Dystonias, Essential Tremor, Parkinson's Disease (PD)
Conditions
Keywords
Deep Brain Stimulation, Attention, Perception, Eye movement
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 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
OTHERNormal therapeutic DBS
Participants will receive deep brain stimulation delivered at the clinically determined therapeutic frequency and current over approximately 20 min.
OTHERReduced current DBS
Participants will receive deep brain stimulation delivered at the clinically determined therapeutic frequency and reduced (50%) current over approximately 20 minutes.
OTHERReduced frequency DBS
Participants will receive deep brain stimulation delivered at the clinically determined therapeutic current and reduced (4 Hz) frequency over approximately 20 min.
Sponsors
University of Nebraska
National Institute of General Medical Sciences (NIGMS)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
19 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Facial Expression Rating | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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. |
| 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). | 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. |
| 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). | 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. |
| 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). | 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. |
| 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). | 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. |
| 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). | 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. |
| 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). | 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. |
Countries
United States
Contacts
CONTACTChristopher K Kovach, PhD
CONTACTDulce Maroni, PhD
PRINCIPAL_INVESTIGATORChristopher K Kovach, PhD
University of Nebraska
Outcome results
None listed