MULTIMODAL MAPPING OF SUBCORTICAL AND CORTICAL FUNCTIONAL NETWORK DISTURBANCES IN FOCAL EPILEPSY
局灶性癫痫皮质下和皮质功能网络紊乱的多模态映射
基本信息
- 批准号:9754262
- 负责人:
- 金额:$ 24.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnatomyAnteriorAtrophicBrainBrain regionCognitionConsciousDependenceDepressed moodDiffuseDiseaseElectrocorticogramEpilepsyExcisionExhibitsFreedomFrequenciesFunctional Magnetic Resonance ImagingFunctional disorderGoalsHumanImage AnalysisImpairmentIndividualLeadLinkMagnetoencephalographyMapsMeasurementMeasuresMedicalModelingMorbidity - disease rateNeocortexNeurocognitiveNeurocognitive DeficitNeuropsychological TestsNeuropsychologyOperative Surgical ProceduresPartial EpilepsiesPatient SelectionPatient-Focused OutcomesPatientsPatternPerioperativePopulationPostoperative PeriodRecording of previous eventsRecurrenceRefractoryReportingRestRodentSeizuresSignal TransductionStructureTechniquesThalamic structureTimealertnessassociation cortexbasal forebrainbasebrain abnormalitiesexecutive functiongray matterimprovedmortalitymultimodalityneocorticalnetwork dysfunctionneural networkneuroregulationneurotransmissionnoveloutcome predictionpreventprofiles in patientsrelating to nervous systemresearch clinical testingtemporal measurement
项目摘要
Epilepsy affects 1% of the population, leading to significant morbidity and mortality. In focal epilepsy, seizures originate from an epileptogenic zone (EZ), and surgical resection leads to seizure-freedom in many patients. However, deleterious effects of focal epilepsy extend beyond the anatomic EZ, including diffuse gray matter atrophy, neocortical hypometabolism, and impaired neurocognitive function. Previous interictal (between seizures) magnetoencephalography studies of functional connectivity in focal epilepsy patients have demonstrated decreased connectivity in association neocortex that is directly related to frequency of consciousness-impairing (but not consciousness-sparing) seizures. Furthermore, prior ictal (during seizures) electrocorticography (ECoG) studies have demonstrated depressed neocortical activity during consciousness-impairing (but not consciousness-sparing) seizures in focal epilepsy. The central hypothesis of the present proposal is that over time, recurrent seizures in focal epilepsy lead to aberrant connections between subcortical activating structures (e.g., thalamus, basal forebrain) and association cortex, resulting in depressed neocortical connectivity that may contribute to neurocognitive dysfunction. To address this hypothesis, the present studies will use functional magnetic resonance imaging (fMRI) to measure interictal functional connectivity between subcortical activating structures and association neocortex in pre-operative focal epilepsy patients vs. controls (Aim 1). Connectivity patterns will be related to seizure type/frequency and neurocognitive parameters. To determine if functional connectivity perturbations are reversible once patients achieve seizure freedom after surgery, fMRI analyses of subcortical-cortical connectivity and neuropsychological tests will be repeated in patients ≥ 1 year post-operatively (Aim 2). Finally, to determine whether abnormal neocortical rhythms during consciousness-impairing seizures (ictal) lead directly to long-term reductions in neocortical connectivity (interictal), dynamic changes in connectivity will be measured before, during, and after seizures using ECoG (Aim 3). It is anticipated that compared to non-epileptic controls, focal epilepsy patients will exhibit reduced subcortical-cortical connectivity on interictal fMRI, which will be related to frequency of consciousness-impairing seizures and neurocognitive dysfunction (Aim 1). However, it is expected that subcortical-cortical functional connectivity perturbations will improve in patients who become seizure free after epilepsy surgery (Aim 2). Finally, it is anticipated that ECoG studies of dynamic functional connectivity will demonstrate ictal reductions in neocortical connectivity during consciousness-impairing seizures compared to baseline, suggesting a direct link between seizure activity and altered neocortical connectivity (Aim 3). A detailed understanding of subcortical-cortical network dysfunction in focal epilepsy gained through these studies may lead to novel targets for neuromodulation-based treatment, improvements in surgical patient selection and outcome prediction, and better strategies to prevent neurocognitive sequelae in this devastating disorder.
癫痫影响1%的人口,导致严重的发病率和死亡率。在局灶性癫痫中,癫痫发作起源于致痫区(EZ),手术切除导致许多患者癫痫发作自由。然而,局灶性癫痫的有害影响超出解剖EZ,包括弥漫性灰质萎缩,新皮层代谢低下和神经认知功能受损。先前局灶性癫痫患者的间歇(癫痫发作之间)脑磁图研究表明,关联新皮层的连通性降低与意识损害(但不是意识保留)癫痫发作的频率直接相关。此外,先前的癫痫发作(癫痫发作期间)脑皮质电图(ECoG)研究表明,在局灶性癫痫的意识损害(但不是意识保留)发作期间,新皮层活动受到抑制。本研究的中心假设是,随着时间的推移,局灶性癫痫的反复发作导致皮层下激活结构(如丘脑、基底前脑)与关联皮层之间的连接异常,导致新皮层连通性下降,可能导致神经认知功能障碍。为了解决这一假设,本研究将使用功能磁共振成像(fMRI)来测量术前局灶性癫痫患者与对照组皮质下激活结构和关联新皮层之间的间期功能连通性(目的1)。连接模式将与癫痫发作类型/频率和神经认知参数有关。为了确定一旦患者术后癫痫发作自由,功能连通性扰动是否可逆,将在术后≥1年的患者中重复皮质下-皮质连通性和神经心理学测试的fMRI分析(目的2)。最后,为了确定在意识受损的癫痫发作(发作间期)期间异常的新皮层节律是否会直接导致新皮层连通性的长期减少(发作间期),将使用ECoG在癫痫发作之前、期间和之后测量连通性的动态变化(目的3)。预计与非癫痫对照相比,局灶性癫痫患者在间期fMRI上表现出皮层下-皮层连通性降低,这将与意识损害癫痫发作和神经认知功能障碍的频率有关(Aim 1)。然而,预计在癫痫手术后无癫痫发作的患者中,皮质下-皮质功能连接紊乱将得到改善(目的2)。最后,预计动态功能连通性的ECoG研究将证明,与基线相比,在意识受损的癫痫发作期间,新皮质连通性显著减少,这表明癫痫发作活动与改变的新皮质连通性之间存在直接联系(目的3)。通过这些研究获得的对局灶性癫痫中皮层下-皮层网络功能障碍的详细了解可能会为基于神经调节的治疗提供新的靶点,改善手术患者的选择和预后预测,以及更好的策略来预防这种毁灭性疾病的神经认知后遗症。
项目成果
期刊论文数量(25)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Deep brain stimulation in pediatric dystonia: a systematic review.
小儿肌张力障碍中的大脑刺激:系统评价。
- DOI:10.1007/s10143-018-1047-9
- 发表时间:2020-06
- 期刊:
- 影响因子:2.8
- 作者:Hale AT;Monsour MA;Rolston JD;Naftel RP;Englot DJ
- 通讯作者:Englot DJ
Seizure Outcomes in Occipital Lobe and Posterior Quadrant Epilepsy Surgery: A Systematic Review and Meta-Analysis.
- DOI:10.1093/neuros/nyx158
- 发表时间:2018-03-01
- 期刊:
- 影响因子:4.8
- 作者:Harward SC;Chen WC;Rolston JD;Haglund MM;Englot DJ
- 通讯作者:Englot DJ
Delayed neurological deficit following resection of tuberculum sellae meningioma: report of two cases, one with permanent and one with reversible visual impairment.
鞍结节脑膜瘤切除术后迟发性神经功能缺损:两例报告,一例为永久性视力障碍,另一例为可逆性视力障碍。
- DOI:10.1007/s00701-014-2046-4
- 发表时间:2014
- 期刊:
- 影响因子:2.4
- 作者:Santarius,T;Jian,BJ;Englot,D;McDermott,MW
- 通讯作者:McDermott,MW
Blunted neural response to emotional faces in the fusiform and superior temporal gyrus may be marker of emotion recognition deficits in pediatric epilepsy.
- DOI:10.1016/j.yebeh.2020.107432
- 发表时间:2020-11
- 期刊:
- 影响因子:0
- 作者:Morningstar M;Hung A;Grannis C;French RC;Mattson WI;Ostendorf AP;Gedela S;Englot DJ;Nelson EE
- 通讯作者:Nelson EE
Multiple Subpial Transections for Medically Refractory Epilepsy: A Disaggregated Review of Patient-Level Data.
医学上难治性癫痫的多次软膜下横切术:患者数据的分类审查。
- DOI:10.1093/neuros/nyx311
- 发表时间:2018
- 期刊:
- 影响因子:4.8
- 作者:Rolston,JohnD;Deng,Hansen;Wang,DorisD;Englot,DarioJ;Chang,EdwardF
- 通讯作者:Chang,EdwardF
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Dario J Englot其他文献
Vagus nerve stimulation versus “best drug therapy” in epilepsy patients who have failed best drug therapy
迷走神经刺激与最佳药物治疗失败的癫痫患者的“最佳药物治疗”
- DOI:
10.1016/j.seizure.2013.02.015 - 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
Dario J Englot - 通讯作者:
Dario J Englot
Dario J Englot的其他文献
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{{ truncateString('Dario J Englot', 18)}}的其他基金
Resting-State Functional Connectivity Analysis in Focal Neocortical Epilepsy
局灶性新皮质癫痫的静息态功能连接分析
- 批准号:
8782165 - 财政年份:2014
- 资助金额:
$ 24.72万 - 项目类别:
Neuroimaging, energetics, and neuronal activity in spike-wave seizures
棘波癫痫发作的神经影像学、能量学和神经元活动
- 批准号:
7620418 - 财政年份:2007
- 资助金额:
$ 24.72万 - 项目类别:
Neuroimaging, energetics, and neuronal activity in spike-wave seizures
棘波癫痫发作的神经影像学、能量学和神经元活动
- 批准号:
7404919 - 财政年份:2007
- 资助金额:
$ 24.72万 - 项目类别:
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