Posttraumatic Stress Disorder, Tinnitus
Conditions
Keywords
resting-state fMRI, PTSD, tinnitus, military, veterans
Brief summary
Psychiatric distress caused by PTSD may increase attention toward tinnitus, as well as perceived loudness and discomfort. It is important to understand how tinnitus-related distress and PTSD negatively interact together, in order to develop more effective therapeutic approaches. Understanding symptoms and neurobiological mechanisms using functional magnetic resonance imaging (fMRI), can lead to the necessary knowledge to develop effective interventions for individuals who suffer from both conditions.
Detailed description
Tinnitus and posttraumatic stress disorder (PTSD) are two of the most common service-connected disabilities for active-duty Service Members and Veterans. Tinnitus and PTSD are highly co-morbid, yet distinct disorders. Tinnitus is an auditory disorder in which an illusory auditory percept is experienced, usually as ringing, buzzing, or whooshing sounds, despite no external objective noise source. On the other hand, PTSD is a trauma-related disorder, and is identified by intrusions of the traumatic event, avoidance of reminders, negative alterations in cognition and mood, and hypervigilance or hyperarousal. Similarities between tinnitus and PTSD have been documented among Cambodian refugees, as well as among U.S. Veteran samples. Moreover, the latest neuroimaging data from a recent clinical trial indicated that the auditory-vigilance network was the most dysregulated among active-duty service members with PTSD, compared to combat controls and civilian controls. Due to similar symptoms between tinnitus-related distress and PTSD, and similar dysregulated resting-state brain networks, it remains important to more fully understand how these two distinct disorders may be related. This study will be the first to prospectively examine the overt emotional, behavioral, and cognitive symptoms related to tinnitus-related distress and PTSD, and the overlapping functional connectivity between tinnitus and PTSD. Investigators will examine the overlapping symptoms and neurobiological mechanisms by conducting audiometric and psychological assessments and resting-state functional magnetic resonance imaging (fMRI) among 120 participants (30 with tinnitus and PTSD, 30 with only PTSD, 30 with only tinnitus, and 30 healthy controls). Participants will be recruited from the Frank Tejeda PTSD Clinic and the Audiology Clinic within the South Texas VA Health Care System, and the Hearing Center of Excellence at Lackland Air Force Base. Canonical correlations will be conducted to examine the symptom overlap between tinnitus and PTSD (Aim 1). Investigators aim to neurobiologically characterize tinnitus and PTSD, both separately and conjointly, by conducting fMRI (Aim 2). Investigators also aim to apply modeling to psychometric and neurofunctional data to identify specific regions of the auditory-vigilance network associated with distress related to tinnitus and PTSD. Understanding the shared cognitive, emotional, and behavioral symptoms and neurobiology associated with tinnitus and PTSD will help clinicians and researchers fully understand tinnitus and PTSD independently and conjointly. Results will lead to the identification of neurobiological markers for tinnitus and PTSD, identification of a different phenotype for individuals with both conditions, and development of behavioral and neuro-modulatory therapies that can reduce distress and impairment.
Interventions
DIAGNOSTIC_TESTresting-state functional MRI
We will acquire BOLD fMRI images in an unstimulated state using an extended time-series (300 whole-brain volumes over \ 60-75 min). These data are a main outcome. Data will be processed on an ongoing basis to ensure integrity, and includes controlling for white matter, cerebral spinal fluid, and movement.
DIAGNOSTIC_TESTClinician Administered PTSD Scale for the DSM-5 (CAPS-5)
The CAPS-5 is a semi-structured interview, conducted by an independent evaluator, that measures DSM-5 symptoms of PTSD. Presence of at least one intrusion symptom, one avoidance symptom, two cognition and mood symptoms, and two arousal symptoms for 1 month or more are required to reach the diagnostic threshold.
DIAGNOSTIC_TESTTympanometry
Tympanometry will be conducted to assess ear canal volume (cm cubed), maximum pressure (daPa) peak compliance (ml), and type (A, AD, AS, B, B-High, C) for each ear) at 226-Hz admittance.
DIAGNOSTIC_TESTTinnitus Assessment
Tinnitus acoustic assessment (for tinnitus participants only): Tinnitus ear (left, right, bilateral), pitch matched frequency (Hz) and loudness matched intensity (dB) will be conducted. When available, the tinnitus acoustic assessment only will be repeated at the RII, on the same day and prior to the fMRI scan, to demonstrate reproducibility of results.
DIAGNOSTIC_TESTOtoscopy
Otoscopy is a clinical procedure used to examine structures of the ear, particularly the external auditory canal, tympanic membrane, and middle ear
DIAGNOSTIC_TESTPure tone air and bone-conduction
Pure tone air- and bone-conduction threshold will be conducted to evaluate audiometry and masking levels in both ears, from 250 Hz. To 16000 Hz.
DIAGNOSTIC_TESTSpeech testing
Speech testing will be conducted in both ears, which will include speech reception threshold, speech reception threshold masking level, word recognition presentation level, and word recognition masking level.
DIAGNOSTIC_TESTLoudness Discomfort
Loudness discomfort levels will be tested in both right and left ears, from 500Hz to 4000Hz and speech reception threshold.
DIAGNOSTIC_TESTQuick Speech in Noise Test
Quick Speech in Noise Test (QuickSIN) is a quick method for clinicians to quantify a patient's ability to hear in noise (1 minute).
DIAGNOSTIC_TESTDistortion-Product Otoacoustic Emissions (DPOAE)
Distortion-Product Otoacoustic Emissions (DPOAE) is an automated evaluation of cochlear function. A sensitive microphone is placed in the ear canal via a probe assembly with a disposable ear-tip attached to perform and record the measurements. DPOAEs will be elicited at multiple frequencies in both ears (10 min).
Sponsors
Hearing Center of Excellence
National Institute of Mental Health (NIMH)
The University of Texas Health Science Center at San Antonio
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and female DEERS eligible veterans and active duty service members, ages 18 and above * preferred language is English and able to read and speak English at a 6th grade level * those with PTSD (T&P; PO) must meet full criteria for PTSD diagnosis based on the DSM-5 and assessed by an independent evaluator using the CAPS-5 * those with chronic, constant tinnitus (T&P, TO) will be identified by self-report and confirmed with the audiometric assessment.
Exclusion criteria
* psychiatric hospitalization in the last 12 months * significant cognitive impairment determined by inability to comprehend screening assessment * psychiatric problems and/or high suicide risk warranting immediate intervention * neurobiological disorders, Meniere's disease * Temporomandibular disorders that affect tinnitus, per self-report * history of major head trauma with loss of consciousness for 20 minutes or more as determined by the History of Head Injuries questionnaire * history of seizures * conditions that would prevent completion of fMRI scan (any type of electronic, mechanical, or magnetic implant, coil, filter, or stent, any type of surgical clip or staple, shunt, any type of metal object, hearing aid, spinal fusion, halo vest, IV access port, eyelid spring, artificial eye, artificial heart valve, biostimulator, severe hyperacusis) * active conductive pathology/hearing loss as determined by audiometric assessment. * Those with tinnitus (T&P; TO) will be excluded if their tinnitus is intermittent, objective, or pulsatile, or present for less than 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting-State Functional MRI | 30 minutes of acquired data | We will acquire BOLD fMRI images in an unstimulated state using an extended time-series (300 whole-brain volumes over \ 30 min) and assess for activation within the Auditory Vigilance Network. These data are a main outcome. Data were be processed on an ongoing basis to ensure integrity, and includes controlling for white matter, cerebral spinal fluid, and movement. BOLD levels were transformed to Z-scores, a statistical measure that conveys how many standard deviations the data points are away from the dataset. A Z-score of 0 represents the population mean. For each of the regions reported in the Auditory Vigilance Network, each positive point represents one standard deviation above the population mean. These positive Z-scores represent more brain activation within these regions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tinnitus and PTSD (T+P) Active duty service members and/or veterans with PTSD and tinnitus. | 16 |
| Tinnitus Only (TO) Active duty service members and/or veterans with only tinnitus/no PTSD. | 25 |
| PTSD Only (PO) Active duty service members and/or veterans with only PTSD/no tinnitus. | 3 |
| Healthy Controls Active duty service members and/or veterans with no PTSD and no tinnitus. | 20 |
| Total | 64 |
Baseline characteristics
| Characteristic | Total | Healthy Controls | PTSD Only (PO) | Tinnitus Only (TO) | Tinnitus and PTSD (T+P) |
|---|---|---|---|---|---|
| Age, Continuous | 48.89 years STANDARD_DEVIATION 15.17 | 45.37 years STANDARD_DEVIATION 16 | 47.69 years STANDARD_DEVIATION 14.87 | 49.39 years STANDARD_DEVIATION 15.5 | 48.98 years STANDARD_DEVIATION 15.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 3 Participants | 1 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 17 Participants | 1 Participants | 18 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 5 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 14 Participants | 1 Participants | 21 Participants | 14 Participants |
| Region of Enrollment United States | 64 participants | 20 participants | 3 participants | 25 participants | 16 participants |
| Sex: Female, Male Female | 19 Participants | 7 Participants | 2 Participants | 8 Participants | 2 Participants |
| Sex: Female, Male Male | 45 Participants | 13 Participants | 1 Participants | 17 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 25 | 0 / 3 | 0 / 24 |
| other Total, other adverse events | 4 / 12 | 1 / 25 | 2 / 3 | 0 / 24 |
| serious Total, serious adverse events | 0 / 12 | 0 / 25 | 0 / 3 | 0 / 24 |
Outcome results
Primary
Resting-State Functional MRI
We will acquire BOLD fMRI images in an unstimulated state using an extended time-series (300 whole-brain volumes over \ 30 min) and assess for activation within the Auditory Vigilance Network. These data are a main outcome. Data were be processed on an ongoing basis to ensure integrity, and includes controlling for white matter, cerebral spinal fluid, and movement. BOLD levels were transformed to Z-scores, a statistical measure that conveys how many standard deviations the data points are away from the dataset. A Z-score of 0 represents the population mean. For each of the regions reported in the Auditory Vigilance Network, each positive point represents one standard deviation above the population mean. These positive Z-scores represent more brain activation within these regions.
Time frame: 30 minutes of acquired data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Right Precuneus | 0.55 Z-Score | Standard Deviation 0.33 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Left Cingulate Gyrus | 1.54 Z-Score | Standard Deviation 0.47 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Right Supramarginal Gyrus | 0.53 Z-Score | Standard Deviation 0.4 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Left Cerebellum | 0.46 Z-Score | Standard Deviation 0.18 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Left Claustrum | 0.66 Z-Score | Standard Deviation 0.2 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Right Lentiform Nucleus | 1.03 Z-Score | Standard Deviation 0.17 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Left Superior Temporal Gyrus | 1.80 Z-Score | Standard Deviation 0.49 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Right Insula | 2.32 Z-Score | Standard Deviation 0.32 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Left Medial Frontal Gyrus | 1.32 Z-Score | Standard Deviation 0.33 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Right Middle Frontal Gyrus | 0.39 Z-Score | Standard Deviation 0.44 |
| Tinnitus and PTSD (T+P) | Resting-State Functional MRI | Left Insula | 0.24 Z-Score | Standard Deviation 0.17 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Right Middle Frontal Gyrus | 0.55 Z-Score | Standard Deviation 0.32 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Left Insula | 0.43 Z-Score | Standard Deviation 0.24 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Left Claustrum | 0.73 Z-Score | Standard Deviation 0.17 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Right Supramarginal Gyrus | 0.98 Z-Score | Standard Deviation 0.52 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Left Superior Temporal Gyrus | 1.67 Z-Score | Standard Deviation 0.44 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Right Insula | 2.82 Z-Score | Standard Deviation 0.59 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Left Cingulate Gyrus | 1.60 Z-Score | Standard Deviation 0.49 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Left Medial Frontal Gyrus | 0.85 Z-Score | Standard Deviation 0.29 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Right Lentiform Nucleus | 1.07 Z-Score | Standard Deviation 0.19 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Left Cerebellum | 0.36 Z-Score | Standard Deviation 0.2 |
| Tinnitus Only (TO) | Resting-State Functional MRI | Right Precuneus | 0.35 Z-Score | Standard Deviation 0.24 |
| PTSD Only (PO) | Resting-State Functional MRI | Left Medial Frontal Gyrus | 0.64 Z-Score | Standard Deviation 0.08 |
| PTSD Only (PO) | Resting-State Functional MRI | Right Precuneus | 0.29 Z-Score | Standard Deviation 0.22 |
| PTSD Only (PO) | Resting-State Functional MRI | Left Cerebellum | 0.47 Z-Score | Standard Deviation 0.27 |
| PTSD Only (PO) | Resting-State Functional MRI | Left Superior Temporal Gyrus | 1.68 Z-Score | Standard Deviation 0.45 |
| PTSD Only (PO) | Resting-State Functional MRI | Left Cingulate Gyrus | 1.49 Z-Score | Standard Deviation 0.44 |
| PTSD Only (PO) | Resting-State Functional MRI | Right Lentiform Nucleus | 0.97 Z-Score | Standard Deviation 0.02 |
| PTSD Only (PO) | Resting-State Functional MRI | Right Middle Frontal Gyrus | 0.37 Z-Score | Standard Deviation 0.55 |
| PTSD Only (PO) | Resting-State Functional MRI | Left Claustrum | 0.84 Z-Score | Standard Deviation 0.15 |
| PTSD Only (PO) | Resting-State Functional MRI | Right Supramarginal Gyrus | 1.16 Z-Score | Standard Deviation 0.97 |
| PTSD Only (PO) | Resting-State Functional MRI | Left Insula | 0.29 Z-Score | Standard Deviation 0.11 |
| PTSD Only (PO) | Resting-State Functional MRI | Right Insula | 0.64 Z-Score | Standard Deviation 0.48 |
| Healthy Controls | Resting-State Functional MRI | Right Middle Frontal Gyrus | 0.84 Z-Score | Standard Deviation 0.29 |
| Healthy Controls | Resting-State Functional MRI | Right Insula | 2.86 Z-Score | Standard Deviation 0.79 |
| Healthy Controls | Resting-State Functional MRI | Left Insula | 0.40 Z-Score | Standard Deviation 0.17 |
| Healthy Controls | Resting-State Functional MRI | Right Lentiform Nucleus | 1.22 Z-Score | Standard Deviation 0.23 |
| Healthy Controls | Resting-State Functional MRI | Left Cingulate Gyrus | 1.99 Z-Score | Standard Deviation 0.38 |
| Healthy Controls | Resting-State Functional MRI | Left Superior Temporal Gyrus | 1.95 Z-Score | Standard Deviation 0.38 |
| Healthy Controls | Resting-State Functional MRI | Left Medial Frontal Gyrus | 0.96 Z-Score | Standard Deviation 0.33 |
| Healthy Controls | Resting-State Functional MRI | Left Cerebellum | 0.54 Z-Score | Standard Deviation 0.28 |
| Healthy Controls | Resting-State Functional MRI | Right Precuneus | 0.59 Z-Score | Standard Deviation 0.28 |
| Healthy Controls | Resting-State Functional MRI | Right Supramarginal Gyrus | 0.95 Z-Score | Standard Deviation 0.49 |
| Healthy Controls | Resting-State Functional MRI | Left Claustrum | 0.82 Z-Score | Standard Deviation 0.26 |
p-value: 0.01t-test, 2 sided