Generalized Anxiety Disorder
Conditions
Brief summary
The purpose of this study is to evaluate the safety and tolerability of 1 Hz parietal stimulation in anxiety. Our approach will be to administer 1 week of open-label accelerated 1 Hz parietal rTMS (5 days, 8 sessions/day, 600 pulses/session) and measure the effect of this neuromodulation on APS, and short term memory in a cohort of anxiety GAD patients.
Detailed description
Aims 1 and 2 of this project will be tested using a within-subjects design where anxiety patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right IPS. In Aim 1, we will test the effects of this stimulation on arousal during the NPU threat task (NPU section). In Aim 2 below, we will test the effects of this stimulation on arousal-related attention control deficits using the VSTM task (VSTM section). Subjects will undergo 7 study visits spaced over a roughly 3-week period depending upon availability. First, subjects will have a pre-stimulation test visit. On this visit they will undergo the following procedures: 1) motor threshold testing, 2) noise habituation, 3) shock workup 4) NPU task, 5) VSTM task. Then they will have 5 rTMS visits. On these visits, subjects will receive 8 trains of 1 Hz rTMS (600 pulses per train, each separated by \ 50 min). Finally, they will have a post-stimulation test visit, which will included the noise habituation, shock workup, NPU task, and VSTM task.
Interventions
DEVICEOpen-label accelerated 1 Hz repetitive transcranial magnetic stimulation
Patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right intraparietal sulcus. Subjects will receive a continuous train of 1 Hz stimulation. They will receive a total of 600 pulses per train. Trains will be separated by \ 50 min rest intervals.
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Aim 1: Outcome measures. Anxiety potentiated startle (APS) Statistical Analysis. The main analysis will be a paired-sample t-test (pre vs. post stimulation). Aim 2: Outcome measures. Accuracy and reaction time during the visual short term memory task (VSTM). Statistical Analysis. The main analysis will be a 2 \[stimulation: pre-stimulation vs. post-stimulation\] by 2 \[load: low vs. high\] repeated-measures ANOVA. Safety and Adverse Events
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Meet the DSM-V criteria for an anxiety disorder (i.e. generalized anxiety disorder, social anxiety disorder, panic disorder, etc.) * Subjects must be 18-50 years old * Able to give their consent * Right-handed
Exclusion criteria
* Non-english speaking * Any significant medical or neurological problems * Current or past (non-anxiety) Axis I psychiatric disorder(s), active or history of active suicidal ideation * Alcohol/drug problems in the past year or lifetime alcohol or drug dependence * Any medical condition that increases risk for TMS * History of seizure * History of epilepsy * Increased risk of seizure for any reason * Pregnancy, or positive pregnancy test * Hearing loss
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anxiety Potentiated Startle (APS) | Post stimulation | Electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm electrodes (Rhythmlink #DECUS10026; Columbia, SC). EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = \[Zx × 10\] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD \> 2x run SD) were excluded, and no blink (peak \< baseline range) trials were coded as 0. To calculate APS within each timepoint, we subtracted the response during the neutral ITI from the response during the unpredictable ITI. T-scores represent the change from baseline to post stimulation. |
| Visual Short Term Memory Performance (VSTM) | Pre and post stimulation | Visual short term memory task: This task has been adapted from Vogel & Machizawa (Vogel & Machizawa, 2004). On each trial, subjects see an arrow (cue) pointing to the left or the right. After a short delay, they see a bilateral array of squares that vary in color, location, and angle of rotation (memory array). Subjects are instructed to encode the squares in the cued hemifield (targets) and ignore the squares contralateral to the cued hemifield (distractors). After another short delay (retention interval), subjects see a single square (response prompt) that is either an exact match (same color/location/angle) or a complete mismatch (different color/location/angle). Subjects are instructed to indicate whether the square is a match or a mismatch. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pilot Arm Aims 1 and 2 of this project will be tested using a within-subjects design where anxiety patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right IPS.
Open-label accelerated 1 Hz repetitive transcranial magnetic stimulation: Patients will receive a 5-day course of accelerated 1 Hz rTMS (8x session x 600 pulses/session) to the right intraparietal sulcus. Subjects will receive a continuous train of 1 Hz stimulation. They will receive a total of 600 pulses per train. Trains will be separated by \
50 min rest intervals. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Pilot Arm |
|---|---|
| Age, Continuous | 29.4 years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Anxiety Potentiated Startle (APS)
Electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm electrodes (Rhythmlink #DECUS10026; Columbia, SC). EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = \[Zx × 10\] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD \> 2x run SD) were excluded, and no blink (peak \< baseline range) trials were coded as 0. To calculate APS within each timepoint, we subtracted the response during the neutral ITI from the response during the unpredictable ITI. T-scores represent the change from baseline to post stimulation.
Time frame: Post stimulation
Population: Outcome measures. Anxiety potentiated startle (APS) contrasted between pre and post stimulation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Arm | Anxiety Potentiated Startle (APS) | 1.89 T-score (pre - post) | Standard Deviation 3.54 |
Primary
Visual Short Term Memory Performance (VSTM)
Visual short term memory task: This task has been adapted from Vogel & Machizawa (Vogel & Machizawa, 2004). On each trial, subjects see an arrow (cue) pointing to the left or the right. After a short delay, they see a bilateral array of squares that vary in color, location, and angle of rotation (memory array). Subjects are instructed to encode the squares in the cued hemifield (targets) and ignore the squares contralateral to the cued hemifield (distractors). After another short delay (retention interval), subjects see a single square (response prompt) that is either an exact match (same color/location/angle) or a complete mismatch (different color/location/angle). Subjects are instructed to indicate whether the square is a match or a mismatch.
Time frame: Pre and post stimulation
Population: Aim 2: Outcome measures. Reaction time during the visual short term memory task (VSTM) contrasted pre and pot stimulation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Arm | Visual Short Term Memory Performance (VSTM) | -58.6 msec | Standard Deviation 495.1 |