Mechanisms of Manual Therapies in CAI Patients

Ankle Inversion Sprain Clinical Trial

Official title:

Neuromuscular Mechanisms of Manual Therapies in Chronic Ankle Instability Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03418051
• Other study ID #: 17-2655
• Secondary ID: 1R21AT009704-01
• Status: Completed
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: October 9, 2020

Study information

• Verified date: July 2021
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ABSTRACT:

Injury associated with sport and recreation is a leading reason for physical activity cessation, which is linked with significant long-term negative consequences. Lateral ankle sprains are the most common injuries associated with physical activity and at least 40% of individuals who sprain their ankle will go on to develop chronic ankle instability (CAI), a multifaceted condition linked with life-long residual symptoms and post-traumatic ankle osteoarthritis. Our long term goal is to develop intervention strategies to decrease disability associated with acute and chronic ankle injury and prevent posttraumatic ankle osteoarthritis. Conventional rehabilitation strategies, are only moderately successful because they ignore the full spectrum of residual symptoms associated with CAI. Manual therapies such as ankle joint mobilizations and plantar massage target sensory pathways not addressed by conventional treatments and have been shown to improve patient-reported outcomes, dorsiflexion range of motion, and postural control in CAI patients. While these early results are promising, the underlying neuromuscular mechanisms of these manual therapies remain unknown. Therefore the objective of this R21 proposal is to determine the neuromuscular mechanisms underlying the improvements observed following independent ankle joint mobilization and plantar massage interventions in CAI patients. To comprehensively evaluate the neuromuscular mechanisms of the experimental treatments, baseline assessments of peripheral (ankle joint proprioception, light-touch detection thresholds, spinal (H-Reflex of the soleus and fibularis longus), and supraspinal mechanisms (cortical activation, cortical excitability, and cortical mapping, sensory organization) will be assessed. Participants will then be randomly assigned to receive ankle joint mobilizations (n=20), plantar massage (n=20), or a control intervention (n=20) which will consist of 6, 5-minute treatments over 2-weeks. Post-intervention assessments will be completed within 48-hours of the final treatment session. Separate ANOVAs will assess the effects of treatment group (ankle joint mobilization, plantar massage, control) and time (baseline, post-treatment) on peripheral, spinal, and supraspinal neuromuscular mechanisms in CAI participants. Associations among neuromuscular mechanisms and secondary measures (biomechanics and postural control) will also be assessed. The results of this investigation will elucidate multifaceted mechanisms of novel and effective manual therapies (ankle joint mobilizations and plantar massage) in those with CAI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 9, 2020
• Est. primary completion date: October 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion criteria:

Individuals with Chronic Ankle Instability which will be defined as those individuals who:

• have sustained at least two lateral ankle sprains;

• have experienced at least one episode of giving way within the past 6-months;

• answer 4 or more questions of "yes" on the Ankle Instability Instrument;

• have self-assessed disability scores of =90% on the Foot and Ankle Ability Measure;

• have self-assessed disability scores =80% on the Foot and Ankle Ability Measure-Sport.

Exclusion criteria for Chronic Ankle Instability will include:

• known vestibular and vision problems,

• acute lower extremities and head injuries (<6 weeks),

• chronic musculoskeletal conditions known to affect balance (e.g., Anterior Cruciate Ligament deficiency) and

• a history of ankle surgeries to fix internal derangement.

Participants will also be excluded if they have any of the following which are contraindications to Transcranial Magnetic Stimulation testing:

• metal anywhere in the head (except in the mouth),

• pacemakers,

• implantable medical pumps,

• ventriculo-peritoneal shunts,

• intracardiac lines,

• history of seizures,

• history of stroke

• history of serious head trauma.

Related Conditions & MeSH terms

• Ankle Inversion Sprain
• Chronic Instability of Joint
• Joint Instability

Intervention

Other:
• Joint Mobilization
Participants will receive 6, 5-minute treatment sessions over 2-weeks. Each session will consist of 2, 2-minute bouts of Grade II anterior to posterior ankle joint mobilizations with 1-minute between sets. Mobilizations will be large-amplitude, 1-s rhythmic oscillations from the mid- to end range of arthrokinematic motion.
• Massage
Participants will receive 6, 5-minute treatment sessions over 2-weeks. Each session will consist of 2, 2-minute bouts of plantar massage with 1-minute between sets. The massage will be a combination of petrissage and effleurage to the entire plantar surface.

Locations

Country	Name	City	State
United States	Fetzer Hall	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Walking Ankle Dorsiflexion at Baseline	Dorsiflexion angle of the ankle at initial contact while walking.	Baseline
Other	Walking Ankle Dorsiflexion Immediately Post Intervention	Dorsiflexion angle of the ankle at initial contact while walking.	24-72 hours post intervention
Other	Walking Ankle Dorsiflexion at 4-weeks Post Intervention	Dorsiflexion angle of the ankle at initial contact while walking.	4-weeks post intervention
Other	Walking Loading Rate at Baseline	Rate of weight acceptance while walking	Baseline
Other	Walking Loading Rate Immediately Post Intervention	Rate of weight acceptance while walking	24-72 hours post intervention
Other	Walking Loading Rate at 4-weeks Post Intervention	Rate of weight acceptance while walking	4-weeks post intervention
Other	Landing Ankle Dorsiflexion at Baseline	Dorsiflexion angle of the ankle at initial contact while landing from a jump	Baseline
Other	Landing Ankle Dorsiflexion Immediately Post Intervention	Dorsiflexion angle of the ankle at initial contact while landing from a jump	24-72 hours post intervention
Other	Landing Ankle Dorsiflexion at 4-weeks Post Intervention	Dorsiflexion angle of the ankle at initial contact while landing from a jump	4-weeks post intervention
Other	Landing Loading Rate at Baseline	Rate of weight acceptance while landing from a jump	Baseline
Other	Landing Loading Rate Immediately Post Intervention	Rate of weight acceptance while landing from a jump	24-72 hours post intervention
Other	Landing Loading Rate at 4-weeks Post Intervention	Rate of weight acceptance while landing from a jump	4-weeks post intervention
Primary	ML COP Velocity From Baseline to Post Intervention	% Modulation of ML COP velocity.; First, center of pressure (COP) is calculated in the mediolateral (ML) direction [side to side] with eyes open and closed. COP velocity represents the average speed at which an individual's COP moves during the 10 second single limb stance trial.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in ML COP Velocity that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes closed balance score - eyes open balance score) / eyes open balance score. Positive scores indicate a greater reliance on visual information as ML COP velocity increased when eyes were closed relative to the eyes open condition. A ML COP velocity change greater than the eyes open value would result in a value >100%. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Primary	ML COP Velocity From Baseline to Follow-Up	% Modulation of ML COP velocity.; First, center of pressure (COP) is calculated in the mediolateral (ML) direction [side to side] with eyes open and closed. COP velocity represents the average speed at which an individual's COP moves during the 10 second single limb stance trial.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in ML COP Velocity that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes closed balance score - eyes open balance score) / eyes open balance score. Positive scores indicate a greater reliance on visual information as ML COP velocity increased when eyes were closed relative to the eyes open condition. A ML COP velocity change greater than the eyes open value would result in a value >100%. This analysis focused on baseline to the Follow-Up assessment.	Baseline and 4-week Follow-Up
Primary	AP COP Velocity From Baseline to Post Intervention	% Modulation of AP COP velocity.; First, center of pressure (COP) is calculated in the anterioposterior (AP) direction [front to back]. COP velocity represents the average speed at which an individual's COP moves during the 10 second single limb stance trial.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in ML COP Velocity that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes closed balance score - eyes open balance score) / eyes open balance score. Positive scores indicate a greater reliance on visual information as ML COP velocity increased when eyes were closed relative to the eyes open condition. A ML COP velocity change greater than the eyes open value would result in a value >100%. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Primary	AP COP Velocity From Baseline to Follow-up	% Modulation of AP COP velocity.; First, center of pressure (COP) is calculated in the anterioposterior (AP) direction [front to back] with eyes open and closed. COP velocity represents the average speed at which an individual's COP moves during the 10 second single limb stance trial.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in ML COP Velocity that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes closed balance score - eyes open balance score) / eyes open balance score. Positive scores indicate a greater reliance on visual information as ML COP velocity increased when eyes were closed relative to the eyes open condition. A ML COP velocity change greater than the eyes open value would result in a value >100%. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up
Primary	ML TTB From Baseline to Post Intervention	% Modulation of ML Time-to-Boundary.; First, time-to-Boundary (TTB) is calculated in the mediolateral (ML) direction [side to side] with eyes open and closed. TTB represents the time (s) it would take for a participant's center of pressure (i.e. vertical projection of the center of mass) to reach their base of support (i.e. boundary) based on the instantaneous position and velocity of the center of pressure. The base of support is represents the length and width of an individual's foot.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in ML TTB that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes open balance score - eyes closed balance score) / eyes open balance score. Negative scores indicate a greater reliance on visual information as ML TTB decreased with eyes closed.	Baseline and 24-72 hours post intervention
Primary	ML TTB From Baseline to Follow-Up	% Modulation of ML Time-to-Boundary.; First, time-to-Boundary (TTB) is calculated in the mediolateral (ML) direction [side to side] with eyes open and closed. TTB represents the time (s) it would take for a participant's center of pressure (i.e. vertical projection of the center of mass) to reach their base of support (i.e. boundary) based on the instantaneous position and velocity of the center of pressure. The base of support is represents the length and width of an individual's foot.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in ML TTB that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes open balance score - eyes closed balance score) / eyes open balance score. Negative scores indicate a greater reliance on visual information as ML TTB decreased with eyes closed.	Baseline and 4-week Follow-Up
Primary	AP TTB From Baseline to Post Intervention	% Modulation of AP Time-to-Boundary.; First, time-to-Boundary (TTB) is calculated in the anterioposterior (AP) direction [front to back] with eyes open and closed. TTB represents the time (s) it would take for a participant's center of pressure (i.e. vertical projection of the center of mass) to reach their base of support (i.e. boundary) based on the instantaneous position and velocity of the center of pressure. The base of support is represents the length and width of an individual's foot.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in AP TTB that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes open balance score - eyes closed balance score) / eyes open balance score. Negative scores indicate a greater reliance on visual information as AP TTB decreased with eyes closed.	Baseline and 24-72 hours post intervention
Primary	AP TTB From Baseline to Follow-Up	% Modulation of AP Time-to-Boundary.; First, time-to-Boundary is calculated in the anterioposterior (AP) direction [front to back] with eyes open and closed. Time-to-boundary represents the time (s) it would take for a participant's center of pressure (i.e. vertical projection of the center of mass) to reach their base of support (i.e. boundary) based on the instantaneous position and velocity of the center of pressure. The base of support is represents the length and width of an individual's foot.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change in AP TTB that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes open balance score - eyes closed balance score) / eyes open balance score. Negative scores indicate a greater reliance on visual information as AP TTB decreased with eyes closed.	Baseline and 4-week Follow-Up
Primary	95% Confidence Ellipse From Baseline to Post Intervention	% Modulation of 95% Confidence Ellipse.; First, center of pressure (COP) excursion [movement] is calculated and the magnitude of an ellipse that contains 95% of all data points is calculated with eyes open and closed. The resulting outcome is calculated from a 10 second single limb stance trial.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes closed balance score - eyes open balance score) / eyes open balance score. Positive scores indicate a greater reliance on visual information as the variable increased when eyes were closed relative to the eyes open condition. A change greater than the eyes open value would result in a value >100%. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Primary	95% Confidence Ellipse From Baseline to Follow-Up	% Modulation of 95% Confidence Ellipse.; First, center of pressure (COP) excursion [movement] is calculated and the magnitude of an ellipse that contains 95% of all data points is calculated with eyes open and closed. The resulting outcome is calculated from a 10 second single limb stance trial.; Next, % modulation is calculated. This estimates the weight given to visual information during eyes open stance based on the magnitude of change that occurs when vision is removed relative to the eyes open condition (control condition). The following formula is used: % Modulation = (eyes closed balance score - eyes open balance score) / eyes open balance score. Positive scores indicate a greater reliance on visual information as the variable increased when eyes were closed relative to the eyes open condition. A change greater than the eyes open value would result in a value >100%. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 4-week Follow-Up
Secondary	Plantar Flexion Joint Position Sense From Baseline to Post Intervention	Amount of error, measured in degrees, from a target angle of plantar flexion. Participants are shown a target ankle and asked to replicate that angle (i.e. joint position) with their eyes closed. The amount of error from the target angle is recorded as the joint position sense. Larger values (i.e. greater error) indicates worse joint position sense. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Plantar Flexion Joint Position Sense From Baseline to Follow-Up	Amount of error, measured in degrees, from a target angle of plantar flexion. Participants are shown a target ankle and asked to replicate that angle (i.e. joint position) with their eyes closed. The amount of error from the target angle is recorded as the joint position sense. Larger values (i.e. greater error) indicates worse joint position sense. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up
Secondary	1st Metatarsal Light-touch Threshold From Baseline to Post Intervention	Minimal amount of pressure that can be detected by an individual at the head of the 1st metatarsal. Semmes-Weinstein monofilaments, of different diameters (mm), are pressed against the skin using an established 4-2-1 stepping algorithm. Higher values (thresholds) indicate worse light touch sensation thresholds. his analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	1st Metatarsal Light-touch Threshold From Baseline to Follow-Up	Minimal amount of pressure that can be detected by an individual at the head of the 1st metatarsal. Semmes-Weinstein monofilaments, of different diameters (mm), are pressed against the skin using an established 4-2-1 stepping algorithm. Higher values (thresholds) indicate worse light touch sensation thresholds. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up
Secondary	5th Metatarsal Light-touch Threshold From Baseline to Post Intervention	Minimal amount of pressure that can be detected by an individual at the base of the 5th metatarsal. Semmes-Weinstein monofilaments, of different diameters (mm), are pressed against the skin using an established 4-2-1 stepping algorithm. Higher values (thresholds) indicate worse light touch sensation thresholds. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	5th Metatarsal Light-touch Threshold From Baseline to Follow-Up	Minimal amount of pressure that can be detected by an individual at the base of the 5th metatarsal. Semmes-Weinstein monofilaments, of different diameters (mm), are pressed against the skin using an established 4-2-1 stepping algorithm. Higher values (thresholds) indicate worse light touch sensation thresholds. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow Up
Secondary	Soleus H:M Ratio From Baseline to Post Intervention	This measure shows the percentage of excited alpha motor neurons (H) within a muscle upon electrical stimulation, relative to the total number of alpha motor neurons in the same muscle (M). Higher scores represent a greater percentage of excitability (i.e. activation) and is thought to represent better function of the spinal motor pathway. This analysis focused on baseline to the immediate post-treatment assessment.; The test is performed using an electric stimulator and electromyography (EMG) to record muscle responses. Stimulation intensity is increased on sequential trials to capture both the H-wave and M-wave responses.	Baseline and 24-72 hours post intervention
Secondary	Soleus H:M Ratio From Baseline to Follow-Up	This measure shows the percentage of excited alpha motor neurons (H) within a muscle upon electrical stimulation, relative to the total number of alpha motor neurons in the same muscle (M). Higher scores represent a greater percentage of excitability (i.e. activation) and is thought to represent better function of the spinal motor pathway. This analysis focused on baseline to the immediate post-treatment assessment.; The test is performed using an electric stimulator and electromyography (EMG) to record muscle responses. Stimulation intensity is increased on sequential trials to capture both the H-wave and M-wave responses.	Baseline and 4-week Follow-Up
Secondary	Fibularis Longus H:M Ratio From Baseline to Post Intervention	This measure shows the percentage of excited alpha motor neurons (H) within a muscle upon electrical stimulation, relative to the total number of alpha motor neurons in the same muscle (M). Higher scores represent a greater percentage of excitability (i.e. activation) and is thought to represent better function of the spinal motor pathway. This analysis focused on baseline to the immediate post-treatment assessment.; The test is performed using an electric stimulator and electromyography (EMG) to record muscle responses. Stimulation intensity is increased on sequential trials to capture both the H-wave and M-wave responses.	Baseline and 24-72 hours post intervention
Secondary	Fibularis Longus H:M Ratio From Baseline to Follow-Up	This measure shows the percentage of excited alpha motor neurons (H) within a muscle upon electrical stimulation, relative to the total number of alpha motor neurons in the same muscle (M). Higher scores represent a greater percentage of excitability (i.e. activation) and is thought to represent better function of the spinal motor pathway. This analysis focused on baseline to the immediate post-treatment assessment.; The test is performed using an electric stimulator and electromyography (EMG) to record muscle responses. Stimulation intensity is increased on sequential trials to capture both the H-wave and M-wave responses.	Baseline and 4-week Follow-Up
Secondary	Fibularis Longus Active Motor Threshold From Baseline to Post Intervention	A measure of cortical excitability using transcranial electromagnetic stimulation. A higher active motor threshold (AMT) indicates decreased excitability, as a greater stimulus intensity is required to elicit a motor evoke potential (MEP). This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Fibularis Longus Active Motor Threshold From Baseline to Follow-Up	A measure of cortical excitability using transcranial electromagnetic stimulation. A higher active motor threshold (AMT) indicates decreased excitability, as a greater stimulus intensity is required to elicit a motor evoke potential (MEP). This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 4-week Follow-Up
Secondary	Cortical Silent Period From Baseline to Post Intervention	A measure of corticospinal inhibition using transcranial electromagnetic stimulation. The cortical silent period (CSP) will be measured as the distance from the end of the motor evoked potential (MEP) to a return of the mean electromyographic (EMG) signal plus two times the standard deviation of the baseline (pre-stimulus) EMG signal. A longer CSP indicates a greater corticospinal inhibition. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Cortical Silent Period From Baseline to Follow-Up	A measure of corticospinal inhibition using transcranial electromagnetic stimulation. The cortical silent period (CSP) will be measured as the distance from the end of the motor evoked potential (MEP) to a return of the mean electromyographic (EMG) signal plus two times the standard deviation of the baseline (pre-stimulus) EMG signal. A longer CSP indicates a greater corticospinal inhibition. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up
Secondary	Corticomotor Map Area From Baseline to Post Intervention	A measure representing the size of a muscle's cortical representation using transcranial electromagnetic stimulation. Map area is the number of stimulus positions whose stimulation evoked an average motor evoked potential = the motor evoked potential threshold. An increase would suggest an expansion of the cortical representation of a selected muscle. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Corticomotor Map Area From Baseline to Follow-Up	A measure representing the size of a muscle's cortical representation using transcranial electromagnetic stimulation. Map area is the number of stimulus positions whose stimulation evoked an average motor evoked potential = the motor evoked potential threshold. An increase would suggest an expansion of the cortical representation of a selected muscle. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up
Secondary	Corticomotor Map Volume From Baseline to Post Intervention	A measure representing the size of a muscle's cortical representation using transcranial electromagnetic stimulation. Map volume will be calculated as the sum of the mean normalized MEPs recorded with an increase suggesting greater cortical excitability. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Corticomotor Map Volume From Baseline to Follow-Up	measure representing the size of a muscle's cortical representation using transcranial electromagnetic stimulation. Map volume will be calculated as the sum of the mean normalized MEPs recorded with an increase suggesting greater cortical excitability. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 4-week Follow-Up
Secondary	Alpha Power Spectral Density From Baseline to Post Intervention	A measure of cortical activation using electroencephalography. Power spectral density (PSD) reflects the distribution of signal power over frequency (micro Volts). Higher PSDs indicate more cortical activity within the alpha bandwidth. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Alpha Power Spectral Density From Baseline to Follow-Up	A measure of cortical activation using electroencephalography. Power spectral density (PSD) reflects the distribution of signal power over frequency (micro Volts). Higher PSDs indicate more cortical activity within the alpha bandwidth. This analysis focused on baseline to the immediate follow-up assessment.	Baseline and 4-week Follow-Up
Secondary	Beta Power Spectral Density From Baseline to Post Intervention	A measure of cortical activation using electroencephalography. Power spectral density (PSD) reflects the distribution of signal power over frequency (micro Volts). Higher PSDs indicate more cortical activity within the beta bandwidth. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Beta Power Spectral Density From Baseline to Follow-Up	A measure of cortical activation using electroencephalography. Power spectral density (PSD) reflects the distribution of signal power over frequency (micro Volts). Higher PSDs indicate more cortical activity within the beta bandwidth. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up
Secondary	Gamma Power Spectral Density From Baseline to Post Intervention	A measure of cortical activation using electroencephalography. Power spectral density (PSD) reflects the distribution of signal power over frequency (micro Volts). Higher PSDs indicate more cortical activity within the gamma bandwidth. This analysis focused on baseline to the immediate post-treatment assessment.	Baseline and 24-72 hours post intervention
Secondary	Gamma Power Spectral Density From Baseline to Follow-Up	A measure of cortical activation using electroencephalography. Power spectral density (PSD) reflects the distribution of signal power over frequency (micro Volts). Higher PSDs indicate more cortical activity within the gamma bandwidth. This analysis focused on baseline to the follow-up assessment.	Baseline and 4-week Follow-Up