Anxiety and prepulse inhibition of acoustic startle in a normative sample: The importance of signal-to-noise ratio
Introduction
The acoustic startle reflex is a defensive reaction that occurs in response to a sufficiently sudden and intense sound (Blumenthal et al., 2005). Although this response can involve a full-body reaction, it is most often quantified as electromyographic (EMG) activity of the orbicularis oculi, the muscle that controls eyeblinking, because the eyeblink component is the most sensitive and is the most resistant to habituation. Prepulse inhibition (PPI) of the acoustic startle response occurs when a stimulus (i.e. the prepulse) is presented 30–500 ms before the startle-eliciting stimulus, and causes a decreased startle response relative to non-prepulse trials (Blumenthal, 1999). PPI traditionally has been theorized to be a psychophysiological index of information processing (e.g. Graham, 1975) and sensorimotor gating (Swerdlow, Braff, & Geyer, 2000), such that less PPI is associated with poorer information processing, and with impairments in sensorimotor gating that are characteristic of schizophrenia spectrum disorders. PPI is due to an inhibitory projection from the tegmentum to the startle center in the brainstem (Swerdlow et al., 2000), and variations in PPI can be used to index variations in functioning of a variety of brain areas. Specifically, frontal lobe deficits may cause less activation of the midbrain inhibitory center responsible for PPI, and therefore a reduction in PPI in this condition.
Although most of the PPI research in clinical populations has focused on the schizophrenia spectrum, with findings of decreased PPI across most of the spectrum (e.g. Cadenhead et al., 2000, Duncan et al., 2006, Swerdlow et al., 1995), over the past decade there has been an increasing focus on the anxiety spectrum. Findings indicate decreased PPI in post-traumatic stress disorder (PTSD; Grillon et al., 1996, Grillon et al., 1998, Ornitz and Pynoos, 1989), obsessive-compulsive disorder (OCD; Hoenig et al., 2005, Swerdlow et al., 1993), and panic disorder (Ludewig et al., 2002, Ludewig et al., 2005), and in college students with high trait anxiety (Duley, Hillman, Coombes, & Janelle, 2007). Five other studies, however, did not find any association between anxiety spectrum constructs and PPI (Butler et al., 1990, Grillon et al., 1997, Larsen et al., 2002, Lipschitz et al., 2005, Morgan et al., 1997).
Although many of the anxiety spectrum PPI studies that yielded null findings had small sample sizes and, therefore, may not have possessed sufficient power to detect PPI differences, many of these null findings also may be explained, in part, by other methodological issues, such as non-optimal signal-to-noise ratio (SnR). The SnR of a PPI study is the difference between the background noise intensity and prepulse intensity (because sound intensity is usually measured in decibels, which are on a logarithmic scale, taking the difference between two intensities yields a ratio). Many PPI labs traditionally have used background noise levels around 70 dB in order to mask variable ambient noise; however, Wynn et al. (2004) posited that if background noise was not used, it may be more difficult to detect associations between PPI and psychological variables. Blumenthal, Noto, Fox, and Franklin (2006) supported this position by finding that PPI decreased as background noise increased above 50 dB, and concluded that when background noise is not used, the prepulse may be so salient that PPI deficits do not appear in clinical populations. It should be noted, however, that ambient noise levels may sometimes approach 70 dB, and these ambient sounds may act like prepulses in some cases, or may mask prepulses in other cases. Based on this and other research (e.g. Franklin et al., 2007, Swerdlow et al., 2007), we propose that the optimal SnR may be +15 dB because the effects of prepulses at SnRs below this level may be obscured by sensory masking effects, and the effects of prepulses at SnRs above this level may be obscured by ceiling effects of prepulse salience.
Supporting this hypothesis, most of the anxiety spectrum PPI studies that have used SnRs between +10 dB and +16 dB have detected significantly decreased PPI in anxiety groups (Duley et al., 2007, Hoenig et al., 2005, Ludewig et al., 2005, Ludewig et al., 2002), with two exceptions: Butler et al. (1990), which used a SnR of +15 dB, but may have possessed limited power because of a small sample size and a combat veteran control group, and Swerdlow et al. (1993), which found that a SnR of +4 dB, but not +16 dB, was associated with decreased PPI in 11 OCD patients. Nevertheless, Hoenig et al. (2005) conducted a study similar to that of Swerdlow et al. (1993), with SnRs between +2 and +16 dB, but with a sample of 34 OCD patients, and found that only the +16 dB condition was associated with decreased PPI. The results of anxiety spectrum PPI studies that either used lower SnRs (<+10 dB), or did not report background noise intensities, have been mixed, with some finding PPI deficits (Grillon et al., 1996, Grillon et al., 1998, Ornitz and Pynoos, 1989, Swerdlow et al., 1993), and others finding no significant effects (Grillon et al., 1997, Larsen et al., 2002, Lipschitz et al., 2005, Morgan et al., 1997). Grillon et al., 1996, Grillon et al., 1998 and Ornitz and Pynoos (1989) did not report background noise intensity but still detected PPI deficits; thus, it may be that the ambient background noise levels in these studies produced SnRs close to +15 dB, as was the case in Duley et al. (2007), which reported an ambient background noise of approximately 60 dB and a prepulse intensity of 70 dB. In any case, a systematic investigation of the effects of different SnRs on PPI in relation to various anxiety spectrum constructs may help to explain the aforementioned discrepancies of PPI findings in the anxiety spectrum.
As mentioned above, the anxiety spectrum is often associated with decreased PPI; nonetheless, it remains unknown if this association is specific to certain disorders (i.e. PTSD, OCD, panic disorder) or if this association applies more generally to the anxiety spectrum as a whole, including Axis II anxiety spectrum disorders (i.e. the Cluster C personality disorders; APA, 1994). Moreover, although Duley et al. (2007) found decreased PPI in a normative sample with high trait anxiety, no studies have explored how PTSD and other anxiety spectrum constructs are associated with PPI in a normative sample. Such an investigation would provide a rigorous test for the hypothesis that decreased PPI is generally associated with the anxiety spectrum. Therefore, one purpose of the present study was to replicate the finding of decreased PPI with increased trait anxiety in a normative sample (Duley et al., 2007), to extend the findings of decreased PPI in PTSD patients to a normative sample (Grillon et al., 1996, Grillon et al., 1998, Ornitz and Pynoos, 1989), and to explore the relationship between PPI and traits of the three Cluster C personality disorders: avoidant personality disorder (APD), dependent personality disorder (DPD), and obsessive-compulsive personality disorder (OCPD). It should be noted that although OCPD sounds similar to OCD, it is a distinct clinical condition.
Because each of these five constructs (i.e. trait anxiety, PTSD, APD, DPD, and OCPD) theoretically belongs to the same spectrum, we hypothesized that they should be significantly intercorrelated. In addition, based on previous studies of decreased PPI in the anxiety spectrum, we hypothesized that each of these constructs should be negatively correlated with PPI. A second purpose of the present study was to examine the hypothesis that the associations between PPI and psychological variables should be most evident at SnRs that approach +15 dB (Franklin et al., 2007, Swerdlow et al., 2007). Accordingly, we posited that, as the SnR approaches +15 dB (in this study, the 85 dB prepulse intensity condition), the associations between anxiety spectrum constructs and PPI would become stronger. The findings of the present study should help to elucidate the relationship between PPI, SnR, and the anxiety spectrum, and would provide strong support for the position that many of the null findings of PPI in the anxiety spectrum may be explained, in part, by the use of non-optimal SnRs. In addition, the findings of this study should demonstrate that PPI is generally sensitive to elevations in anxiety, even in a subclinical normative sample.
Section snippets
Participants
Female participants (N = 53) ranging from 18 to 22 years of age were randomly selected from a group of Wake Forest University introductory psychology students earning credit for a research participation option. As this study was part of a larger project necessitating a predominantly female sample, only females participated in this study. Participants signed an informed consent form and all procedures were approved by the Institutional Review Board of Wake Forest University. In the first portion
Results
Correlational analyses revealed that all anxiety spectrum constructs were significantly positively intercorrelated (p < .05; see Table 1), with the exception of intercorrelations with OCPD, which was only significantly associated with PTSD and, moreover, this association was negative (p < .05; see Table 1). Correlational analyses also revealed that all anxiety spectrum constructs, with the exception of OCPD, were significantly negatively associated with PPI in the 85 dB prepulse condition (p < .05),
Discussion
In the present study, we examined the association between PPI, SnR, and various anxiety spectrum constructs in a normative sample. Our hypotheses were mostly confirmed as all anxiety spectrum constructs were significantly positively intercorrelated, with the exception of OCPD, and all anxiety spectrum constructs were significantly negatively correlated with PPI, again with the exception of OCPD. Additionally, there was support for the hypothesis that the association between anxiety constructs
Acknowledgements
This project was supported in part by the Social, Behavioral, and Economic Sciences Research Fund of Wake Forest University (awarded to JCF).
References (36)
- et al.
Background noise decreased both prepulse elicitation and inhibition of acoustic startle blink responding
Biological Psychology
(2006) - et al.
Sensorimotor gating and anxiety: Prepulse inhibition following acute exercise
International Journal of Psychophysiology
(2007) - et al.
Medication status affects the relationship of symptoms to prepulse inhibition of acoustic startle in schizophrenia
Psychiatry Research
(2006) - et al.
Startle modulation in children at risk for anxiety disorders and/or alcoholism
Journal of the American Academy of Child & Adolescent Psychiatry
(1997) - et al.
Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorders
Biological Psychiatry
(1998) - et al.
Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder
Psychiatry Research
(1996) - et al.
Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder
Biological Psychiatry
(2005) - et al.
Baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder
Journal of the American Academy of Child & Adolescent Psychiatry
(2005) - et al.
A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder
Biological Psychiatry
(1993) - et al.
Effects of prepulse intensity, duration, and bandwidth on perceived intensity of startling acoustic stimuli
Biological Psychology
(2007)
‘Normal’ personality correlates of sensorimotor, cognitive, and visuospatial gating
Biological Psychiatry
Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings
Biological Psychiatry
Diagnostic and statistical manual of mental disorders
Diagnostic and statistical manual of mental disorders
Short lead interval modification
Committee report: Guidelines for human startle eyeblink electromyographic studies
Psychophysiology
A comparison of several methods used to quantify prepulse inhibition of eyeblink responding
Psychophysiology
Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD
American Journal of Psychiatry
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