|Year : 2019 | Volume
| Issue : 2 | Page : 80-85
Prepulse inhibition and acoustic startle response in young healthy Chinese
Renying He1, Guang-Yan Wu2, Bing Wu2, Juan Yao2, Yi Yang2, Jian-Feng Sui2, Xuan Li2
1 Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University; Department of Dermatology, Chongqing General Hospital, Chongqing, China
2 Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing, China
|Date of Submission||28-Nov-2018|
|Date of Decision||08-Mar-2019|
|Date of Acceptance||14-Mar-2019|
|Date of Web Publication||25-Apr-2019|
Dr. Xuan Li
Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Gaotanyan Street 30, Shapingba District, Chongqing 400038
Source of Support: None, Conflict of Interest: None
Prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR) are considered to be effective neurobiological measures of sensorimotor gating and information processing. The deficit of PPI and habituation of ASR has been proposed to be candidate endophenotypes of schizophrenia spectrum disorders. However, there has been little information on PPI and ASR measures in Chinese. The present study aimed to provide more information about the characteristics of PPI and ASR in young healthy Chinese and investigate their sensitivity to experimental parameters and characteristics of population. In this study, we examined the PPI and habituation of ASR in 41 young healthy adults (21 males and 20 females), using an acoustic startle stimulus of 115 dB and a prepulse of 75 dB at a lead interval (LI) of 60 ms and 120 ms, respectively. The behavioral performance demonstrated that the PPI and habituation of ASR in all the young participants were robust. The significant difference was not observed in PPI and habituation between male and female. The block effect on PPI was significant; PPI reduces with increasing training. Latency facilitation was observed under prepulse conditions, with a significant effect of LI. Compared to previous studies in Caucasians, Chinese in this study shows a higher habituation and PPI. In conclusion, this research provides more data of behavioral characteristics of PPI and ASR in young healthy Chinese. Chinese in this study shows a higher habituation and PPI than Caucasians in previous studies.
Keywords: Acoustic startle response, Chinese, habituation, prepulse inhibition
|How to cite this article:|
He R, Wu GY, Wu B, Yao J, Yang Y, Sui JF, Li X. Prepulse inhibition and acoustic startle response in young healthy Chinese. Chin J Physiol 2019;62:80-5
|How to cite this URL:|
He R, Wu GY, Wu B, Yao J, Yang Y, Sui JF, Li X. Prepulse inhibition and acoustic startle response in young healthy Chinese. Chin J Physiol [serial online] 2019 [cited 2020 Sep 25];62:80-5. Available from: http://www.cjphysiology.org/text.asp?2019/62/2/80/257183
| Introduction|| |
Prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR) are considered to be effective neurobiological measures that are used to investigate sensorimotor gating and information processing., The startle reflex (SR) is defined as a general defensive response which is elicited by a sudden intense auditory, visual, or tactile stimulus in animals and human. The startle response can be inhibited when a weak sensory stimulation is preceded 30–500 ms; this phenomenon is termed as PPI. PPI is believed to index a sensorimotor gating mechanism, which reflects the ability to filter out irrelevant or distracting stimulus to allow for selective and efficient processing of relevant information. Habituation is defined as the decrement in behavioral responses to a repeatedly presented stimulus, which is not due to sensory adaptation or effector fatigue. Deficiency in habituation is also thought to reflect impaired gating of repeated presentation of simple stimuli, which might result in sensory overload and thus cognitive disruption.
Some studies showed deficient PPI and habituation of ASR in patients with schizophrenia, Tourette syndrome, depression, and obsessive–compulsive disorder,,,,, while some other studies failed to find such results., This inconsistency may be caused by a variety of reasons. The PPI and ASR are affected by characteristics of population such as sex, age, and ethnicity.,,, Many studies reported that women show lower PPI than men;, however, some studies did not find this sex difference. An ethnic difference was reported by Swerdlow et al., who suggested that Asian-Americans (Asian or Pacific Islander) showed higher magnitude of ASR and lower PPI percent than Caucasian-Americans, but the difference was eliminated when groups were matched for startle magnitude on pulse-alone trials. Moreover, the cultural difference should also be considered into the ethnic difference of PPI and ASR. However, to the best of our knowledge, only one study reported the PPI and habituation of ASR of Chinese, and it provides little information of healthy population.
In addition, PPI and ASR are substantially dependent on experimental parameters such as startle stimuli, prepulse, lead interval (LI), and background noise.,,, ASR is enhanced with startle stimulus intensity increasing and is generally used in PPI studies of human in the 100–115 dB range. A more effective inhibition was elicited by 20 ms pure tone prepulses that were 15–20 dB over background noise. The background noise was usually used to mask unpredictable environmental sounds. However, some studies found that although background noise can increase the startle reactivity, it also impaired PPI. The LI between prepulse and startle stimuli is affected by the sensory modality of prepulse stimuli and was reported to be robust at the 60 ms and 120 ms when the PPI was elicited by auditory stimuli.
To promote the PPI and ASR study in normal and disordered populations, it is important to collect the PPI and ASR data of target population. Using the parameters suggested in previous studies, the present study was designed to acquire the data of PPI and ASR in normal young Chinese and investigate their sensitivity to experimental parameters and characteristics of population.
| Materials and Methods|| |
Participants included 21 male and 20 female healthy Chinese, ranging from 18 to 30 years of age, with no history of neurological or psychiatric disorder and no self-reported recent hearing impairment. All participants were medical students and staff members, recruited by campus newsletter and print advertisement. Before experiment, participants received a simple description of the study and gave informed consent. The research was approved by the Ethics Committee of the Third Military Medical University.
Startle stimuli was 115 dB 1000 Hz pure tone, with a 40-ms duration. Prepulse was 75 dB, 1000 Hz pure tone, with a 20-ms duration. LI, from prepulse end to startle stimuli onset, was 60 or 120 ms. Stimulus was delivered through a headphone. A sound-level meter (type 2240, Brüel and Kjær) was used to measure the intensity of the acoustic stimuli.
An infrared emitter/detector (FBCB30/TBBB30, Heng Sheng, Shenzhen, China) attached to goggles for eyeblink responses recording. During testing, participants were required to wear the goggles and keep the infrared emitter/detector aim at the left eyelid. The recorded voltage was linear with the eyeblink responses magnitude.
A data acquisition system (RM6240BDJ, Cheng Yi, Chengdu, China) was used to digitize markers of the applied stimuli and the eyeblink, and the data were acquired by the system software v.4.7 (Cheng Yi, Chengdu, China). The storage and analysis of data were carried out on a dedicated Windows PC.
The experiment took place in a dimly and quiet room, and the environmental noise is not >50 dB. Before test, the procedure was explained to the participant. During test, the participant was asked to sit still and look forward with the headphones, and goggles were placed on.
The test session began with a 5-min acclimation period, and then, they will accept a test which included 4 blocks, a total of 58 trials, lasted approximately 15 min [Figure 1]. In blocks 1 and 4, five startle stimuli were presented in each block. Block 2 consisted of eight trials of pulse-alone, eight trials of prepulse-pulse at 60-ms LI, and eight trials of prepulse-pulse at 120-ms LI, and all trials were presented in a fixed pseudorandom order. Block 3 was the same as block 2. All trials were separated by intertrial intervals of 20–40 s (30s on average).
|Figure 1: Experiment procedure. (Top) three types of trials: pulse-alone, prepulse-pulse at 60-ms lead interval, or 120-ms lead interval. (Middle) four blocks: blocks 1 and 2 include 5 pulse-alone trials; blocks 2 and 3 include three types of trials, and each type of trials presented eight times. (Bottom) full experiment procedure|
Click here to view
Response magnitude was the average of the difference between peak and baseline voltage (the mode voltage recorded for the 3.5 s before stimulus presentation) of the infrared voltage, within a window of 40–120 ms after startle stimulus onset, for all trials except those trials contaminated by artifact. On trials, in which no response could be detected, a response magnitude of zero was assigned. Startle response latency (to peak startle response) was the time between startle stimulus onset and response peak. Habituation of the startle response in three blocks was calculated as the proportion of the response magnitude difference from block 1 (1 − mean response magnitude to pulse-alone in block 2[3/4]/mean response magnitude to pulse-alone in block 1). PPI was calculated as the proportion of the response magnitude difference between pulse-alone trials and prepulse-pulse trials in each block (1 − mean response magnitude with prepulse trials/mean response magnitude to pulse-alone). Latency facilitation was calculated as latency difference between pulse-alone trials and prepulse-pulse trials in block 2 or block 3.
All the statistical analyses were performed with the SPSS Version 18.0 (SPSS Inc., Chicago, USA).
| Results|| |
Magnitude and habituation of startle response
Startle responses magnitude and habituation to pulse-alone in the four blocks are illustrated in [Figure 2]. Response magnitude within each participant revealed considerable variability, with the ratio of most to least response magnitude being 12 in block 1, 45 in block 2, 56 in block 3, and more than 100 in block 4.
|Figure 2: Startle responses magnitude and habituation to pulse-alone startle stimuli in male and female. Comparison of responses magnitude (solid lines) and habituation (broken lines) between male and female. Differences between groups were statistically significant in the indicated sessions. *P < 0.05|
Click here to view
Startle magnitude across blocks was assessed in Sex × Block repeated measures ANOVA. There was a significant effect of block (F(3,117) =84.413, P < 0.001), reflecting the phenomenon of habituation. There was no effect of sex, but the interaction of Sex × Block (F(3,117) =9.814, P < 0.001) was significant. Furthermore, a separate one-way ANOVA revealed that the magnitude of female was significantly higher than male in block 1 (F(1,39) =12.2, P = 0.01).
For the percentage of habituation, one-way ANOVA yielded that there was no sex difference in any blocks. We observed about 20% of participants (5 males and 6 females) show rapid habituation, who performed weak blink or not blink in block 2 and the later blocks. The startle responses of these participants in block 2 and block 3 were too weak to measure the PPI, so their data were excluded from PPI analysis.
Prepulse inhibition of startle response
PPI measured in two LIs in male and female are presented in [Figure 3]a. The percentage of PPI was assessed in Sex × LI (LI: 120 ms, 60 ms) repeated measures ANOVA. There was no difference in PPI between male and female participants and no significant effect of LI or interaction of Sex × LI.
|Figure 3: Percentage of prepulse inhibition. (a) Comparison of PPI between male and female with two lead intervals (120 ms and 60 ms). (b) Comparison of PPI between block 2 and block 3 with two lead intervals (120 ms, 60 ms). Differences between groups were statistically significant in the indicated sessions. *P < 0.05|
Click here to view
PPI measured in two LIs in block 2 and block 3 is presented in [Figure 3]b, and data of men and women were merged. A Block × LI repeated measures ANOVA was used to assess the effect of habituation on PPI. There was a significant main effect of Block (F(1,58) =11.749, P = 0.001), with more PPI in block 2 than in block 3 both when LI is 60 and 120 ms.
Peak latency and latency facilitation in prepulse inhibition
Peak latency to all conditions and latency facilitation in prepulse conditions are provided in [Table 1]. Latencies to pulse-alone in the four blocks were assessed in Sex × Block repeated measures ANOVA. The result revealed a significant effect of block (F(3,84) =9.545, P < 0.001), a significant of interaction of Sex × Block (F(3,84) =2.892, P < 0.05) but no effect of sex.
|Table 1: Mean peak latency to all conditions and latency facilitation in prepulse conditions|
Click here to view
Latency facilitation in the prepulse conditions was assessed in Sex × LI repeated measures ANOVA. There was a significant effect of LI (F [1,28] =2.44, P < 0.001) but on the effect of sex or interaction of Sex × LI.
| Discussion|| |
Magnitude and habituation of the startle response
The magnitude of the eyeblink response in the pulse-alone trials varied over a considerable range between participants in this study. Consistent with our results, Blumenthal et al. reported a major individual difference of approximately 30–45 times. Different from previous studies which measured eyeblink by EMG of orbicularis oculi musculus, this study measured eyelid movement directly through an infrared emitter/detector. The different measure methods caused an incomparability of the values of ASR magnitude and latency, and thus, we did not discuss the difference of ASR magnitude and latency between this study and previous studies.
In this study, the sex difference was only observed in block 1, in which response magnitude was greater in female than in male, while in block 2, the response magnitude of female decreased rapidly, and no sex difference existed in the later blocks. Consistent with our result in block 1, Kofler et al. reported a greater ASR magnitude in female in his study with the entire test of eight trials. By contrast, many studies did not observe the sex difference in ASR magnitude.,,, Noteworthy, a total of 8 trials were included in Kofler's study, and 5 trials were included in block 1 of our study. By contrast, over 50 trials were included in our entire test as well as these studies which reported no sex difference in ASR magnitude. Together, we speculate that female may show more intense response to a novel stimulus than male at the beginning of the stimulation, and this difference vanished soon because of the effect of adaptation to stimulation. This may be a possible reason for our results that sex difference in ASR magnitude was observed only in block 1.
Robust habituation of the startle response was observed in all participants in the present study, and the sex difference was not found. Although ethnic difference was not found in habituation in the study by Swerdlow et al., compared to the many previous studies which used Caucasian as the participants,,,, our study reported a higher habituation rate in block 4 (male: 66% and female: 77% in our study; lower than 50% in these studies). Moreover, one study reported a comparable habituation rate of 65%, who used Asian (Japanese) as the participants also. These data together indicated that Asian shows a higher habituation than Caucasians. However, considering the different experimental parameters used in these studies, the effect of ethnic in habituation needs further investigation.
Prepulse inhibition of startle response
Consistent with previous studies,, we found a significant effect of block on PPI. In block 2, PPI was significant higher than that in block 3, suggesting that PPI will reduce with increasing training. The possibility that the habituation of prepulse is a result of the reduction in PPI was excluded by Blumenthal, and he suggests that the reduction of PPI is related to the reduced startle reactivity by habituation.
This study did not find a significant difference in PPI between male and female. Some studies reported that PPI in female was mediated by fluctuation in hormonal levels across the menstrual cycle., However, Kumari et al. reported that females show lower PPI than males whatever phase of the menstrual cycle, and thus, some other factors may contribute to male PPI advantage, such as the sex difference in the testosterone and dopaminergic system.,, This study did not assess menstrual cycle state of female; further investigation is needed in this regard. Moreover, differing from some previous studies which measured EMG of relevant somatic muscles where the SR manifests, in this study, we measured startle response with eyelid movement recorded through an infrared emitter/detector. This procedure might result in problems when compared with others which evaluating startle behavior with somatic muscle EMG; this difference may also affect the lack of gender differences in PPI found in this study.
In the study by Swerdlow et al., the PPI was significantly greater in Asian versus Caucasian at 60 and 120 LI (about 45% in Asian and 38% in Caucasian at 60 LI; about 55% in Asian and 45% in Caucasian at 120 LI). As observed in other previous studies, using Asian as participant, Zhiren Wang et al. reported a PPI of 28.5% when LI was 60 ms and 42% when LI was 120 ms; Takahashi et al. reported a PPI of 41.7% when LI was 120 ms; using Caucasian as participant, Kumari et al. reported a PPI of 30% when LI was 60 ms and about 40% when LI was 120 ms; Ludewig et al. reported a PPI of about 60% when LI was 60 ms and about 50% when LI was 120 ms. In addition, compared with these studies, this study reported a much higher PPI (64% at 60 LI and 71% at 120 LI). Considering the PPI was modulated by experiment parameter, these data cannot provide a further assessment of the ethnic effect on PPI. The mark higher PPI in the present study may due to the difference in the background noise. The background noise was 70 dB in the above studies, whereas the background noise was a 45 dB ambient noise in the present study. Blumenthal et al. reported that PPI was significantly decreased as background noise intensity was increased from 50 to 70 dB.
In the present study, latency facilitation was clearly observed under the prepulse conditions, and it was significantly affected by LI. The latency facilitation was greater at 60-ms LI than at 120-ms LI. Inconsistent with our results, Cadenhead et al. reported a greater latency facilitation at 120-ms LI than at 30-ms LI. In the study of Blumenthal et al., latency facilitation was observed at 60-ms LI, but not at 120-ms LI, when the prepulse intensity was 70 dB (compared to 75 dB in our study and 78 dB in Kristin's study). However, when prepulse intensity was reduced to 55 dB, the latency facilitation was not observed either at 60-ms or 120-ms LI. Taken together, the effect of LI on latency facilitation is not clear, and the intensity of prepulse may be a key factor.
In summary, this study shows that PPI and habituation of ASR are robust in healthy Chinese. PPI reduces with train increasing; it may be a result of habituation of startle response. We do not observe sex differences in PPI and habituation. Compared to previous studies in Caucasians, Chinese in the present study shows a higher habituation and PPI. Further investigation is needed to elucidate the population characteristic effects in both PPI and ASR.
The authors gratefully thank Hong-mei Zhao for the technical assistance.
Financial support and sponsorship
This research was supported by the Major State Basic Research Development Program of China (973 program, no. 2014CB541600) and the National Natural Science Foundation of China (no. 81171249).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L. Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 1978;15:339-43.
Saletti PG, Maior RS, Hori E, Almeida RM, Nishijo H, Tomaz C. Whole-body prepulse inhibition protocol to test sensorymotor gating mechanisms in monkeys. PLoS One 2014;9:e105551.
Le Duc J, Fournier P, Hébert S. Modulation of prepulse inhibition and startle reflex by emotions: A comparison between young and older adults. Front Aging Neurosci 2016;8:33.
Graham FK. Presidential address, 1974. The more or less startling effects of weak prestimulation. Psychophysiology 1975;12:238-48.
Geyer MA, Braff DL. Habituation of the blink reflex in normals and schizophrenic patients. Psychophysiology 1982;19:1-6.
Ludewig K, Geyer MA, Vollenweider FX. Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Biol Psychiatry 2003;54:121-8.
Matsuo J, Ota M, Hidese S, Teraishi T, Hori H, Ishida I, et al.
Sensorimotor gating in depressed and euthymic patients with bipolar disorder: Analysis on prepulse inhibition of acoustic startle response stratified by gender and state. Front Psychiatry 2018;9:123.
Swerdlow NR. Update: Studies of prepulse inhibition of startle, with particular relevance to the pathophysiology or treatment of tourette syndrome. Neurosci Biobehav Rev 2013;37:1150-6.
Hoenig K, Hochrein A, Quednow BB, Maier W, Wagner M. Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder. Biol Psychiatry 2005;57:1153-8.
Mena A, Ruiz-Salas JC, Puentes A, Dorado I, Ruiz-Veguilla M, De la Casa LG. Reduced prepulse inhibition as a biomarker of schizophrenia. Front Behav Neurosci 2016;10:202.
Feifel D, Minassian A, Perry W. Prepulse inhibition of startle in adults with ADHD. J Psychiatr Res 2009;43:484-9.
Kohl S, Heekeren K, Klosterkötter J, Kuhn J. Prepulse inhibition in psychiatric disorders – Apart from schizophrenia. J Psychiatr Res 2013;47:445-52.
Steinman SA, Ahmari SE, Choo T, Kimeldorf MB, Feit R, Loh S, et al.
Prepulse inhibition deficits only in females with obsessive-compulsive disorder. Depress Anxiety 2016;33:238-46.
Moran LM, Hord LL, Booze RM, Harrod SB, Mactutus CF. The role of sensory modality in prepulse inhibition: An ontogenetic study. Dev Psychobiol 2016;58:211-22.
Swerdlow NR, Bhakta SG, Rana BK, Kei J, Chou HH, Talledo JA. Sensorimotor gating in healthy adults tested over a 15 year period. Biol Psychol 2017;123:177-86.
Rahman Q, Kumari V, Wilson GD. Sexual orientation-related differences in prepulse inhibition of the human startle response. Behav Neurosci 2003;117:1096-102.
Aasen I, Kolli L, Kumari V. Sex effects in prepulse inhibition and facilitation of the acoustic startle response: Implications for pharmacological and treatment studies. J Psychopharmacol 2005;19:39-45.
Kilpatrick LA, Ornitz E, Ibrahimovic H, Treanor M, Craske M, Nazarian M, et al.
Sex-related differences in prepulse inhibition of startle in irritable bowel syndrome (IBS). Biol Psychol 2010;84:272-8.
Swerdlow NR, Talledo JA, Braff DL. Startle modulation in caucasian-americans and asian-americans: A prelude to genetic/endophenotypic studies across the 'pacific rim'. Psychiatr Genet 2005;15:61-5.
Wang Z, Tan Y, Yang F, Zhang W, Zou Y, Song C, et al.
The study of acoustic startle reflex in male patients with chronic schizophrenia. Asian J Psychiatr 2012;5:54-7.
Blumenthal TD. Inhibition of the human startle response is affected by both prepulse intensity and eliciting stimulus intensity. Biol Psychol 1996;44:85-104.
Swerdlow NR, Blumenthal TD, Sutherland AN, Weber E, Talledo JA. Effects of prepulse intensity, duration, and bandwidth on perceived intensity of startling acoustic stimuli. Biol Psychol 2007;74:389-95.
Blumenthal TD, Noto JV, Fox MA, Franklin JC. Background noise decreases both prepulse elicitation and inhibition of acoustic startle blink responding. Biol Psychol 2006;72:173-9.
Valls-Solé J, Valldeoriola F, Molinuevo JL, Cossu G, Nobbe F. Prepulse modulation of the startle reaction and the blink reflex in normal human subjects. Exp Brain Res 1999;129:49-56.
Blumenthal TD, Elden A, Flaten MA. A comparison of several methods used to quantify prepulse inhibition of eyeblink responding. Psychophysiology 2004;41:326-32.
Kofler M, Müller J, Reggiani L, Valls-Solé J. Influence of gender on auditory startle responses. Brain Res 2001;921:206-10.
Kumari V, Aasen I, Sharma T. Sex differences in prepulse inhibition deficits in chronic schizophrenia. Schizophr Res 2004;69:219-35.
Ludewig K, Ludewig S, Seitz A, Obrist M, Geyer MA, Vollenweider FX, et al.
The acoustic startle reflex and its modulation: Effects of age and gender in humans. Biol Psychol 2003;63:311-23.
Csomor PA, Vollenweider FX, Feldon J, Yee BK. On the feasibility to detect and to quantify prepulse-elicited reaction in prepulse inhibition of the acoustic startle reflex in humans. Behav Brain Res 2005;162:256-63.
Cadenhead KS, Carasso BS, Swerdlow NR, Geyer MA, Braff DL. Prepulse inhibition and habituation of the startle response are stable neurobiological measures in a normal male population. Biol Psychiatry 1999;45:360-4.
Kunugi H, Tanaka M, Hori H, Hashimoto R, Saitoh O, Hironaka N, et al.
Prepulse inhibition of acoustic startle in Japanese patients with chronic schizophrenia. Neurosci Res 2007;59:23-8.
Dahmen JC, Corr PJ. Prepulse-elicited startle in prepulse inhibition. Biol Psychiatry 2004;55:98.
Lipp OV, Krinitzky SP. The effect of repeated prepulse and reflex stimulus presentations on startle prepulse inhibition. Biol Psychol 1998;47:65-76.
Blumenthal TD. Prepulse inhibition decreases as startle reactivity habituates. Psychophysiology 1997;34:446-50.
Swerdlow NR, Hartman PL, Auerbach PP. Changes in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders. Biol Psychiatry 1997;41:452-60.
Kumari V, Konstantinou J, Papadopoulos A, Aasen I, Poon L, Halari R, et al.
Evidence for a role of progesterone in menstrual cycle-related variability in prepulse inhibition in healthy young women. Neuropsychopharmacology 2010;35:929-37.
Kumari V, Aasen I, Papadopoulos A, Bojang F, Poon L, Halari R, et al.
A comparison of prepulse inhibition in pre- and postmenopausal women and age-matched men. Neuropsychopharmacology 2008;33:2610-8.
Takahashi H, Hashimoto R, Iwase M, Ishii R, Kamio Y, Takeda M, et al.
Prepulse inhibition of startle response: Recent advances in human studies of psychiatric disease. Clin Psychopharmacol Neurosci 2011;9:102-10.
[Figure 1], [Figure 2], [Figure 3]