Neuromodulation and Neuroimaging in Older Children With Mild Traumatic Brain Injury

Assessing the Efficacy of Alterations in Subcortical-Cortical Functional Connectivity From Transcranial Direct Current Stimulation in Older Children After Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) often causes persistent motor and cognitive deficits in children resulting in functional limitations. We are testing a brain stimulation method along with evaluating objective tools to help record and restore communication among affected brain areas, which will facilitate recovery in youth after mTBI.

About 1.9 million children sustain mTBI per year from sports injuries alone in the US. In about 30% of children, the cognitive-motor effects of mTBI interrupt typical neurodevelopment leading to chronic neurological conditions. The limited evidence available on mTBI suggests that residual symptoms may involve the brain stem (BS); the subcortical region that is now shown to influence cognitive-motor control. The BS also has functional interconnections to other cortical regions involved in cognitive-motor learning such as the dorsolateral prefrontal cortex, premotor cortex, and primary motor cortex. While clinicians examine certain risk factors such as amnesia and history of prior concussions, they lack objective biomarkers to accurately predict the post-mTBI prognosis in children, and to accurately guide treatment. Further, there is no evidence-based standard of care established, so children may be released to pre-injury activity levels before full neurophysiological recovery, predisposing them to further mTBI and associated sequelae.

Transcranial Direct Current Stimulation (tDCS), a non-invasive treatment, has been demonstrated to positively influence cognitive-motor control by modulating the excitability of both cortical and subcortical structures. Additionally, resting state functional connectivity has shown promise in diagnosing and predicting recovery in adult TBI. However, the efficacy of tDCS for children with mTBI is not yet established due to their atypical cortical activity and variable symptomology. Consequently, we aim to determine the efficacy of tDCS for promoting recovery in 10 youths (aged 10 to 15 years) who exhibit persistent symptoms of mTBI using a cross-over design compared with 10 never-injured youths as controls, and to test the application of neural correlates to provide insights into their functional change and recovery by comparing group differences.

Experimental Cohort:

Inclusion Criteria:

• age 10-15 years at enrollment
• enrolled after 6 weeks of mTBI injury
• exhibiting post-concussive symptoms (e.g., difficulty planning, sequencing, and executing a motor action)
• Sustained an mTBI or concussion within the past 12 months
• Parent and child proficient in English

Healthy Controls Cohort:

Inclusion Criteria:

• 10 to 15 years old
• no concussion history
• Parent and child proficient in English

Experimental Cohort:

Exclusion Criteria:

• loss of consciousness > 30 minutes
• post-traumatic amnesia > 24 hours
• intracranial findings on clinical imaging
• history of developmental delay
• history of learning disability or ADHD
• Sustained a lower limb or upper limb injury that has not healed
• History of Seizures
• Noticeable skin lesions/burns or any other severe skin problems at the site of the electrodes before the start of the stimulation.
• Parent/guardian report metal implants anywhere in the head/ncek/body on the MRI screening form (see attached).
• Parent/guardian report shrapnel/bullets in the body on the MRI screening form.
• Parent/guardian report any electronic implant such as a cardiac pacemaker, cochlear implant, ventricular shunt, cardiac defibrillator, aneurysm clips, pacing wires, any implant held in place with a magnet, heart valve, or deep brain stimulator on the MRI screening form.
• Parent/guardian report a craniotomy or any other surgery in the past 6 weeks on the MRI screening form.
• Parent/guardian report being claustrophobic on the MRI screening form.
• Parent/guardian report and provide orbit x-ray after the eye injury involving a metal that the subject is cleared as indicated on the MRI screening form.
• Pregnant females as reported by parent/guardian on the pre-consent screening form. Pubertal/post-pubertal female participants14 and above will be provided a separate post-consent screening form at each MRI visit to ensure the female reports accurately without fear.

Healthy Controls Cohort:

Exclusion Criteria:

• diagnosed with developmental delay
• sustained a lower limb or upper limb injury that has not healed
• history of Learning Disability and/or ADHD
• Parent/guardian report metal implants anywhere in the head/ncek/body on the MRI screening form (see attached).
• Parent/guardian report shrapnel/bullets in the body on the MRI screening form.
• Parent/guardian report any electronic implant such as a cardiac pacemaker, cochlear implant, ventricular shunt, cardiac defibrillator, aneurysm clips, pacing wires, any implant held in place with a magnet, heart valve, or deep brain stimulator on the MRI screening form.
• Parent/guardian report a craniotomy or any other surgery in the past 6 weeks on the MRI screening form.
• Parent/guardian report being claustrophobic on the MRI screening form.
• Parent/guardian report and provide orbit x-ray after the eye injury involving a metal that the subject is cleared as indicated on the MRI screening form.
• Pregnant females as reported by parent/guardian on the pre-consent screening form. Post-pubertal females 14 and above will be provided a separate post-consent screening form at each MRI visit to ensure the female reports accurately without fear.