Investigating the Role of Attention in Perceptual and Cognitive Consequences of Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Facial Expression Rating
研究概览
简要总结
The goal of this observational and interventional study is to understand how therapeutic deep brain stimulation (DBS) affects attention, perception and cognition in participants with Parkinson's disease (PD) and non-PD movement disorders, including essential tremor (ET) and dystonia (DT). The main questions it aims to answer are:
- Does impaired control of attention and eye movement in PD alter how social cues are perceived and interpreted?
- Does therapeutic DBS improve or worsen attentional and perceptual deficits for social cues in PD, ET and DT?
- Can DBS be optimized to restore normal attentional control in PD while remaining an effective therapy for other aspects of the disorder.
- What do parts of the brain targeted by DBS contribute to the control of attention?
Using an eye tracking camera, investigators will study how participants with PD, ET and DT look at and perceive facial expressions of emotion before and after starting DBS therapy, in comparison to a group of healthy participants without ET, PD, DT or DBS. Participants with PD, ET and DT will see and rate morphed facial expressions on a computer screen in three conditions:
- Before starting DBS therapy (over approximately 1 hour).
- In the operating room, during the standard procedure to implant DBS electrodes, while the participant is awake (for no more than 15 minutes).
- After starting DBS therapy, with brief experimental changes of DBS stimulation level and frequency (over approximately 1 hour).
详细描述
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, with approximately 90,000 new cases diagnosed annually in North America. Although motor symptoms define the disorder, PD also leads to cognitive and emotional changes, such as difficulties in recognizing facial expressions and regulating attention, which often overshadow motor issues as the disease progresses. The goal of this study is to better understand the link between attention, eye movement, and emotional perception in PD, testing the hypothesis that disrupted attention leads to altered perception of facial emotions. The study will also investigate how deep brain stimulation (DBS) of the subthalamic nucleus (STN) affects these processes, providing critical insights into the cognitive and perceptual consequences of the treatment.
This research addresses a critical gap in understanding non-motor symptoms of Parkinson's disease by exploring how attention, eye movement, and perception interact. Findings will provide evidence on whether cognitive and emotional symptoms in PD stem from impaired attentional control, offering a new framework for treating these deficits. Additionally, the study will shed light on how different DBS frequencies affect perception and cognition, potentially guiding personalized stimulation strategies to alleviate both motor and non-motor symptoms. The insights gained may influence future therapies for PD, advancing both scientific knowledge and patient care.
Participants will be divided into three groups: PD undergoing DBS, non-PD movement disorders, essential tremor (ET) and dystonia (DT) undergoing DBS (as a comparison group for non-PD DBS effects) and healthy age- and sex-matched controls. Participants will complete facial morph rating tasks (rating faces as happy, neutral, or sad) and visual search tasks (finding faces among distractors), while their eye movements are tracked.
The first study aim is to measure how altered attention influences facial emotion perception in PD by tracking eye movements while participants view and categorize emotional face stimuli. The second aim is to characterize brain activity in the STN related to attentional and perceptual processes during awake DBS surgery by capturing microelectrode recordings (MER) of neural activity while participants view emotional faces, allowing researchers to map STN's role in guiding attention and eye movements. The third aim is to test how DBS stimulation at different frequencies (high, low, or off) affects attention, eye movement, and emotional perception by having participants perform visual and perceptual tasks under varying DBS settings to evaluate how brain stimulation influences cognitive and perceptual functions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Participants (Aim 1):
- •Ability and willingness to provide signed informed consent for this study
- •Ability to express perceptual judgments through a button press or mouse- controlled computerized slider
- •Age 19 - 90 years
- •DBS Participants (Aim 1):
- •Diagnosis of idiopathic Parkinson's disease (PD), essential tremor (ET) or dystonia (DT).
- •Scheduled for new implantation of a therapeutic DBS device targeted to subthalamic nucleus (STN), ventral intermediate nucleus of thalamus (VIM) or internal globus pallidus (GPi)
- •Comparison Participants (Aim 1):
- •o Selection by age matching to participants in PD group
- •Parkinson's disease (PD), essential tremor (ET) and dystonia (DT) Participants (Aim 2):
- •Ability and willingness to provide signed informed consent for this study
- •Ability to express perceptual judgments through a button press or mouse- controlled computerized slider
- •Age 19 - 90 years
- •Scheduled for awake DBS implantation with clinical micro-electrode recordings (MER)
- •Willing and able to engage in tasks during an awake surgical procedure
- •Parkinson's disease (PD), essential tremor (ET) and dystonia (DT) Participants (Aim 3):
- •Ability and willingness to provide signed informed consent for this study
- •Ability to express perceptual judgments through a button press or mouse- controlled computerized slider
- •Age 19 - 90 years
- •Willing to undergo acute manipulations of DBS
- •Able to tolerate acute changes of DBS
排除标准
- •All Participants (Aim 1):
- •Corrected visual acuity insufficient to perceptually judge face stimuli
- •Inability to understand task instructions or complete task requirements
- •DBS Participants (Aim 1):
- •o Insufficient therapeutic control of motor symptoms to engage in tasks requiring button press or use of a mouse to control a slider
- •Healthy Comparison Participants (Aim 1):
- •o History of neurodegenerative disorder
- •Parkinson's disease (PD), essential tremor (ET) and dystonia (DT) Participants (Aim 2):
- •Corrected visual acuity insufficient to perceptually judge face stimuli
- •Inability to understand task instructions or complete task requirements
- •Not undergoing awake DBS implantation
- •Uncorrected visual acuity insufficient to perceptually judge face stimuli
- •Parkinson's disease (PD), essential tremor (ET) and dystonia (DT) Participants (Aim 3):
- •Corrected visual acuity insufficient to perceptually judge face stimuli
- •Inability to understand task instructions or complete task requirements
- •Failure of DBS to achieve a therapeutic effect on motor symptoms
研究组 & 干预措施
Acute alteration of DBS
All participants in the single arm of this study will undergo acute alteration of DBS stimulation under three conditions in randomized order over the course of 1 hour.
干预措施: Normal therapeutic DBS (Other)
Acute alteration of DBS
All participants in the single arm of this study will undergo acute alteration of DBS stimulation under three conditions in randomized order over the course of 1 hour.
干预措施: Reduced current DBS (Other)
Acute alteration of DBS
All participants in the single arm of this study will undergo acute alteration of DBS stimulation under three conditions in randomized order over the course of 1 hour.
干预措施: Reduced frequency DBS (Other)
结局指标
主要结局
Facial Expression Rating
时间窗: 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).
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.
Eye Tracking
时间窗: 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).
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.
Intraoperative Microrecordings
时间窗: Intraoperative (Day 0; day of DBS implantation surgery).
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.
次要结局
- EEG beta-band power during emotional face rating(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)
- EEG event-related potential (ERP) amplitude at saccade onset(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)
- LFP theta-band (4-8 Hz) power during emotional face viewing(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)
- EEG beta burst rate, frequency and amplitude during emotional face viewing(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)
- LFP beta-band (12-30 Hz) power during emotional face viewing(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)
- LFP beta burst rate, frequency and amplitude during emotional face viewing(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)
- EEG-LFP coherence during emotional face viewing(Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).)