The purpose of the study is to determine whether familiar vocal stimulation, provided during coma recovery, improves outcomes for persons who are unconscious after severe TBI. The primary hypothesis is that unconscious persons who receive standard rehabilitation (SR) plus a high-dose of Familiar Voice stimulation (FVs) compared to unconscious persons who receive SR plus a low-dose of FVs (Low Dose Group) and/or unconscious persons receiving SR and sham stimulation (Sham Group) will demonstrate:

1. Significantly more neurobehavioral functioning post-intervention compared to pre-intervention.
2. Using Functional Magnetic Resonance Imaging (fMRI), significantly higher average measures of volumetric activity in the whole brain, middle temporal gyrus bilaterally, pri-mary auditory area, bilateral pre-frontal cortex, hippocampus and/or the cerebellum post-intervention compared to pre-intervention.

Medical advances have improved the odds of surviving a severe traumatic brain injury (TBI) thereby increasing demands for rehabilitation. Medical rehabilitation management during coma recovery, however, has been hampered by a paucity of rigorous clinical trials examining rehabilitation effectiveness. This randomized clinical trial addresses this knowledge gap. The purpose of the study is to determine whether a high dose of familiar vocal stimulation (FVs) improves outcomes for persons who are unconscious after severe TBI. The research objectives are to:

1. Determine whether neural responses elicited with FVs improve neurobehavioral outcomes and/or elicit activations in expected regions.
2. Examine the relationship between neurobehavioral and neurophysiological responses to high doses of FVs during coma recovery.

There are three study cohorts and each group receives standard rehabilitation. The experimental group or High-Dose Group will, in addition to standard rehabilitation, be exposed daily to 40 minutes of FVs for 6 weeks. The Low-Dose Group (Control Group 1) will receive standard rehabilitation plus 5 minutes of FVs and 35 minutes of sham treatment daily for 6 weeks. The Sham Group (Control Group 2) will receive standard rehabilitation plus 40 minutes of sham treatment daily for 6 weeks.

The 40 minutes of FVs treatment will be provided in four 10 minutes sessions. Each FV session will start with the subject hearing a familiar voice call the 'Subject's Own Name' aloud and then that same voice re-telling a memory or an event familiar to the subject. The person re-telling the event will be a person who experienced the event with the subject and who interacted with the subject on a daily basis for at least 1 year prior to injury.

• Traumatic Brain Injury
• Coma
• Vegetative State
• Minimally Conscious State

• Behavioral: Familiar Voice Stimulation High Dose
• Behavioral: Familiar Voice Stimulation Low Dose
• Behavioral: Sham Auditory Stimulation

• Experimental: high dose of familiar voice stimulation
• Active Comparator: low dose of familiar voice stimulaiton
• Sham Comparator: sham auditory stimulaiton

Inclusion Criteria:

• Severe brain injury of traumatic origin
• Non-brain penetrating gun shot wound
• Blunt trauma with subsequent closed head injuries such as diffuse axonal injury
• 18 years of age or older
• Unconscious for at least 28 days consecutively
• Medically Stable
• Does not have active seizures

Exclusion Criteria:

• History of brain injury
• More than 180 days post injury
• MRI is contraindicated (e.g., metal, titanium in brain)
• Ventilator dependent
• Cardiac contraindications
• The definition of traumatic brain injury excludes: (a) Lacerations or contusions of the face, eye, ear or scalp and fractures of facial bones with-out loss of consciousness; (b) Primary cause of injury is blunt trauma (e.g., contusion from blow to head) without subsequent closed head injuries such as contra coup or diffuse axonal injury; (c) Brain-penetrating gun shot wound; (d) Primary BI due to anoxic, inflammatory, infectious, toxic metabolic encephalopathies; (e) Cancer, brain infarction (ischemic stroke), intracranial hemorrhage (hemorrhagic stroke) aneurysms and arterio-venous malformations.

• Rehabilitation Institute of Chicago
• Northwestern Memorial Hospital
• Feinberg School of Medicine, Northwestern University