Disrupting Fear-based Memory Consolidation

Preprocessing of neuroimaging data will be conducted using fMRI prep. Pre-processed neuroimaging data will undergo first and second level modeling in Statistical Parametric Mapping. First level analysis include an event-related model with the onset and duration of each event included for each condition, and motion included as a regressor. A high-pass filter of 128s will be applied to account for low-frequency drifts. Amygdala regions of interest (ROIs) will be defined anatomically using California Institute of Technology (CIT168) Subcortical Atlas. Primary sensory cortex ROI & seed coordinates will be defined utilizing voxels within a V1 region mask showing maximal functional connectivity with the amygdala during conditioning.

Preprocessing of neuroimaging data will be conducted using fMRI prep. Pre-processed neuroimaging data will undergo first and second level modeling in Statistical Parametric Mapping. First level analysis include an event-related model with the onset and duration of each event included for each condition, and motion included as a regressor. A high-pass filter of 128s will be applied to account for low-frequency drifts. Whole-brain analysis of changes in local regions of activity will be measured by change in blood-oxygen-level-dependent (BOLD) signal from resting activity. Multiple comparisons using permutation-based methods to control the false positive rate to p<.05.

Skin conductance response (SCR) will be recorded during localization, conditioning, and fear retention tasks using the BIOPAC system MP150 (BIOPAC systems, Inc.) and parameters previously utilized in the lab. SCR is a validated physiological measure of sympathetic arousal, with higher SCR indicating a higher arousal response to conditioned stimuli. Change in SCR from early to late extinction is our primary indicator of the degree of extinction learning. SCR will be scored as a response to individual Conditioned Stimulus (CS)+E and CS- stimuli (maximum SC within 6 seconds post-CS onset, minus average SC over a 2-second prestimulus baseline) and will be square-root transformed for normalization. Early fear extinction will be defined as occurring within the first fear extinction run, with late fear extinction being defined as the second extinction run.

Heart rate and heart-rate variability (HRV) will be measured using the ECG module of the BIOPAC system at a sampling rate of 1 kilo Hertz (kHz). One 5mm Ag/AgCl (Silver/Silver Chloride) electrode will be placed on the chest above the right clavicle, another electrode will be placed on the chest under the left side of the ribcage.

The acoustic startle response (eyeblink component) will be measured via electriomyography (EMG) of the right orbicularis oculi muscle. Two 5 mm Ag/AgCl pre-gelled disposable electrodes will be positioned approximately 1 cm under the pupil and 1 cm below the lateral canthus. The startle probe (noise burst) will be a 108-decibel (dB) (A) Sound Pressure Level (SPL), 40-ms burst of broadband noise with a near instantaneous rise time . The startle probe is a white noise burst that is affectively neutral and clearly differentiable from the aversive sound used for the US.

Participants will view pictures of animals and tools which will not be repeated. During the 1st phase, 3 categories of images will be displayed: animals, tools, and animal/tool images phase-scrambled. Blocks of 10 images of each category will be displayed 4 times, with each image displayed for 0.75 seconds with a 0.25 s delay between images and 11 s inter-block interval. This task will allow for localization of brain areas activated by animal images vs. tool images, with the phase scrambled images serving as a control. 15 animal and 15 tool images will be randomly displayed for 4.5 s with a fixation cross displayed between each image for 6, 8, or 10 seconds. For the 2nd phase, 10 of either the animal or tool images are assigned as the CS+, and paired with the US, a 1-second loud screeching sound at the end of the image presentation. The other image type, the CS-, will not be paired with the US. In the fear retention phase on Day 2, the CS+ and CS- will be presented without the US.