Neuroimaging Biomarker for Seizures

Numerous Veterans and civilians have seizures, which can be epileptic or nonepileptic in
nature. Epileptic seizures are caused by abnormal brain cell firing. Nonepileptic seizures
appear similar to epileptic seizures, but are associated with traumatic experiences and
underlying psychological stressors. Both types of seizure are common and disabling, and many
patients with seizures do not have adequate control resulting in loss of quality of life.

In this proposed 3-site study ( Providence, RI and Birmingham, AL), which are epilepsy
centers with expertise both in epilepsy and psychogenic nonepileptic seizures (PNES), we will
enroll 88 patients with video-EEG confirmed PNES and 88 with confirmed post-traumatic
epilepsy (PTE) and will obtain functional neuroimaging before and after they receive a
behavioral treatment - Cognitive Behavioral Therapy for Seizures. The functional neuroimaging
studies in these 176 Veterans will be compared to 88 Veterans with traumatic brain injury
without seizures to test the hypothesis that the faulty processing of emotions and stress in
patients with PNES/PTE and abnormal brain connectivity have unique signals in patients with
seizures compared to Veterans without seizures and that the neuroimaging signatures can be
modified using behavioral intervention.

Impact: This grant application for the first study investigating mechanisms of PNES and PTE
will provide increased understanding of neural circuitry in PTE and PNES, which can inform
PTE and PNES treatments and could change clinical neurologic and psychiatric practice for PTE
and PNES.

Participants will be recruited at the Providence VA Medical Center, Rhode Island Hospital,
and University of Alabama, Birmingham (UAB).

Inclusion Criteria:

- Inclusion criteria for PNES, ES and TBI (w/o PNES or ES) participants

- Individuals with history of documented TBI (any severity).

- Males and Females ages 18-60 years .

- Women of child bearing potential, if currently using appropriate contraception.

Inclusion criteria of PNES and ES participants.

- Diagnosed by video/EEG with lone PNES or by EEG with lone ES.

- Patients must have at least 1 PNES or 1 ES during the year prior to enrollment.

Exclusion Criteria:

- Exclusion Criteria of PNES, ES and TBI (w/o PNES or ES) participants

- Current or past year self-injurious behavior.

- Current suicidal intent (BDI suicide question 9 score of >1).

- Current or past year psychosis.

- Pending litigation or current application for long term disability.

- Active substance or alcohol use disorder (dependence), per discretion of the
investigators.

- Serious illness requiring systemic treatment or hospitalization; the participant
either completes therapy or is clinically stable on therapy, for at least 30 days
prior to study entry.

- Inability to fill out the self-report surveys.

- Women who are or/are attempting to become pregnant during the study.

- Ineligible or unwilling to complete MRI imaging.

- Inability to document TBI.

Exclusion Criteria for PNES and ES participants

- Inability or unwillingness to participate in CBT and assigned homework.

- Currently enrolled in cognitive therapy aimed at PNES (Current CBT or other
psychotherapy may be administered).

- Concurrent mixed ES/PNES or equivocal video/EEG findings in discerning between ES and
PNES will not be enrolled.