52(2014), (2015),••–••. 745–753. Periodicals, Inc. Printed the USA. Psychophysiology, •• WileyWiley Periodicals, Inc. Printed in the in USA. C 2014 Society for Psychophysiological V Psychophysiological Research Research Copyright © 10.1111/psyp.12400 DOI: 10.1111/psyp.12400

Effects of a startle stimulus on response speed and inhibition in a go/no-go task

JESSICA R. WASHINGTON, and TERRY D. BLUMENTHAL Department of Psychology, Wake Forest University, Winston-Salem, North Carolina, USA

Abstract Two studies examined the interaction of an acoustic startle stimulus and visual go/no-go task stimuli on startle reactivity and task performance. In the first study, an acoustic stimulus (50 ms, 100 dB noise) was presented alone or with a green (go) or red (no-go) circle; in the second study, a prepulse (50 ms, 75 dB noise) was presented alone or 120 ms before the startle stimulus or circle. The startle stimulus speeded responses to the go stimuli and increased the covert false alarm rate in the no-go condition (measured by EMG activity in the hand), although very few overt errors were made in the no-go condition. Startle response magnitude was increased by a circle but decreased by a prepulse. The speeding of go responses caused by a startle stimulus was attenuated by the occurrence of a startle response, suggesting that an intense accessory stimulus can facilitate responding to an imperative stimulus, and that the startle response to that intense stimulus can interfere with that facilitation. Descriptors: Startle, Go/no-go, Accessory stimulus effect, Prepulse, Reaction time et al., 1998). In fact, the former term may be the more accurate, since this reaction time (RT) speeding does not depend upon the startle response elicited by the intense “accessory” stimulus. If the startle response is minimized by increasing the rise time of the startle stimulus (Lipp, Kaplan, & Purkis, 2006) or by inhibiting the startle response with a prepulse (Valls-Solé, Kofler, Kumru, Castellote, & Sanegre, 2005), the speeding of RT is still found. In fact, the speeding of task RT is caused by the startle stimulus, and this speeding is actually attenuated by the startle response (Blumenthal et al., 2015). Hence, the term ASE, rather than StartReact, will be used to refer to this effect. The findings of Lipp et al. (2006) suggest that the ASE is explained by cross-modality facilitation, where an additional stimulus can speed RT to an imperative stimulus in another modality, when the two stimuli are presented in close temporal proximity. More recently, Jepma et al. (2008) argue that the ASE is due to stimulus energies converging across modalities, causing an increase in perceived intensity of the imperative stimuli. The additional stimulus need not elicit a startle response. Hackley and Valle-Inclán (1999) had participants perform a complex go/no-go task in which they were asked to respond to a colored letter that indicated whether the right or left hand was to be used, if a response were required. Five colors were used: one indicating that no response should be made and the other four indicating which finger should be used to make the response. By using this complicated version of the task, the researchers were able to show that reaction speeding occurred in the initial stage of response selection, before motor processes come online. Carlsen et al. (2004) suggest that the speeding of RT by a startle stimulus is due to the launching of a preloaded response pattern by the startle stimulus, and the effect is much less pronounced, if present at all, when the task is a choice rather than a simple RT task

The present paper describes the findings of two studies that examined the interactive effects of acoustic and visual stimuli on task performance and startle responding. Previous research has shown that an intense stimulus presented slightly before, concurrent with, or slightly after a target stimulus can speed reaction time to the target (Blumenthal, Reynolds, & Spence, 2015; Jepma, Wagenmakers, Band, & Nieuwenhuis, 2008). The present study looked at task performance, but also measured the impact of the intense stimulus on response inhibition in a go/no-go task. The intense stimuli in these studies were designed to elicit the startle eyeblink response, and the impact of a prepulse on startle reactivity was also measured. Prepulse inhibition of startle (PPI) is a sensitive measure of processing of both the prepulse and the startle stimulus, and it is also a way to modify the impact of the startle response on subsequent or ongoing processing (Blumenthal, 1999; Blumenthal et al., 2015; Graham, 1975). The differential effects of startle stimuli versus startle responses were also studied, as were the effects of the target stimulus on the startle response magnitude. All of these effects point to a complex interaction between sensory input and response output in the processing of multimodal stimuli. Several studies have shown that the presentation of a startle stimulus can modify motor activity and decrease response time to a target stimulus (Anzak, Tan, & Pogosyan, 2011; Jepma et al., 2008). This speeded responding to the imperative stimulus in the presence of an intense stimulus in another sensory modality has been referred to as the accessory stimulus effect (ASE: Hackley & Valle-Inclan, 1998; Jepma et al., 2008), or the StartReact effect (Carlsen, Chua, Inglis, Sanderson, & Franks, 2004; Valldeoriola Address correspondence to: Terry D. Blumenthal, Department of Psychology, Wake Forest University, Winston-Salem, NC 27109, USA. E-mail: [email protected]

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746 2 (Carlsen et al., 2008). To evaluate the ASE in a choice reaction time task, Carlsen et al. (2008) used a go/no-go task in which the go stimulus was either presented on 80% of the trials or 20% of the trials. They found no evidence to support the ASE. That is, the presence of a startle stimulus did not affect response time on the go/no-go task. According to Carlsen et al. (2008), this suggests that the response could not have been prepared in advance since the participants could not predict whether the subsequent trial would require a response (go) or not (no-go). However, they found an increase in response errors in the startle stimulus conditions compared to the control conditions, which they attributed to a disruption in cortical processes needed to make a correct decision. An alternative explanation for this increased error rate in the presence of startle stimuli is that the startle stimulus could have been launching a response on no-go trials, as shown in elevated probability of a false alarm response. The ability to inhibit inappropriate responses while selecting appropriate ones is essential to cognitive control. Response inhibition, one of the most highly evolved executive functions, refers to the suppression of inappropriate actions in a given context. It is commonly measured using tasks like the go/no-go task, which asks participants to respond (go) to a certain category of stimuli while withholding responses (no-go) to another category (Smith, Jamadar, Provost, & Michie, 2013). The present studies made use of a modified version of a go/no-go task that is similar to a traditional choice reaction time task, with equally probable go and no-go conditions. Equiprobable go and no-go conditions were used in order to have equal trial numbers in all conditions and avoid the impact of learning contingencies across trials (Barry & De Blasio, 2013). In order to bias participants toward responding, participants in the present studies were urged to respond as quickly as possible. Earlier, we discussed the idea that an intense accessory stimulus has the ability to speed reaction time. We were interested in what may happen if the response that is activated was intended to be inhibited. In both studies presented here, the imperative stimulus was a colored circle, presented in a modified go/no-go task that required a button press whenever a green (go) circle was presented. On some trials, an acoustic startle stimulus was also presented, either alone or with the colored circle. The ASE would predict that RT should be speeded on go trials that also have a startle stimulus. However, what would be expected on no-go trials? If the intense acoustic stimulus is in fact “launching” a response (e.g., Carlsen et al., 2004), we would expect more errors on no-go trials with than without a startle stimulus. Even if the overt error rate on no-go trials were not affected by the presentation of an accessory stimulus, the covert error rate might show some level of inhibitory failure. Covert errors are often referred to as “partial errors” or “partial inhibition” (van de Laar, van den Wildenberg, van Boxtel, & van der Molen, 2014; Vidal, Burle, Grapperon, & Hasbroucq, 2011), and are often measured as electromyographic (EMG) activity greater than baseline, but insufficient to cause an overt response (e.g., button press). In the present study, these EMG signals were recorded from one or both hands (our Study 1 and 2, respectively), to indicate the extent to which response inhibition was successful, partially successful, or overtly unsuccessful. The startle response is often considered to be a defensive response serving to protect an organism or prepare it to flee. However, Graham (1975, 1992) proposed that startle might also serve another function, that of interrupting ongoing processing so that cognitive resources could be redirected. Graham specifically referred to the startle response as the interrupter, and suggested that

PPI might serve to reduce the interruption of processing of the prepulse. As mentioned above, PPI occurs when a less intense stimulus is presented shortly before the startle stimulus, resulting in an attenuation of the startle response (Blumenthal, 1999). PPI occurs on the first trial containing the prepulse and startle stimulus pairing, indicating that it is not a learned association but rather an automatic function of stimulus processing. Graham (1975, 1992) suggested that two automatic processes occur when a prepulse is presented shortly before a startle stimulus. The first process involves identifying the prepulse, whereas the second involves the inhibition of the startle response, resulting in the protection of the processing of the prepulse from the interrupting effect of the startle reflex. Blumenthal et al. (2015) consider these concepts in terms of two component hypotheses: (1) the interruption hypothesis, which states that the startle response interrupts ongoing processing of stimuli; and (2) the protection hypothesis, which states that the purpose of PPI is to protect the processing of the prepulse from the interrupting effects of the startle response. In fact, the elevated error rate in the go/no-go study of Carlsen et al. (2008) described above could be seen as support for the interruption hypothesis, with the startle response interfering with accurate processing of the target stimuli. In opposition to prepulse inhibition of startle, a startle response can be facilitated when a stimulus in another modality precedes the startle stimulus by 50 ms or less (Burke & Hackley, 1997; Graham, 1980; Sarno, Blumenthal, & Boelhouwer, 1997). Boelhouwer, Teurlings, and Brunia (1991) suggest that this facilitation is the result of crossmodal temporal summation. When two stimuli are presented in two different sensory modalities, the presentation of the stimuli need not be simultaneous (though it can be). The important factor is that the two sensory pathways converge on a common point, and the arrival of the neural energies resulting from the two sensory pathways overlap in time. In this context, prepulse facilitation can serve as a useful tool in examining the convergence of separate sensory pathways as well as the conduction speeds of these pathways. This startle facilitation at short latencies is likely due to a summing of stimulus energy, analogous to the ASE, but expressed very rapidly (the summation is seen in a startle response that has an onset latency of approximately 50 ms, whereas the ASE is seen in reaction time, which is determined much later). Although the startle response is not necessary for the ASE (Lipp et al., 2006), it may still have some impact on processing of the task stimuli, as suggested by Graham (1975, 1992). Graham proposed that the startle response may interrupt ongoing cognitive processing, which would suggest that the ASE might be attenuated on trials with a more pronounced startle response (Blumenthal et al., 2015). To test this hypothesis, we preceded some of the intense acoustic stimuli with weaker acoustic prepulses, which results in a significant inhibition of the startle response (Blumenthal, 1999; Graham, 1975). If the ASE is purely a stimulus effect, caused by the intense acoustic stimulus, the RT speeding should not be affected by the presence of a prepulse. However, if the startle response is interfering with, or attenuating, the ASE, then the ASE should be more pronounced on trials with than without a prepulse. In this way, the present study allowed for the concurrent testing of both the ASE and the hypothesis of startle as an interrupting system. Method Participants Forty-eight participants provided written informed consent for participation in Study 1. Five were excluded due to the use of

Startle Startle and and go/no-go go/no-go medication or experimenter error, leaving a final sample of 43 participants (15 men, 28 women) ranging from 18–22 years of age. A new group of 50 students provided consent for Study 2. Eight were excluded due to the use of medications or experimenter error, leaving a final sample of 42 participants (12 men, 30 women) ranging from 17–22 years of age. Participants in both studies were undergraduate psychology students who received course credit for their participation. The Institutional Review Board of Wake Forest University approved all procedures. Stimuli In both studies, auditory stimuli were generated by Audacity software, controlled by SuperLab 4.5 (Cedrus) stimulus presentation software, passed through a PreSonus HP4 amplifier, and delivered through Sennheiser PX200 headphones. The visual stimuli in both studies were green or red circles 5.5 cm in diameter, generated using SuperLab, and presented on a computer screen, 45 cm from the participant, for a maximum of 2 s or until a button press was made. Button press responses in both studies were made using a Cedrus RB-610 response box. The startle stimulus used in both studies was a 50-ms 100dB(A) broadband noise (20 Hz to 20 kHz) with a near instantaneous rise time, delivered binaurally through headphones. Intertrial intervals (ITIs) varied randomly from 8–16 s in Study 1 and 8–12 s in Study 2. Study 2 also included a 50-ms 75-dB(A) broadband noise (20 Hz to 20 kHz) prepulse on some trials. Sound intensity was calibrated by presenting a 5-s broadband noise at each intensity (75 and 100 dbA) to a Quest 215 sound level meter, and a segment of these noises was used as the prepulse and startle stimuli. Response Measures In both studies, eyeblink EMG responses were measured from the left orbicularis oculi muscle using two Ag/AgCl surface recording electrodes. Hand EMG responses were measured in the same way with two electrodes placed on the thenar eminence on the palmar surface of the dominant thumb in Study 1, and on the same location on both hands in Study 2. A ground electrode was placed on the left temple. EMG activity of both the face and hand(s) was amplified using separate Biopac EMG amplifiers with filters passing 1–500 Hz, and sampled (1000 Hz) by a Biopac MP150 workstation. Raw, unfiltered EMG was then software filtered using a passband of 28–500 Hz. The signal was then rectified and smoothed using a five-sample boxcar filter. The data reported here were based on this rectified and smoothed EMG signal.

7473 left temple; in Study 2, two additional electrodes were placed on the nondominant hand in a position to mirror those on the dominant hand. Participants were then informed about the visual and auditory stimuli before headphones were comfortably placed and the experiment began. In Study 1, the following different trial types were presented: (a) startle stimulus alone trials, containing a startle stimulus only; (b) go trials, containing a green circle only; (c) no-go trials, containing a red circle only; (d) go-startle stimulus trials, containing a green circle paired with a simultaneous startle stimulus; and (e) no-go-startle stimulus trials, containing a red circle paired with a simultaneous startle stimulus. Study 2 had all of the five previously mentioned trial types in addition to trials in which a prepulse (50-ms, 75-dB broadband noise) was presented. The trial types unique to Study 2 were as follows: (f) prepulse alone trials, containing a prepulse only; (g) prepulse-startle stimulus trials, containing a prepulse presented 120 ms before a startle stimulus; (h) prepulse-go trials, containing a prepulse presented 120 ms before a green circle; (i) prepulse-no-go trials, containing a prepulse presented 120 ms before a red circle; (j) prepulsestartle stimulus-go trials, containing a prepulse presented 120 ms before a green circle and startle stimulus presented simultaneously; (k) prepulse-startle stimulus-no-go trials, containing a prepulse presented 120 ms before a red circle and startle stimulus presented simultaneously; and, finally (l) a catch trial condition in which no stimuli were presented but response lines were recorded and scored blind. The go/no-go task was the same in both studies; participants were informed that their only task was to press a button as quickly as possible on the response pad with their dominant thumb whenever a green circle appeared on the screen. They were asked to not press the button when a red circle appeared. They were told that they would hear sudden bursts of noise but that they could ignore the sounds. In both studies, after the presentation of an instruction screen, six startle stimulus-only acclimation trials were presented, with ITIs ranging from 8–16 ms. In Study 1, the acclimation block was followed by two experimental blocks, each containing 25 trials, five of each trial type, with each trial type presented once in each group of five trials, in randomized order.1 Study 2 consisted of an acclimation block followed by four experimental blocks, each containing 48 trials, four of each trial type, presented in random order, with a 1-min rest period between blocks. Data collection took approximately 10 min in Study 1 and approximately 40 min in Study 2. After the session, electrodes were removed and participants were given a brief summary of the aims of the study. They were then given a copy of their consent form and allowed to leave. Data Reduction and Analysis

Procedure In both studies, participants were seated in a sound-attenuated and electrically shielded room in front of a computer screen and asked to complete the informed consent and health history questionnaire. For eligible participants, the skin below the left eye on the left temple and on the palm of the dominant thumb (both thumbs in Study 2) was cleaned with 70% isopropyl alcohol. Surface electrodes were filled with conducting paste and placed on the following cleaned areas: two electrodes measuring the eyeblink were placed under the left eye over the orbicularis oculi muscle approximately 15 mm apart; two electrodes measuring EMG responses were placed on the palm of the dominant hand at the base of the thumb 15 mm apart; a single ground electrode was placed on the

Startle response magnitude was scored trial by trial using a custom scoring program (Schulz et al., 2009) according to guidelines proposed by Blumenthal et al. (2005). Startle responses were considered valid if they began within 20–120 ms after the onset of the startle stimulus. Trials that were unable to be scored (less than 1% of trials) due to movement artifacts, extraneous blinks, or noise

1. An exception was the no-go trial type in Block 1: the first trial of this type was a catch trial, consisting of only a fixation cross, which was used in the initial block to determine the base level of EMG activity when no stimulus was present. This trial was later scored blind so as to not bias interpretation of the presence of EMG activity. The second block contained 25 trials, five of each trial type.

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than two levels used Greenhouse-Geisser corrected degrees of freedom to determine significance, though uncorrected degrees of freedom are reported. A round of analyses was conducted with gender as a variable, but no main effects nor interactions were found on any measure, so the analyses reported here are pooled across gender. Results Startle Reactivity A repeated measures ANOVA showed that startle magnitude in control conditions habituated across time, from the acclimation block through the two trial blocks, in both Study 1, F(2,84) = 26.51, p < .001, ε = .619, and Study 2, F(4,64) = 60.79, p < .001, ε = .42. Startle magnitude in Study 1 was facilitated on trials containing a visual stimulus (either go or no-go) compared to trials containing a startle stimulus alone (see Figure 1). A 2 × 3 Trial Block × Circle Condition repeated measures ANOVA showed a main effect of block, F(1,42) = 19.40, p < .001, ε = 1.00, and a main effect of circle condition, F(2,84) = 35.79, p < .001, ε = .83. Pairwise comparisons revealed that this effect was fueled by larger startle magnitude in the conditions containing a circle than in conditions without a circle, regardless of whether the circle was a green go stimulus or a red no-go stimulus. Furthermore, a significant Circle Condition × Block interaction was observed, F(2,84) = 6.52, p < .01, ε = .96, in that startle habituated in the go-startle stimulus and startle stimulus alone conditions but not in the no-go-startle stimulus condition. In Study 2, a 4 × 3 Trial Block × Circle Condition ANOVA, including only those conditions with no prepulses, showed that startle magnitude decreased across blocks, F(3,123) = 13.06, p < .001, ε = .82. Additionally, there was a main effect of circle condition F(2,82) = 37.61, p < .001, ε = .76, such that startle magnitude was greatest in the go-startle stimulus condition (M = 2.57, SE = .34), followed by the no-go-startle stimulus condition

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were excluded from analysis. Trials on which no startle response occurred were assigned a magnitude of zero and included in the analyses. Startle magnitude was averaged across trials within each condition within each trial block. For all analyses, rectified and smoothed EMG voltage data were used (standardized data were inspected and yielded essentially the same statistical outcomes). The effect of trial block and circle condition (no circle, go circle, no-go circle) on startle reactivity was evaluated with a 2 × 3 analysis of variance (ANOVA) in Study 1 and a 4 × 3 ANOVA in Study 2. In order to assess the effect of the prepulse on startle reactivity in Study 2, PPI values were calculated by subtracting the average reactivity of the startle stimulus alone condition in each block from the reactivity of the task conditions (either prepulsestartle stimulus, prepulse-startle stimulus-go, or prepulse-startle stimulus-no-go), the result of which was then divided by the reactivity of the startle stimulus alone condition. Evidence of PPI was that the 95% confidence interval did not overlap zero. These PPI values were then subjected to a 4 × 3 Trial Block × Circle Condition ANOVA. To further examine the combined effects of an auditory prepulse and a visual stimulus on startle magnitude, a 4 × 2 × 3 Trial Block × Sound Condition (startle stimulus alone or prepulse plus startle stimulus) × Circle Condition (no circle, go circle, no-go circle) repeated measures ANOVA was performed on raw startle data in conditions containing either a startle stimulus or a startle stimulus paired with a prepulse. This analysis involves both control startle reactivity and startle reactivity on prepulse trials, uncorrected for individual differences in startle reactivity. Two types of task performance responses were measured in the hand: (1) response time, the time it took the participant to make a button press response after the onset of the visual stimulus; and (2) premotor response time, how long after the onset of the visual stimulus a burst of EMG activity occurred in the hand. An EMG response was considered valid if the peak was more than twice baseline and occurred between 120–500 ms after the onset of the visual stimulus. In all cases, a button press was preceded by EMG activity, so the premotor EMG data on go trials will not be discussed further (since that premotor response is entirely redundant with the button press response). The impact of a startle stimulus on task performance was evaluated in Study 1 with a t test comparison of average RT on go trials with versus without a startle stimulus. Since Study 2 involved additional auditory stimuli relative to Study 1, a 4 × 4 Trial Block × Sound Condition ANOVA was conducted, in the go conditions only, to determine the effects of the startle stimulus and prepulse on RT. Two measures of accuracy were measured in the hand: overt errors (false alarms resulting from a button press on no-go trials or misses due to the lack of a button response on go trials) and covert errors (false alarms resulting from significant premotor activity in the hand on no-go trials). Any activity in the EMG more than twice the baseline and between 120–500 ms after the onset of the stimulus was counted as significant activity warranting classification as a response. Button press accuracy on go trials was greater than 98.5% in both studies, and overt false alarms (involving a button press) occurred on less than 5% of the no-go trials. Covert errors of commission (measureable EMG activity without a button press) in the no-go conditions were analyzed with a t test comparing conditions with and without a startle stimulus in Study 1. In Study 2, a 4 × 4 Trial Block × Sound Condition ANOVA was conducted to determine covert response rates in the no-go conditions. All ANOVAs were conducted using an alpha level of .05 in SPSS 19 in Study 1 and SPSS 21 in Study 2. Analyses with more

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Figure 1. Study 1: Startle magnitude was facilitated by the addition of a visual stimulus. Error bars represent one SEM.

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(M = 2.38, SE = .33), with the startle stimulus alone condition (M = 1.46, SE = .22) having the smallest startle magnitude (see Figure 2). No significant interaction was found. Prepulse Inhibition in Study 2 Startle magnitude was significantly inhibited by a prepulse in every condition. A 4 × 3 Trial Block × Circle Condition ANOVA on proportional PPI scores showed a significant main effect of block, F(3,114) = 3.00, p < .05, ε = .88, whereby the degree of PPI decreased slightly from the first to the second block, irrespective of circle condition. No significant effect of circle condition, nor an interaction, was found. A 4 × 2 × 3 Trial Block × Sound Condition (startle stimulus alone or prepulse plus startle stimulus) × Circle Condition (no circle, go circle, no-go circle) repeated measures ANOVA showed main effects of sound condition, F(1,41) = 64.86, p < .001; ε = 1.00, circle condition, F(2,82) = 32.77, p < .001; ε = .71, and block, F(3,123) = 11.25, p < .001; ε = .90. There was also a significant Sound Condition × Circle Condition interaction, F(2,82) = 40.45, p < .001, ε = .83, such that the presence of a circle facilitated startle reactivity only when no prepulse was present. That is, PPI of startle prevented the circle from facilitating reactivity. The prepulse also attenuated the habituation effect across blocks compared to the startle stimulus alone conditions, as seen in the significant interaction between sound condition and block, F(3,123) = 13.67, p < .001, ε = .75. Figure 3 shows the effect of both the inhibitory auditory prepulse and the facilitatory effects of the visual stimuli. Startle magnitude was increased by the circle stimuli, and decreased by the prepulse, with the latter effect being stronger than the former. Response Time and Premotor Response Time In Study 1, the presence of a startle stimulus reduced response time, t(42) = 7.17, p < .001, from a mean of 453.17 ms when the go stimulus was presented alone to 343.60 ms on trials with both a go stimulus and a startle stimulus.

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Figure 3. Study 2: The presence of a prepulse reduced startle magnitude. This effect was attenuated by the presence of a visual stimuli. On trials where no prepulse was present, visual stimuli increased startle magnitude. Error bars represent one SEM.

In Study 2, a 4 × 4 Trial Block × Sound Condition ANOVA revealed a significant effect of block, F(3,123) = 3.25, p < .05, ε = .86, as well as sound condition, F(3,123) = 69.18, p < .001, ε = .83, but no interaction. The overt RT decreased across blocks, plateauing at Block 3. RT was fastest in the prepulse-startle stimulus-go condition (M = .396 s, SE = .013), followed by the go-startle stimulus condition (M = .442 s, SE = .013), then the prepulse-go condition (M = .455 s, SE = .013), with the go condition containing no sounds having the slowest button press response times (M = .526 s, SE = .013; see Figure 4).

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Figure 4. Study 2: Overt response time on go trials was fastest in the prepulse-startle stimulus condition and slowest on the trials containing no auditory stimuli.

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and those with only a startle stimulus and a go circle, with this difference then divided by reactivity in the condition with just a startle stimulus and a go circle (proportional PPI). The data were then divided into conditions with a startle response (either less than 100% PPI or with prepulse facilitation, which occurred in 2 of 164 cases) versus conditions with no startle response (100% PPI). When the startle response was absent, RT was faster than when any startle response occurred, t(162) = 2.17, p < .05 (means of 379.71 and 408.85 ms, respectively). This suggests that the maximal ASE occurred when no startle response was seen, and that the presence of a startle response attenuated the ASE.

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Figure 5. Study 2: The presence of a startle stimulus increased covert response rates in the no-go condition. Error bars represent one SEM.

Covert and Overt Error Rates Button press accuracy on go trials was greater than 98.5% in both studies, and overt false alarms (involving a button press) occurred on less than 5% of the no-go trials. In Study 1, covert errors of commission in the no-go condition (measureable EMG activity in the hand without a button press) was increased by the presence of a startle stimulus, t(42) = 5.12, p < .001, with mean error rates of 16.38% without a startle stimulus and 31.94% with a startle stimulus. A catch trial without any stimuli revealed that EMG activity meeting the covert response threshold was detected in the hand EMG 5% of the time. Covert error rates in all no-go conditions were at least three times that, indicating that these responses were not a result of scoring random noise in the EMG. In Study 2, a 4 × 4 Trial Block × Sound Condition ANOVA revealed significant main effects of block, F(3,123) = 2.94, p < .05, ε = .90, and sound condition, F(3,123) = 32.35, p < .001, ε = .87. The probability of a covert response was increased in the presence of a startle stimulus, regardless of whether or not a prepulse was present (see Figure 5). Relationship Between PPI and RT The ASE predicts that a startle stimulus will speed task-related RT to a go stimulus, whereas the interruption hypothesis predicts that a startle response will slow RT to the go stimulus (Blumenthal et al., 2015). These predictions were tested by reconfiguring the data of Study 2 according to the degree of PPI in each trial block for the condition that included a prepulse, startle stimulus, and go circle. Data from one participant were eliminated due to a failure to respond to any startle stimuli in more than half of the control trials. This yielded a data set with 164 cases (41 participants × 4 trial blocks). The degree of PPI was then calculated in each trial block for each participant, based on the difference in startle reactivity between trials with a startle stimulus and go circle plus a prepulse

The present data showed a clear accessory stimulus effect (ASE), with task RT being speeded when a startle stimulus was presented concurrent with a task-related visual stimulus, or when a prepulse was presented 120 ms before visual stimulus onset. The fact that the ASE was similar whether or not the accessory stimulus reliably elicited startle (comparing the ASE effect of the startle stimulus and that of the prepulse) suggests that the ASE is not dependent upon elicitation of the startle response. However, on trials with both a prepulse and a startle stimulus, the ASE was more pronounced when the startle response was absent, suggesting that the startle stimulus speeds RT and the startle response attenuates that effect. The startle response to the intense acoustic stimulus was also potentiated by the presentation of a visual stimulus, illustrating reflex facilitation. The startle response has been used in many contexts to examine stimulus processing and the ways in which components of this processing may interact with one another. This study sought to examine the ways in which the startle response and task-dictated response inhibition may interact. Several hypotheses were explored: (a) an auditory prepulse would inhibit startle magnitude following a startle stimulus (PPI: Blumenthal, 1999; Graham 1975); (b) presentation of a visual stimulus in addition to a startle stimulus would facilitate startle magnitude (Boelhouwer et al., 1991; Sarno et al., 1997); (c) reaction times would be speeded on trials containing a startle stimulus compared to trials without a startle stimulus regardless of the presence of a prepulse, consistent with the accessory stimulus effect (Jepma et al., 2008); and (d) more covert and overt errors would be made on no-go trials containing a startle stimulus than no-go trials without a startle stimulus, consistent with the interruption hypothesis of startle (Blumenthal et al., 2015; Graham, 1975). The facilitation of reaction time by a startle stimulus was found in the go conditions of both of our studies. This effect was seen regardless of the presence of a prepulse in Study 2, suggesting that it is the startle stimulus rather than the startle response that caused this speeding. In fact, Study 2 might be seen as a replication of the RT speeding effect seen in Study 2, under slightly different circumstances. This is in line with previous findings on the StartReact effect and accessory stimulus effect (Carlsen et al., 2004; Lipp et al., 2006; Valls-Solé, Rothwell, Goulart, Cossu, & Muñoz, 1999; Valls-Solé et al., 2005). Those earlier studies used startle stimuli ranging in duration from 40–66.6 ms with intensities ranging from 95 dB to 130 dB, presented 0–150 ms before the onset of the imperative stimulus. What this tells us is that stimuli within a range of intensities, durations, and lead intervals can result in facilitated reaction times. Furthermore, Valls-Solé and colleagues (2005) utilized tactile prepulses to illustrate that speeding of reaction time was independent of startle magnitude, as found in our Study 2. Our

Startle Startle and and go/no-go go/no-go study applied stimulus parameters (50 ms, 100 dB, and a simultaneous presentation with the imperative stimulus) that fell in the middle range of parameters found in previous studies. It is reasonable to assume then, that the speeding that we found is evidence of an accessory stimulus effect. The startle response data showing evidence for summation of stimulus energies was found in both studies, in that the presence of a circle presented concurrently with a startle stimulus increased startle magnitude compared to trials containing a startle stimulus only. This effect was found regardless of whether the trial was a go trial or a no-go trial, which is no surprise, considering the fact that the response that was affected is a brainstem reflex with a latency of approximately 50 ms, occurring well before the discrimination of go and no-go circles occurs. The increase in startle magnitude is likely the result of the startle stimulus and visual stimulus summing across modalities, as suggested by Boelhouwer and colleagues (1991). In the second study, the addition of a prepulse before a startle stimulus-circle pairing produced a startle magnitude intermediate between that of the prepulse-startle stimulus conditions and startle stimulus-circle conditions, consistent with our hypothesis. However, the startle magnitude on trials in the prepulse-startle stimulus-circle conditions was much less than in the startle stimulus alone condition. These data show that the facilitatory effect of the circle was considerably weaker than the inhibitory effect of the acoustic prepulse. It is unlikely that the facilitatory effect of the circle increased startle due to the increased demand characteristics of the circles. Valls-Solé, Valldeoriola, Tolosa, and Nobbe (1997) conducted a study in which a startling stimulus was presented either 500 ms before or concurrently with a go signal in a reaction time task. They found that habituation of the startle response, as measured from the sternocleidomastoid and masseter muscles, was reduced when preparing for a reaction time task (Valls-Solé et al., 1997). They proposed that motor preparation for the response task induces a more excitable motor response pathway: since attention is focused on perception of the go signal from the expected sensory channel, the startle response may be temporarily liberated due to reduced cortical inhibitory control coupled with enhanced excitability of the motor pathway. Valls-Solé et al. argue that making a response requires allocation of attention as well as other cortical resources when responding to the go stimulus. However, Valls-Solé and colleagues did not have a no-go condition in their study, and the addition of a no-go condition in the present study showed that there was little difference between the startle responses in the go and no-go conditions. Therefore, the effect is more likely driven by the lower processing of the visual stimulus and not the response demands of each condition (either initiating or inhibiting a response). Higher attentional processes such as vigilance might increase startle reactivity on all trials, but the same resources would be utilized in all conditions, go, no-go, and control. In our studies, we hypothesized that a startling stimulus would result in increased no-go error rates compared to no-go trials without a startle stimulus. Contrary to our hypothesis, there was no significant difference in overt task activity (false alarms) in the two conditions, with overt errors being very low in all cases. However, covert error rates, as measured from hand EMG, were markedly higher on trials containing a startle stimulus compared to nonstartle trials. This effect occurred regardless of whether or not a prepulse was present in Study 2. It is important to note that these EMG responses were not simply startle responses being recorded from the hand. A startling stimulus can generate a whole-body response that might be seen in the hand, but this response rapidly habituates

7517 in distal muscles, and startle is often limited to only an eyeblink after relatively few stimuli (Brown et al., 1991; Davis, 1984). Furthermore, the covert errors in our studies had an average latency of approximately 250 ms after the onset of the startle stimulus. This is substantially later than the latency of the average startle response in the hand, which is approximately 110 ms (Brown et al., 1991). Post hoc descriptive analyses of hand activity during the startle stimulus-only acclimation trials in Study 1 found a response in the hand on 8% and 7% of the first two trials, respectively. The following four acclimation trials had such activity less than 5% of the time, illustrating that EMG activity in the responding hand was equivalent to that on the catch trial included in Study 1, which showed activity on 5% of trials even when no stimulus was present. Evidence from both studies points to the startle stimulus, as opposed to the startle response, as the driving force behind these covert errors. Other studies have shown covert errors, using EMG measures similar to those of the present study, and these are based on increased peripheral excitability and inadequate suppression of cortical output (Vidal et al., 2011). Successful inhibition is associated with increased activation in several brain areas, including the right dorsolateral and ventrolateral prefrontal cortices (Smith et al., 2013). The prefrontal cortex has been implicated in studies of PPI deficits in schizophrenia patients (Hazlett et al., 1998). It is possible, then, that the prefrontal cortex may be sensitive to incoming stimuli and may temporarily release the response circuit from inhibition as a result of the arousal from the accessory stimulus. This leads to temporary muscle activity in the hand but ultimately no overt response. Startle magnitude was modified in the expected direction in the presence of lead stimuli in Study 2. The interruption and protection hypotheses (Blumenthal et al., 2015; Graham, 1975) propose that PPI has a protective effect on stimulus processing: by reducing the interrupting effects of the startle response, the prepulse can be more fully processed. The relevant stimulus to be responded to in the present study was the go circle. The fact that the startle stimuli resulted in speeded reaction times seems to argue against the interruption hypothesis. However, the same startle stimuli produced increased response activation in the form of increased covert error rates in the no-go condition, which may suggest an interruption of response inhibition potentially caused by the startle response. The protection hypothesis states that PPI exists to protect the processing of the prepulse from the interrupting effects of the startle response. Thus, we may assume that accuracy and reaction time should be optimal in conditions where a prepulse was present. In the present studies, response accuracy was so high that small differences may not be meaningful. With that said, the presence of a prepulse tended to increase accuracy on go trials and decrease accuracy on no-go trials, in addition to speeding RT on go trials—trends that would be consistent with the prepulse serving as an accessory stimulus. The degree of speeding of RT was slightly greater when the target stimulus was preceded by a more intense acoustic stimulus (the startle stimulus, as compared to the prepulse), although this difference was small. This is evidence for the fact that large differences in accessory stimulus intensity might have small effects of task RT, in support of early research (Miller, Franz, & Ulrich, 1999). We might also consider the possibility that the prepulse acted as a warning stimulus, since it began 120 ms before the target circle. Although the distinction between an “accessory” stimulus and a “warning” stimulus has been proposed to occur at a 500-ms lead interval (Hackley, 2006; Welch & Warren, 1986), the processes on which this cutoff is based may not be discrete, such that some warning effect is possible at the 120-ms lead interval used here.

J.R. J.R. Washington Washington and and T.D. T.D. Blumenthal

752 8 Finally, these effects are unlikely to be entirely due to the prepulse acting as a warning stimulus predicting an imperative stimulus, since the prepulse was as likely to occur either without a circle or before a no-go stimulus as before a go stimulus. Overt (button press) RT was speeded by the presentation of a startle stimulus by an average of 87 ms in our Study 2, but when that startle stimulus was preceded by a prepulse, RT speeding rose to an average of 133 ms, t(41) = 8.17, p < .001 (see Figure 4). In fact, when the startle response was inhibited to the point of complete prevention, the RT speeding was maximal at 149 ms. These results suggest that the speeding of RT in the ASE in these studies was due to the startle stimulus, but that the startle response attenuated the ASE. When that startle response was itself inhibited, or even prevented, by a prepulse, the full ASE was actualized. These results are similar to those of Blumenthal et al. (2015). These data also provide further support for the conclusion that the StartReact effect is not based on the startle response; in fact, the startle response attenuates the RT speeding seen in earlier studies. The fact that the go and no-go conditions were equally probable in these studies might be seen as a limitation, since lower probability no-go trials might have been expected to result in more false alarms. However, equiprobable go and no-go conditions stabilize the data across a session by preventing the advantage of learning the target contingency (Barry & De Blasio, 2013). Also, the addition of a measure of covert errors (partial inhibition) suggests that some level of failure of response inhibition on no-go trials was

rather likely. It would be interesting to see whether these covert errors would be different if the proportion of go and no-go trials were unequal. It would also be interesting to use a different response inhibition task, such as the stop-signal task (van de Laar et al., 2014), and see whether the startle stimulus and response might affect RT and error rate in that task. In fact, a wider variety of measures of ongoing processing would be useful in testing the interruption and protection hypotheses (Blumenthal et al., 2015; Graham, 1975). Finally, the extent to which these RT and startle response changes are due to general arousal might be evaluated, either by adding measures of arousal (e.g., electrodermal activity) or by modifying arousal (e.g., with caffeine). These are topics for future research. In conclusion, the current studies provide support for the accessory stimulus effect, the speeding of reaction time when a target stimulus is paired with an intense stimulus in another modality. These studies further show that the ASE is due to the combination of two stimuli, a combination which facilities responding to both stimuli (faster RT, larger startle), as shown in previous studies (e.g., Jepma et al, 2008; Sarno et al., 1997). Finally, this effect is not dependent upon the startle response, it is caused by the startle stimulus (e.g., Lipp et al., 2006). In fact, the startle response attenuates the ASE, and inhibition of startle decreases this attenuation and allows for maximal RT speeding in the ASE, in support of the interruption hypothesis of startle (Blumenthal et al., 2015; Graham, 1992).

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