Generalization of conditioned fear-potentiated startle in humans: experimental validation and clinical relevance

Abstract

Though generalization of conditioned fear has been implicated as a central feature of pathological anxiety, surprisingly little is known about the psychobiology of this learning phenomenon in humans. Whereas animal work has frequently applied methods to examine generalization gradients to study the gradual weakening of the conditioned-fear response as the test stimulus increasingly differs from the conditioned stimulus (CS), to our knowledge no psychobiological studies of such gradients have been conducted in humans over the last 40 years. The current effort validates an updated generalization paradigm incorporating more recent methods for the objective measurement of anxiety (fear-potentiated startle). The paradigm employs 10, quasi-randomly presented, rings of gradually increasing size with extremes serving as CS+ and CS-. The eight rings of intermediary size serve as generalization stimuli (GSs) and create a continuum-of-similarity from CS+ to CS-. Both startle data and online self-report ratings demonstrate continuous decreases in generalization as the presented stimulus becomes less similar to the CS+. The current paradigm represents an updated and efficacious tool with which to study fear generalization--a central, yet understudied conditioning-correlate of pathologic anxiety.

Figure 1

Conditioning and generalization stimuli for counterbalancing groups A and B. Half of participants were assigned to counterbalancing group A and half to B. The numbers 1-10 at the bottom of the rings label the stimuli from smallest (1) to largest (10) but did not appear when the rings were presented to participants. For both counterbalancing groups A and B, Class 4 consisted of the two rings closest in size to the CS+ and Classes 3-1 gradually decreased in similarity to the CS+. Prior to data analysis, startle and behavioral responses to every two neighboring intermediaries were averaged to form the mean level of responding for that class of ring (e.g., [Ring 2 + Ring 3] / 2 = Class 1). This allowed for the capture of a more gradual slope of generalization—produced by eight rather than four gradations— while requiring half the number of trials per intermediary. This methodological decision was made to avoid an unrealistically long experiment (leading to undue habituation of the startle reflex and subject fatigue) while achieving a gradual continuum of similarity. The diameter for the smallest ring (Ring #1) was 2.00 inches and subsequent rings increased by 20% with Ring #2 increasing 20% from Ring#1 (2.40 inches), Ring #3 increasing 40% from Ring #1 (2.80 inches), Ring #4 increasing 60% from #1 (3.20 inches), and so on. Such size increments resulted in ring diameters, from smallest to largest, of 2.00, 2.40, 2.80, 3.20, 3.60, 4.00, 4.40, 4.80, 5.20, and 5.60. CS+ = conditioned stimulus paired with shock, CS- = conditioned stimulus unpaired with shock.

Figure 2

Results for both psychophysiological (standardized startle EMG) and behavioral indices (risk ratings [1= no risk, 2 = some risk, 3 = high risk], reaction times [ms]) of conditioned fear generalization. Error bars reflect the standard error of the mean. CS+ = conditioned stimulus paired with shock; CS- = conditioned stimulus unpaired with shock; C1, C2, C3, and C4 = generalization stimulus Classes 1, 2, 3, and 4; ITI = inter-trial-interval.