Clinical trial NCT06899022: Attention and Eye Movement in Parkinson's Disease
Official title: Investigating the Role of Attention in Perceptual and Cognitive Consequences of Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Essential Tremor
Parkinson&#39;s Disease (PD)
Keywords: Deep Brain Stimulation
Attention
Perception
Eye movement
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2025-03-27
Enrollment: 138
Sex: ALL
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The interventional component of the study examines whether and how altered level and frequency of deep brain stimulation (DBS) acutely affects eye movement and perception of facial emotion. Participants will be tested in 3 stimulation conditions in random order: normal therapeutic DBS, reduced (50%) current DBS at the normal therapeutic frequency and reduced frequency (4 Hz) at the normal therapeutic current.
Primary purpose: BASIC_SCIENCE

Brief summary: 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 essential tremor (ET). 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 and ET?
* 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 and ET 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 or DBS. Participants with PD and ET 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).

Detailed description: 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, essential tremor (ET) 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.

Eligibility criteria: Inclusion Criteria

* 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) or essential tremor (ET)
  * 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) and essential tremor (ET) 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) and essential tremor (ET) 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

Exclusion Criteria

* 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) and essential tremor (ET) 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) and essential tremor (ET) 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

Primary outcomes:
measure: Facial Expression Rating
timeFrame: Over two experimental sessions, once prior to DBS surgery and once 2-3 weeks after surgery, following clinical optimization of DBS.
measure: Eye Tracking
timeFrame: Over two experimental sessions, once prior to DBS surgery and once 2-3 weeks after surgery, following clinical optimization of DBS.
Secondary outcomes:
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Christopher K Kovach, PhD
role: PRINCIPAL_INVESTIGATOR
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