Cortical Correlates of Gait in Parkinson's Disease: Impact of Medication and Cueing (cueing)

The purpose of the study is to determine the effects of a novel, personalized, tactile cueing system on gait automaticity. The researchers hypothesized that step-synchronized tactile cueing will reduce prefrontal cortex activity (improve automaticity) and improve gait variability (as well as gait speed). The researchers predict that improved automaticity with improved gait variability will be associated with increased activation of other than prefrontal cortical areas while walking (i.e., sensory-motor). To determine the effects of cueing, 60 participants with PD from will be randomized into one, of two, cueing interventions: 1) personalized, step-synchronized tactile cueing and 2) tactile cueing at fixed intervals as an active control group. In addition, the researchers will explore the feasibility and potential benefits of independent use of tactile cueing during a week in daily life for a future clinical trial.

This project will characterize the cortical correlates of gait automaticity, the changes in gait automaticity with cueing in people with Parkinson's Disease, and how these changes translate to improvement in gait and turning. The long-term goal is to unravel the mechanisms of impaired gait automaticity in Parkinson's Disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Diseases; Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Gait Disorders, Neurologic
• Intervention / Treatment: Device: Personalized tactile cueing; Device: Fixed tactile cueing

Detailed Description

Cortical correlates of gait automaticity in Parkinson's disease: impact of cueing

A well-recognized hallmark of healthy walking is automaticity, defined as the ability of the nervous system to successfully coordinate movement with minimal use of attention-demanding, executive resources. It has been proposed that many walking abnormalities in people with Parkinson's disease (PD) are characterized by a shift in locomotor control from healthy automaticity to compensatory, executive control. This shift to less automaticity is potentially detrimental to walking performance as executive control strategies are not optimized for locomotor control, place excessive demands on a limited cognitive reserve, and continuously require attention. It has been hypothesized that as gait becomes more variable, as in people with Parkinson's Disease, control of gait is less automatic, i.e., requires more prefrontal cortex involvement. However, as gait variability is not a direct measure of automaticity, it is controversial whether it truly reflects impaired gait automaticity or impaired gait stability (i.e., dynamic balance). The recent development of wireless, functional, near-infrared spectroscopy (fNIRS) of the brain provides more direct, physiological measures of automaticity, such as reduced prefrontal cortex activity. However, the contribution of other cortical areas to the concept of gait automaticity is largely unknown. Here, for the first time, the researchers will use a full cap fNIRS system to monitor cortical activity in multiple brain areas and wearable, inertial sensors to determine how cognitive abilities, levodopa, and cueing influence gait automaticity.

The effects of cognitive dysfunction and interventions on gait in people with Parkinson's Disease are complex. Impaired executive function has been associated with impaired gait and balance in PD, but it is not known if this relationship is due to the inability to compensate for poor basal ganglia control of gait automaticity with increased prefrontal cortex activity while walking. Sensory cueing may increase gait speed and reduce prefrontal activity but unlike levodopa, it may result in reduced gait variability due to enhanced automaticity. The researchers recently developed a novel type of personalized (triggered by the subject's own walking pattern), step-synchronized tactile stimulation on the wrists to improve the quality of gait and turning in people with Parkinson's Disease. The researchers will now compare the effects of cognitive dysfunction, dopaminergic medication, and tactile cueing on the quality of gait and turning and investigate whether improvements reflect changes in prefrontal activity.

This project will characterize the cortical correlates of gait automaticity, the changes in gait automaticity with cueing in people with PD, and how these changes translate to improvement in gait and turning. The long-term goal is to unravel the mechanisms of impaired gait automaticity in Parkinson's Disease.

The purpose of the study is to determine the effects of a novel, personalized, tactile cueing system on gait automaticity. The researchers hypothesized that step-synchronized tactile cueing will reduce prefrontal cortex activity (improve automaticity) and improve gait variability (as well as gait speed). We predict that improved automaticity with improved gait variability will be associated with increased activation of other than prefrontal cortical areas while walking (i.e., sensory-motor). To determine the effects of cueing, 60 participants with PD from will be randomized into one, of two, cueing interventions: 1) personalized, step-synchronized tactile cueing and 2) tactile cueing at fixed intervals as an active control group. A secondary analysis will explore whether the effect of cueing on gait automaticity is influenced by cognitive dysfunction. In addition, we will explore the feasibility and potential benefits of independent use of tactile cueing during a week in daily life for a future clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martina Mancini, PhD; Phone Number: 5034182600; Email: mancinim@ohsu.edu
• Study Contact Backup: Name: Pablo Burgos, PhD; Phone Number: 9713314101; Email: burgosp@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of idiopathic Parkinson's Disease from movement disorders neurologist with the United Kingdom Brain Bank criteria of bradykinesia with 1 or more of the following - rest tremor, rigidity, and balance problems not from visual, vestibular, cerebellar or proprioceptive conditions
• Without musculoskeletal or peripheral or central nervous system disorders (other than PD) that could significantly affect their balance and gait
• All subjects will be capable of following directions for the protocols and to give informed consent.
• Hoehn & Yahr Levels II-III.

Exclusion Criteria:

• Severe dyskinesia that may affect quality of fNIRS.
• Major musculoskeletal or neurological disorders, structural brain disease, epilepsy, acute illness or health history, other than Parkinson's Disease, significantly affecting gait and turning i.e., peripheral neuropathy with proprioceptive deficits (detected as lack of toe proprioception assessed during the neurological exam at Day 1), musculoskeletal disorders, vestibular problem, head injury, stroke.
• Montreal cognitive assessment (MoCA) score < 21 or dementia that precludes consent to participate or ability to follow testing procedures
• Inability to stand or walk for 2 minutes without an assistive device.
• Idiopathic Parkinson's Disease exclusion criteria: Parkinson plus syndromes such as progressive supranuclear palsy, multiple system atrophy, or corticobasal syndrome or implanted electrodes for deep brain stimulation (DBS), possible vascular parkinsonism, current use of dopamine-blocking agents or cholinesterase inhibitor (as may affect Prefrontal cortical activity while walking).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized cueing; Personalized, step-synchronized tactile cueing, enhancing proprioceptive inputs, in the form of real-time, closed-loop tactile feedback signaling left and right stance times while walking	Device: Personalized tactile cueing; We will use as an external cue, a system of tactile cueing with the purpose of enhancing proprioceptive inputs, in the form of real-time(synchronized to the gait heel strike), closed-loop tactile feedback signaling left and right stance times while walking. Also, the participants use the same system cueing in closed-loop feedback during daily life for one week.; Other Names: personalized
Active Comparator: Fixed cueing; Tactile cueing at fixed intervals, enhancing proprioceptive inputs, in the form of open-loop tactile feedback (fixed rhythm) signaling left and right stance times while walking	Device: Fixed tactile cueing; We will use as an external cue, a system of tactile cueing with the purpose of enhancing proprioceptive inputs, in the form of real-time, open-loop(fixed rhythm) tactile feedback signaling left and right stance times while walking. Also, the participants use the same system cueing in open-loop feedback during daily life for one week.; Other Names: fixed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prefrontal cortex activity	The automaticity of the gait will be measured by the mean of the Prefrontal Cortex activity recorded by an fNIRS system (Artinis Octamon)	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensory, motor and occipital cortex activity	By mean a full cap fnirs device we will estimate the activities of the cortex in the motor, sensorial and parietal regions during 2 minutes of recording during gait, and during turning.	1 day
Gait Variability	Using 6 Opals of the system mobility lab, we will compute the stride time variability	1 week
Gait speed	Using 6 Opals of the system mobility lab, we will compute the gait speed	1 week
Turning duration	Using 6 Opals of the system mobility lab, we will compute the turning duration	1 week
Turning jerkiness	Using 6 Opals of the system mobility lab, we will compute the turning jerkiness as a metrics of smoothness of motion.	1 week

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Study Chair: Patty Carlson-Kuhta, PhD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: April 5, 2023
• First Submitted That Met QC Criteria: April 5, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Balance; Fixed vibrotactile cueing; Personalized vibrotactile cueing
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Neurologic Manifestations; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Nervous System Diseases; Brain Diseases; Movement Disorders; Parkinsonian Disorders; Gait Disorders, Neurologic; Basal Ganglia Diseases
• Other Study ID Numbers: R01HD110389 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request, we can share de-identified data related to study outcomes measures.
• IPD Sharing Time Frame: Data would be available 6 months after the end of data collection. Data will be stored in our laboratory data repository and so will be available indefinitely.
• IPD Sharing Access Criteria: Data will not be stored on a public website, however researchers may contact us for access to the data. We will send data electronically via a secure server.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No