Neurofeedback Technology (GZNT) for Persistent Post-Concussive Symptoms in Soldiers

Research Design: This will be a single group design, treatment effect and feasibility study
to demonstrate GZNT technology, examining electrocortical changes, and comparing
emotional/vocational functioning, and post concussive symptoms before and after intensive
GZNT treatment, and at three months follow-up. Up to 50 subjects with a history of traumatic
brain injury and persistent cognitive and emotional symptoms will be enrolled following
screening and baseline evaluation. Resting and event-related EEG (electroencephalograph)
recordings, a physiological stress evaluation, neuropsychological tests, self-report symptom
scales, and psychosocial/vocational functioning measures will be performed at each
evaluation. All subjects will receive the study treatment intervention. Subjects will be
scheduled to receive twenty treatment sessions of GZNT over a six week period, but will be
counted as having completed treatment if they attend fifteen or more sessions. At least
twenty-five subjects will need to complete treatment to meet statistical requirements for the
study hypotheses.

Primary outcome measures will include electrocortical indices under resting and mental task
states and will evaluate the degree of neuro-physiological and cortical functional
connectivity change following treatment as a proxy measure for neuroplastic response to the
GZNT training. Secondary outcomes will include physiological stress response (as an objective
measure of emotional regulation), neuropsychological test performance (as an objective
measure of cognition), and self-reported symptom and emotional well-being measures.
Feasibility outcomes will include number of visits completed within the six weeks, number and
reason for drop-outs, adverse event profiles, and patient satisfaction questionnaires.

Methodology/Technical: For this pilot study, the investigators will require twenty-five
patients to complete the study. The investigators will therefore recruit as many as are
necessary to achieve this goal, to a maximum of 50 patients. However, since this is a
feasibility study, the dropout rate and reasons for drop outs will be monitored and reported.
Completion of a minimum of fifteen study treatment visits will satisfy requirements for
"study completion." (This is based on clinical experience data with this technology.)
Therefore, only those who complete fourteen or fewer sessions within the six week study
treatment time window will be counted as drop outs. The planned total number of study
sessions for the study will be twenty. Data analysis will be carried out on pre and post
metrics for the group who completed the trial, and secondary analyses will be carried out on
all subjects using an intention-to-treat paradigm, to evaluate feasibility, and acceptance of
this intervention.

Subjects will be recruited from the Warrior Recovery Center, the Soldier Readiness Center,
and Evans Army Hospital Primary Care Clinics. Subjects will be pre-screened by signing an
initial consent and completing a preliminary set of self-report forms, followed by a review
of medical records in order to determine eligibility. Following eligibility determination,
full consent discussion will be held, and baseline evaluations will be completed and study
visits scheduled.

For this pilot efficacy/feasibility study, all study subjects will receive the study
treatment intervention. Dose exposure will begin at 10 minutes of GZNT at the first session
and progress to a maximum of thirty minutes of training by the sixth or seventh visit, and
continue at thirty minutes per visit for the remainder of the study.

Inclusion Criteria:

- Mild to Moderate Traumatic brain injury patients at least three months and not more
than 5 years post-injury with recovery to a Rancho los Amigos level of seven or eight
(alert and oriented);

- Brain injury documented in the medical record by a history of an injury event and at
least one of the following:

- loss of consciousness of any duration after the injury event;

- post-traumatic amnesia after the injury event;

- alteration in mental status (dazed/confused) after the injury event;

- physical evidence of brain trauma (MRI/CT hemorrhage/contusion);

- Persistent symptoms thought to be related to or co morbid with the brain injury event,
to include two or more complaints related to problems with attention, memory,
concentration, speed of processing, judgment, executive control, depression, anxiety,
agitation, irritability, impulsivity, or aggression, headaches, and sleep disturbance;

- Evidence of emotional problems as defined by scores on the Post-Traumatic Stress
Disorder Checklist, Military version (PCL-M) of 33 or more, or 9 or more on the
Patient Health Questionnaire (PHQ-9);

- Military or Veteran beneficiary;

- Males and females aged 18-50.

Exclusion Criteria:

- Current/prior (last six months) unstable medical or psychiatric condition that could
confound the effect of the TBI event on brain function (e.g. clear anoxic episode,
cardiac arrest, current uncontrolled diabetes, psychosis)

- A previous history of severe TBI prior to the current injury;

- Current (last three months) active suicidal or homicidal ideation or intent;

- Current (last month) drug/alcohol abuse or dependence as determined by clinical
assessment in addition to the AUDIT-C screening tool. Patients with problem drinking
as defined by a score of 6 or higher on the AUDIT-C will not be eligible to
participate due to concerns regarding the neurotoxic effects of alcohol following TBI.
Those with scores of 4 or 5 will be counseled to reduce their intake of alcohol during
the time course of the study, and a clinical determination will be made by the PI or
Sub-I as to whether they can be included in the study.

- Use of certain medications due to potential interference with assessments and
treatment response: benzodiazepines - excluded; narcotic analgesics - allowed only if
occasional use, and not within 24 hrs of any evaluation or treatment session;
nootropic medications - excluded.

- Participation in a concurrent drug or treatment trial;

- Any physical impairment that prevents the patient from being able to complete the
assessment or treatment tasks (including sensory functions) or failure on effort
measures at baseline evaluation.