Insufficient staff and equipment challenges

PTSD is a debilitating and costly condition and currently available treatment options have risks and limitations that necessitate development of novel interventions. Collectively, the functional brain imaging reports suggest that patients with PTSD, especially those with the re-experiencing and hypervigilence phenotype, show ventromedial PFC hypoactivation and amygdala hyperactivation in response to symptom provocation, and that treatment, when successful is associated with reduced amygdala and increased ventromedial PFC activation. This project is guided by a neurocircuit model of PTSD dysfunction in which abnormalities in fronto-limbic imbalance, which diminishes capacity for fear extinction learning, and produces PTSD symptoms of re-experiencing and hyperarousal. Thus, our studies aim to bridge the translational gap between theoretical and neurobiological models of PTSD to implementation of clinical practice. The Target Engagement and Dosing Phase of this project, which is a pilot study, will demonstrate target engagement and its association with laboratory measures of PTSD-relevant neural processes.

The proposed treatment is expected to reduce symptoms of PTSD particularly re-experiencing and hyperarousal symptoms. These improvements in symptoms are expected to translate into improved social and occupational function for subjects with PTSD.

Specific Aim 1: The investigators will test (1) the efficacy of neurofeedback in subjects with PTSD attempting to upregulate ventral medial PFC and simultaneously downregulate amygdala, and (2) determine the number of neurofeedback sessions (dose) needed for target engagement and transfer. Prior to the neurofeedback training, participants' baseline ability to regulate in the absence of neurofeedback from real-time fMRI will be ascertained. Then during session, participants will receive veridical real-time feedback in the scanner indicating the activation level of ventromedial PFC minus amygdala. Participants will attempt to regulate to achieve a predetermined target level known to the participant. Neurofeedback conditions will include (1) false feedback (sham) shows a thermometer that indicates false feedback consisting of noise, (2) view condition shows a thermometer that indicates true activation of ventromedial PFC minus amygdala but the participant is asked not to attempt neuroregulation, (3) free regulate shows a thermometer that indicates true activation of ventromedial PFC minus amygdala while the participant attempts neuroregulation. The investigators will enroll 10 participants who will engage in a six weekly neurofeedback sessions to assess target engagement and dosing.

Specific Aim 2: The ability for participants to regulate will be further challenged by explicit exposure to trauma relevant stimuli that elicit increased amygdala activation in patients with PTSD. The investigators will follow the same procedure as the previous aim except that free regulate condition (condition #3) will be replaced with conditions (4) trauma regulate shows a participant-specific trauma-relevant image and the thermometer that indicates true activation of ventromedial PFC minus amygdala while the participant attempts neuroregulation, and (5) neutral regulate shows a trauma-unrelated image and the thermometer that indicates true activation of ventromedial PFC minus amygdala while the participant attempts neuroregulation. The investigators will enroll 10 participants who will engage in a six weekly neurofeedback sessions to assess target engagement and dosing.

Participants will be assessed for PTSD and related symptoms before and after to the 6-week intervention using the Clinician Administered PTSD Scale (CAPS) (Appendix XVI) and Beck Depression Inventory (BDI-II) (Appendix IX). The investigators hypothesize enhanced neuroregulation and transfer will be associated with a concomitant reduction in PTSD severity and lower comorbid anxiety symptoms.

Specific Aim 3: Participants will be assessed before and after the 6-week intervention with a brief neurocognitive battery of episodic memory, working memory, executive function, and sustained attention. The investigators hypothesize that successful neuroregulation and transfer will be associated with concomitant cognitive performance improvements.

Inclusion Criteria:

• Fluent in English and capable of informed consent
• free of implanted metal objects
• 18-50 years of age
• Antidepressant sleep and anti-anxiety medication use is permitted

Exclusion Criteria:

• Claustrophobia
• Neurological disorders, History of learning disability or developmental delay
• Current substance abuse or history of substance dependence
• Psychotic disorders
• Significant medical conditions
• Current suicidality or attempt within the previous year
• History of neurological injury or disease
• Pregnancy
• Major Axis 1 Psychiatric Disorders (exceptions are unipolar depression, past substance abuse, current or past nicotine dependence)
• Metal in the body

Except when required by law, the investigators will not identify subjects by name, social security number, address, telephone number, or any other personal identifier in study records disclosed outside DUMC. For records disclosed outside DUMC, only the subjects' identification numbers will be used. Coded data that includes MRI images, MRI task based responses, psychometric, and diagnostic information will be released to collaborating investigators. The study results will be retained in subjects' research records for an indefinite time after completion of the study.

Participants will be unaware of whether the thermometer ratings they see while in the scanner are false feedback consisting of noise or true activation.