- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT06899022
파킨슨 병의 관심과 눈 운동
파킨슨 병의 지각적이고인지 적 결과에서 관심의 역할 조사
이 관찰 및 중재 연구의 목표는 치료 적 심해 뇌 자극 (DBS)이 파킨슨 병 (PD) 및 필수 진전 (ET)의 참가자의 관심, 인식 및인지에 어떤 영향을 미치는지 이해하는 것입니다. 대답하려는 주요 질문은 다음과 같습니다.
- PD에서주의와 시력 운동에 대한 통제 장애가 사회적 신호가 어떻게 인식되고 해석되는지를 바꾸는가?
- 치료 적 DBS는 PD와 ET의 사회적 신호에 대한 관심과 지각 적자를 개선하거나 악화합니까?
- DBS는 장애의 다른 측면에 대한 효과적인 치료를 유지하면서 PD에서 정상적인주의 조절을 회복하도록 최적화 될 수 있습니다.
- DBS가 목표로하는 뇌의 일부는주의 통제에 기여합니까?
눈 추적 카메라를 사용하여 조사관은 ET, PD 또는 DBS가없는 건강한 참가자 그룹과 비교하여 PD 및 ET의 참가자가 DBS 요법을 시작하기 전후에 감정의 표현을보고 인식하는 방법을 연구합니다. PD 및 ET를 가진 참가자는 세 가지 조건에서 컴퓨터 화면에서 형태의 얼굴 표정을보고 평가합니다.
- DBS 요법을 시작하기 전에 (약 1 시간 이상).
- 수술실에서, DBS 전극을 이식하는 표준 절차 중에는 참가자가 깨어있는 반면 (15 분 이하).
- DBS 요법을 시작한 후, DBS 자극 수준 및 빈도의 간단한 실험 변화 (약 1 시간 이상).
연구 개요
상세 설명
파킨슨 병 (PD)은 두 번째로 흔한 연령 관련 신경 퇴행성 장애이며, 매년 북미에서 약 90,000 건의 새로운 사례가 진단됩니다. 운동 증상은 장애를 정의하지만 PD는 또한 얼굴 표정을 인식하는 데 어려움과주의를 조절하는 것과 같은인지 및 정서적 변화를 초래하며, 이는 종종 질병이 진행됨에 따라 운동 문제를 어둡게합니다. 이 연구의 목표는 PD의주의, 눈 운동 및 정서적 인식 사이의 연관성을 더 잘 이해하여 관심을 방해하는 가설을 테스트하여 얼굴 감정에 대한 인식을 변화시킨다. 이 연구는 또한 서상상 핵 (STN)의 깊은 뇌 자극 (DBS)이 이러한 과정에 어떤 영향을 미치는지 조사하여 치료의인지 적 및 지각 적 결과에 대한 중요한 통찰력을 제공합니다.
이 연구는주의, 눈의 움직임 및 인식이 어떻게 상호 작용하는지 탐구함으로써 파킨슨 병의 비 운동 증상을 이해하는 데 중요한 차이를 해결합니다. 결과는 PD의인지 및 정서적 증상이주의 조절 조절 장애로 인한 것인지에 대한 증거를 제공하여 이러한 결함을 치료하기위한 새로운 프레임 워크를 제공합니다. 또한,이 연구는 다른 DBS 주파수가 인식과인지에 어떤 영향을 미치는지에 대해 밝히고, 모터 및 비 운동 증상을 완화하기 위해 개인화 된 자극 전략을 안내 할 수 있습니다. 얻은 통찰력은 과학 지식과 환자 치료를 발전시켜 PD에 대한 미래의 요법에 영향을 줄 수 있습니다.
참가자는 DBS를 겪는 PD, DBS (비 PD DBS 효과의 비교 그룹) 및 건강한 연령 및 성별 일치 제어의 세 가지 그룹으로 나뉩니다. 참가자는 안면 모프 등급 작업 (행복, 중립적이거나 슬픈 등급) 및 시각적 검색 작업 (산만 자 사이의 얼굴 찾기)을 완료하고 눈 움직임이 추적됩니다.
첫 번째 연구 목표는 참가자가 감정적 인 얼굴 자극을보고 분류하는 동안 눈 움직임을 추적하여 PD에서 변화된주의가 PD에서 얼굴 감정 인식에 어떤 영향을 미치는지 측정하는 것입니다. 두 번째 목표는 신경 활동의 미세 전극 기록 (MER)을 캡처하여 감정적 인 얼굴을보고 연구자들이주의와 안구 운동을 안내하는 데 STN의 역할을 매핑 할 수 있도록하는 반면, 신경 활동의 미세 전극 기록 (MER)을 포착하여 깨어있는 DBS 수술 중에 주의력 및 지각 과정과 관련된 STN에서 뇌 활동을 특성화하는 것입니다. 세 번째 목표는 다양한 주파수 (높음, 낮음 또는 끄기)에서의 DBS 자극이 다양한 DBS 설정 하에서 뇌 자극이인지 및 지각 기능에 어떤 영향을 미치는지 평가하여 참가자가 시각적 및 지각 적 작업을 수행하도록함으로써주의, 눈 운동 및 정서적 인식에 어떻게 영향을 미치는지 테스트하는 것입니다.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Dulce Maroni, PhD
- 전화번호: 402-836-9751
- 이메일: dmaroni@unmc.edu
연구 연락처 백업
- 이름: Christopher K Kovach, PhD
- 전화번호: 319-471-3372
- 이메일: ckovach@unmc.edu
연구 장소
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Nebraska
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Omaha, Nebraska, 미국, 68198
- 모병
- University of Nebraska Medical Center
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연락하다:
- Dulce V Maroni, PhD
- 전화번호: 402-836-9751
- 이메일: dmaroni@unmc.edu
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수석 연구원:
- Christopher K Kovach, PhD
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
포함 기준
모든 참가자 (AIM 1) :
- 이 연구에 대한 서명 된 사전 동의를 제공하는 능력과 의지
- 버튼 프레스 또는 마우스 제어 전산화 슬라이더를 통해 지각 판단을 표현하는 능력
- 19-90 세
DBS 참가자 (AIM 1) :
- 특발성 파킨슨 병 진단 (PD) 또는 필수 진전 (ET)
- 시상 하부 핵 (STN), 시상의 복부 중간 핵 (VIM) 또는 내부 Globus pallidus (GPI)를 대상으로 한 치료 DBS 장치의 새로운 이식으로 예정되어 있습니다.
비교 참가자 (AIM 1) :
o PD 그룹의 참가자와 일치하는 연령별 선택
파킨슨 병 (PD) 및 필수 진전 (ET) 참가자 (AIM 2) :
- 이 연구에 대한 서명 된 사전 동의를 제공하는 능력과 의지
- 버튼 프레스 또는 마우스 제어 전산화 슬라이더를 통해 지각 판단을 표현하는 능력
- 19-90 세
- 임상 미세 전극 기록을 사용한 Awake DBS 이식 예정 (MER)
- 깨어있는 수술 절차 중에 업무에 기꺼이 참여할 수 있습니다.
파킨슨 병 (PD) 및 필수 진전 (ET) 참가자 (AIM 3) :
- 이 연구에 대한 서명 된 사전 동의를 제공하는 능력과 의지
- 버튼 프레스 또는 마우스 제어 전산화 슬라이더를 통해 지각 판단을 표현하는 능력
- 19-90 세
- DBS의 급성 조작을 기꺼이합니다
- DBS의 급성 변화를 견딜 수 있습니다
제외 기준
모든 참가자 (AIM 1) :
- 얼굴 자극을 지각 적으로 판단하기에 불충분 한 시력을 수정했습니다
- 작업 지침 또는 완전한 작업 요구 사항을 이해할 수 없습니다
DBS 참가자 (AIM 1) :
o 버튼 누르거나 슬라이더를 제어하기 위해 마우스의 사용이 필요한 작업에 관여하기위한 운동 증상의 치료 제어가 충분하지 않음
건강한 비교 참가자 (AIM 1) :
o 신경 퇴행성 장애의 병력
파킨슨 병 (PD) 및 필수 진전 (ET) 참가자 (AIM 2) :
- 얼굴 자극을 지각 적으로 판단하기에 불충분 한 시력을 수정했습니다
- 작업 지침 또는 완전한 작업 요구 사항을 이해할 수 없습니다
- 깨어있는 DBS 이식을받지 않습니다
- 수정되지 않은 시각적 시력은 얼굴 자극을 지각 적으로 판단하기에 불충분합니다
파킨슨 병 (PD) 및 필수 진전 (ET) 참가자 (AIM 3) :
- 얼굴 자극을 지각 적으로 판단하기에 불충분 한 시력을 수정했습니다
- 작업 지침 또는 완전한 작업 요구 사항을 이해할 수 없습니다
- 운동 증상에 대한 치료 효과를 달성하지 못하는 DBS의 실패
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: DBS의 급성 변경
이 연구의 단일 팔에있는 모든 참가자는 1 시간 동안 무작위 순서로 세 가지 조건 하에서 DBS 자극의 급성 변화를 겪게됩니다.
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참가자는 임상 적으로 결정된 치료 빈도 및 약 20 분 동안 전류에서 전달되는 깊은 뇌 자극을 받게됩니다.
참가자는 임상 적으로 결정된 치료 빈도에서 전달 된 깊은 뇌 자극을 받고 약 20 분 동안 전류 감소 (50%).
참가자는 임상 적으로 측정 된 치료 전류 및 약 20 분 동안 감소 된 (4Hz) 빈도에서 전달되는 깊은 뇌 자극을 받게됩니다.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Facial Expression Rating
기간: Baseline (within 2 weeks pre-DBS implantation), intraoperative (Day 0; day of DBS implantation surgery, and post-operative follow-up (2-3 weeks after DBS implantation, following clinical optimization of stimulation parameters).
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Participants will rate facial expression along a continuous scale using a computerized slider, following the affective bias task (ABT) of Bijanki et al. (2014).
The scale is anchored with three descriptors, "Very Sad" at slider value 0 (left), "Neutral", at position 0.5 (middle), and "Very Happy" at 1.0 (right).
Responses are compared between two time points: (1) at the initial pre-surgical testing session and post DBS implantation and (2) at the post-implantation session following clinical optimization of therapeutic parameters, 2-3 weeks after surgery.
The comparison will examine both the direction of any bias of the rating, against normative ratings, and the magnitude of average deviation from normative ratings.
Finally, the ratings will be incorporated into a generalized linear model of gaze position (Kovach 2014) to identify the association between perceived facial expression and characteristic fixation patterns.
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Baseline (within 2 weeks pre-DBS implantation), intraoperative (Day 0; day of DBS implantation surgery, and post-operative follow-up (2-3 weeks after DBS implantation, following clinical optimization of stimulation parameters).
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Eye Tracking
기간: Baseline (within 2 weeks pre-DBS implantation), intraoperative (Day 0; day of DBS implantation surgery, and post-operative follow-up (2-3 weeks after DBS implantation, following clinical optimization of stimulation parameters).
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The location and duration of gaze fixations will be recorded with a remote eye tracking camera.
The location of gaze fixations will be treated as the dependent measure within a generalized linear modeling (GLM) framework for spatial point processes, described in Kovach and Adolphs (2014).
Parameter estimates of the model give the log relative risk of fixation at different locations in the visual scene as a function of the independent measures of the model.
Independent measures include the main effect of (1) Fourier basis functions encoding scene location and its interactions with (2) image rating in the affective bias task of Bijanki et.
al (2014), (3) session and (4) DBS stimulation state.
Measures derived from the GLM model will also include the statistical deviation (e.g.
Kullback-Leibler divergence) from the average distribution of fixations observed in healthy comparison subjects for each image.
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Baseline (within 2 weeks pre-DBS implantation), intraoperative (Day 0; day of DBS implantation surgery, and post-operative follow-up (2-3 weeks after DBS implantation, following clinical optimization of stimulation parameters).
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Intraoperative Microrecordings
기간: Intraoperative (Day 0; day of DBS implantation surgery).
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During the Aim 2 portion of the study, patients undergoing awake DBS surgery as part of standard clinical care will engage in a subset of the face rating tasks during the surgery.
Invasive recordings will be obtained from DBS target structures, including STN, VIM, and GPi using microelectrodes that are placed as part of standard clinical practice.
Spike sorting will be used to identify firing of individual cells and firing rate will compared to eye movements to identify responses associated with shifts of attention in the targeted deep brain structures .
These measures will be compared across movement-disorders populations using mixed-effects linear modeling and other standard statistical procedures.
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Intraoperative (Day 0; day of DBS implantation surgery).
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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EEG beta-band power during emotional face rating
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Spectral power in the beta frequency band (12-30 Hz), expressed in microvolts squared (µV²) and normalized to a pre-stimulus baseline, computed from non-invasive scalp EEG over posterior electrodes during the emotional face rating component of the task.
Measurement tool: 64-channel research-grade scalp EEG with time-frequency decomposition (demodulated band transform).
Group comparisons across PD, ET, DT, and healthy controls and within-participant comparisons across DBS conditions will be made using mixed-effects linear models, comparing power at baseline and modulation of power within a -0.5 to 0.5 s peri-saccade window.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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EEG event-related potential (ERP) amplitude at saccade onset
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Mean amplitude (µV) of the stimulus-locked event-related potential at saccade onset, measured over occipito-temporal electrodes during the 100-300 ms post-stimulus interval (encompassing the N170 component).
Measurement tool: 64-channel research-grade scalp EEG with stimulus-locked averaging.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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EEG beta burst rate, frequency and amplitude during emotional face viewing
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Modulation of beta band activity (12-30 Hz), will be studied in scalp EEG recordings using a published method (Kovach 2026) for identifying oscillatory bursts based on estimation and decomposition of the fourth order spectrum (trispectrum).
Group comparisons across PD, ET, DT, and healthy controls and within-participant comparisons across DBS conditions will be made using mixed-effects linear models, comparing burst rate, amplitude and frequency comparing power at baseline and modulation of power within a -0.5 to 0.5 s peri-saccade window.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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LFP beta-band (12-30 Hz) power during emotional face viewing
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Spectral power in the beta band (12-30 Hz), expressed in microvolts squared (µV²), recorded from chronically implanted DBS electrodes targeting the subthalamic nucleus during eye-tracked task performance.
Measurement tool: voltage telemetry through clinical leads using the BrainSense capability of the Medtronic Percept implantable pulse generator.
Power will be computed via time-frequency decomposition (demodulated band transform) and compared across DBS conditions (normal therapeutic, reduced current, reduced frequency) and across movement-disorder populations using mixed-effects linear models.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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LFP beta burst rate, frequency and amplitude during emotional face viewing
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Modulation of beta band activity (12-30 Hz), will be studied in intracranial LFP recordings using a published method (Kovach et al. 2026) for identifying oscillatory bursts based on estimation and decomposition of the fourth order spectrum (trispectrum).
Group comparisons across PD, ET, DT, and healthy controls and within-participant comparisons across DBS conditions will be made using mixed-effects linear models, comparing burst rate, amplitude and frequency comparing power at baseline and modulation of power within a -0.5 to 0.5 s peri-saccade window.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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LFP theta-band (4-8 Hz) power during emotional face viewing
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Spectral power in the theta frequency band (4-8 Hz), expressed in microvolts squared (µV²) and normalized to a pre-stimulus baseline, computed from non-invasive scalp EEG over fronto-central electrodes during presentation of morphed emotional face stimuli in the affective bias task (Bijanki et al., 2014).
Measurement tool: voltage telemetry through clinical leads using the BrainSense capability of the Medtronic Percept implantable pulse generator.Group comparisons across PD, ET, DT, and healthy controls and within-participant comparisons across DBS conditions will be made using mixed-effects linear models, comparing power at baseline and modulation of power within a -0.5 to 0.5 s peri-saccade window.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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EEG-LFP coherence during emotional face viewing
기간: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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Coherence between scalp EEG recordings and intracranial LFP recordings will be examined across multiple frequencies from 1 Hz to 30 Hz using a time-frequency decomposition (demodulated band transform, Kovach 2016) with 1 Hz frequency bins.
Measurement tool: 64 channel scalp EEG and concurrent voltage telemetry through clinical leads using the BrainSense capability of the Medtronic Percept implantable pulse generator.
Group comparisons of subject-level coherence values across PD, ET, DT, and healthy controls and within-participant comparisons across DBS conditions will be made using mixed-effects linear models, comparing power at baseline and modulation of power within a -0.5 to 0.5 s peri-saccade window.
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Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).
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공동 작업자 및 조사자
수사관
- 수석 연구원: Christopher K Kovach, PhD, University of Nebraska
간행물 및 유용한 링크
일반 간행물
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