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Aandacht en oogbeweging bij de ziekte van Parkinson
Onderzoek naar de rol van aandacht in perceptuele en cognitieve gevolgen van de ziekte van Parkinson
Het doel van dit observationele en interventionele onderzoek is om te begrijpen hoe therapeutische diepe hersenstimulatie (DBS) de aandacht, perceptie en cognitie bij deelnemers met de ziekte van Parkinson (PD) en essentiële tremor (ET) beïnvloedt. De belangrijkste vragen die het wil beantwoorden zijn:
- Verandert een verminderde controle over aandacht en oogbeweging in PD hoe sociale signalen worden waargenomen en geïnterpreteerd?
- Verbetert therapeutische DB's de aandachts- en perceptuele tekorten voor sociale signalen in PD en ET?
- Kunnen DB's worden geoptimaliseerd om de normale aandachtscontrole in PD te herstellen en tegelijkertijd een effectieve therapie te blijven voor andere aspecten van de aandoening.
- Wat dragen delen van de hersenen die door DBS zijn gericht op de controle van de aandacht?
Met behulp van een eye -trackingcamera zullen onderzoekers bestuderen hoe deelnemers met PD en ET kijken naar gezichtsuitdrukkingen van emotie voor en na het starten van DBS -therapie, in vergelijking met een groep gezonde deelnemers zonder ET, PD of DBS. Deelnemers met PD en ET zullen veranderde gezichtsuitdrukkingen op een computerscherm zien en beoordelen in drie voorwaarden:
- Voordat u begint met DBS -therapie (meer dan ongeveer 1 uur).
- In de operatiekamer, tijdens de standaardprocedure om DBS -elektroden te implanteren, terwijl de deelnemer wakker is (voor niet meer dan 15 minuten).
- Na het starten van DBS -therapie, met korte experimentele veranderingen van DBS -stimulatieniveau en frequentie (gedurende ongeveer 1 uur).
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
De ziekte van Parkinson (PD) is de tweede meest voorkomende leeftijdsgebonden neurodegeneratieve aandoening, met ongeveer 90.000 nieuwe gevallen die jaarlijks worden gediagnosticeerd in Noord-Amerika. Hoewel motorische symptomen de aandoening definiëren, leidt PD ook tot cognitieve en emotionele veranderingen, zoals moeilijkheden bij het herkennen van gezichtsuitdrukkingen en het reguleren van aandacht, die vaak motorische problemen overschaduwen naarmate de ziekte vordert. Het doel van deze studie is om het verband tussen aandacht, oogbeweging en emotionele perceptie in PD beter te begrijpen, het testen van de hypothese die verstoorde aandacht leidt tot een veranderde perceptie van gezichtsemoties. De studie zal ook onderzoeken hoe diepe hersenstimulatie (DBS) van de subthalamische kern (STN) deze processen beïnvloedt, waardoor kritische inzichten worden geboden in de cognitieve en perceptuele gevolgen van de behandeling.
Dit onderzoek behandelt een kritische kloof bij het begrijpen van niet-motorische symptomen van de ziekte van Parkinson door te onderzoeken hoe aandacht, oogbeweging en perceptie interageren. Bevindingen zullen bewijs leveren over de vraag of cognitieve en emotionele symptomen in PD voortkomen uit een verminderde aandachtscontrole, die een nieuw kader bieden voor de behandeling van deze tekorten. Bovendien zal de studie licht werpen op hoe verschillende DBS-frequenties de perceptie en cognitie beïnvloeden, waardoor gepersonaliseerde stimulatiestrategieën mogelijk worden geleid om zowel motorische als niet-motorische symptomen te verlichten. De verkregen inzichten kunnen de toekomstige therapieën voor PD beïnvloeden en zowel wetenschappelijke kennis als patiëntenzorg bevorderen.
Deelnemers worden onderverdeeld in drie groepen: PD die DBS ondergaan, essentiële tremor (ET) die DB's ondergaan (als een vergelijkingsgroep voor niet-PD DBS-effecten) en gezonde leeftijds- en geslachtsgebonden controles. Deelnemers zullen de gezichtstaken voor gezichtsbeoordeling voltooien (beoordelingsgezichten als gelukkig, neutraal of verdrietig) en visuele zoektaken (het vinden van gezichten onder afleiders), terwijl hun oogbewegingen worden gevolgd.
Het eerste onderzoeksdoel is om te meten hoe veranderde aandacht de perceptie van de gezichtsemotie in PD beïnvloedt door oogbewegingen te volgen, terwijl deelnemers emotionele gezichtsstimuli bekijken en categoriseren. Het tweede doel is om hersenactiviteit in de STN te karakteriseren die verband hield met aandachts- en perceptuele processen tijdens wakkere DBS -chirurgie door micro -elektrode -opnames (MER) van neurale activiteiten vast te leggen, terwijl deelnemers emotionele gezichten bekijken, waardoor onderzoekers de rol van STN in kaart kunnen brengen bij het begeleiden van aandacht en oogbewegingen. Het derde doel is om te testen hoe DBS -stimulatie bij verschillende frequenties (hoog, laag of uit) de aandacht, oogbeweging en emotionele perceptie beïnvloedt door deelnemers visuele en perceptuele taken uit te voeren onder verschillende DBS -instellingen om te evalueren hoe hersenstimulatie cognitieve en perceptuele functies beïnvloedt.
Studietype
Inschrijving (Geschat)
Fase
- Niet toepasbaar
Contacten en locaties
Studiecontact
- Naam: Dulce Maroni, PhD
- Telefoonnummer: 402-836-9751
- E-mail: dmaroni@unmc.edu
Studie Contact Back-up
- Naam: Christopher K Kovach, PhD
- Telefoonnummer: 319-471-3372
- E-mail: ckovach@unmc.edu
Studie Locaties
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Nebraska
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Omaha, Nebraska, Verenigde Staten, 68198
- Werving
- University of Nebraska Medical Center
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Contact:
- Dulce V Maroni, PhD
- Telefoonnummer: 402-836-9751
- E-mail: dmaroni@unmc.edu
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Hoofdonderzoeker:
- Christopher K Kovach, PhD
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
Inclusiecriteria
Alle deelnemers (doel 1):
- Vermogen en bereidheid om ondertekende geïnformeerde toestemming voor deze studie te bieden
- Mogelijkheid om perceptuele oordelen uit te drukken via een knop Druk op of muisgestuurde geautomatiseerde schuifregelaar
- Leeftijd 19 - 90 jaar
DBS -deelnemers (doel 1):
- Diagnose van de ziekte van idiopathische Parkinson (PD) of Essential Tremor (ET)
- Gepland voor nieuwe implantatie van een therapeutisch DBS -apparaat gericht op subthalamische kern (STN), ventrale intermediaire kern van thalamus (vim) of interne globus pallidus (GPI)
Vergelijking Deelnemers (Doel 1):
o Selectie per leeftijd matching met deelnemers aan PD Group
De ziekte van Parkinson (PD) en Essential Tremor (ET) deelnemers (AIM 2):
- Vermogen en bereidheid om ondertekende geïnformeerde toestemming voor deze studie te bieden
- Mogelijkheid om perceptuele oordelen uit te drukken via een knop Druk op of muisgestuurde geautomatiseerde schuifregelaar
- Leeftijd 19 - 90 jaar
- Gepland voor wakker DBS-implantatie met klinische micro-elektrode-opnames (MER)
- Bereid en in staat om taken uit te voeren tijdens een wakkere chirurgische procedure
De ziekte van Parkinson (PD) en Essential Tremor (ET) deelnemers (AIM 3):
- Vermogen en bereidheid om ondertekende geïnformeerde toestemming voor deze studie te bieden
- Mogelijkheid om perceptuele oordelen uit te drukken via een knop Druk op of muisgestuurde geautomatiseerde schuifregelaar
- Leeftijd 19 - 90 jaar
- Bereid om acute manipulaties van DBS te ondergaan
- In staat om acute veranderingen van DBS te verdragen
Uitsluitingscriteria
Alle deelnemers (doel 1):
- Gecorrigeerde gezichtsscherpte onvoldoende om de gezichtsstimuli perceptueel te beoordelen
- Onvermogen om taakinstructies te begrijpen of taakvereisten te volledige taakvereisten
DBS -deelnemers (doel 1):
o Onvoldoende therapeutische controle van motorische symptomen om taken uit te voeren die knop moeten drukken op of gebruik van een muis om een schuifregelaar te regelen
Gezonde vergelijking deelnemers (doel 1):
o Geschiedenis van neurodegeneratieve stoornis
De ziekte van Parkinson (PD) en Essential Tremor (ET) deelnemers (AIM 2):
- Gecorrigeerde gezichtsscherpte onvoldoende om de gezichtsstimuli perceptueel te beoordelen
- Onvermogen om taakinstructies te begrijpen of taakvereisten te volledige taakvereisten
- Geen wakker DBS -implantatie ondergaan
- Niet -gecorrigeerde gezichtsscherpte onvoldoende om de gezichtsstimuli perceptueel te beoordelen
De ziekte van Parkinson (PD) en Essential Tremor (ET) deelnemers (AIM 3):
- Gecorrigeerde gezichtsscherpte onvoldoende om de gezichtsstimuli perceptueel te beoordelen
- Onvermogen om taakinstructies te begrijpen of taakvereisten te volledige taakvereisten
- Falen van DBS om een therapeutisch effect op motorische symptomen te bereiken
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Fundamentele wetenschap
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Acute wijziging van DBS
Alle deelnemers aan de enkele arm van deze studie zullen acute wijziging van DBS -stimulatie ondergaan onder drie omstandigheden in gerandomiseerde volgorde gedurende 1 uur.
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Deelnemers ontvangen diepe hersenstimulatie geleverd op de klinisch bepaalde therapeutische frequentie en stroom gedurende ongeveer 20 minuten.
Deelnemers ontvangen diepe hersenstimulatie geleverd bij de klinisch bepaalde therapeutische frequentie en verminderde (50%) stroom gedurende ongeveer 20 minuten.
Deelnemers ontvangen diepe hersenstimulatie geleverd bij de klinisch bepaalde therapeutische stroom en verminderde (4 Hz) frequentie gedurende ongeveer 20 minuten.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Facial Expression Rating
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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EEG beta-band power during emotional face rating
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Hoofdonderzoeker: Christopher K Kovach, PhD, University of Nebraska
Publicaties en nuttige links
Algemene publicaties
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- C. K. Kovach and M. A. Howard III. Decomposition of higher-order spectra for blind multiple-input deconvolution, pattern identification and separation. Signal Processing, 165:357-379, 2019.
- 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.
- 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.
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