Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

BACKGROUND: Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). METHOD: Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. RESULTS: euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). CONCLUSIONS: Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Development of a rule-based automatic five-sleep-stage scoring method for rats.

BACKGROUND: Sleep problem or disturbance often exists in pain or neurological/psychiatric diseases. However, sleep scoring is a time-consuming tedious labor. Very few studies discuss the 5-stage (wake/NREM1/NREM2/transition sleep/REM) automatic fine analysis of wake-sleep stages in rodent models. The present study aimed to develop and validate an automatic rule-based classification of 5-stage wake-sleep pattern in acid-induced widespread hyperalgesia model of the rat. RESULTS: The overall agreement between two experts' consensus and automatic scoring in the 5-stage and 3-stage analyses were 92.32% (κ = 0.88) and 94.97% (κ = 0.91), respectively. Standard deviation of the accuracy among all rats was only 2.93%. Both frontal-occipital EEG and parietal EEG data showed comparable accuracies. The results demonstrated the performance of the proposed method with high accuracy and reliability. Subtle changes exhibited in the 5-stage wake-sleep analysis but not in the 3-stage analysis during hyperalgesia development of the acid-induced pain model. Compared with existing methods, our method can automatically classify vigilance states into 5-stage or 3-stage wake-sleep pattern with a promising high agreement with sleep experts. CONCLUSIONS: In this study, we have performed and validated a reliable automated sleep scoring system in rats. The classification algorithm is less computation power, a high robustness, and consistency of results. The algorithm can be implanted into a versatile wireless portable monitoring system for real-time analysis in the future.

Portable wireless neurofeedback system of EEG alpha rhythm enhances memory.

BACKGROUND: Effect of neurofeedback training (NFT) on enhancement of cognitive function or amelioration of clinical symptoms is inconclusive. The trainability of brain rhythm using a neurofeedback system is uncertainty because various experimental designs are used in previous studies. The current study aimed to develop a portable wireless NFT system for alpha rhythm and to validate effect of the NFT system on memory with a sham-controlled group. METHODS: The proposed system contained an EEG signal analysis device and a smartphone with wireless Bluetooth low-energy technology. Instantaneous 1-s EEG power and contiguous 5-min EEG power throughout the training were developed as feedback information. The training performance and its progression were kept to boost usability of our device. Participants were blinded and randomly assigned into either the control group receiving random 4-Hz power or Alpha group receiving 8-12-Hz power. Working memory and episodic memory were assessed by the backward digital span task and word-pair task, respectively. RESULTS: The portable neurofeedback system had advantages of a tiny size and long-term recording and demonstrated trainability of alpha rhythm in terms of significant increase of power and duration of 8-12 Hz. Moreover, accuracies of the backward digital span task and word-pair task showed significant enhancement in the Alpha group after training compared to the control group. CONCLUSIONS: Our tiny portable device demonstrated success trainability of alpha rhythm and enhanced two kinds of memories. The present study suggest that the portable neurofeedback system provides an alternative intervention for memory enhancement.

Neurofeedback training of EEG alpha rhythm enhances episodic and working memory.

Neurofeedback training (NFT) of the alpha rhythm has been used for several decades but is still controversial in regards to its trainability and effects on working memory. Alpha rhythm of the frontoparietal region are associated with either the intelligence or memory of healthy subjects and are also related to pathological states. In this study, alpha NFT effects on memory performances were explored. Fifty healthy participants were recruited and randomly assigned into a group receiving a 8-12-Hz amplitude (Alpha) or a group receiving a random 4-Hz amplitude from the range of 7 to 20 Hz (Ctrl). Three NFT sessions per week were conducted for 4 weeks. Working memory was assessed by both a backward digit span task and an operation span task, and episodic memory was assessed using a word pair task. Four questionnaires were used to assess anxiety, depression, insomnia, and cognitive function. The Ctrl group had no change in alpha amplitude and duration. In contrast, the Alpha group showed a progressive significant increase in the alpha amplitude and total alpha duration of the frontoparietal region. Accuracies of both working and episodic memories were significantly improved in a large proportion of participants of the Alpha group, particularly for those with remarkable alpha-amplitude increases. Scores of four questionnaires fell in a normal range before and after NFT. The current study provided supporting evidence for alpha trainability within a small session number compared with that of therapy. The findings suggested the enhancement of working and episodic memory through alpha NFT. Hum Brain Mapp 37:2662-2675, 2016. © 2016 Wiley Periodicals, Inc.

Distinct Somatic Discrimination Reflected by Laser-Evoked Potentials Using Scalp EEG Leads.

Discrimination is an important function in pain processing of the somatic cortex. The involvement of the somatic cortex has been studied using equivalent dipole analysis and neuroimaging, but the results are inconsistent. Scalp electroencephalography (EEG) can reflect functional changes of particular brain regions underneath a lead. However, the responses of EEG leads close to the somatic cortex in response to pain have not been systematically evaluated. The present study applied CO2 laser stimulation to the dorsum of the left hand. Laser-evoked potentials (LEPs) of C4, T3, and T4 leads and pain ratings in response to four stimulus intensities were analyzed. LEPs started earlier at the C4 and T4 leads. The onset latency and peak latency of LEPs for C4 and T4 leads were the same. Only 10 of 22 subjects (45 %) presented equivalent current dipoles within the primary somatosensory or motor cortices. LEP amplitudes of these leads increased as stimulation intensity increased. The stimulus-response pattern of the C4 lead was highly correlated with pain rating. In contrast, an S-shaped stimulus-response curve was obtained for the T3 and T4 leads. The present study provides supporting evidence that particular scalp channels are able to reflect the functional characteristics of their underlying cortical areas. Our data strengthen the clinical application of somatic-cortex-related leads for pain discrimination.

Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury.

Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616.

The zona incerta modulates spontaneous spike-wave discharges in the rat.

The contribution of the zona incerta (ZI) of the thalamus on spike-wave discharges (SWDs) was investigated. Chronic recordings of bilateral cortices, bilateral vibrissa muscle, and unilateral ZI were performed in Long-Evans rats to examine the functional role of SWDs. Rhythmic ZI activity appeared at the beginning of SWD and was accompanied by higher-oscillation frequencies and larger spike magnitudes. Bilateral lidocaine injections into the mystacial pads led to a decreased oscillation frequency of SWDs, but the phenomenon of ZI-related spike magnitude enhancement was preserved. Moreover, 800-Hz ZI microstimulation terminates most of the SWDs and whisker twitching (WT; >80%). In contrast, 200-Hz ZI microstimulation selectively stops WTs but not SWDs. Stimulation of the thalamic ventroposteriomedial nucleus showed no obvious effect on terminating SWDs. A unilateral ZI lesion resulted in a significant reduction of 7- to 12-Hz power of both the ipsilateral cortical and contralateral vibrissae muscle activities during SWDs. Intraincertal microinfusion of muscimol showed a significant inhibition on SWDs. Our present data suggest that the ZI actively modulates the SWD magnitude and WT behavior.

Early- and late-phase changes of brain activity and early-phase neuromodulation in the posttraumatic stress disorder rat model.

Posttraumatic stress disorder (PTSD) is a complex syndrome that may occur after life-threatening events. Fear memory abnormalities may play vital roles in the pathogenesis of PTSD. Previous work has found that fear memories are not rigid; the retrieval of fear memories may change over time. Furthermore, prior studies suggest that theta wave (4 Hz) activity is highly correlated with fear expression in an animal model. However, the relationship between pathological fear memory and potential brain wave features in PTSD remains largely uncharacterized. Here, we hypothesized that after traumatic stress exposure, the longitudinal dynamics of abnormal fears in PTSD animal models could be reflected by the measurement of local field potentials (LFPs). Using a well-established modified single-prolonged stress and footshock (SPS & FS) PTSD rat model, animals were restrained for 2 h and subsequently subjected to 20 min of forced swimming, then exposed to diethyl ether until they lost consciousness and placed in a conditioning chamber for fear conditioning. To characterize the temporal changes, we characterized freezing behavior brain wave features during the conditioning chamber re-exposure in the early (10 and 30 min; 2, 4, and 6 h) and late (day 1, 3, 7, and 14) phases after traumatic stress exposure. Our results indicate that SPS & FS rats showed co-morbid PTSD phenotypes including significantly higher levels of anxiety-, depression-, and anhedonia-like behaviors, and impaired fear extinction. Delta wave (0.5-4 Hz) suppression in the medial prefrontal cortex, amygdala, and ventral hippocampus occurred 10 and 30 min after traumatic stress, followed by continuous delta wave activity from 2 h to day 14, correlating with fear levels. tDCS reduced delta activity and alleviated PTSD-like phenotypes in the SPS & FS group. In this study, profiling abnormal fears with brain wave correlates may improve our understanding of time-dependent pathological fear memory retrieval in PTSD and facilitate the development of effective intervention strategies.

Seed correlation analysis based on brain region activation for ADHD diagnosis in a large-scale resting state data set.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder of multifactorial pathogenesis, which is often accompanied by dysfunction in several brain functional connectivity. Resting-state functional MRI have been used in ADHD, and they have been proposed as a possible biomarker of diagnosis information. This study's primary aim was to offer an effective seed-correlation analysis procedure to investigate the possible biomarker within resting state brain networks as diagnosis information. Method: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 149 childhood ADHD were analyzed. In this study, we proposed a two-step hierarchical analysis method to extract functional connectivity features and evaluation by linear classifiers and random sampling validation. Result: The data-driven method-ReHo provides four brain regions (mPFC, temporal pole, motor area, and putamen) with regional homogeneity differences as second-level seeds for analyzing functional connectivity differences between distant brain regions. The procedure reduces the difficulty of seed selection (location, shape, and size) in estimations of brain interconnections, improving the search for an effective seed; The features proposed in our study achieved a success rate of 83.24% in identifying ADHD patients through random sampling (saving 25% as the test set, while the remaining data was the training set) validation (using a simple linear classifier), surpassing the use of traditional seeds. Conclusion: This preliminary study examines the feasibility of diagnosing ADHD by analyzing the resting-state fMRI data from the ADHD-200 NYU dataset. The data-driven model provides a precise way to find reliable seeds. Data-driven models offer precise methods for finding reliable seeds and are feasible across different datasets. Moreover, this phenomenon may reveal that using a data-driven approach to build a model specific to a single data set may be better than combining several data and creating a general model.

Time-course analysis of frontal gene expression profiles in the rat model of posttraumatic stress disorder and a comparison with the conditioned fear model.

Posttraumatic stress disorder (PTSD) is a complex disorder that involves physiological, emotional, and cognitive dysregulation that may occur after exposure to a life-threatening event. In contrast with the condition of learned fear with resilience to extinction, abnormal fear with impaired fear extinction and exaggeration are considered crucial factors for the pathological development of PTSD. The prefrontal cortex (mPFC) is considered a critical region of top-down control in fear regulation, which involves the modulation of fear expression and extinction. The pathological course of PTSD is usually chronic and persistent; a number of studies have indicated temporal progression in gene expression and phenotypes may be involved in PTSD pathology. In the current study, we use a well-established modified single-prolonged stress (SPS&FS) rat model to feature PTSD-like phenotypes and compared it with a footshock fear conditioning model (FS model); we collected the frontal tissue after extreme stress exposure or fear conditioning and extracted RNA for transcriptome-level gene sequencing. We compared the genetic profiling of the mPFC at early (<2 h after solely FS or SPS&FS exposure) and late (7 days after solely FS or SPS&FS exposure) stages in these two models. First, we identified temporal differences in the expressional patterns between these two models and found pathways such as protein synthesis factor eukaryotic initiation factor 2 (EIF2), transcription factor NF-E2-related factor 2 (NRF2)-mediated oxidative stress response, and acute phase responding signaling enriched in the early stage in both models with significant p-values. Furthermore, in the late stage, the sirtuin signaling pathway was enriched in both models; other pathways such as STAT3, cAMP, lipid metabolism, Gα signaling, and increased fear were especially enriched in the late stage of the SPS&FS model. However, pathways such as VDR/RXR, GP6, and PPAR signaling were activated significantly in the FS model's late stage. Last, the network analysis revealed the temporal dynamics of psychological disorder, the endocrine system, and also genes related to increased fear in the two models. This study could help elucidate the genetic temporal alteration and stage-specific pathways in these two models, as well as a better understanding of the transcriptome-level differences between them.

EEG correlates of haptic feedback in a visuomotor tracking task.

This study investigates the temporal brain dynamics associated with haptic feedback in a visuomotor tracking task. Haptic feedback with deviation-related forces was used throughout tracking experiments in which subjects' behavioral responses and electroencephalogram (EEG) data were simultaneously measured. Independent component analysis was employed to decompose the acquired EEG signals into temporally independent time courses arising from distinct brain sources. Clustering analysis was used to extract independent components that were comparable across participants. The resultant independent brain processes were further analyzed via time-frequency analysis (event-related spectral perturbation) and event-related coherence (ERCOH) to contrast brain activity during tracking experiments with or without haptic feedback. Across subjects, in epochs with haptic feedback, components with equivalent dipoles in or near the right motor region exhibited greater alpha band power suppression. Components with equivalent dipoles in or near the left frontal, central, left motor, right motor, and parietal regions exhibited greater beta-band power suppression, while components with equivalent dipoles in or near the left frontal, left motor, and right motor regions showed greater gamma-band power suppression relative to non-haptic conditions. In contrast, the right occipital component cluster exhibited less beta-band power suppression in epochs with haptic feedback compared to non-haptic conditions. The results of ERCOH analysis of the six component clusters showed that there were significant increases in coherence between different brain networks in response to haptic feedback relative to the coherence observed when haptic feedback was not present. The results of this study provide novel insight into the effects of haptic feedback on the brain and may aid the development of new tools to facilitate the learning of motor skills.

Lamotrigine ameliorates seizures and psychiatric comorbidity in a rat model of spontaneous absence epilepsy.

PURPOSE: Lamotrigine (LTG) is an effective clinical treatment for epilepsy associated with absence seizures. However, the impact of LTG administration in studies employing various animal models of epilepsy remains controversial. This study aimed to clarify the outcomes of LTG treatment on absence seizures and comorbid anxiety and depression disorders in Long-Evans rats with spontaneous spike-wave discharges (SWDs). METHODS: LTG (10 mg/kg) or water vehicle was chronically administered perorally to Long-Evans rats (twice daily for 35 days). Cortical activities were recorded to assess the presence of SWDs. Five behavioral tests, including the open field (OF), elevated plus maze (EPM), sucrose consumption (SC), sucrose preference, and forced swimming (FS) tests, were performed after LTG/vehicle treatment. The behavioral indexes of these tests were designed to assess anxiety (OF and EPM tests), depression (SC and FS tests), and preference for hedonistic stimuli (sugar preference test). KEY FINDINGS: Total SWD duration, SWD number, and mean SWD duration were significantly decreased in rats that received 35-day LTG treatment compared with rats that received vehicle treatment. Rats with spontaneous SWDs versus rats with no SWDs showed significant levels of anxiety and depression in the OF, EPM, and SC tests. Rats with SWDs also showed longer immobility in the FS test. However, the LTG-treated group compared with the vehicle group presented with significantly lower manifestations of anxiety and depression in the OF, EPM, SC, and sucrose preference tests and shorter immobility in the FS test. SIGNIFICANCE: The results of this study suggest that chronic LTG treatment can benefit patients with epilepsy via suppression of absence seizures and amelioration of comorbid anxiety and depression.

Equivalent current dipole sources of neurofeedback training-induced alpha activity through temporal/spectral analytic techniques.

Much of the work in alpha NFT has focused on evaluating changes in alpha amplitude. However, the generation mechanism of training-induced alpha activity has not yet been clarified. The present study aimed to identify sources of training-induced alpha activity through four temporal/spectral analytic techniques, i.e., the max peak average (MPA), positive average (PA), negative average (NA) and event-related spectral perturbation average (ERSPA) methods. Thirty-five healthy participants were recruited into an alpha group receiving feedback of 8-12-Hz amplitudes, and twenty-eight healthy participants were recruited into a control group receiving feedback of random 4-Hz amplitudes from the range of 7 to 20 Hz. Twelve sessions were performed within 4 weeks (3 sessions per week). The control group had no change in the amplitude spectrum. In contrast, twenty-nine participants in the alpha group showed significant alpha amplitude increases exclusively and were identified as "responders". A whole-head EEG was recorded for the "responders" after NFT. The epochs of training-induced alpha activity from whole-head EEG were averaged by four different methods for equivalent current dipole source analysis. High agreement and Cohen's kappa coefficients on dipole source localization between each method were observed, showing that the dipole clusters of training-induced alpha activity were consistently located in the precuneus, posterior cingulate cortex (PCC) and middle temporal gyrus. The residual variance (goodness of fit) for dipole estimation of the MPA was significantly smaller than that of the others. Our findings indicate that the precuneus, PCC and middle temporal gyrus play important roles in enhancing training-induced alpha activity. The four averaging methods (especially the MPA method) were suitable for investigating sources of brainwaves. Additionally, three dipoles can be used for dipole source analysis of training-induced alpha activity in future research, especially the training sites are around the central regions.

Effect of intracranial administration of ethosuximide in rats with spontaneous or pentylenetetrazol-induced spike-wave discharges.

PURPOSE: Generalized absence seizures are characterized by bilateral spike-wave discharges (SWDs), particularly in the frontoparietal cortical region. In WAG/Rij and GAERS rats with absence epilepsy, recent evidence indicates that SWDs arise first from the lateral somatosensory cortex (LSC), that is, the cortical focus theory. To further understand the cortical role in SWD generation, two epileptic rat models were assessed. METHODS: Two models, Long-Evans rats with spontaneous SWDs and Wistar rats with low-dose pentylenetetrazol-induced SWDs (20 mg/kg, i.p.), were administered intracortical or intrathalamic ethosuximide (ESM) or saline. Electroencephalographic recordings were analyzed before and after intracranial microinfusion to evaluate onset, frequency, and duration of SWDs. KEY FINDINGS: In both epileptic rat models, ESM in the LSC significantly reduced SWD number, shortened SWD duration, and delayed SWD onset compared to saline. By contrast, ESM in the medial somatosensory cortex had little effect compared to saline. Intrathalamic infusion of ESM only delayed SWD onset. SIGNIFICANCE: These findings suggest that the LSC may be essential for the occurrence of SWDs. Our data support the cortical focus theory for the generation of absence seizures.

Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia.

The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC1-α). PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

Validation of eyes-closed resting alpha amplitude predicting neurofeedback learning of upregulation alpha activity.

Neurofeedback training (NFT) enables users to learn self-control of EEG activity of interest and then to create many benefits on cognitive function. A considerable number of nonresponders who fail to achieve successful NFT have often been reported in the within-session prediction. This study aimed to investigate successful EEG NFT of upregulation alpha activity in terms of trainability, independence, and between-session predictability validation. Forty-six participants completed 12 training sessions. Spectrotemporal analysis revealed the upregulation success on brain activity of 8-12 Hz exclusively to demonstrate trainability and independence of alpha NFT. Three learning indices of between-session changes exhibited significant correlations with eyes-closed resting state (ECRS) alpha amplitude before the training exclusively. Through a stepwise linear discriminant analysis, the prediction model of ECRS's alpha frequency band amplitude exhibited the best accuracy (89.1%) validation regarding the learning index of increased alpha amplitude on average. This study performed a systematic analysis on NFT success, the performance of the 3 between-session learning indices, and the validation of ECRS alpha activity for responder prediction. The findings would assist researchers in obtaining insight into the training efficacy of individuals and then attempting to adapt an efficient strategy in NFT success.

Directions of Deep Brain Stimulation for Epilepsy and Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders and neurological/psychiatric disorders. DBS has been approved for the control of Parkinson disease (PD) and epilepsy. OBJECTIVES: A systematic review and possible future direction of DBS system studies is performed in the open loop and closed-loop configuration on PD and epilepsy. METHODS: We searched Google Scholar database for DBS system and development. DBS search results were categorized into clinical device and research system from the open-loop and closed-loop perspectives. RESULTS: We performed literature review for DBS on PD and epilepsy in terms of system development by the open loop and closed-loop configuration. This study described development and trends for DBS in terms of electrode, recording, stimulation, and signal processing. The closed-loop DBS system raised a more attention in recent researches. CONCLUSION: We overviewed development and progress of DBS. Our results suggest that the closed-loop DBS is important for PD and epilepsy.

Portable rotating grating stimulation for anisometropic amblyopia with 6 months training.

Treatment of grating stimulation has been used in amblyopia for decades, but high dropout rate and inconvenience for daily practice occur in previous studies. We developed a home-based portable system with rotating grating stimulation on a tablet. Thirty anisometropic amblyopic children were randomly allocated into the control or Grating group. They drew contour of the picture under patch of a better eye for 6 months. Best-corrected visual acuity (BCVA), grating acuity (GA), and contrast sensitivity (CS) were assessed at the baseline, 1st, 2nd, 3rd, and 6th months of training. All participants completed the 6-month training. Patched eyes of both groups exhibited no difference. Trained eyes of the control group had significantly slight improvement in BCVA and GA. In particular, the Grating group exhibited significantly higher BCVA, GA, and CS compared with those of the control group at the 3rd and 6th months of training. Moreover, percentage of the Grating group with great improvement (BCVA ≥ 0.3 or CS ≥ 0.3) was significantly larger than those of the control group at the 3rd or 6th months of training. The portable grating stimulation system demonstrates its trainability by no dropout and effectiveness by significant improvements in all assessments through a well experimental design.Trial Registration: ClinicalTrials.gov NCT04213066, registered 30/12/2019, https://clinicaltrials.gov/ct2/show/NCT04213066 .

Protective effects of peroxisome proliferator-activated receptors gamma coactivator-1alpha against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia.

Peroxisome proliferator-activated receptors gamma coactivator-1alpha (PGC-1alpha) may regulate the mitochondrial antioxidant defense system under many neuropathological settings. However, the exact role of PGC-1alpha in ischemic brain damage is still under debate. Based on an experimental model of transient global ischemia (TGI), this study evaluated the hypothesis that the activation of PGC-1alpha signaling pathway protects hippocampal CA1 neurons against delayed neuronal death after TGI. In Sprague-Dawley rats, significantly increased content of oxidized proteins in the hippocampal CA1 tissue was observed as early as 30 min after TGI, followed by augmentation of PGC-1alpha expression at 1 hr. Expression of uncoupling protein 2 (UCP2) and superoxide dismutases 2 (SOD2) in the hippocampal CA1 neurons was upregulated 4-48 hr after TGI. In addition, knock-down of PGC-1alpha expression by pretreatment with a specific antisense oligodeoxynucleotide in the hippocampal CA1 subfield downregulated the expression of UCP2 and SOD2 with resultant exacerbation of oxidative stress and augmentation of delayed neuronal cell death in the hippocampus after TGI. Overall, our results indicate that PGC-1alpha is induced by cerebral ischemia leading to upregulation of UCP2 and SOD2, thereby providing a neuroprotective effect against ischemic brain injury in the hippocampus by ameliorating oxidative stress.

Activation of calcium/calmodulin-dependent protein kinase IV and peroxisome proliferator-activated receptor γ coactivator-1α signaling pathway protects against neuronal injury and promotes mitochondrial biogenesis in the hippocampal CA1 subfield after transient global ischemia.

Delayed neuronal cell death occurs in the vulnerable CA1 subfield of the hippocampus after transient global ischemia (TGI). We demonstrated previously, based on an experimental model of TGI, that the significantly increased content of oxidized proteins in hippocampal CA1 neuron was observed as early as 30 min after TGI, followed by augmentation of PGC-1α expression at 1 hr, as well as up-regulation of mitochondrial uncoupling protein 2 (UCP2) and superoxide dismutases 2 (SOD2). Using the same animal model, the present study investigated the role of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and PGC-1α in delayed neuronal cell death and mitochondrial biogenesis in the hippocampus. In Sprague-Dawley rats, significantly increased expression of nuclear CaMKIV was noted in the hippocampal CA1 subfield as early as 15 min after TGI. In addition, the index of mitochondrial biogenesis, including a mitochondrial DNA-encoded polypeptide, cytochrome c oxidase subunit 1 (COX1), and mitochondrial number significantly increased in the hippocampal CA1 subfield 4 hr after TGI. Application bilaterally into the hippocampal CA1 subfield of an inhibitor of CaMKIV, KN-93, 30 min before TGI attenuated both CaMKIV and PGC-1α expression, followed by down-regulation of UCP2 and SOD2, decrease of COX1 expression and mitochondrial number, heightened protein oxidation, and enhanced hippocampal CA1 neuronal damage. This study provides correlative evidence for the neuroprotective cascade of CaMKIV/PGC-1α which implicates at least in part the mitochondrial antioxidants UCP2 and SOD2 as well as mitochondrial biogenesis in ischemic brain injury.