Deciphering principles of network dynamics underlying depression symptom severity from multi-day intracranial recordings in patients with major depression
Deciphering principles of network dynamics underlying depression symptom severity from multi-day intracranial recordings in patients with major depression
批准号:
10321656
负责人:
ANDREW D KRYSTAL
金额:
$20.19万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-01-01 至 2023-12-31
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
中文摘要
项目总结/文摘
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Responsive Neurostimulation for Treatment Resistant Depression
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批准号:10513243
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项目类别:
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财政年份:2023
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负责人:ANDREW D KRYSTAL
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依托单位:
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批准号:9750700
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资助金额:$80.18万
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财政年份:2018
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负责人:ANDREW D KRYSTAL
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依托单位:
Tissue-Specific Insulin Resistance in Obstructive Sleep Apnea: Role of Hypoxia
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批准号:10242721
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项目类别:
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资助金额:$80.41万
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财政年份:2018
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负责人:ANDREW D KRYSTAL
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依托单位:
Tissue-Specific Insulin Resistance in Obstructive Sleep Apnea: Role of Hypoxia
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批准号:10693797
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项目类别:
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资助金额:$80.39万
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财政年份:2018
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负责人:ANDREW D KRYSTAL
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Transcranial Direct Current Stimulation (tDCS) as a Treatment for Acute Fear
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批准号:8874641
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财政年份:2015
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负责人:ANDREW D KRYSTAL
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依托单位:
MGT SVCS/CONTRACT & PROCUREMENT SUP - New Experimental Medicine Studies: Fast-Fail Trials in Mood and Anxiety
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批准号:8919169
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项目类别:
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资助金额:$42.67万
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财政年份:2014
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负责人:ANDREW D KRYSTAL
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依托单位:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
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批准号:8370417
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项目类别:
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资助金额:$23.55万
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财政年份:2012
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负责人:ANDREW D KRYSTAL
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依托单位:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
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批准号:8675289
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项目类别:
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资助金额:$23.55万
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财政年份:2012
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负责人:ANDREW D KRYSTAL
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依托单位:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
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批准号:8839298
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项目类别:
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资助金额:$19.63万
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财政年份:2012
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负责人:ANDREW D KRYSTAL
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依托单位:
2/3-Reducing Suicide Ideation Through Insomnia Treatment (REST-IT)
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批准号:8519569
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项目类别:
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资助金额:$18.84万
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财政年份:2012
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负责人:ANDREW D KRYSTAL
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依托单位:
Nocturnal Deterusor Overactivity In Overactive Bladder Syndrome
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项目类别:
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资助金额:$23.55万
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财政年份:2010
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负责人:ANDREW D KRYSTAL
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依托单位:
Nocturnal Deterusor Overactivity In Overactive Bladder Syndrome
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批准号:8135516
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项目类别:
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资助金额:$23.31万
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财政年份:2010
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负责人:ANDREW D KRYSTAL
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依托单位:
Nocturnal Deterusor Overactivity In Overactive Bladder Syndrome
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批准号:8322514
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项目类别:
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资助金额:$23.31万
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财政年份:2010
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负责人:ANDREW D KRYSTAL
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依托单位:
Biomarkers of the Response to CBT for Insomnia in Major Depression
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批准号:8310260
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项目类别:
-
资助金额:$38.66万
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财政年份:2009
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负责人:ANDREW D KRYSTAL
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依托单位:
Biomarkers of the Response to CBT for Insomnia in Major Depression
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批准号:7936298
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项目类别:
-
资助金额:$39.13万
-
财政年份:2009
-
负责人:ANDREW D KRYSTAL
-
依托单位:
Biomarkers of the Response to CBT for Insomnia in Major Depression
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批准号:8120261
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项目类别:
-
资助金额:$39.06万
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财政年份:2009
-
负责人:ANDREW D KRYSTAL
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依托单位:
Biomarkers of the Response to CBT for Insomnia in Major Depression
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批准号:7763322
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项目类别:
-
资助金额:$41.83万
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财政年份:2009
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负责人:ANDREW D KRYSTAL
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依托单位:
3/3-Improving Depression Outcome by Adding CBT for Insomnia to Antidepressants
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批准号:8072077
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项目类别:
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资助金额:$12.16万
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财政年份:2008
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负责人:ANDREW D KRYSTAL
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依托单位:
3/3-Improving Depression Outcome by Adding CBT for Insomnia to Antidepressants
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批准号:8311829
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项目类别:
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资助金额:$17.83万
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财政年份:2008
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负责人:ANDREW D KRYSTAL
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依托单位:
Behavioral Insomnia Treatment in Chronic Fatigue Syndrome
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项目类别:
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资助金额:$18.83万
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财政年份:2007
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负责人:ANDREW D KRYSTAL
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依托单位:
海外基金