Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 26;20(23):6751.
doi: 10.3390/s20236751.

Behavioral, Physiological and EEG Activities Associated with Conditioned Fear as Sensors for Fear and Anxiety

Jui-Hong Chien  1 , Luana Colloca  2   3 , Anna Korzeniewska  4 , Timothy J Meeker  1 , O Joe Bienvenu  5 , Mark I Saffer  1 , Fred A Lenz  1
Affiliations
Review

Behavioral, Physiological and EEG Activities Associated with Conditioned Fear as Sensors for Fear and Anxiety

Jui-Hong Chien et al. Sensors (Basel). .

Abstract

Anxiety disorders impose substantial costs upon public health and productivity in the USA and worldwide. At present, these conditions are quantified by self-report questionnaires that only apply to behaviors that are accessible to consciousness, or by the timing of responses to fear- and anxiety-related words that are indirect since they do not produce fear, e.g., Dot Probe Test and emotional Stroop. We now review the conditioned responses (CRs) to fear produced by a neutral stimulus (conditioned stimulus CS+) when it cues a painful laser unconditioned stimulus (US). These CRs include autonomic (Skin Conductance Response) and ratings of the CS+ unpleasantness, ability to command attention, and the recognition of the association of CS+ with US (expectancy). These CRs are directly related to fear, and some measure behaviors that are minimally accessible to consciousness e.g., economic scales. Fear-related CRs include non-phase-locked phase changes in oscillatory EEG power defined by frequency and time post-stimulus over baseline, and changes in phase-locked visual and laser evoked responses both of which include late potentials reflecting attention or expectancy, like the P300, or contingent negative variation. Increases (ERS) and decreases (ERD) in oscillatory power post-stimulus may be generalizable given their consistency across healthy subjects. ERS and ERD are related to the ratings above as well as to anxious personalities and clinical anxiety and can resolve activity over short time intervals like those for some moods and emotions. These results could be incorporated into an objective instrumented test that measures EEG and CRs of autonomic activity and psychological ratings related to conditioned fear, some of which are subliminal. As in the case of instrumented tests of vigilance, these results could be useful for the direct, objective measurement of multiple aspects of the risk, diagnosis, and monitoring of therapies for anxiety disorders and anxious personalities.

Keywords: Event Related Potential; Event Related Spectral Perturbation; anxiety; expectation; fear; fear conditioning; human; scalp EEG.

PubMed Disclaimer

Conflict of interest statement

None of the authors has conflicts of interest related to this work. The manuscript is in accordance with the statement of ethical standards for manuscripts submitted to MDPI (Sensors).

Figures

Figure 1
Figure 1
Aversive Conditioning Protocol: (A) Cartoon of stages including the cued stage composed of a train of visual stimuli in which an unconditioned stimulus (US—painful laser pulse) is paired with one conditioned light stimulus in 75% of trials (CS+, image of a lamp lighted red signaling threat—80 total (see Panel B), while the second light is not paired (CS−, lamp lighted blue signaling safety—80), and the CS+ and CS− are presented randomly in the cued context (CX+, yellow underline, image of an office with lamp as above). CX, green underline is the extinction context, not reported here. After pairing of stimuli, the CS+ elicits a conditioned response (CR) including the Skin Conductance Response (SCR) and the ratings described below. The protocol is randomized for the (i) order of CSs and pairing of CS+ and US (ii) duration (within limits) of intertrial intervals, CSs, CXs, and CX onset to onset of CS. (B) Each stage has 2 blocks. The protocol begins with 2 blocks in the Nociceptive Stage (total of 80 stimuli) followed by the Habituation stage (160 CSs total). Ratings are performed in all intervals between blocks, and after the protocol. Anticipation is measured by the contrast between CS+ vs. CS− in the Cued Stage; experience of cued pain is measured by the contrast of US between the Cued vs. the Nociceptive Stage, and the US skin conductance response (SCR) following CS+ vs. CS− in the cued stage. This Figure is adapted from [12].
Figure 2
Figure 2
Skin conductance response (SCR) and CS Ratings during the Acquisition stage. (A) SCR ((mean +/− SEM)) at intervals after the CS+ (red line) and CS− (blue line). (B,C) are linear regression models (solid line) plus the 5% and 95% confidence bounds, dotted lines of WIII ERD vs. CS Salience and Valence across Subjects. See Text. Adapted from [12].
Figure 3
Figure 3
Activations (ERP see Abbreviations) during visual and nociceptive stages for AMY, HIPP, and dlPFC (dorsolateral prefrontal cortex). (A) Visual Evoked Responses (VER) where Baseline +/− 3SD is indicated by short horizontal bars on the vertical axis. P3 corresponds to P300 here and is related to the novelty of infrequent stimuli. Horizontal axes (A,B) −30 to 600 ms. Vertical bar 10 µV, 5 µV in (A). (B) LEPs shown in black traces. Red and blue traces (right) demonstrate LEPs averaged from separate series of the stimuli included in the black trace and show reproducibility. Vertical bar 10 µV, 5 µV in A.
Figure 4
Figure 4
Time Frequency plots of ERSP in (D,B) across Channels and subjects. CS− and CS+ are shown in the lower and upper rows, respectively. The three columns denote the stage of fear conditioning as labelled. The Habituation stage corresponds to Visual stage in Figure 1 and there are two sequential intervals for the Acquisition stage, i.e., as labelled Acquisition 1 (C,D) and Acquisition 2 (E,F) (Figure 1 Legend). Units for the axes of the time frequency plot are shown in (A) where time is shown relative to the CS at 0. Windows from I to V are presented in Table 1 (lower 3 rows) and illustrated in (C). Within these plots, hot and cold colors show significant increases and decreases in ERSP from that expected at random (green). Adapted from [12].
Figure 5
Figure 5
Time-frequency plots of activity in response to the laser pulse. Upper image (A): ERS/ERD induced by the laser during the attend laser task averaged across all subjects and channels with subtraction of phase-locked activity. The middle image (B) is without subtraction; while the lowest image (C) is the plot for ERP evoked by for the LEP. Other conventions as in Figure 4. Adapted from [88].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Demyttenaere K., Bruffaerts R., Posada-Villa J., Gasquet I., Kovess V., Lepine J.P., Angermeyer M.C., Bernert S., de Girolamo G., Morosini P., et al. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys. JAMA. 2004;291:2581–2590. doi: 10.1001/jama.291.21.2581. - DOI - PubMed
    1. Kessler R.C., Avenevoli S., Costello E.J., Georgiades K., Green J.G., Gruber M.J., He J.P., Koretz D., McLaughlin K.A., Petukhova M., et al. Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement. Arch. Gen. Psychiatry. 2012;69:372–380. doi: 10.1001/archgenpsychiatry.2011.160. - DOI - PMC - PubMed
    1. Kessler R.C., Lane M.C., Shahly V., Stang P.E. Accounting for comorbidity in assessing the burden of epilepsy among US adults: Results from the National Comorbidity Survey Replication (NCS−R) Mol. Psychiatry. 2011;17:747–758. doi: 10.1038/mp.2011.56. - DOI - PMC - PubMed
    1. Gustavsson A., Svensson M., Jacobi F., Allgulander C., Alonso J., Beghi E., Dodel R., Ekman M., Faravelli C., Fratiglioni L., et al. Cost of disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 2011;21:718–779. doi: 10.1016/j.euroneuro.2011.08.008. - DOI - PubMed
    1. Smit F., Cuijpers P., Oostenbrink J., Batelaan N., de Graaf R., Beekman A. Costs of nine common mental disorders: Implications for curative and preventive psychiatry. J. Ment. Health Policy Econ. 2006;9:193–200. - PubMed