The neurophysiological mechanisms of medial prefrontal-perirhinal cortex circuit mediating temporal order memory decline in early stage of AD rats.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.

Brain waves and landscape settings: emotional responses to attractiveness.

Neuro-architecture is a specific branch of architecture that studies how the physical environment can change our mental processes and influence our behaviors. One of the main purposes of this field is to use changes in brain activities as a measure to quantify attractiveness of the landscapes. In this study, we investigated how changes in elements of attractiveness influence ones' emotional perception and present the related pattern of changes in brain activities. Therefore, we implied five elements of attractiveness including mystery, visual openness, landscape or greenness, walkability, and social interaction using the Delphi method. Then, we made changes in each element separately to make the landscape more attractive and assessed their effects on a group of young adults. We used the self-assessment manikin questionnaire to measure the participants' emotional perception while the participants' brain activities were recorded using a 32-channel EEG while exposed to the landscape images. The results showed that changes in attractive elements of the landscape could significantly improve ones' emotional perception of the landscape. In addition, these changes are perceived by changing the oscillatory pattern of brain activities. We hope these findings could shed a light to use of neural markers in measurement of place attractiveness.

cTBS to Right DLPFC Modulates Physiological Correlates of Conflict Processing: Evidence from a Stroop task.

Conflict typically occurs when goal-directed processing competes with more automatic responses. Though previous studies have highlighted the importance of the right dorsolateral prefrontal cortex (rDLPFC) in conflict processing, its causal role remains unclear. In the current study, the behavioral experiment, the continuous theta burst stimulation (cTBS), and the electroencephalography (EEG) were combined to explore the effects of behavioral performance and physiological correlates during conflict processing, after the cTBS over the rDLPFC and vertex (the control condition). Twenty-six healthy participants performed the Stroop task which included congruent and incongruent trials. Although the cTBS did not induce significant changes in the behavioral performance, the cTBS over the rDLPFC reduced the Stroop effects of conflict monitoring-related frontal-central N2 component and theta oscillation, and conflict resolution-related parieto-occipital alpha oscillation, compared to the vertex stimulation. Moreover, a significant hemispheric difference in alpha oscillation was exploratively observed after the cTBS over the rDLPFC. Interestingly, we found the rDLPFC stimulation resulted in significantly reduced Stroop effects of theta and gamma oscillation after response, which may reflect the adjustment of cognitive control for the next trial. In conclusion, our study not only demonstrated the critical involvement of the rDLPFC in conflict monitoring, conflict resolution processing, and conflict adaptation but also revealed the electrophysiological mechanism of conflict processing mediated by the rDLPFC.

The neural oscillations in delta- and theta-bands contribute to divided attention in audiovisual integration.

One of key mechanisms implicated in multisensory processing is neural oscillations in distinct frequency band. Many studies explored the modulation of attention by recording the electroencephalography signals when subjects attended one modality, and ignored the other modality input. However, when attention is directed toward one modality, it may be not always possible to shut out completely inputs from a different modality. Since many situations require division of attention between audition and vision, it is imperative to investigate the neural mechanisms underlying processing of concurrent auditory and visual sensory streams. In the present study, we designed a task of audiovisual semantic discrimination, in which the subjects were asked to share attention to both auditory and visual stimuli. We explored the contribution of neural oscillations in lower-frequency to the modulation of divided attention on audiovisual integration. Our results implied that theta-band activity contributes to the early modulation of divided attention, and delta-band activity contributes to the late modulation of divided attention to audiovisual integration. Moreover, the fronto-central delta- and theta-bands activity is likely a marker of divided attention in audiovisual integration, and the neural oscillation on delta- and theta-bands is conducive to allocating attention resources to dual-tasking involving task-coordinating abilities.

Neural Oscillations and Multisensory Processing.

Neural oscillations play a role in sensory processing by coordinating synchronized neuronal activity. Synchronization of gamma oscillations is engaged in local computation of feedforward signals and synchronization of alpha-beta oscillations is engaged in feedback processing over long-range areas. These spatially and spectrally segregated bi-directional signals may be integrated by a mechanism of cross-frequency coupling. Synchronization of neural oscillations has also been proposed as a mechanism for information integration across multiple sensory modalities. A transient stimulus or rhythmic stimulus from one modality may lead to phase alignment of ongoing neural oscillations in multiple sensory cortices, through a mechanism of cross-modal phase reset or cross-modal neural entrainment. Synchronized activities in multiple sensory cortices are more likely to boost stronger activities in downstream areas. Compared to synchronized oscillations, asynchronized oscillations may impede signal processing, and may contribute to sensory selection by setting the oscillations in the target-related cortex and the oscillations in the distractor-related cortex to opposite phases.

Frequency-Specific Modulation of Slow-Wave Neural Oscillations via Weak Exogeneous Extracellular Fields Reveals a Resonance Pattern.

Single neurons often exhibit endogenous oscillatory activity centered around a specific frequency band. Transcranial alternating current stimulation (tACS) can generate a weak oscillating extracellular field in the brain that causes subthreshold membrane potential shifts that can affect spike timing at the single neuron level. Many studies have now shown that the endogenous oscillation can be entrained when the tACS frequency matches that of the exogenous extracellular field. However, the effect of tACS on the amplitude of the endogenous oscillation has been less well studied. We investigated this by using exogenous extracellular fields to modulate slow-wave neural oscillations in the ketamine anesthetized male Wistar rat. We applied spatially broad extracellular fields of different frequencies while recording spiking activity from single neurons. The effect of the exogenous extracellular field on the slow-wave neural oscillation amplitude (NOA) followed a resonance pattern: large modulations were observed when the extracellular frequency matched the endogenous frequency of the neuron, while extracellular fields with frequencies far away from the endogenous frequency had little effect. No changes in spike-rate were observed for any of the extracellular fields applied. Our results demonstrate that in addition to the previously reported entrainment and Arnold tongue patterns, weak oscillating extracellular fields modulate the amplitude of the endogenous neural oscillation without any changes in spike-rate, and that this modulation follows a frequency-specific resonance pattern.SIGNIFICANCE STATEMENT Neural activity often oscillates around specific endogenous frequencies. Transcranial alternating current stimulation (tACS) is a neuromodulation method which biases spike-times and alter endogenous activity. Most tACS studies focus on entrainment effects which occur when tACS and endogenous neural frequencies are matched. In this study we varied the frequency of the applied tACS and investigated its effect on amplitude of the neural oscillation. Our results revealed a resonance pattern where tACS frequencies close to the endogenous frequency caused an increase in neural oscillation amplitude (NOA) specifically at the applied tACS frequency, while applying tACS frequencies farther away caused little or no change in NOA. Furthermore, applying tACS at differing frequencies caused the amplitude of the neural oscillation at the prestimulation endogenous frequency to decrease.

Human MECP2 transgenic rats show increased anxiety, severe social deficits, and abnormal prefrontal neural oscillation stability.

Methylated CpG binding protein 2 (MeCP2) plays an important role in the development and normal function of the neural system. Abnormally high expression of MECP2 leads to a subtype of autism called MECP2 duplication syndrome and MECP2 is considered one of the key pathogenic genes for autism spectrum disorders. However, the effect of MECP2 overexpression on neural activity is still not fully understood. Thus, transgenic (TG) animals that abnormally overexpress MeCP2 are important disease models in research on neurological function and autism. To create an animal model with a stronger and more stable autism phenotype, this study established a human MECP2 TG rat model and evaluated its movement ability, anxiety, and social behavior through behavioral tests. The results showed that MECP2 TG rats had an abnormally increased anxiety phenotype and social deficits in terms of abnormal social approach and social novelty preference, but no movement disorder. These autism-like behavioral phenotypes suggest that human MECP2 TG rats are suitable models for studying autism as they show more severe social deficit phenotypes and without interference from movement disorders affecting other phenotypes, which is an issue for mouse models with MECP2 duplication. In addition, this study performed preliminary exploration of the influence of the human MECP2 transgene on neural oscillation stability of the medial prefrontal cortex (mPFC), which is an important brain region for social interactions. Oscillation stability in MECP2 TG rats showed abnormal responses to social conditions. Overall, the results of this study provide a new research tool for understanding the mechanism of social impairment and treatment of autism. The results also provide evidence for the influence of MECP2 duplication on mPFC neural activity.

Ketamine-induced 1-Hz oscillation of spontaneous neural activity is not directly visible in the hemodynamics.

The extent to which resting-state hemodynamics reflects the underlying neural activity is still under debate. Especially in the delta frequency band (0.5-4 Hz), it is unclear whether the hemodynamics can directly track the dynamics of underlying neural activity. Based on a recent report showing that ketamine administration induced a 1-Hz neural activity oscillation in the retrosplenial cortex, we conducted simultaneous recordings of the calcium signal and hemodynamics in mice and examined whether the hemodynamics tracked the oscillatory neural activity. Although we observed that the oscillation induced by ketamine appeared in the calcium signal, no sign of oscillation was detected in the simultaneously recorded hemodynamics. Consistently, there was a notable decrease in the correlation between simultaneously recorded calcium signal and hemodynamics. However, on a much longer time scale (10-60 min), we unexpectedly observed an ultraslow increase of hemodynamic signals specifically in the same cortical region exhibiting the neural activity oscillation. These results indicated that hemodynamics cannot track the 1-Hz oscillation in neural activity, although the presence of neural activity oscillation was detectable on a longer timescale. Such ultraslow hemodynamics may be useful for detecting abnormal neural activity induced by psychotic drugs or mental disorders.

Long-Term Flexible Neural Interface for Synchronous Recording of Cross-Regional Sensory Processing along the Olfactory Pathway.

Humans perceive the world through five senses, of which olfaction is the oldest evolutionary sense that enables the detection of chemicals in the external environment. Recent progress in bioinspired electronics has boosted the development of artificial sensory systems. Here, a biohybrid olfactory system is proposed by integrating living mammals with implantable flexible neural electrodes, to employ the outstanding properties of mammalian olfactory system. In olfactory perception, the peripheral organ-olfactory epithelium (OE) projects axons into the olfactory relay station-olfactory bulb (OB). The olfactory information encoded in the neural activity is recorded from both OE and OB simultaneously using flexible neural electrodes. Results reveal that spontaneous slow oscillations (<12 Hz) in both OE and OB closely follow respiration. This respiration-locked rhythm modulates the amplitude of fast oscillations (>20 Hz), which are associated with odor perception. Further, by extracting the characteristics of odor-evoked oscillatory signals, responses of different odors are identified and classified with 80% accuracy. This study demonstrates for the first time that the flexible electrode enables chronic stable electrophysiological recordings of the peripheral and central olfactory system in vivo. Overall, the method provides a novel neural interface for olfactory biosensing and cognitive processing.

Characterization of the planarian surface electroencephalogram.

BACKGROUND: Despite large morphological differences between the nervous systems of lower animals and humans, striking functional similarities have been reported. However, little is known about how these functional similarities translate to cognitive similarities. As a first step towards studying the cognitive abilities of simple nervous systems, we here characterize the ongoing electrophysiological activity of the planarian Schmidtea mediterranea. One previous report using invasive microelectrodes describes that the ongoing neural activity is characterized by a 1/fx power spectrum with the exponent 'x' of the power spectrum close to 1. To extend these findings, we aimed to establish a recording protocol to measure ongoing neural activity safely and securely from alive and healthy planarians under different lighting conditions using non-invasive surface electrodes. RESULTS: As a replication and extension of the previous results, we show that the ongoing neural activity is characterized by a 1/fx power spectrum, that the exponent 'x' in living planarians is close to 1, and that changes in lighting induce changes in neural activity likely due to the planarian photophobia. CONCLUSIONS: We confirm the existence of continuous EEG activity in planarians and show that it is possible to noninvasively record this activity with surface wire electrodes. This opens up broad possibilities for continuous recordings across longer intervals, and repeated recordings from the same animals to study cognitive processes.

Rhythmic activation of excitatory neurons in the mouse frontal cortex improves the prefrontal cortex-mediated cognitive function.

The prefrontal cortex (PFC) plays essential roles in cognitive processes. Previous studies have suggested the layer and the cell type-specific activation for cognitive enhancement. However, the mechanism by which a temporal pattern of activation affects cognitive function remains to be elucidated. Here, we investigated whether the specific activation of excitatory neurons in the superficial layers mainly in the PFC according to a rhythmic or nonrhythmic pattern could modulate the cognitive functions of normal mice. We used a C128S mutant of channelrhodopsin 2, a step function opsin, and administered two light illumination patterns: (i) alternating pulses of blue and yellow light for rhythmic activation or (ii) pulsed blue light only for nonrhythmic activation. Behavioral analyses were performed to compare the behavioral consequences of these two neural activation patterns. The alternating blue and yellow light pulses, but not the pulsed blue light only, significantly improved spatial working memory and social recognition without affecting motor activity or the anxiety level. These results suggest that the rhythmic, but not the nonrhythmic, activation could enhance cognitive functions. This study indicates that not only the population of neurons that are activated but also the pattern of activation plays a crucial role in the cognitive enhancement.

Cortical mu rhythms during action and passive music listening.

Brain systems supporting body movement are active during music listening in the absence of overt movement. This covert motor activity is not well understood, but some theories propose a role in auditory timing prediction facilitated by motor simulation. One question is how music-related covert motor activity relates to motor activity during overt movement. We address this question using scalp electroencephalogram by measuring mu rhythms-cortical field phenomena associated with the somatomotor system that appear over sensorimotor cortex. Lateralized mu enhancement over hand sensorimotor cortex during/just before foot movement in foot versus hand movement paradigms is thought to reflect hand movement inhibition during current/prospective movement of another effector. Behavior of mu during music listening with movement suppressed has yet to be determined. We recorded 32-channel EEG (n = 17) during silence without movement, overt movement (foot/hand), and music listening without movement. Using an independent component analysis-based source equivalent dipole clustering technique, we identified three mu-related clusters, localized to left primary motor and right and midline premotor cortices. Right foot tapping was accompanied by mu enhancement in the left lateral source cluster, replicating previous work. Music listening was accompanied by similar mu enhancement in the left, as well as midline, clusters. We are the first, to our knowledge, to report, and also to source-resolve, music-related mu modulation in the absence of overt movements. Covert music-related motor activity has been shown to play a role in beat perception (Ross JM, Iversen JR, Balasubramaniam R. Neurocase 22: 558-565, 2016). Our current results show enhancement in somatotopically organized mu, supporting overt motor inhibition during beat perception.NEW & NOTEWORTHY We are the first to report music-related mu enhancement in the absence of overt movements and the first to source-resolve mu activity during music listening. We suggest that music-related mu modulation reflects overt motor inhibition during passive music listening. This work is relevant for the development of theories relating to the involvement of covert motor system activity for predictive beat perception.

Target enhancement or distractor suppression? Functionally distinct alpha oscillations form the basis of attention.

Recent advances in attention research have been propelled by the debate on target enhancement versus distractor suppression. A predominant neural correlate of attention is the modulation of alpha oscillatory power (~10 Hz), which signifies shifts of attention in time, space and between sensory modalities. However, the underspecified functional role of alpha oscillations limits the progress of tracking down the neurocognitive basis of attention. In this short opinion article, we review and critically examine a synthesis of three conceptual and methodological aspects that are indispensable for a mechanistic understanding of the role of alpha oscillations for attention. (a) Precise mapping of the anatomical source and the temporal response profile of neural signals reveals distinct alpha oscillatory processes that implement facilitatory versus suppressive components of attention. (b) A testable framework enables unanimous association of alpha modulation with either target enhancement or different forms of distractor suppression (active vs. automatic). (c) Linking anatomically specified alpha oscillations to behavior reveals the causal nature of alpha oscillations for attention. The three reviewed aspects substantially enrich study design, data analysis and interpretation of results to achieve the goal of understanding how anatomically specified and functionally relevant neural oscillations contribute to the implementation of facilitatory versus suppressive components of attention.

Spontaneous alpha-band amplitude predicts subjective visibility but not discrimination accuracy during high-level perception.

Near-threshold perception is a paradigm case of awareness diverging from reality - the perception of an unchanging stimulus can vacillate from undetected to clearly perceived. The amplitude of low-frequency brain oscillations - particularly in the alpha-band (8-13 Hz) - has emerged as a reliable predictor of trial-to-trial variability in perceptual decisions based on simple, low-level stimuli. Here, we addressed the question of how spontaneous oscillatory amplitude impacts subjective and objective aspects of perception using high-level visual stimuli. Human observers completed a near-threshold face/house discrimination task with subjective visibility ratings while electroencephalograms (EEG) were recorded. Using single-trial multiple regression analysis, we found that spontaneous fluctuations in prestimulus alpha-band amplitude were negatively related to visibility judgments but did not predict trial-by-trial accuracy. These results extend previous findings that indicate that strong prestimulus alpha diminishes subjective perception without affecting the accuracy or sensitivity (d') of perceptual decisions into the domain of high-level perception.

Alternations in neural oscillation related to attention network reveal influence of indoor toluene on cognition at low concentration.

Despite accumulative literature reporting negative impacts of high-concentration toluene, cognitive effects of toluene at low concentration are still unclear. Twenty-two healthy college students were exposed in a closed environmental chamber to investigate the influence of indoor toluene on cognitive performance and brain activity. During each toluene exposure condition (0 ppb, 17.5 ppb, 35 ppb, and 70 ppb), attention network test and electroencephalogram (EEG) recording were synchronously performed after 4-hour toluene exposure. Characteristic neural oscillation patterns in three attention networks were compared between four groups. The statistical analyses indicated that short-term exposure to toluene had no significant impact on behavioral performance of attention network. However, there was a significant increase in the power of theta and alpha band of executive network and orienting network in the whole brain, especially in frontal region when exposed to toluene. Besides, no significant difference was observed in alerting network. The alternations in neural oscillation demonstrated that more effort was required to accomplish the same tasks when exposed to toluene. The present study revealed that short-term exposure to toluene affected brain activity of attention network even at low concentration, which provided a theoretical basis for the development of safer evaluation methods and standards in the future.

Reinvestigation of the Psychological Mechanisms of Construction Experience on Hazard Recognition Performance.

OBJECTIVE: The study aimed to reinvestigate psychological mechanisms of the influence of construction workers' experience on hazard recognition performance, with signal detection theory (SDT) and electroencephalogram (EEG) readings. BACKGROUND: Existing evidence regarding the effect of experience on hazard recognition performance in the construction industry remains inconsistent. Behavior-wise, identification of dominant hazard recognition factors (sensitivity or response bias, or both) would help determine appropriate training strategies to improve hazard recognition. In terms of neuro-responses, induced gamma-band activity was expected to reflect the cognitive functions mediating the psychological effects of experience. METHOD: Seventy-seven construction workers participated in a predesigned hazard recognition task, in which participants judged whether a hazard was present from a series of construction scenario pictures. We computed and compared the sensitivity and response bias of SDT and time-frequency representations of recorded EEG signals of the two experience-level groups. RESULTS: Novice workers had higher hazard recognition rates. Behavior-wise, novices were more sensitive than more experienced workers. Compared with experienced workers, novices showed stronger gamma-band difference power (hazardous minus safe) in the left frontal and right posterior parietal areas during the hazard recognition process. CONCLUSION: Novices performed better at hazard recognition, indicating their sensitivity to the hazards without a clear difference in response bias. Based on the EEG data, novices' sensitivity may be attributed to more efficient working memory and attentional control. APPLICATION: There is a need for continuous refreshment of hazard recognition skills for experienced workers for safety interventions.

Multifrequency Hebbian plasticity in coupled neural oscillators.

We study multifrequency Hebbian plasticity by analyzing phenomenological models of weakly connected neural networks. We start with an analysis of a model for single-frequency networks previously shown to learn and memorize phase differences between component oscillators. We then study a model for gradient frequency neural networks (GrFNNs) which extends the single-frequency model by introducing frequency detuning and nonlinear coupling terms for multifrequency interactions. Our analysis focuses on models of two coupled oscillators and examines the dynamics of steady-state behaviors in multiple parameter regimes available to the models. We find that the model for two distinct frequencies shares essential dynamical properties with the single-frequency model and that Hebbian learning results in stronger connections for simple frequency ratios than for complex ratios. We then compare the analysis of the two-frequency model with numerical simulations of the GrFNN model and show that Hebbian plasticity in the latter is locally dominated by a nonlinear resonance captured by the two-frequency model.

Current findings and perspectives on aberrant neural oscillations in schizophrenia.

There is now consistent evidence that neural oscillation at low- and high-frequencies constitute an important aspect of the pathophysiology of schizophrenia. Specifically, impaired rhythmic activity may underlie the deficit to generate coherent cognition and behavior, leading to the characteristic symptoms of psychosis and cognitive deficits. Importantly, the generating mechanisms of neural oscillations are relatively well-understood and thus enable the targeted search for the underlying circuit impairments and novel treatment targets. In the following review, we will summarize and assess the evidence for aberrant rhythmic activity in schizophrenia through evaluating studies that have utilized Electro/Magnetoencephalography to examine neural oscillations during sensory and cognitive tasks as well as during resting-state measurements. These data will be linked to current evidence from post-mortem, neuroimaging, genetics, and animal models that have implicated deficits in GABAergic interneurons and glutamatergic neurotransmission in oscillatory deficits in schizophrenia. Finally, we will highlight methodological and analytical challenges as well as provide recommendations for future research.

Effect of θ­Î³ neural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats

Objective: To investigate the effects of θ­Î³ neural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats. Methods: According to the results of Y maze shock avoidance training, the rats were divided into fast avoidance response group and general avoidance response group. Using endogenous θ­Î³ neural oscillations from the fast avoidance response rats to perform deep brain stimulation in vivo to the left and right hippocampal CA3 region of rats with general avoidance response, then the spatial cognition was tested by Y maze shock avoidance training. The variation of θ oscillation and low-γ neural oscillation phase-amplitude coupling (PAC) in CA3 area was analyzed by wavelet packet extraction technique. Western blotting was used to detect the expression of N-methyl-D-aspartate receptor 2B subunit (NR2B) and postsynaptic density(PSD)-95 in hippocampal tissues of rats to explore its molecular mechanism. Results: Compared with the general avoidance response rats, the days to reach the standard, the training number, the correct response time and the error reaction number in simulated stimulus avoidance response rats were significantly reduced, but the correct response rate was significantly increased (all P<0.01); the θ­Î³ neural oscillations PAC in the hippocampal CA3 region in the simulated stimulus avoidance response rats (3­5 Hz and 30­34, 38­42, 44­48 Hz; 5­7 Hz and 42­46, 44­48, 54­58 Hz) were significantly higher than that in the general avoidance response rats (all P<0.05). Meanwhile, the protein expressions of NR2B and PSD-95 in hippocampal tissues were significantly increased (both P<0.05) in simulated stimulus avoidance response rats. Conclusion: The spatial cognition of normal avoidance response rats can be significantly improved by endogenous θ­Î³ neural oscillation stimulation to hippocampal CA3 region, which may be caused by the enhancement of synaptic plasticity mediated by NR2B and PSD-95.

Functional dynamics of thalamic local field potentials correlate with modulation of neuropathic pain.

Understanding the functional dynamics of neural oscillations in the sensory thalamus is essential for elucidating the perception and modulation of neuropathic pain. Local field potentials were recorded from the sensory thalamus of twelve neuropathic pain patients. Single and combinational neural states were defined by the activity state of a single or paired oscillations. Relationships between the duration or occurrence rate of neural state and pre-operative pain level or pain relief induced by deep brain stimulation were evaluated. Results showed that the occurrence rate of the single neural state of low-beta oscillation was significantly correlated with pain relief. The duration and occurrence rate of combinational neural states of the paired low-beta with delta, theta, alpha, high-beta or low-gamma oscillations were more significantly correlated with pain relief than the single neural states. Moreover, these significant combinational neural states formed a local oscillatory network with low-beta oscillation as a key node. The results also showed correlations between measures of combinational neural states and subjective pain level as well. The duration of combinational neural states of paired alpha with delta or theta oscillations and the occurrence rate of neural states of the paired delta with low-beta or low-gamma oscillations were significantly correlated with pre-operative pain level. In conclusion, this study revealed that the integration of oscillations and the functional dynamics of neural states were differentially involved in modulation and perception of neuropathic pain. The functional dynamics could be biomarkers for developing neural state-dependent deep brain stimulation for neuropathic pain.