Current Projects
Project 1 (Estrogen)
The influence of gonadal hormones on fear extinction
The purpose of this research study is to determine if taking a pill of estradiol together with prolonged exposure therapy can improve this treatment outcome in women diagnosed with Post-Traumatic Stress Disorder (PTSD). Prolonged exposure therapy is a specific type of cognitive behavioral therapy that teaches patients to gradually approach trauma-related memories. By approaching trauma-related memories, PTSD patients who undergo prolonged exposure therapy experience fear extinction. The fear extinction that is achieved by prolonged exposure therapy leads to symptom improvements in many patients. Prolonged exposure therapy is a gold-standard therapy for PTSD, but as many as half of patients still have PTSD after completing this therapy. To help improve treatment outcomes for people with PTSD, it is important to identify medications that can be combined with prolonged exposure therapy to enhance its effectiveness.
One medication that may be useful to enhance prolonged exposure therapy effectiveness is Estradiol. Estradiol is an estrogen-based medication that is used to manage and treat postmenopausal symptoms in women. Estradiol works by increasing the levels of estrogen in the body. Previous research has shown that women with low levels of estrogen who are diagnosed with PTSD are less able to extinguish fear and are less able to retain fear extinction memory. The ability to extinguish fear and to retain fear extinction memory are critical for prolonged exposure therapy to work. Thus, this study seeks to determine whether the combined use of estradiol together with prolonged exposure therapy is more effective than prolonged exposure therapy alone at helping patients to achieve fear extinction, fear extinction retention, and PTSD symptom reduction.
We have enrolled research participants from three different sites: UTHealth Houston, NYU Langone, and University of Pennsylvania. All participants were females ages 18-45 with chronic PTSD symptoms. Participants were randomly assigned to one of two groups. One group received a combined treatment of prolonged exposure therapy plus estradiol. The second group received prolonged exposure therapy plus a placebo. In addition to receiving treatments, participants complete an experimental fear learning task. During this experiment, a magnetic resonance imaging (MRI) scanner measures their brain activity and electrodes measure sweat or stress responses (also known as skin conductance responses). Clinical interviews and self-report measures were utilized. The initial study took 6 weeks for each participant, with follow-up visits at 3- and 6-months post-completion of the initial study. Thank you for your interest—unfortunately, recruitment for this study has closed. If you are interested in other studies that are actively recruiting, please visit: https://redcap.link/generalprescreen
Project 2 (TMS)
Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans
The purpose of this research study is to understand how transcranial magnetic stimulation (TMS) impacts the way our brains learn to fear and extinguish those fears. TMS is a non-invasive tool that uses electromagnetic stimulation to temporarily alter brain activity. The overall objective of the study is to understand how to maximize the potential for TMS to enhance fear extinction memory consolidation in individuals with PTSD. This will be accomplished by studying the effect of TMS on fear memory and comparing differences in the timing of TMS administration and in the specific location within the brain that is targeted with TMS.
Specific regions of the brain that are being investigated have been chosen due to their role in the fear extinction circuit. The regions being targeted by TMS are: the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Brain activity is measured using MRI. Stress or sweat responses is measured via skin conductance. Additionally, clinician-rated and self-report assessments are administered during the clinical evaluation, and questionnaires are administered to measure shock expectancy and other subjective reports during the experiment. In addition to examining the impact of TMS on brain and stress responses, advanced statistical models called probability models will be developed to predict the success of TMS.
This ongoing study will include 250 research participants at UTHealth Houston. Participants will be individuals between the ages of 18 and 70, male or female, including 50 who have PTSD and 200 who do not. Those who do not have PTSD will serve as the control group. Each participant in this study will participate in four study visits over the course of 4-7 days. To participate in this study, click here.
Project 3 (Avoidance)
Neural Correlates of Active Avoidance Learning and their Interactions with Fear Extinction Mechanisms in PTSD Patients
The purpose of this research study is to understand how our brains learn to fear, to extinguish fear, and to avoid learned fear. Avoidance of fear is common among individuals with PTSD and often hinders the success of prolonged exposure therapy and other extinction-based exposure therapies for PTSD and other fear-related disorders. Thus, by shedding light on brain mechanisms of fear extinction and avoidance, this study has the potential to inform advances in the treatment of PTSD and other fear-related disorders. The main objective of the study is to measure brain mechanisms of avoidance, and how fear extinction learning and monetary cost of avoidance impact these avoidance responses.
To study fear and avoidance, this study uses an experimental task where participants learn fear, have opportunities to avoid this learned fear, and extinguish this learned fear. Brain activity is measured using MRI and stress or sweat response is measured using skin conductance. Brain regions of interest for MRI analyses are chosen based on their role in the fear circuit or in avoidance. These regions include: ventromedial prefrontal cortex, hippocampus, nucleus accumbens, ventral tegmental area, and striatum. Additionally, clinician-rated and self-report assessments will be administered during the clinical evaluation, and questionnaires will also be administered to measure shock expectancy and other subjective reports during the experiment.
The ongoing study will include 300 research participants at UTHealth Houston. Participants will be individuals between the ages of 18 and 70 male or female, including 100 who have PTSD, 100 who have trauma exposure but not PTSD, and 100 who do not have trauma exposure. To participate in this study, click here.
Project 4 (EEG)
Use Electroencephalogram to Study Neural Dynamics of Fear Conditioning and Avoidance Learning Circuit in Humans
The purpose of this research study is to expand our understanding of fear learning and active avoidance mechanisms in individuals by using electroencephalogram (EEG) recording for improved temporal resolution. Avoidance is common and often hinders the progression and success of extinction-based exposure therapy in many anxiety and fear-related disorders. The data to be gathered will provide an integrated platform for studying the mechanisms of fear learning and avoidance, which has important implications for understanding the psychopathology of anxiety and fear-related disorders.
This study aims to examine the neural correlates of fear and avoidance learning using a conditioning and active avoidance paradigm (CAAP). In this study, EEG recordings will be collected from research participants during the experiment. EEG data are used in neuroimaging studies to assess neural activations in resting-state and in response to a specific stimulus. Skin Conductance Response (SCR) will also be collected. SCR is used by many psychological experiments to measure the participants’ stress/sweat, or level of anxiety in a particular moment, or response to a specific cue. Questionnaires will also be administered to measure shock expectancy, willingness to avoid shock, and other subjective reports about the experiment. Additionally, clinician/trained-rater administered measures and self-report measures will be administered during the recruitment assessments.
The ongoing study will include 150 research participants at UTHealth Houston. Participants will be individuals between the ages of 18 and 70 male or female, with no significant current/past serious psychiatric diagnoses. To participate in this study, click here.