Attention and Eye Movement in Parkinson's Disease

Official title

Investigating the Role of Attention in Perceptual and Cognitive Consequences of Parkinson's Disease

Overview

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).

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, 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.

Interventions

• Other Normal therapeutic DBS
  Participants will receive deep brain stimulation delivered at the clinically determined therapeutic frequency and current over approximately 20 min.
• Other Reduced current DBS
  Participants will receive deep brain stimulation delivered at the clinically determined therapeutic frequency and reduced (50%) current over approximately 20 minutes.
• Other Reduced frequency DBS
  Participants will receive deep brain stimulation delivered at the clinically determined therapeutic current and reduced (4 Hz) frequency over approximately 20 min.

Primary outcome measures

• Facial Expression Rating [Time frame: 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).]
• Eye Tracking [Time frame: 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).]
• Intraoperative Microrecordings [Time frame: Intraoperative (Day 0; day of DBS implantation surgery).]

Secondary outcome measures (7)

• EEG beta-band power during emotional face rating [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Single experimental visit during the Aim 3 study session (third study visit; through study completion, an average of 6 months).]

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), 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

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), 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Nebraska Medical Center — Omaha

Publications

• McIntyre CC, Hahn PJ. Network perspectives on the mechanisms of deep brain stimulation. Neurobiol Dis. 2010 Jun;38(3):329-37. doi: 10.1016/j.nbd.2009.09.022. Epub 2009 Oct 3. PMID 19804831
• Sugita Y. Face perception in monkeys reared with no exposure to faces. Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):394-8. doi: 10.1073/pnas.0706079105. Epub 2008 Jan 2. PMID 18172214
• W. Penny and A. Holmes. Random effects analysis. Statistical parametric mapping: The analysis of functional brain images, 156:165, 2007.
• Kovach CK, Howard MA 3rd. Decomposition of Higher-Order Spectra for Blind Multiple-Input Deconvolution, Pattern Identification and Separation. Signal Processing. 2019 Dec;165:357-379. doi: 10.1016/j.sigpro.2019.07.007. Epub 2019 Jul 26. PMID 41647176
• C. Kovach, J. Moreira, J. Berger, M. Howard III, L. Gwilliams, A. Fallah, L. Comstock, and E. Mendes. Higher-order spectral decomposition applied to spike sorting. Feb. 2023.
• Tottenham N, Tanaka JW, Leon AC, McCarry T, Nurse M, Hare TA, Marcus DJ, Westerlund A, Casey BJ, Nelson C. The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Res. 2009 Aug 15;168(3):242-9. doi: 10.1016/j.psychres.2008.05.006. Epub 2009 Jun 28. PMID 19564050
• X. Fan, M. Mocchi, B. Pascuzzi, J. Xiao, B. A. Metzger, R. K. Mathura, C. Hacker, J. A. Adkinson, E. Bartoli, S. Elhassa, et al. Brain mechanisms underlying the emotion processing bias in treatment- resistant depression. Nature Mental Health, pages 1-10, 2024.
• Metzger BA, Kalva P, Mocchi MM, Cui B, Adkinson JA, Wang Z, Mathura R, Kanja K, Gavvala J, Krishnan V, Lin L, Maheshwari A, Shofty B, Magnotti JF, Willie JT, Sheth SA, Bijanki KR. Intracranial stimulation and EEG feature analysis reveal affective salience network specialization. Brain. 2023 Oct 3;146(10):4366-4377. doi: 10.1093/brain/awad200. PMID 37293814

Identifiers

NCT: NCT06899022 · 0082-25-FB · P20GM130447

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗