controls were recruited to perform the CR task with concurrent 8-channel EEG recordings. Reaction time and accuracy of the CR task were recorded. Topological network analysis of various frequency bands was performed using the phase lag index (PLI) technique to avoid volume conduction effects. The wiring number of connections and mean frequency were calculated to reflect the wiring and activity cost, respectively. Results showed that professional athletes demonstrated better eye-hand-foot coordination than controls when performing the CR task, indexing by faster reaction time and higher accuracy. Comparing to controls, athletes' brain demonstrated significantly less connections and weaker correlations in upper beta frequency band between the frontal and parietal regions, while demonstrated stronger connectivity in the low theta frequency band between sites of F3 and Cz/C4. Additionally, athletes showed highly stable and low eye-blinking rates across different reaction performance, while controls had high blinking frequency with high variance. Elite athletes' brain may be characterized with energy efficient sparsely wiring connections in support of superior motor performance and better cognitive performance in the eye-hand-foot complex reaction task.

Faded Critical Dynamics in Adult Moyamoya Disease Revealed by EEG and fMRI.

Criticality is considered a dynamic signature of healthy brain activity that can be measured on the short-term timescale with neural avalanches and long-term timescale with long-range temporal correlation (LRTC). It is unclear how the brain dynamics change in adult moyamoya disease (MMD). We used BOLD-fMRI for LRTC analysis from 16 hemorrhagic (H MMD) and 34 ischemic (I MMD) patients and 25 healthy controls. Afterwards, they were examined by EEG recordings in the eyes-closed (EC), eyes-open (EO), and working memory (WM) states. The EEG data of 11 H MMD and 13 I MMD patients and 21 healthy controls were in good quality for analysis. Regarding the 4 metrics of neural avalanches (e.g., size (α), duration (ß), κ value, and branching parameter (σ)), both MMD subtypes exhibited subcritical states in the EC state. When switching to the WM state, H MMD remained inactive, while I MMD surpassed controls and became supercritical (p < 0.05). Regarding LRTC, the amplitude envelope in the EC state was more analogous to random noise in the MMD patients than in controls. During state transitions, LRTC decreased sharply in the controls but remained chaotic in the MMD individuals (p < 0.05). The spatial LRTC reduction distribution based on both EEG and fMRI in the EC state implied that, compared with controls, the two MMD subtypes might exhibit mutually independent but partially overlapping patterns. The regions showing decreased LRTC in both EEG and fMRI were the left supplemental motor area of H MMD and right pre-/postcentral gyrus and right inferior temporal gyrus of I MMD. This study not only sheds light on the decayed critical dynamics of MMD in both the resting and task states for the first time but also proposes several EEG and fMRI features to identify its two subtypes.

Effects of exercise programs on neuroelectric dynamics in drug addiction.

Exercise interventions have been considered to be an effective treatment for drug addiction. However, there is little dirct evidence that exercise affects brain activity in individuals afftected by drug addiction. Therefore, the aim of the present study was to investigate the effects of different exercise programs on detoxification. Cognitive recovery with 64-channel electroencephalography (EEG) recordings was obtained before and after three months of daily aerobic and anaerobic exercise. A total of 63 subjects with methamphetamine addiction were recruited and randomly divided into three groups for cognitive study in four behavioral states: an anaerobic resistance treatment group, an aerobic cycling treatment group and a control group. In addition, four behavioral states were examined: eyes-closed and eyes-open resting states, and exploratory behavior states following either drug- or neutral-cue exposure. Over a 12-week period,the alpha block ratio in the control group showed a slight decrease, while clear increases were observed in the resistance exercise and cycling treatment groups, particularly under the frontal and temporal regions in the eyes-open and drug-cue conditions. The major EEG activity frequency in the resistance treatment group during the drug-cue behavior task decreased compared with the frequencies of the cycling exercise and control groups. Meanwhile, the power of higher brain rhythms in the resistance treatment group was increased. Finally, the brain alpha wave left-lateralization index from EEG recording sites, F1-F2, in the resistance and cycling treatment groups under the eyes-closed condition positively decreased, while the control groups only showed slight decreases. Taken together, these results suggest that different types of exercise may induce distince and different positive therapeutic effects to facilitate detoxification.

Human visual search follows a suboptimal Bayesian strategy revealed by a spatiotemporal computational model and experiment.

There is conflicting evidence regarding whether humans can make spatially optimal eye movements during visual search. Some studies have shown that humans can optimally integrate information across fixations and determine the next fixation location, however, these models have generally ignored the control of fixation duration and memory limitation, and the model results do not agree well with the details of human eye movement metrics. Here, we measured the temporal course of the human visibility map and performed a visual search experiment. We further built a continuous-time eye movement model that considers saccadic inaccuracy, saccadic bias, and memory constraints. We show that this model agrees better with the spatial and temporal properties of human eye movements and predict that humans have a memory capacity of around eight previous fixations. The model results reveal that humans employ a suboptimal eye movement strategy to find a target, which may minimize costs while still achieving sufficiently high search performance.

Mental Calculation Drives Reliable and Weak Distant Connectivity While Music Listening Induces Dense Local Connectivity.

Mathematical calculation usually requires sustained attention to manipulate numbers in the mind, while listening to light music has a relaxing effect on the brain. The differences in the corresponding brain functional network topologies underlying these behaviors remain rarely known. Here, we systematically examined the brain dynamics of four behaviors (resting with eyes closed and eyes open, tasks of music listening and mental calculation) using 64-channel electroencephalogram (EEG) recordings and graph theory analysis. We developed static and dynamic minimum spanning tree (MST) analysis method and demonstrated that the brain network topology under mental calculation is a more line-like structure with less tree hierarchy and leaf fraction; however, the hub regions, which are mainly located in the frontal, temporal and parietal regions, grow more stable over time. In contrast, music-listening drives the brain to exhibit a highly rich network of star structure, and the hub regions are mainly located in the posterior regions. We then adopted the dynamic dissimilarity of different MSTs over time based on the graph Laplacian and revealed low dissimilarity during mental calculation. These results suggest that the human brain functional connectivity of individuals has unique dynamic diversity and flexibility under various behaviors. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-021-00027-w.

Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain.

Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

Reconfigured functional network dynamics in adult moyamoya disease: a resting-state fMRI study.

Treatment of vascular cognitive impairment (VCI) in adult moyamoya disease (MMD) is still unclear because of its unveiled neural synchronization. This study introduced a dynamic measurement of connectivity number entropy (CNE) to characterize both spatial and temporal dimensions of network interactions. Fifty-one patients with MMD were recruited (27 with VCI and 24 with intact cognition), as well as 26 normal controls (NCs). Static network properties were first examined to confirm its aberrance in MMD with VCI. Then, the dynamic measurement of CNE was used to detect the deteriorated flexibility of MMD with VCI at global, regional, and network levels. Finally, dynamic reconfiguration of flexible and specialized regions was traced across the three groups. Graph theory analysis indicated that MMD exhibited "small-world" network topology but presented with a deviating pattern from NC as the disease progressed in all topologic metrics of integration, segregation, and small-worldness. Subsequent dynamic analysis showed significant CNE differences among the three groups at both global (p < 0.001) and network levels (default mode network, p = 0.004; executive control network, p = 0.001). Specifically, brain regions related to key aspects of information processing exhibited significant CNE changes across the three groups. Furthermore, CNE values of both flexible and specialized regions changed with impaired cognition. This study not only sheds light on both the static and dynamic organizational principles behind network changes in adult MMD for the first time, but also provides a new methodologic viewpoint to acquire more knowledge of its pathophysiology and treatment direction.

The Impact of Frequency Scale on the Response Sensitivity and Reliability of Cortical Neurons to 1/fß Input Signals.

What type of principle features intrinsic inside of the fluctuated input signals could drive neurons with the maximal excitations is one of the crucial neural coding issues. In this article, we examined both experimentally and theoretically the cortical neuronal responsivity (including firing rate and spike timing reliability) to input signals with different intrinsic correlational statistics (e.g., white-type noise, showed 1/f0 power spectrum, pink noise 1/f, and brown noises 1/f2) and different frequency ranges. Our results revealed that the response sensitivity and reliability of cortical neurons is much higher in response to 1/f noise stimuli with long-term correlations than 1/f0 with short-term correlations for a broad frequency range, and also higher than 1/f2 for all frequency ranges. In addition, we found that neuronal sensitivity diverges to opposite directions for 1/f noise comparing with 1/f0 white noise as a function of cutoff frequency of input signal. As the cutoff frequency is progressively increased from 50 to 1,000 Hz, the neuronal responsiveness increased gradually for 1/f noise, while decreased exponentially for white noise. Computational simulations of a general cortical model revealed that, neuronal sensitivity and reliability to input signal statistics was majorly dominated by fast sodium inactivation, potassium activation, and membrane time constants.

Loss of homeoprotein Msx1 and Msx2 leading to athletic and kinematic impairment related to the increasing neural excitability of neurons in aberrant neocortex in mice.

Although homeoproteins Msx1 and Msx2, the cell-specific transcription regulators, have been proven to play multiple roles in the embryogenesis of bone, muscle and tooth, the functions and mechanisms of Msx1 and Msx2 in the development of the central nervous system of mice after birth are not clear because of the death of Msx1 and Msx1/2 germline-deleted embryo at late gestation of mouse. In current research, Nestin-Cre mice was introduced to generate the central nervous system-specific knockout mice (Nestin-Cre;Msx1,Msx2fl/fl). We found that besides the falling of the body mass and the brain volume, the cortical tissue sections and staining showed the decreasing thickness of layer II-IV and declining number of vertebral cells in layer V resulting from Msx1/2 deletion. In addition, electrophysiological tests revealed the aberrant action potential parameters of deep pyramidal neurons in Nestin-Cre;Msx1,2 fl/fl mice, which may be related with the ethology impairment displayed in further experiments. We discovered Nestin-Cre;Msx1,2 fl/fl mice had severe impairment in their athletic ability and kinematic learning ability in rotate test, and exhibited hyperactivity in open-field test. Above all, our results revealed that deletion of homeoproteins Msx1 and Msx2 could lead to behavioral disorders and suggested that Msx1 and Msx2 played a crucial role in regulating the development and function of the neocortex. In addition, our current research provided a new mouse model for understanding the pathogenesis of human central nervous system disease.

Synaptic Excitatory-Inhibitory Balance Underlying Efficient Neural Coding.

Both theoretical and experimental evidence indicate that synaptic excitation and inhibition in the cerebral cortex are well-balanced during the resting state and sensory processing. Here, we briefly summarize the evidence for how neural circuits are adjusted to achieve this balance. Then, we discuss how such excitatory and inhibitory balance shapes stimulus representation and information propagation, two basic functions of neural coding. We also point out the benefit of adopting such a balance during neural coding. We conclude that excitatory and inhibitory balance may be a fundamental mechanism underlying efficient coding.

Therapeutic effects of targeted nursing interventions combined with auricular-plaster therapy on anxiety level and life quality of Hepatitis B patients.

Mood disorders are common problems in patients with chronic hepatitis B virus (HBV) infection, most clinical treatment focus on anti-viral and anti-fibrosis rather than taking care of mood disorders. In the past decades, we have developed a Chinese medicine treatment method together with nursing intervention, which shows a positive treatment effect on patients. 158 cases of hepatitis B patients were randomly divided into one control group (78 cases), and one observation group (80 cases). The patients in control group received hepatology nursing, liver protecting and transaminase lowering medicine, and ear acupoint bean pressing treatment. In addition to the nursing and treatment as the control group, the patients in observation group were given targeted nursing interventions, including psychological intervention, emotional intervention, cognitive intervention, and systematic family and community support intervention. The anxiety level and sleep quality of patients in both groups were compared. The improvement of hepatic indexes was checked and life qualities in both groups were also compared. Compared to the control group, the patients in the observation group provided have statistically significant mprovement on anxiety control, sleep quality, and hepatic indexes changes (P<0.05). The observation group also showed remarkably better life quality scores (GQLI-64) than the control group (P<0.01). This research confirmed that targeted nursing intervention coupled with ear acupoint bean pressing showed effective improvement on the anxiety control and sleep quality of chronic hepatic B patients, and demonstrated better hepatic index recovery. Patients in the observation group also have higher life quality scores than the control group.