Deciphering principles of network dynamics underlying depression symptom severity from multi-day intracranial recordings in patients with major depression
从重度抑郁症患者多日颅内记录中解读抑郁症症状严重程度的网络动态原理
基本信息
- 批准号:10321656
- 负责人:
- 金额:$ 20.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:Absence EpilepsyAcuteAddressAffectAmygdaloid structureAncillary StudyAreaBiological MarkersBrainChronicClinical TrialsConsensusDataData SetDeep Brain StimulationDevelopmentDiagnosisDiagnosticDiseaseElectric StimulationElectrodesElectroencephalographyEpilepsyEtiologyFunctional disorderGoalsHamilton Rating Scale for DepressionHeterogeneityImageImplantIndividualInformation TheoryMachine LearningMajor Depressive DisorderMapsMeasuresMental DepressionMethodsMoodsParentsParticipantPatientsPatternPeriodicityPharmaceutical PreparationsPhysiologic pulsePopulationPropertyPublishingResearchResistanceResolutionRestSeveritiesSiteStructureSymptomsTechniquesTestingTherapeuticTimeWorkbasebiomarker developmentcomorbid depressiondepressive symptomsdiagnostic biomarkerdisabilityexperimental studyinnovationinsightneural networkneuroregulationnovelnovel strategiespatient subsetsrelating to nervous systemresponsetargeted treatmenttemporal measurementtherapeutic targettooltraittranslational potentialtreatment-resistant depression
项目摘要
PROJECT SUMMARY/ABSTRACT
Major depressive disorder (MDD) is common and causes significant disability world-wide. While typically
responsive to medications and therapy, there remain a subset of patients who are treatment resistant. Novel
approaches are critical to treat these patients. MDD is likely caused by dysfunction in distributed neural networks,
a perspective consistent with the etiological and diagnostic heterogeneity of this disorder. While imaging and
electroencephalography (EEG) have helped identify MDD circuitry, no consensus has been reached on the
identification of diagnostic biomarkers. Furthermore, the dynamics of MDD circuitry in relation to symptom
severity is unknown. Characterization of circuit signatures that define MDD symptom severity states and the
extent to which these circuits are modifiable using electrical stimulation are critical for therapeutic advancement.
Intracranial EEG (iEEG) offers a high spatial and temporal resolution method to study depression networks.
For the first time, we have an unparalleled opportunity to study such circuits in MDD patients participating in a
clinical trial of personalized responsive neurostimulation for treatment resistant depression (PRESIDIO). In stage
1 of this trial, participants are implanted with 160 electrodes from 10 sub-chronic intracranial leads across 10
brain sites for 10 days. The goal of this parent study stage is to optimize brain-site targeting for deep brain
stimulation. In this proposal, we will leverage the opportunity to study MDD circuit principles from cortical and
deep brain structures over a multi-day time period.
In an ancillary study to this parent clinical trial, we propose a set of experiments that establish basic principles
of network dynamics underlying MDD from direct neural recordings. This proposal is organized around the
principal concept that brain circuit dysfunction is reflected in abnormal signatures of functional connectivity and
rhythmic local-field activity. This concept is supported by our pilot work where we found evidence of distinct MDD
networks characterized by functional connectivity and spectral activity. Furthermore, in the first parent trial
participant we successfully mapped MDD circuits at the individual level and found that gamma power in the
amygdala could successfully decode mood state (AUC = 86%). This proposal builds on these preliminary findings
in two aims. In Aim 1, we will characterize state-dependent functional connectivity and spectral activity in relation
to symptom severity. In Aim 2, we will examine the manner and time course in which targeted electrical
stimulation acutely modifies circuits. Together, this research will yield the first characterization of connectivity
and activity dynamics in MDD over a multi-day period from direct neural recordings. This rare insight into MDD
circuity provided by this novel dataset establishes proof-of-concept principles for biomarker development and
therapeutic target selection that could critically advance personalized MDD treatments.
项目概要/摘要
重度抑郁症 (MDD) 很常见,并在世界范围内导致严重残疾。虽然通常
对药物和治疗有反应,但仍有一小部分患者对治疗有抵抗力。小说
方法对于治疗这些患者至关重要。 MDD 很可能是由分布式神经网络功能障碍引起的,
与该疾病的病因学和诊断异质性一致的观点。在成像和
脑电图 (EEG) 有助于识别 MDD 电路,但尚未达成共识
诊断生物标志物的鉴定。此外,MDD 电路的动态与症状相关
严重程度未知。定义 MDD 症状严重程度状态的电路签名特征和
使用电刺激可在多大程度上修改这些电路对于治疗进展至关重要。
颅内脑电图 (iEEG) 提供了一种高空间和时间分辨率的方法来研究抑郁网络。
这是我们第一次有无与伦比的机会来研究 MDD 患者的此类回路,参与一项研究。
个性化反应性神经刺激治疗难治性抑郁症的临床试验(PRESIDIO)。舞台上
在该试验的第 1 项中,参与者被植入来自 10 个亚慢性颅内导线的 160 个电极,分布在 10
大脑部位10天。该父级研究阶段的目标是优化深部大脑的大脑部位靶向
刺激。在本提案中,我们将利用这个机会从皮质和
多天时间内的深层大脑结构。
在该母体临床试验的辅助研究中,我们提出了一系列实验来建立基本原理
来自直接神经记录的 MDD 背后的网络动力学。该提案围绕
主要概念是脑回路功能障碍反映在功能连接和功能的异常特征中
有节奏的局部场活动。这个概念得到了我们的试点工作的支持,我们发现了不同 MDD 的证据
以功能连接和频谱活动为特征的网络。此外,在第一次家长审判中
参与者,我们成功地绘制了个体层面的 MDD 电路,并发现伽马功率
杏仁核可以成功解码情绪状态(AUC = 86%)。该提案建立在这些初步发现的基础上
有两个目标。在目标 1 中,我们将描述与状态相关的功能连接性和光谱活动的关系
症状的严重程度。在目标 2 中,我们将研究目标电力的方式和时间过程。
刺激会急剧改变电路。总之,这项研究将得出连接性的第一个特征
以及来自直接神经记录的多日内 MDD 的活动动态。这种对 MDD 的罕见洞察
这个新颖的数据集提供的电路建立了生物标志物开发的概念验证原则
治疗靶点的选择可以极大地推进个性化 MDD 治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ANDREW D KRYSTAL其他文献
ANDREW D KRYSTAL的其他文献
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{{ truncateString('ANDREW D KRYSTAL', 18)}}的其他基金
Responsive Neurostimulation for Treatment Resistant Depression
反应性神经刺激治疗难治性抑郁症
- 批准号:
10513243 - 财政年份:2023
- 资助金额:
$ 20.19万 - 项目类别:
Tissue-Specific Insulin Resistance in Obstructive Sleep Apnea: Role of Hypoxia
阻塞性睡眠呼吸暂停中的组织特异性胰岛素抵抗:缺氧的作用
- 批准号:
9750700 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
Tissue-Specific Insulin Resistance in Obstructive Sleep Apnea: Role of Hypoxia
阻塞性睡眠呼吸暂停中的组织特异性胰岛素抵抗:缺氧的作用
- 批准号:
10693797 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
Tissue-Specific Insulin Resistance in Obstructive Sleep Apnea: Role of Hypoxia
阻塞性睡眠呼吸暂停中的组织特异性胰岛素抵抗:缺氧的作用
- 批准号:
10242721 - 财政年份:2018
- 资助金额:
$ 20.19万 - 项目类别:
Transcranial Direct Current Stimulation (tDCS) as a Treatment for Acute Fear
经颅直流电刺激 (tDCS) 治疗急性恐惧
- 批准号:
8874641 - 财政年份:2015
- 资助金额:
$ 20.19万 - 项目类别:
MGT SVCS/CONTRACT & PROCUREMENT SUP - New Experimental Medicine Studies: Fast-Fail Trials in Mood and Anxiety
MGT SVCS/合同
- 批准号:
8919169 - 财政年份:2014
- 资助金额:
$ 20.19万 - 项目类别:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
2/3-通过失眠治疗减少自杀意念 (REST-IT)
- 批准号:
8839298 - 财政年份:2012
- 资助金额:
$ 20.19万 - 项目类别:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
2/3-通过失眠治疗减少自杀意念 (REST-IT)
- 批准号:
8675289 - 财政年份:2012
- 资助金额:
$ 20.19万 - 项目类别:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
2/3-通过失眠治疗减少自杀意念 (REST-IT)
- 批准号:
8519569 - 财政年份:2012
- 资助金额:
$ 20.19万 - 项目类别:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
2/3-通过失眠治疗减少自杀意念 (REST-IT)
- 批准号:
8370417 - 财政年份:2012
- 资助金额:
$ 20.19万 - 项目类别:
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