Maladaptive behavioral consequences of conditioned fear-generalization: a pronounced, yet sparsely studied, feature of anxiety pathology

Abstract

Fear-conditioning experiments in the anxiety disorders focus almost exclusively on passive-emotional, Pavlovian conditioning, rather than active-behavioral, instrumental conditioning. Paradigms eliciting both types of conditioning are needed to study maladaptive, instrumental behaviors resulting from Pavlovian abnormalities found in clinical anxiety. One such Pavlovian abnormality is generalization of fear from a conditioned danger-cue (CS+) to resembling stimuli. Though lab-based findings repeatedly link overgeneralized Pavlovian-fear to clinical anxiety, no study assesses the degree to which Pavlovian overgeneralization corresponds with maladaptive, overgeneralized instrumental-avoidance. The current effort fills this gap by validating a novel fear-potentiated startle paradigm including Pavlovian and instrumental components. The paradigm is embedded in a computer game during which shapes appear on the screen. One shape paired with electric-shock serves as CS+, and other resembling shapes, presented in the absence of shock, serve as generalization stimuli (GSs). During the game, participants choose whether to behaviorally avoid shock at the cost of poorer performance. Avoidance during CS+ is considered adaptive because shock is a real possibility. By contrast, avoidance during GSs is considered maladaptive because shock is not a realistic prospect and thus unnecessarily compromises performance. Results indicate significant Pavlovian-instrumental relations, with greater generalization of Pavlovian fear associated with overgeneralization of maladaptive instrumental-avoidance.

Keywords: Anxiety disorders; Behavioral-avoidance; Fear-potentiated startle; Generalization; Instrumental conditioning; Pavlovian fear-conditioning.

Figure 1

Picture of the virtual-farmer computer paradigm displaying the short and long roads connecting the tool shed to the garden. Also pictured are the conditioned and generalization stimulipresented in the center of the screen during the task. Half of subjects were presented the stimulus set as displayed above, with the largest and smallest ring serving as CS+ and CS−, respectively. For the second half of subjects this was reversed with the largest and smallest rings serving as CS− and CS+, respectively. The diameters of rings from smallest to largest was .8”, .96”, 1.12”, 1.28”, 1.44”, 1.60”, 1.76”, 1.92” (size increases were established in 20% increments). Width and height are .8” for the small triangle, and 1.92” for the large triangle. CS− = conditioned safety cue; GS = generalization stimulus; CS+= conditioned danger cue; _ΔCS−= triangular CS−; GS₁, GS₂, GS₃ = generalization stimulus classes 1-3.

Figure 2

Examples of acquisition and generalization trials with the largest ring serving as CS+. (A) Pavlovian acquisition trials start with presentation of one of four stimulus types (CS+, CS−, _ΔCS−, and no shape [NS]) coincident with the farmer beginning to travel the short path between shed and garden (the long path is blocked). While traveling the short path, startle probes (represented by audio speakers) are delivered at 2.5 or 3.5 s post-trial-onset on all trials. For half of these trials, risk for shock is assessed at 6.5 s post-trial-onset. Actual shock is given together with virtual shock (graphic of farmer being shocked) on 50% of CS+ trials at 4 or 9 s post-trial-onset. The remaining 50% of CS+ trials are reinforced with virtual shock alone. Of note, when both risk ratings and actual shocks occurred on a given CS+ trial, actual shocks are always administered at 9 s post-trial-onset. Following acquisition, the generalization sequence begins, during which Pavlovian and instrumental trials alternate. (B) Pavlovian generalization trials begin with presentation of 1 of 7 stimulus types (CS+, GS₃, GS₂, GS₁, CS−, _ΔCS−, and NA) followed by the farmer automatically traveling the short path. Startle probes at 2.5 or 3.5 s post-trial-onset are delivered on all trials and risk ratings at 6.5 s post-trial-onset are assessed on 50% of trials. Shock reinforcement (actual and virtual) occurs in the identical manner described above for acquisition trials. (C) Instrumental generalization trials begin with presentation of 1 of 7 stimuli (CS+, GS₃, GS₂, GS₁, CS−, _ΔCS−, and NS) coincident with the question “Which way would you like to go”? Using a handheld button box, participants select “1” for the short, but contingently dangerous road, and “2” for the long, safe road that will likely result in an unsuccessful harvest. On CS+ trials, selecting “1” sends the farmer down the short path with actual and virtual shocks administered at 4 s post-choice. Selecting “2” allows the subject to eliminate any chance of shock and thus constitutes an instrumental avoidance response.

Figure 3

(A) Pavlovian generalization-gradients for standardized startle-EMG magnitudes and online risk ratings (0=no risk, 1=some risk, 2=high risk) across the conditioned danger cue (CS+) generalization-stimulus classes 3, 2, and 1 (GS₃, GS₂, GS₁), the circular conditioned safety cue (CS−), the triangular CS− (_ΔCS−), and no-shape (NS) conditions. (B) Instrumental generalization gradients reflecting percent of trials during which avoidance responses were displayed across CS+, GS₃, GS₂, GS₁, CS−, _ΔCS−, and NS conditions. Data points outlined in red mark stimulus classes for which startle is potentiated relative to the CS− (at the Hochberg-adjusted p value). Startle EMG was standardized using within-subject T score transformations ([([EMG_{single trial} — EMG_mean]/SD)*10]+50).

Figure 4

Reaction times for risk ratings and avoidance decisions during the generalization phase. NS = no shape; CS− = conditioned safety cue; ΔCS− = triangular shaped CS−; GS₁, GS₂, GS₃ = generalization stimulus classes 1-3; CS+=conditioned danger cue.

Figure 5

Relations between Pavlovian fear-potentiated startle (FPS) and percent avoidance for (A) generalization stimulus class 3 (GS₃), (B) generalization stimulus class 2 (GS₂), and (C) generalization stimulus class 1 (GS₁). FPS and avoidance are expressed as difference scores between a given GS and the conditioned safety-cue (CS−). *p≤.05, **p≤.01, ***p≤.001.