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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
5
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.
University of Pennsylvania
Philadelphia, Pennsylvania, United States
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
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
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