Elsevier

Clinical Neurophysiology

Volume 114, Issue 9, September 2003, Pages 1557-1579
Clinical Neurophysiology

Invited review
A review of the modulation of the startle reflex by affective states and its application in psychiatry

https://doi.org/10.1016/S1388-2457(03)00202-5Get rights and content

Abstract

Objective: To provide an overview of startle reflex methodologies applied to the examination of emotional and motivational states in humans and to review the findings in different forms of psychopathology.

Methods: Pertinent articles were searched mostly via MEDLINE and PsycINFO.

Results: The startle reflex is a non-invasive translational tool of research that bridges the gap between animal and human investigations. Startle is used to study fear and anxiety, affective disturbances, sensitization, motivational states, and homeostasis.

Conclusions: The startle reflex is highly sensitive to various factors that are of interest in the studies of emotional disorders and has promoted new areas of investigations in psychiatry. However, research in psychiatry is still in its infancy and most findings await replication. Future progress will benefit from the development of innovative and powerful designs tailored to investigate specific disorders.

Significance: The startle reflex has utility as a research tool to examine trauma-related disorders, fear learning, drug addiction, and to contrast affective states and emotional processing across diagnostic groups, but its usefulness as a diagnostic tool is limited.

Introduction

Over the last two decades, there has been a steady increase in the number of human studies using the startle reflex to investigate normal and abnormal emotional and attentional processes. The growing interest can be attributed to several factors. First is the high sensitivity of the startle reflex to processes such as habituation, sensitization, sensorimotor gating, and affective modulation, which are of interest to psychophysiologists, experimental, developmental, and clinical psychologists, psychiatrists, and neuroscientists. Because startle is an automatic/reflexive response, it is not primarily influenced by intentional control and is resistant to demand effects and response biases that can interfere with verbal reports and voluntary motor responses (e.g. reaction time). In addition, startle stimuli can be delivered at any time to probe ongoing affective and mental processes. Another major incentive for the startle reflex methodology is that more than any other psychophysiological technique, it serves as an integrative tool of research that links preclinical to clinical research. The cross-fertilization between psychophysiology and neuroscience has led to the replication of human findings in animals and vice versa. This enables human research to take advantage of advanced knowledge about neurobiological mechanisms of emotional behaviors and attention in animals. A final advantage is the logistical ease with which startle methodologies can be applied. Startle is straightforward to elicit, record, and quantify. Startle procedures are easily implemented requiring relatively inexpensive equipment. Thus, startle research can be developed with limited resources in settings that are not primarily dedicated to psychophysiological investigations.

The startle reflex is a ubiquitous, cross-species response to abrupt and intense stimulation. It consists of a rapid sequential muscle contraction with the likely purpose of facilitating the flight reaction and/or to protect the body from a sudden attack. The ‘startle pattern’ consists of a forward thrusting of the head and a descending flexor wave reaction, extending through the trunk and the knees (Landis and Hunt, 1939). Startle is stereotyped, but not invariant. Its amplitude shows a relatively high variability that reflects variation in the internal state of the organism. To the extent that these changes are under experimental control, the startle reflex can serve as a probe of this internal state.

Three broad areas of research have emerged with regard to startle investigations of psychiatric disorders. One is concerned with the studies of startle reactivity or ‘baseline’ startle in the absence of any experimental manipulation. Underlying such studies is the idea that inter-individual difference in baseline startle reactivity may be influenced by activity of brain structures (e.g. limbic) due to constitutional or acquired (e.g. sensitization) factors. A second approach uses startle to infer a psychological state, usually an emotional experience or a motivational state. These studies are grounded on the observation that startle amplitude varies with the organism's changes in affective states (Lang et al., 1990). The notion that startle can track the valence dimension of emotion is considered an invaluable methodological advantage for the study of emotion. Traditional psychophysiological indices such as electrodermal, cardiovascular, and facial electromyographic measures do not reliably index the valence of emotion. Electrodermal activity is best viewed as a non-specific measure of (emotional) arousal, regardless of the valence of the eliciting stimulus (Greenwald et al., 1989, Lang et al., 1990). Similarly, cardiovascular activity is primarily influenced by metabolic activity and attentional demands (Lacey, 1967) and facial electromyogram (EMG) reflects emotional expression (Dimberg, 1990). The absence of an objective measure of emotion has been an impediment to psychophysiological research on emotion and its application to psychopathology. The startle reflex can very well complement verbal reports, which are vulnerable to individual perception, demand characteristics, and intentional distortion.

Another important area of investigation is concerned with startle as an index of sensorimotor gating. Sensory stimuli presented shortly (e.g. 30–200 ms) before the startle-eliciting stimulus can inhibit the magnitude of the startle response (Graham, 1975, Hoffman and Ison, 1980). This inhibition of the startle reflex by a pre-stimulus, or prepulse, is thought to reflect low-level gating of information processing (Braff et al., 1992) or protection of preattentive processing (Graham, 1975). The application of this paradigm, known as prepulse inhibition (PPI), in psychiatry derives from the observation that psychiatric patients who suffer from difficulties in filtering or gating unwanted thoughts (e.g. schizophrenia) or movements (e.g. obsessive–compulsive disorders) show little or no PPI (Braff et al., 1992). This application has generated a large body of literature that will not be covered in this paper. The reader interested in PPI studies is referred to several excellent recent reviews on PPI (Braff et al., 2001, Cadenhead and Braff, 1999).

This review focuses on the application of startle modulation to assess emotional states in psychiatric disorders. Following a brief methodological introduction, we describe the various procedures developed to modulate startle. We relate startle modulation to neurobiological mechanisms, as inferred from animal studies, and then review results in psychiatric populations.

Section snippets

Startle reflex methodology

In humans, the startle response is measured by recording the eyeblink reflex, the most consistent and persistent component of the startle pattern (Landis and Hunt, 1939). The eyeblink consists of a rapid contraction of the orbicularis oculi muscle, which is innervated by the facial nerve. Measurement of the eyeblink startle is straightforward and relatively inexpensive. The ease and applicability of the startle reflex are factors that contribute to the growing usage of this measure. A brief

Modulation of startle by aversive states

The translational nature of the startle reflex methodology may be best exemplified by paradigms that deal with the impact of aversive events or situations. Very similar procedures designed to engender aversive states in humans and in animals result in the same outcome, namely, an increase in startle amplitude. These procedures are reviewed below.

Affective modulation of startle

Another extension of the animal fear-potentiated startle paradigm is the presentation of slides depicting scenes of varying emotional valence to modulate the startle response in humans. Vrana et al. (1988) assessed startle in subjects viewing aversive/unpleasant (spiders, mutilated bodies), neutral (household objects), and appetitive/pleasant slides (erotica, baby faces). In line with the fear-potentiated startle effect, startle was enhanced during unpleasant slides compared to neutral slides.

Neurobiological substrate of startle modulation by emotional states

One of the most compelling features of the startle reflex is the abundant basic research that informs its underlying anatomic and functional basis. Just a few synapses make up the primary acoustic startle pathway in the rat. These involve the cochlear root neurons, neurons in the nucleus reticularis pontis caudalis, and motoneurons in the spinal cord (Lee et al., 1996). Among the projections to the motoneurons is the facial motor nucleus, which is likely to be critical for the eyeblink

Emotional valence

Extrapolating from studies in animals on the neural systems involved in fear-potentiated startle, several authors have suggested that startle modulation in the affective valence paradigm may be mediated by the amygdala and related structures (Lang et al., 1990, Patrick et al., 1993). This assumption is supported by a growing literature on the activation of the amygdala by various kinds of emotional manipulations, such as processing of emotional facial expressions (Breiter et al., 1996, Morris

Application to psychiatry

With the establishment of basic startle procedures in humans, there is an emerging literature on baseline startle, fear-potentiated startle, and affective startle modulation in psychopharmacology and psychopathology. Psychopharmacological studies of affective modulation and fear-potentiated startle in humans are relevant to psychiatric disorders for several reasons. First, such studies contribute to our understanding of the psychopharmacology of mood and emotion. Second, startle has become a

Conclusions and future directions

Fifteen years ago, Vrana et al.'s (1988) study on the affective modulation of startle by emotional stimuli, the growing interest in the startle methodology demonstrated by psychologists has spilled over to the clinical domain with investigations in psychiatric populations. Startle has great potential as an investigative tool, but its validity as a diagnostic tool is at best limited. Startle may have a potential prognostic value in PTSD and acute stress disorder, based on data that show the

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