Retraining Neural Pathways Improves Cognitive Skills After A Mild Traumatic Brain Injury

NCT03655782 | Active Not Recruiting DMC

• 1 other identifier: PerceptionDI
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The proposed study tests the efficacy (Phase II) of 36 30-minute training sessions of PATH neurotraining followed by digit memory exercises to improve working memory, processing speed and attention in mTBI patients rapidly and effectively to provide clinical testing of a therapeutic training for the remediation of cognitive disorders caused by a concussion. This study will contribute to the fundamental knowledge of how to remediate concussions from a mTBI to enhance the health, lengthen the life and reduce the disabilities that result from a mTBI.

Conditions

MTBI - Mild Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Change in Visual Working Memory

  Visual Working Memory (VWM) using Test of Information Processing Skills (TIPS), having two distractor tasks to measure Sequential Processing: the subject must remember a sequence of letters, that are shown one at a time for 2 seconds each, for sequences of from 2 up to 9 letters right after seeing the entire sequence of letters. Short Term that are shown one at a time for 2 seconds each, for sequences of from 2 up to 9 letters right after seeing the entire sequence of letters. Short Term VWM is assessed by recalling the correct sequence of letters after counting from 1 to 10 numbers in sequence, starting at different initial numbers, slowly, and after repeating a short sentence with an animal subject for VWM. Delayed Recall is assessed by remembering all animal names in repeated sentences 3 minutes after finish the VWM tests. The TIPS VWM Standardized Percentile Rank goes from \<1% to 99%.

  Immediately before begin intervention and 3, 6, and 12 months later.

Secondary Outcomes (13)

• Change in Processing Speed

  Immediately before begin intervention and 3, 6, and 12 months later.

• Change in Attentional Focus

  Immediately before begin intervention and 3, 6, and 12 months later.

• Change in Cognitive Flexibility

  Immediately before begin intervention and 3, 6, and 12 months later.

• Change in Auditory Working Memory

  Immediately before begin intervention and 3, 6, and 12 months later.

• Change in Reading Proficiency

  Immediately before begin intervention and 3, 6, and 12 months later.

Study Arms (3)

PATH+DM neurotraining three times a week for 36 30-minute sessions

EXPERIMENTAL

Subject looks at computer screen to determine whether dim gray stripes in fish-shaped window move left or right relative to gray stationary background stripes. The subject reports which way center stripes move by pushing left or right arrow key, receiving brief tone if incorrect. Program adaptively changes the contrast of the test pattern in order to keep subject at 79% correct. There are levels of difficulty introduced by making the background pattern more similar to that in fish, by increasing pattern's complexity level, and by increasing number of directions of movement from one to two directions of motion. Intervention will be trained for 20 minutes, followed by 10 minutes of digit memory exercises 3 times each week for 12 weeks. Ten minutes of digit memory (DM) practice, recalling the correct sequence of digits, each presented for 500 msec, from 5 digits up to 10 digits will be completed for 10 minutes following 20-minutes of PATH neurotraining.

Behavioral: PATH + DigitMemory (DM) neurotraining

PATH+DM neurotraining two times a week for 36 30-minute sessions

EXPERIMENTAL

Subject looks at computer screen to determine whether dim gray stripes in fish-shaped window move left or right relative to gray stationary background stripes. The subject reports which way center stripes move by pushing left or right arrow key, receiving brief tone if incorrect. Program adaptively changes the contrast of the test pattern in order to keep subject at 79% correct. There are levels of difficulty introduced by making the background pattern more similar to that in fish, by increasing pattern's complexity level, and by increasing number of directions of movement from one to two directions of motion. Intervention will be trained for 20 minutes, followed by 10 minutes of digit memory exercises 2 times each week for 18 weeks. Ten minutes of digit memory (DM) practice, recalling the correct sequence of digits, each presented for 500 msec, from 5 digits up to 10 digits will be completed for 10 minutes following 20-minutes of PATH neurotraining.

Behavioral: PATH + DigitMemory (DM) neurotraining

PATH+DM neurotraining once a week for 36 30-minute sessions

EXPERIMENTAL

Subject looks at computer screen to determine whether dim gray stripes in fish-shaped window move left or right relative to gray stationary background stripes. The subject reports which way center stripes move by pushing left or right arrow key, receiving brief tone if incorrect. Program adaptively changes the contrast of the test pattern in order to keep subject at 79% correct. There are levels of difficulty introduced by making the background pattern more similar to that in fish, by increasing pattern's complexity level, and by increasing number of directions of movement from one to two directions of motion. Intervention will be trained for 20 minutes, followed by 10 minutes of digit memory exercises once a week for 36 weeks. Ten minutes of digit memory (DM) practice, recalling the correct sequence of digits, each presented for 500 msec, from 5 digits up to 10 digits will be completed for 10 minutes following 20-minutes of PATH neurotraining.

Behavioral: PATH + DigitMemory (DM) neurotraining

Interventions

PATH + DigitMemory (DM) neurotraining BEHAVIORAL

Improve visual timing and sensitivity in the dorsal stream. The mTBI subject will sit 57 cm in front of a computer monitor. During the presentation, the bars in the 'fish-shaped' window in the center of the screen formed by a sinusoidal grating, move left or right very briefly. When the screen goes blank, the subject reports which way the center pattern moved by pushing the left or right arrow key. A brief tone is presented after incorrect responses. The program adaptively changes the contrast of the test pattern so that the subject detects motion at lowest contrast possible. A sequence of patterns in each training cycle that are designed to optimally activate magnocellular neurons are shown to the subject. There are two programs, the first measures the contrast needed to see one direction of movement, and the second program measures the contrast needed to see two directions of movement, requiring memory. Both are followed by digit memory exercises.

Also known as: PATH to Insight, PATH to Reading

PATH+DM neurotraining once a week for 36 30-minute sessions; PATH+DM neurotraining three times a week for 36 30-minute sessions; PATH+DM neurotraining two times a week for 36 30-minute sessions

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Referred by Clinician verifying that patient has an mTBI (also includes moderate TBI: those who had a severe TBI with a loss of consciousness more than 30 minutes that is now an mTBI) and has a visual working memory loss as determined by first neuropsychological pre-test administered: The Test of Information Processing Skills (TIPS),
• One or more concussions,
• Any loss of consciousness from 5- 30 min (not longer than 30 min) to be in mTBI group, otherwise in moderate TBI group.
• Any loss of memory for events immediately before or after the accident for 24 hours is in mTBI group, otherwise is in moderate TBI group,
• Any alteration of mental state at the time of the accident (e.g. feeling dazed, disoriented, or confused),
• Be between the ages of 18 to 60 years, when development and aging are not factors,
• Agrees to complete the study after hearing the time commitment involved,
• Has corrected 20/20 visual acuity, and normal motor control so can do PATH neurotraining (signal direction that dim gray stripes move by pushing arrow keys on the computer),
• Can sign and understand the informed consent form themself,
• Can drive to test sites or capable of using public transportation (bus or train) to test site.
• Reads English fluently, so can follow instructions.

You may not qualify if:

• mTBI occurred less than 3 months earlier \[While post-concussive symptoms (PCS) resolve within days post injury in the majority of individuals with mTBI,127 symptoms can endure 3 months post injury or longer, indicating spontaneous recovery and chronic sequela.128 In the general public, between 8% to 33% of mTBI patients have persistent PCS and long-term cognitive and/or behavioral impairments129 that negatively impact quality of life. In the proposed study, we will try to minimize the confound from the spontaneous recovery by only recruiting chronic mTBI subjects, and not recruiting mTBI subjects with mTBI less than 3 months.\] with no maximum time if still experiencing memory problems which will be measured by the TIPS visual working memory (VWM) scores.
• diagnosis of epilepsy or seizure disorder in last 12 months,
• diagnosis of moderate depressive disorder or moderate anxiety, having driving limitations in traffic
• answers 'Yes' to any of the questions on the Columbia Suicide Severity Rating Scale,
• had a stroke or metabolic derangements causing cognitive impairments, i.e. alcohol or substance abuse,
• And for those chosen to undergo MEG exams:
• has extensive metal dental hardware (e.g., braces and large metal dentures; fillings are acceptable) or other metal objects in head, neck, or face areas that cause artifacts in MEG data, and are not removable during pre-processing, and
• has claustrophobia since MRI scanner is in small enclosed space,
• has a cardiac pacemaker, or 9) is pregnant.

Sponsors & Collaborators

• Perception Dynamics Institute: lead
• University of California, San Diego: collaborator
• University of South Alabama: collaborator
• University of California, Riverside: collaborator

Study Sites (2)

University of California at San Diego

San Diego, California, 92121, United States

Location

Perception Dynamics Institute

Solana Beach, California, 92075, United States

Location

MeSH Terms

Conditions

Brain Concussion

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Study Officials

• Teri Lawton, Ph.D.

  Perception Dynamics Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Staff will not be told which treatment group the subject was in.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The investigators will show that working memory, processing speed, reading speed, and attention improve significantly in mTBI patients after 36 30-minute training sessions of PATH training followed by digit memory exercises for different doses (once, twice or three times a week) to determine which dose improves cognitive skills the most, and whether the improvements are sustained over time. MEG brain imaging will be used to show that PATH neurotraining followed by digit memory exercises improves the function of the dorsal, attention, and working memory networks (e.g., PPC, DLPFC and ACC/PCC areas), reducing over recruitment, as found during Phase I.

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: August 31, 2018
• Study Start: July 1, 2023
• Primary Completion: August 30, 2025
• Study Completion (Estimated): September 30, 2029
• Last Updated: September 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: November 2025 for 10 years.
• Access Criteria: Qualified investigator

Locations

US (2)