​1.Science—钾通道功能障碍可能是引起天使人综合症癫痫的分子机制

Abstract

Disruptions in the ubiquitin protein ligaseE3A (UBE3A) gene cause Angelman syndrome (AS). Whereas AS model mice have associatedsynaptic dysfunction and altered plasticity with abnormal behavior, whethersimilar or other mechanisms contribute to network hyperactivity and epilepsysusceptibility in AS patients remains unclear. Using human neurons and brainorganoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability viaubiquitin-mediated degradation of calcium- and voltage-dependent big potassium(BK) channels. We provide evidence that augmented BK channel activity manifestsas increased intrinsic excitability in individual neurons and subsequentnetwork synchronization. BK antagonists normalized neuronal excitability inboth human and mouse neurons and ameliorated seizure susceptibility in an ASmouse model. Our findings suggest that BK channelopathy underlies epilepsy inAS and support the use of human cells to model human developmental diseases.

参考文献：Potassium channel dysfunction in humanneuronal models of Angelman syndrome. Science. 2019 Dec 20;366(6472):1486-1492.

2. Nature—重磅！！小胶质细胞反馈抑制神经元活动，消除小胶质细胞促进癫痫发生，ATP-腺苷-A1R通路介导其反馈抑制作用

Abstract

Microglia, the brain's resident macrophages,help to regulate brain function by removing dying neurons, pruningnon-functional synapses, and producing ligands that support neuronal survival1.Here we show that microglia are also critical modulators of neuronal activityand associated behavioural responses in mice. Microglia respond to neuronal activationby suppressing neuronal activity, and ablation of microglia amplifies andsynchronizes the activity of neurons, leading to seizures. Suppression ofneuronal activation by microglia occurs in a highly region-specific fashion anddepends on the ability of microglia to sense and catabolize extracellular ATP,which is released upon neuronal activation by neurons and astrocytes. ATPtriggers the recruitment of microglial protrusions and is converted by themicroglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then convertedinto adenosine by CD73, which is expressed on microglia as well as other braincells. Microglial sensing of ATP, the ensuing microglia-dependent production ofadenosine, and the adenosine-mediated suppression of neuronal responses via theadenosine receptor A1R are essential for the regulation of neuronal activityand animal behaviour. Our findings suggest that this microglia-driven negativefeedback mechanism operates similarly to inhibitory neurons and is essentialfor protecting the brain from excessive activation in health and disease.

参考文献：Negative feedback control of neuronal activityby microglia. Nature. 2020 Oct;586(7829):417-423.

3. Nat Rev Drug Discov+Sci Transl Med—Filamin A 小分子抑制剂PTI-125可显著抑制小鼠癫痫模型癫痫的发生

Abstract

Epilepsy treatments for patients withmechanistic target of rapamycin (mTOR) disorders, such as tuberous sclerosiscomplex (TSC) or focal cortical dysplasia type II (FCDII), are urgently needed.In these patients, the presence of focal cortical malformations is associatedwith the occurrence of lifelong epilepsy, leading to severe neurologicalcomorbidities. Here, we show that the expression of the actin cross-linkingprotein filamin A (FLNA) is increased in resected cortical tissue that isresponsible for seizures in patients with FCDII and in mice modeling TSC andFCDII with mutations in phosphoinositide 3-kinase (PI3K)-ras homolog enrichedin brain (Rheb) pathway genes. Normalizing FLNA expression in these mice throughgenetic knockdown limited cell misplacement and neuronal dysmorphogenesis, twohallmarks of focal cortical malformations. In addition, Flna knockdown reducedseizure frequency independently of mTOR signaling. Treating mice with a smallmolecule targeting FLNA, PTI-125, before the onset of seizures alleviatedneuronal abnormalities and reduced seizure frequency compared tovehicle-treated mice. In addition, the treatment was also effective when injected after seizure onset in juvenile and adult mice. These data suggestthat targeting FLNA with either short hairpin RNAs or the small molecule PTI-125 might be effective in reducing seizures in patients with TSC and FCDIIbearing mutations in PI3K-Rheb pathway genes.

参考文献：Filamin A inhibition reduces seizure activity in a mouse model of focal cortical malformations. Sci Transl Med. 2020 Feb 19;12(531):eaay0289.

Villanueva MT. Small molecule reduces epileptic seizures in mice.  Nat Rev DrugDiscov. 2020 Apr;19(4):238. doi: 10.1038/d41573-020-00042-y.

4. N Engl J Med—最新证据！！这是最新的癫痫患者怀孕期间癫痫发生频率和癫痫用药的情况分析

Abstract

Background: Among women with epilepsy, studiesregarding changes in seizure frequency during pregnancy have been limited bythe lack of an appropriate nonpregnant comparator group to provide data on thenatural course of seizure frequency in both groups.

Methods: In this prospective, observational,multicenter cohort study, we compared the frequency of seizures duringpregnancy through the peripartum period (the first 6 weeks after birth) (epoch1) with the frequency during the postpartum period (the following 7.5 monthsafter pregnancy) (epoch 2). Nonpregnant women with epilepsy were enrolled ascontrols and had similar follow-up during an 18-month period. The primaryoutcome was the percentage of women who had a higher frequency of seizures thatimpaired awareness during epoch 1 than during epoch 2. We also compared changesin the doses of antiepileptic drugs that were administered in the two groupsduring the first 9 months of epoch 1.

Results: We enrolled 351 pregnant women and109 controls with epilepsy. Among the 299 pregnant women and 93 controls whohad a history of seizures that impaired awareness and who had available datafor the two epochs, seizure frequency was higher during epoch 1 than duringepoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio, 0.93;95% confidence interval [CI], 0.54 to 1.60). During pregnancy, the dose of anantiepileptic drug was changed at least once in 74% of pregnant women and in 31%of controls (odds ratio, 6.36; 95% CI, 3.82 to 10.59).

Conclusions: Among women with epilepsy, thepercentage who had a higher incidence of seizures during pregnancy than duringthe postpartum period was similar to that in women who were not pregnant duringthe corresponding epochs. Changes in doses of antiepileptic drugs occurred morefrequently in pregnant women than in nonpregnant women during similar timeperiods. (Funded by the National Institutes of Health; MONEADClinicalTrials.gov number, NCT01730170.).

参考文献：Changes in Seizure Frequency and AntiepilepticTherapy during Pregnancy. N Engl J Med. 2020 Dec 24;383(26):2547-2556.

5. Lancet—左乙拉西坦、磷苯妥英和丙戊酸钠均可作为苯二氮卓类药物难治性癫痫持续状态的首选治疗

Abstract

Background:Benzodiazepine-refractory, orestablished, status epilepticus is thought to beof similar pathophysiology inchildren and adults, but differences in underlyingaetiology andpharmacodynamics might differentially affect response to therapy.In theEstablished Status Epilepticus Treatment Trial (ESETT) we compared theefficacyand safety of levetiracetam, fosphenytoin, and valproate in establishedstatusepilepticus, and here we describe our results after extending enrolmentinchildren to compare outcomes in three age groups.

Methods:In this multicentre, double-blind,response-adaptive, randomised controlledtrial, we recruited patients from 58hospital emergency departments across theUSA. Patients were eligible forinclusion if they were aged 2 years or older,had been treated for ageneralised convulsive seizure of longer than 5 minduration with adequate dosesof benzodiazepines, and continued to havepersistent or recurrent convulsionsin the emergency department for at least 5min and no more than 30 min afterthe last dose of benzodiazepine. Patients wererandomly assigned in aresponse-adaptive manner, using Bayesian methods andstratified by age group(<18 years, 18-65 years, and >65 years), tolevetiracetam, fosphenytoin,or valproate. All patients, investigators, studystaff, and pharmacists weremasked to treatment allocation. The primary outcomewas absence of clinicallyapparent seizures with improved consciousness andwithout additionalantiseizure medication at 1 h from start of drug infusion.The primary safetyoutcome was life-threatening hypotension or cardiacarrhythmia. The efficacyand safety outcomes were analysed by intention totreat. This study isregistered in ClinicalTrials.gov, NCT01960075.

Findings:Between Nov 3, 2015, and Dec 29,2018, we enrolled 478 patients and 462 uniquepatients were included: 225children (aged <18 years), 186 adults (18-65years), and 51 older adults(>65 years). 175 (38%) patients were randomlyassigned to levetiracetam, 142(31%) to fosphenyltoin, and 145 (31%) were tovalproate. Baselinecharacteristics were balanced across treatments within agegroups. The primaryefficacy outcome was met in those treated with levetiracetamfor 52% (95%credible interval 41-62) of children, 44% (33-55) of adults, and37% (19-59) ofolder adults; with fosphenytoin in 49% (38-61) of children, 46%(34-59) ofadults, and 35% (17-59) of older adults; and with valproate in 52%(41-63) ofchildren, 46% (34-58) of adults, and 47% (25-70) of older adults.Nodifferences were detected in efficacy or primary safety outcome by drug withineachage group. With the exception of endotracheal intubation in children,secondarysafety outcomes did not significantly differ by drug within each agegroup.

Interpretation:Children, adults, and olderadults with established status epilepticus respond similarlyto levetiracetam,fosphenytoin, and valproate, with treatment success inapproximately half ofpatients. Any of the three drugs can be considered as apotential first-choice,second-line drug for benzodiazepine-refractory statusepilepticus.

参考文献：Efficacy oflevetiracetam, fosphenytoin, andvalproate for established status epilepticus byage group (ESETT): adouble-blind, responsive-adaptive, randomised controlledtrial. Lancet. 2020Apr 11;395(10231):1217-1224.

6. Lancet Neurol—慢性脑电图可用于预测未来局部癫痫的发生

Abstract

Background: People with epilepsy are burdenedwith the apparent unpredictability of seizures. In the past decade, convergingevidence from studies using chronic EEG (cEEG) revealed that epileptic brainactivity shows robust cycles, operating over hours (circadian) and days(multidien). We hypothesised that these cycles can be leveraged to estimate futureseizure probability, and we tested the feasibility of forecasting seizures daysin advance.

Methods: We did a feasibility study indistinct development and validation cohorts, involving retrospective analysisof cEEG data recorded with an implanted device in adults (age ≥18 years) withdrug-resistant focal epilepsy followed at 35 centres across the USA between Jan19, 2004, and May 18, 2018. Patients were required to have had 20 or moreelectrographic seizures (development cohort) or self-reported seizures(validation cohort). In all patients, the device recorded interictal epileptiform activity (IEA; ≥6 months of continuous hourly data), thefluctuations in which helped estimate varying seizure risk. Point processstatistical models trained on initial portions of each patient's cEEG data(both cohorts) generated forecasts of seizure probability that were tested onsubsequent unseen seizure data and evaluated against surrogate time-series. Theprimary outcome was the percentage of patients with forecasts showingimprovement over chance (IoC).

Findings: We screened 72 and 256 patients, andincluded 18 and 157 patients in the development and validation cohorts,respectively. Models incorporating information about multidien IEA cycles alonegenerated daily seizure forecasts for the next calendar day with IoC in 15(83%) patients in the development cohort and 103 (66%) patients in thevalidation cohort. The forecasting horizon could be extended up to 3 days whilemaintaining IoC in two (11%) of 18 patients and 61 (39%) of 157 patients.Forecasts with a shorter horizon of 1 h, possible only for electrographicseizures in the development cohort, showed IoC in all 18 (100%) patients.

Interpretation: This study shows that seizureprobability can be forecasted days in advance by leveraging multidien IEA cyclesrecorded with an implanted device. This study will serve as a basis forprospective clinical trials to establish how people with epilepsy might benefitfrom seizure forecasting over long horizons.

参考文献：Forecasting seizure risk in adults with focalepilepsy: a development and validation study. Lancet Neurol. 2020 Dec17;S1474-4422(20)30396-3.

7. Lancet Neurol—癫痫研究重大突破！！组织病理学诊断、手术时的年龄和癫痫患病时间是决定癫痫手术后临床预后的关键因素

Abstract

Background: Surgery is a widely acceptedtreatment option for drug-resistant focal epilepsy. A detailed analysis oflongitudinal postoperative seizure outcomes and use of antiepileptic drugs fordifferent brain lesions causing epilepsy is not available. We aimed to analysethe association between histopathology and seizure outcome and drug freedom upto 5 years after epilepsy surgery, to improve presurgical decision making andcounselling.

Methods: In this retrospective, multicentre,longitudinal, cohort study, patients who had epilepsy surgery between Jan 1,2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18European countries of the European Epilepsy Brain Bank consortium wereassessed. We included patients of all ages with histopathology available afterepilepsy surgery. Histopathological diagnoses and a minimal dataset of clinicalvariables were collected from existing local databases and patient records. Theprimary outcomes were freedom from disabling seizures (Engel class 1) and drugfreedom at 1, 2, and 5 years after surgery. Proportions of individuals who wereEngel class 1 and drug-free were reported for the 11 main categories ofhistopathological diagnosis. We analysed the association betweenhistopathology, duration of epilepsy, and age at surgery, and the primaryoutcomes using random effects multivariable logistic regression to control forconfounding.

Findings: 9147 patients were included, of whomseizure outcomes were available for 8191 (89·5%) participants at 2 years, andfor 5577 (61·0%) at 5 years. The diagnoses of low-grade epilepsy associatedneuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosishad the best seizure outcome at 2 years after surgery, with 77·5% (1027 of1325) of patients free from disabling seizures for LEAT, 74·0% (328 of 443) forvascular malformation, and 71·5% (2108 of 2948) for hippocampal sclerosis. Theworst seizure outcomes at 2 years were seen for patients with focal corticaldysplasia type I or mild malformation of cortical development (50·0%, 213 of426 free from disabling seizures), those with malformation of corticaldevelopment-other (52·3%, 212 of 405 free from disabling seizures), and forthose with no histopathological lesion (53·5%, 396 of 740 free from disablingseizures). The proportion of patients being both Engel class 1 and drug-freewas 0-14% at 1 year and increased to 14-51% at 5 years. Children were moreoften drug-free; temporal lobe surgeries had the best seizure outcomes; and alonger duration of epilepsy was associated with reduced chance of favourableseizure outcomes and drug freedom. This effect of duration was evident for alllesions, except for hippocampal sclerosis.

Interpretation: Histopathological diagnosis,age at surgery, and duration of epilepsy are important prognostic factors foroutcomes of epilepsy surgery. In every patient with refractory focal epilepsypresumed to be lesional, evaluation for surgery should be considered.

参考文献：Seizure outcome and use of antiepileptic drugsafter epilepsy surgery according to histopathological diagnosis: aretrospective multicentre cohort study. Lancet Neurol. 2020 Sep;19(9):748-757.

8. Lancet Neurol—未控制局部癫痫用药突破：Cenobamate可有效降低未控制局部癫痫的复发

Abstract

Background: More than a third of patients withepilepsy are treatment resistant, and thus new, more effective therapies toachieve seizure freedom are needed. Cenobamate (YKP3089), an investigationalantiepileptic drug, has shown broad-spectrum anticonvulsant activity inpreclinical studies and seizure models. We aimed to evaluate the safety,efficacy, and tolerability of adjunctive cenobamate in patients withuncontrolled focal (partial)-onset epilepsy.

Methods: We did a multicentre, double-blind,randomised, placebo-controlled, dose-response study at 107 epilepsy andneurology centres in 16 countries. Adult patients (aged 18-70 years) with focalseizures despite treatment with 1-3 antiepileptic drugs were randomly assigned(1:1:1:1) via an interactive web response system, by block sizes of 4 withineach country, to adjuvant once daily oral cenobamate at dose groups of 100 mg,200 mg, or 400 mg, or placebo following an 8-week baseline assessment.Patients, investigators, and study personnel were masked to treatmentassignment. The study included a 6-week titration phase and 12-week maintenancephase. The primary efficacy outcomes were percentage change in 28-day focalseizure frequency (focal aware motor, focal impaired awareness, or focal tobilateral tonic-clonic seizures) from baseline analysed in the modifiedintention-to-treat population (≥1 dose and any post-baseline seizure data) andresponder rates (≥50% reduction) analysed in the maintenance phase population(≥1 dose in the maintenance phase and any maintenance phase seizure data). Theprimary efficacy outcomes were analysed using a hierarchal step-down procedurecomparing 200 mg versus placebo, 400 mg versus placebo, then 100 mg versusplacebo. Safety and tolerability were compared descriptively across treatmentgroups for all randomised patients. This study is registered withClinicalTrials.gov, number NCT01866111.

Findings: Between July 31, 2013, and June 22,2015, 437 patients were randomly assigned to either placebo (n=108) or cenobamate100 mg (n=108), 200 mg (n=110), or 400 mg (n=111). Of these patients, 434 (106[98%] in placebo group, 108 [100%] in 100 mg group, 109 [99%] in 200 mg group,and 111 [100%] in 400 mg group) were included in the modifiedintention-to-treat population, and 397 (102 [94%] in placebo group, 102 [94%]in 100 mg group, 98 [89%] in 200 mg group, and 95 [86%] in 400 mg group) wereincluded in the modified intention-to-treat maintenance phase population. Medianpercentage changes in seizure frequency were -24·0% (IQR -45·0 to -7·0%) forthe placebo group compared with -35·5% (-62·5 to -15·0%; p=0·0071) for the 100mg dose group, -55·0% (-73·0 to -23·0%; p<0·0001) for the 200 mg dose group,and -55·0% (-85·0 to -28·0%; p<0·0001) for the 400 mg dose group. Responderrates during the maintenance phase were 25% (26 of 102 patients) for theplacebo group compared with 40% (41 of 102; odds ratio 1·97, 95% CI 1·08-3·56;p=0·0365) for the 100 mg dose group, 56% (55 of 98; 3·74, 2·06-6·80;p<0·0001) for the 200 mg dose group, and 64% (61 of 95; 5·24, 2·84-9·67;p<0·0001) for the 400 mg dose group. Treatment-emergent adverse eventsoccurred in 76 (70%) of 108 patients in the placebo group, 70 (65%) of 108 inthe 100 mg group, 84 (76%) of 110 in the 200 mg group, and 100 (90%) of 111 inthe 400 mg group. Treatment-emergent adverse events led to discontinuation infive (5%) patients in the placebo group, 11 (10%) in the 100 mg dose group, 15(14%) in the 200 mg dose group, and 22 (20%) in the 400 mg dose group. One seriouscase of drug reaction with eosinophilia and systemic symptoms occurred in the200 mg cenobamate group. No deaths were reported.

Interpretation: Adjunctive cenobamate reducedfocal (partial)-onset seizure frequency, in a dose-related fashion. Treatment-emergentadverse events were most frequent in the highest dose group. Cenobamate appearsto be an effective treatment option in patients with uncontrolled focalseizures.

参考文献：Safety and efficacy of adjunctivecenobamate (YKP3089) in patients with uncontrolled focal seizures: amulticentre, double-blind, randomised, placebo-controlled, dose-response trial.Lancet Neurol. 2020 Jan;19(1):38-48.

9. Nature—这是从基础神经科学向临床转化的好案例！！Karl Deisseroth组揭示脑深后内皮层节律可能是引起解离的根源

Abstract

Advanced imaging methods now allow cell-type-specificrecording of neural activity across the mammalian brain, potentially enablingthe exploration of how brain-wide dynamical patterns give rise to complexbehavioural states1-12. Dissociation is an altered behavioural state in whichthe integrity of experience is disrupted, resulting in reproducible cognitivephenomena including the dissociation of stimulus detection fromstimulus-related affective responses. Dissociation can occur as a result oftrauma, epilepsy or dissociative drug use13,14, but despite its substantialbasic and clinical importance, the underlying neurophysiology of this state isunknown. Here we establish such a dissociation-like state in mice, induced byprecisely-dosed administration of ketamine or phencyclidine. Large-scale imagingof neural activity revealed that these dissociative agents elicited a 1-3-Hzrhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiologicalrecording with four simultaneously deployed high-density probes revealedrhythmic coupling of the retrosplenial cortex with anatomically connectedcomponents of thalamus circuitry, but uncoupling from most other brain regionswas observed-including a notable inverse correlation with frontally projectingthalamic nuclei. In testing for causal significance, we found that rhythmicoptogenetic activation of retrosplenial cortex layer 5 neurons recapitulateddissociation-like behavioural effects. Local retrosplenialhyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1)pacemakers were required for systemic ketamine to induce this rhythm and toelicit dissociation-like behavioural effects. In a patient with focal epilepsy,simultaneous intracranial stereoencephalography recordings from across thebrain revealed a similarly localized rhythm in the homologous deepposteromedial cortex that was temporally correlated with pre-seizureself-reported dissociation, and local brief electrical stimulation of thisregion elicited dissociative experiences. These results identify the molecular,cellular and physiological properties of a conserved deep posteromedialcortical rhythm that underlies states of dissociation.

参考文献：Deep posteromedial cortical rhythm indissociation. Nature. 2020 Oct;586(7827):87-94.

10. Nature nanotechnology—钾离子探针来了！！！科学家开发钾离子纳米探针以监测小鼠脑中的细胞外钾离子浓度

Abstract

Extracellular potassium concentration affectsthe membrane potential of neurons, and, thus, neuronal activity. Indeed,alterations of potassium levels can be related to neurological disorders, suchas epilepsy and Alzheimer's disease, and, therefore, selectively detectingextracellular potassium would allow the monitoring of disease. However,currently available optical reporters are not capable of detecting smallchanges in potassium, in particular, in freely moving animals. Furthermore,they are susceptible to interference from sodium ions. Here, we report a highlysensitive and specific potassium nanosensor that can monitor potassium changesin the brain of freely moving mice undergoing epileptic seizures. An opticalpotassium indicator is embedded in mesoporous silica nanoparticles, which areshielded by an ultrathin layer of a potassium-permeable membrane, whichprevents diffusion of other cations and allows the specific capturing ofpotassium ions. The shielded nanosensor enables the spatial mapping ofpotassium ion release in the hippocampus of freely moving mice.

参考文献：A sensitive and specific nanosensor formonitoring extracellular potassium levels in the brain. Nat Nanotechnol. 2020Apr;15(4):321-330.

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2020年十大研究进展名录

2019年十大研究进展名录

1. 年终盘点：2019年帕金森病十大基础研究进展

2. 年终盘点：2019年帕金森病十大临床研究进展

3. 年终盘点：2019年阿尔茨海默病十大基础研究进展

4. 年终盘点：2019年阿尔茨海默病十大临床研究进展

5. 年终盘点：2019年神经科学领域十大基础研究进展

6. 年终盘点：2019年抑郁症领域十大基础研究进展（一半来自中国）

7. 年终盘点：2019年脑血管病领域十大基础研究进展

8. 年终盘点：2019年神经炎症领域十大基础研究进展

9. 年终盘点：2019年神经活动记录十大基础研究进展

10. 年终盘点：2019年ALS/FTD十大基础研究进展

11. 年终盘点：2019年医学和生物学领域深度学习和神经网络十大基础研究进展

12. 年终盘点：2019年神经内科十大临床研究突破

13. 年终盘点：2019年疼痛防治和痛觉机制十大研究突破

14. 年终盘点：2019年睡眠和失眠领域十大研究突破

15.年终盘点：2019年神经发育及成年神经再生十大研究突破

16. 年终盘点：2019年大脑学习和记忆的十大研究突破

17. 年终盘点：2019年衰老和长寿十大研究突破

18. 年终盘点：2019年自闭症十大研究突破

2018年十大研究进展名录

1.盘点2018年阿尔茨海默病十大研究突破

2.盘点2018年帕金森病十大研究突破

3. 盘点2018年神经科学二十大研究突破

4. 盘点2018年渐冻症（ALS）十大研究进展

5. 盘点2018年全球脑卒中十大研究进展

6. 盘点2018年神经影像十大研究进展

7. 盘点2018年神经炎症领域的十大研究突破

8. 盘点2018年神经变性痴呆十大研究突破

9. 2018年神经科学“学习和记忆”领域十大研究进展

10. 2018年抑郁症领域的十大研究突破

11. 2018年痛觉和疼痛领域的十大研究突破

12. 2018年的神经干细胞研究十大研究进展

13. 2018年的神经干细胞研究十大研究进展

14. 2018年的十大睡眠研究突破

15. 2018年“衰老和长生不老”领域的十大研究突破

16. 2018年自闭症领域的十大研究突破

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20个神经科学领域的突破可能获得诺贝尔奖

1. 意识研究：意识的本质、组成、运行机制及其物质载体；不同意识层次的操控和干预，意识障碍性疾病的治疗。

2. 学习和记忆的机制及其调控：记忆的形成和消退机制，记忆的人为移植和记忆的人为消除等；

3. 痴呆研究：阿尔茨海默病的机制和治疗研究，血管性痴呆、额颞叶痴呆、路易体痴呆的机制研究和治疗。

4. 睡眠和睡眠障碍的机制和干预研究。

5. 情绪研究：喜、怒、哀、恐等基本情绪的机制和相关疾病的治疗。

6. 计算和逻辑推理的神经科学基础研究。

7. 语言的神经科学基础研究。

8. 视觉图像形成和运用的神经科学基础研究。

9. 创造力、想象力和艺术文学创造的神经基础研究。

10. 痛觉的神经科学基础及其干预研究

11. 性行为研究：性行为的神经科学基础研究和性行为的调控和干预。

12. 脑和脊髓损伤的机制及其干预研究，包括脑卒中、脊髓损伤机制研究，神经干细胞移植研究，新型神经修复技术，神经康复技术。

13. 精神类疾病的机制和干预研究：自闭症、精分、抑郁症、智能障碍、药物成瘾等；

14. 运动神经元病等神经变性病机制研究及其干预。

15. 衰老的机制和永生研究，包括大脑衰老的机制和寿命延长研究。

16. 神经系统遗传病的机制研究及基因治疗。

17. 神经操纵和调控技术：光遗传技术、药物遗传技术、基因编辑技术、经颅磁刺激、深部脑刺激和电刺激等。

18. 脑组织兼容性电子微芯片及脑机互动装置研究，包括脑机接口、神经刺激芯片、记忆存储芯片，意识存储芯片，人脑非语言互动装置等。

19. 半人半机器人的设计、完善和修复技术：包括任何机械肢体的人类移植，大脑移植入机器体内等。

20. 新型大脑成像和神经元活动记录技术：高分辨率成像技术、大型电极微阵列技术等。

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