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Is there more to discrete prepulses than meets the eye?
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Is there more to discrete prepulses than meets the eye?
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IS THERE MORE TO DISCRETE PREPULSES THAN MEETS THE EYE?
by
Jonathan Kajzovar Wynn
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF ARTS
(Psychology)
August 1998
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UMI Number: 1393190
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UNIVERSITY OF SOUTHERN CALIFORNIA
T H E G R A O U A T E S C H O O L
U N IV E R S IT Y P A R K
L O S A N G E L E S . C A L IF O R N IA 00007
This thesis, w ritten by
_________ J o ja a ± h a jL j!C a jz a Y 5 r _ W y !lD ______________
under the direction of h js Thesis Committee,
and approved by a ll its members, has been p re
sented to and accepted by the D ean of The
Graduate School, in p a rtia l fu lfillm e n t of ike
requirements fo r the degree o f
Master of Arts
August 18, 1998
THESIS COM MITTEE
C h a ir m ax
— .—
cAM-
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Jonathan Kajzovar Wynn Dr. Michael E. Dawson
Is there More to Discrete Prepulses than Meets the Eye?
The effectiveness of different types of auditory prepulses in producing
prepulse inhibition (PPI) of the acoustic startle eyeblink was studied in two
experiments. It was found that the optimal auditory prepulse to produce the
greatest amount of PPI of startle was a discrete (20 ms) white noise. It was found
that a discrete white noise prepulse produced greater PPI than either a discrete
tone or a continuous tone (Experiment 1) and that this discrete white noise
advantage was not due to any similarity in bandwidth to the startle pulse or to
any refractory effect of the prepulse (Experiment 2). Prepulse inhibition, using
auditory prepulses and startle pulses, may be dependent upon the transient
nature of the prepulse as well as the physical characteristics of the prepulse.
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ACKNOWLEDGMENTS
I would like to express my appreciation and gratitude to my adviser, Dr.
Michael E. Dawson for his generous help and support throughout this
experiment. I would also like to thank Dr. Anne Schell for her invaluable insight
and comments that helped with this project.
I also want to thank my fellow students Veronica Mejia and Anna Marie
Medina who offered their constructive criticisms and support throughout this
project. Most of all, however, I extend my deepest gratitude to Serkan Oray
without whom this project would not have been possible.
This project was supported by a National Institute of Mental Health Grant
MH46433 to Dr. Michael E. Dawson.
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Table of Contents
iii
Page
Acknowledgments ii
List of Figures iv
Abstract V
Introduction 1
Experiment 1 Methods 15
Experiment 1 Results 18
Experiment 1 Discussion 21
Experiment 2 Methods 24
Experiment 2 Results 26
General Discussion 30
References 37
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iv
List of Figures
page
1. Demonstration of a Prepulse Inhibition Paradigm 2
2. Demonstration of a Discrete and Continuous PPI Paradigm 8
3. Experiment 1: SCOR Results 19
4. Experiment 1: PPI Results 21
5. Experiment 2: SCOR Results 27
6. Experiment 2: Raw EMG for Unprobed Prepulses 28
7. Experiment 2: PPI Results 29
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V
Abstract
Research into deficits of prepulse inhibition (PPI) in schizophrenia patients
has revealed two different interpretations from results in different labs. The first is
that patients are deficient in automatic attentional processes, as evidenced by
impaired PPI using discrete white noise prepulses. The second interpretation is
that the patients are deficient in controlled attentional processes, as evidenced
by a failure to show significant attentional modulation of PPI using continuous
pure tone prepulses. The differences between these two different findings may
be due to the types of prepulses used in the different labs. The effectiveness of
different types of auditory prepulses in PPI of the acoustic startle eyeblink was
studied in two experiments. In Experiment 1, 42 college student subjects were
presented three different prepulses: a discrete white noise, a discrete tone, and
a continuous tone (all 75 dB(A)). The startle probe was a 104 dB(A) white noise
burst presented at lead intervals of 60 and 120 ms. Analyses showed that the
discrete white noise, across both lead intervals, produced greater PPI than either
the discrete tone or the continuous tone. Experiment 2, conducted on 61 college
students, attempted to determine if the superiority of the discrete white noise
was due to the acoustic similarity of the prepulse and the startle. The prepulse
stimuli received by all subjects were a discrete white noise, a continuous white
noise, a discrete tone, and a continuous tone (all 75 dB(A)). The startle stimuli,
varied between groups, were a 104 dB(A) white noise burst and a 104 dB(A)
1000 Hz tone burst. Results from Experiment 2 showed that the discrete white
noise prepulse, probed either with a white noise or a tone startle stimulus,
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produced the greatest amount of inhibition. The results of the two experiments
suggest that the optimal auditory prepulse for producing PPI is a discrete white
noise. Prepulse inhibition may be dependent on the transient nature of the
prepulse as well as the physical characteristics of the auditory prepulse used.
These findings still leave the differences seen in PPI deficits in schizophrenia
patients not fully explained, however, possible theories are discussed.
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1
Is There More to Discrete Prepulses than Meets the Eye?
The startle eyeblink is part of the more general startle reflex, a set of
physiological changes which occur in response to any rapid change in
stimulation of sufficient intensity. It is a very robust and reliable indicator of startle
(Graham, 1975). Startle eyeblink is an automatic reflexive response mediated at
the brainstem level, but the magnitude of the startle reflex can be reliably and
predictably modified if a nonstartling stimulus (the prepulse) is presented prior to
a startling stimulus (Graham, 1975; Hoffman & Ison, 1980). Specifically, the
startle eyeblink is inhibited if the interval (referred to as the lead interval)
between the onsets of the prepulse and the startle stimulus is relatively short
(between 30 and 500 ms), and may be either inhibited or facilitated if the interval
is relatively long, i.e. greater than 1000 ms, at least if the startle stimulus and the
prepulse are in the same modality (Anthony & Putnam, 1985; Graham, 1975;
see Filion, Dawson, & Schell, 1998). The former condition results in a
phenomenon known as prepulse inhibition (PPI) and is represented in Figure 1.
Prepulse inhibition of the startle eyeblink is thought to reflect preattentive
protection of processing or an automatic sensorimotor gating process (Braff &
Geyer, 1990; Graham, 1975).
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2
baseline startle blink
prepulse inhibition
EM G
^ _ _ _ _ _ _ _ _ _ n_ _ _ _ _ _ _ _ _ _ _
startle alone p re pulse + startle
Stimuli Events
Figure 1: Demonstration of a Prepulse Inhibition Paradigm
Prepulses can be any change in a stimulus (onsets, offsets, gaps, etc.)
which precede a startle-eliciting event. Auditory prepulses (or any non-startling
auditory stimuli) can activate two different auditory systems: short-time constant
neurons (transient neurons) and long-time constant neurons (sustained
neurons). Graham and Murray (1977), basing their hypotheses on the work of
Gersuni (1971), hypothesized that short-time constant neurons are sensitive to
stimulus transients, such as onsets and offsets of stimuli, whereas long-time
constant neurons are sensitive to the sustained aspects of stimuli, such as
duration. Graham and Murray state that, “Gersuni (1971) proposed that one
function of the short-time system was rapid conduction to higher centers of the
information that an environmental change had been detected, while the more
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slowly acting long-time system allowed for finer analysis of stimulus information”
(p. 114). Gersuni (1971) hypothesized that the short-time constant mechanism
functions to discriminate the spectral properties of sounds within short segments
of time and measures time intervals between transients. The long-time constant
mechanism functions to more precisely discriminate the spectral properties of
sounds and “is likely to be more closely concerned with the sensation of the
chromatic pitch, with musical perception, as well as with the emotional side of
sound perception in general" (Gersuni, 1971, p. 109).
It has been hypothesized that acoustic elicitation of startle and prepulse
inhibition are controlled by the activation of short-time constant neurons (Graham
& Murray, 1977). Similar short time constant systems have been found for visual
and tactile stimuli (see Blumenthal, in press). Transient neurons are thought to
function as stimulus detectors and sustained neurons are thought to function as
stimulus identifiers or “ discriminators” (Berg, 1985). Several studies have
suggested that it is the transient system that makes the greatest contribution to
prepulse inhibition (Blumenthal & Levey, 1989; Graham & Murray, 1977; Lane,
Ornitz, & Guthrie, 1991).
Graham and Murray (1977) used either 20 ms discrete tone prepulses
(prepulses with onsets and offsets prior to startle onset) or continuous tone
prepulses (prepulses that continued until startle onset) at lead intervals (the
amount of time between initial onset of the prepulse and onset of the startle-
eliciting stimulus) of 30, 60, 120, and 240 ms in three separate experiments. In
Experiments 1 and 2, the prepulse was 70 dB(A) and in Experiment 3 the
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4
prepulse was 60 dB(A). In all experiments the tone prepulse was a 1000 Hz
pure tone and the startle burst was a 50 ms, 105 dB(A) broad-band white noise
burst. The results of the experiments showed that there was no difference in
inhibition seen to either discrete or continuous prepulses, inhibition was seen at
all lead intervals and was maximal at a lead interval of 120 ms for both discrete
and continuous prepulses, and that the two experiments that used the prepulses
of greater intensity (70 dB) produced significantly more inhibition than the one
experiment with the prepulse at a lower intensity (60 dB). Although the discrete
and continuous prepulses did not produce any differential prepulse inhibition,
Graham and Murray concluded that “ the absence of any increase in inhibition
with increase in stimulus duration beyond 20 msec, taken in conjunction with the
finding of greater inhibition with greater lead stimulus intensity, implies that it is
the magnitude of the change in intensity and not total stimulus energy that
produces the inhibitory effect” (p. 112, emphasis in original article). Graham and
Murray therefore concluded that prepulse inhibition is due solely to the transient,
not steady-state, characteristics of the prepulse.
Blumenthal and Levey (1989), in two experiments, examined whether
prepulse inhibition was due to the transient system or the sustained system. The
first experiment used broadband noise (20 Hz-20 kHz) discrete prepulses (20
ms) that were 20 dB(A) above each subject’s psychophysical threshold, all with
fall times of 0.1 ms and rise times that ranged from 0.1 ms to 20 ms, and a 95
dB(A) broadband noise startle 50 ms in duration with a rise/fall time of 0.1 ms. All
lead intervals were 150 ms long. The results of Experiment 1 showed that
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5
varying the rise time of discrete prepulses had no effect on prepulse inhibition,
with significant prepulse inhibition seen for each varied rise time. The second
experiment used similar startle and prepulse properties with the exception that
the prepulses were continuous (continued throughout the lead interval). There
were a total of nine prepulses used: five of the prepulses were 150 ms in
duration with rise times of 0.1, 20, 50,100, or 150 ms; three of the prepulses had
rise times of 0.1 ms with durations (and lead intervals) of 50,100 or 130 ms; and
a final prepulse was 300 ms in duration with a 150 ms rise time. The results of
this experiment showed that continuous prepulses produced startle inhibition at
short lead intervals (at the 50 ms lead interval with a rise/fall time of 0.1 ms) but
not at longer lead intervals. Blumenthal and Levey showed that the transient
aspect of prepulses inhibits startle (Experimentl) and that the steady-state
portion of a prepulse produces startle facilitation (Experiment 2). The results
show different time courses for inhibition and facilitation of startle, with the
transient system responsible for inhibition and the sustained system responsible
for facilitation. The combination of the inhibitory and facilitatory effects
determines the amount of startle modulation with the two different effects
resulting from two different mechanisms.
Lane, Omitz, and Guthrie (1991) also found supporting evidence from
three separate experiments that prepulse inhibition is due to the transient system
responding to transient changes in the environment. Discrete prepulses were
either tone onset (a 25 ms 1000 Hz, 75 dB(A) prepulse with rise/fall times of 4
ms with no background noise, lead interval of 120 ms) or two different tone
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6
offsets: (1) a continuous 1000 Hz, 75 dB(A) background noise with offset for 25
ms and lead interval of 120 ms and (2) a 2000 ms 1000 Hz, 75 dB(A) tone with
no background noise offset at 100 ms before the startle probe. Lane et al. found
that prepulse inhibition was elicited by both tone onset or tone offset discrete
prepulses, with tone onset producing more inhibition than tone offset. The
important finding was that inhibition was due to the transient changes in the
environment (tone onset or tone offset) detected by the transient neurons.
Graham (1992) hypothesizes that the onset of a lead stimulus initiates two
automatic processes that serve to identify and then to protect the processing of
that lead stimulus. The amount of startle inhibition seen reflects the degree to
which this protection is activated. Lead stimuli that are more intense (Blumenthal,
1995) or discrete prepulses that are longer in duration (e.g., 50 ms instead of 20
ms) activate the protective mechanism more strongly. The first automatic
process is the transient-detecting response (TDR), which is elicited by transient
changes in the environment and rapidly conveys the information that a transient
change has been detected, but not necessarily discriminated from any other
stimulus. The TDR, Graham argues, serves as the mechanism for gating
subsequent stimuli or attenuating the effects of high intensity stimuli, such as a
startle burst. The second automatic process activated is the generalized
orienting response (OR), which is elicited by a stimulus that is novel or
unexpected. This is slightly different from the “localized/signal OR, directed in
anticipation of a particular significant stimulus" (Graham, 1992, p. 4), which is
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7
thought to measure the amount of attention allocated to a stimulus and the
extent to which that stimulus is processed (Dawson, Filion, & Schell, 1989).
Graham (1992) conceptualizes the OR and the TDR as two different
processing “ filters”: a low-pass filter (the orienting response) and a high-pass
filter (the transient-detecting response), respectively. The low-pass filter has the
characteristics of responding to long latency and prolonged output, shows rapid
habituation, and functions to “ enhance” stimulus input. The high-pass filter has
the characteristics of responding to short latency and brief output, shows slow
habituation, and functions as a detection-gating mechanism. Low-pass filtering,
therefore, would be responsible for processing continuous stimuli, such as a
2000 ms tone, whereas high-pass filtering would be responsible for processing
discrete stimuli, such as a transient change in the environment. However, if a
stimulus has characteristics that would activate both filters, such as the transient
onset of a tone with a sustained output, the filters can sum algebraically and
partially cancel each other out.
Discrete prepulses have two transients (an onset and an offset), both
generated before the startle stimulus, whereas continuous prepulses that are
sustained until the startle stimulus is delivered have one transient (an onset, with
a sustained portion). Transients that are “independent” of each other (i.e., that
are more separated in time) are more effective in inhibiting startle, with maximal
effectiveness at 20-50 ms (time from onset to offset) (Blumenthal, in press). The
difference between a discrete prepulse paradigm and a continuous prepulse
paradigm is represented in Figure 2. Discrete prepulses activate only the
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8
transient neurons whereas continuous prepulses activate both the transient and
sustained neurons. The steady state portion of a continuous prepulse, the
portion following the single onset transient of the prepulse, activates the
sustained neurons which can attenuate the inhibition produced by the activation
of the transient neurons. Thus, the transient neurons are presumed to be
responsible for inhibitory effects of prepulse inhibition whereas sustained
neurons are responsible for facilitatory effects (Graham, 1979; Graham &
Murray, 1977; Hoffman & Wibble, 1969). These two effects, inhibition and
facilitation, occur simultaneously in continuous prepulses, algebraically
summating and partially cancel each other. Therefore, Blumenthal (in press) has
called this a “ transient advantage”, since a discrete prepulse makes a greater
contribution to the inhibition of startle.
Discrete Prepulse Paradigm
104
dB
40 ms startle
75
<50
1000
500
Time (ms)
/ 120 ms
20 ms discrete prepulse
Continuous Prepulse Paradigm
104
40 ms startle
dB
75
<50
1000
500
Time (ms)
120 ms
120 ms continuous prepulse
Figure 2: Demonstration of a Discrete and Continuous PPI Paradigm
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9
Prepulse inhibition is hypothesized to be automatic, or “hard wired” into
the brain, because it requires only midbrain and lower brain structures (Leitner &
Cohen, 1985), occurs in decorticate animals (Ison, O’Conner, Bowen, &
Bocimea, 1991), occurs in human adults while they are asleep (Silverstein,
Graham, & Calloway, 1980), and does not habituate with repeated presentations
of the prepulse (Blumenthal, 1997; Wynn, Schell, & Dawson, 1996). Moreover,
prepulse inhibition is seen on the first pairing of prepulse and startle,
demonstrating that the inhibition is not due to classical conditioning or any form
of learning (Acocella & Blumenthal, 1990; Graham, Putnam, & Leavitt, 1975).
Graham (1975,1980) hypothesized that PPI reflects low-level inhibition that acts
as a mechanism to protect lead stimulus processing. Braff and his colleagues
have also proposed that PPI is a measure of sensorimotor gating, or the
mechanism which protects the processing of new stimuli (the prepulse) by
screening out competing or non-relevant (startling) stimuli (Braff & Geyer, 1990;
Cadenhead, Geyer, & Braff, 1993).
Although PPI is viewed as an automatic process, it has been shown that
by voluntarily directing attention towards some aspect of a prepulse, PPI can be
increased, indicating that PPI can be influenced by higher cortical functions
(DelPezzo & Hoffman, 1980; Filion, Dawson, & Schell, 1993; Hackley & Graham,
1983). Filion et al. (1993) presented to-be-attended and to-be-ignored prepulses
which were manipulated by instructing the subject to attend to and count how
many of one tone of a certain pitch (e.g., 800 Hz) were longer than usual (7 s
versus the standard 5 s) and to simply ignore the other tone (e.g., 1200 Hz) and
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10
not to count it. They found that PPI at a 120 ms lead interval was greater
during a to-be-attended prepulse than during a to-be-ignored prepulse in this
“attentional modulation” paradigm. Furthermore, a significant correlation of -0.48
was found between the difference of PPI to to-be-attended versus to-be-ignored
tones and the difference of SCORs to to-be-attended versus to-be-ignored tones
(that is, the correlation is between the PPI difference and the SCOR difference
measures) at a lead interval of 120 ms. This indicated that those who could
allocate more attention to the discrimination of to-be-attended and to-be-ignored
prepulses, as indexed by the SCOR, were able to produce greater PPI to a to-
be-attended prepulse than those who were not able to allocate greater attention
to the discrimination of the two different prepulses. This would substantiate
Graham's (1992) distinction between the OR and the TDR, where the OR is
elicited by prolonged stimuli and functions to enhance incoming stimuli. These
results show an effect of controlled attentive processes on startle modulation.
The finding of attentional modulation of startle has been replicated in several
studies (Dawson et al., 1993; Filion et al., 1994; Hazlett et al., 1998; Jennings,
Schell, Filion, & Dawson, 1996; Schell et al., 1995).
Several studies, however, have shown that those who have been
diagnosed with schizophrenia or schizotypal personality disorder, or who are at-
risk (psychosis-prone) as assessed by the Chapman scales for perceptual
aberrations and magical ideations (Chapman & Chapman, 1987) are either
deficient in PPI or are deficient in the attentional modulation of PPI. Braff and
colleagues (Braff, Grillon, & Geyer, 1992; Braff, Stone, Callaway, Geyer, Glick, &
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11
Bali, 1978; Grillon, Ameli, Chamey, Krystal, & Braff, 1992) have shown that
schizophrenia patients are deficient in PPI in a passive attention paradigm.
Grillon et al. (1992) used prepulses ranging from 75-90 dB imposed on a
constant 70 dB background noise and found that schizophrenia patients had
impairments in PPI across all prepulse intensities, indicating that this impairment
does not seem to be due to an inability to detect prepulses that are minimally
different from background noise. This would seem to indicate that the
schizophrenia patients’ transient detectors are functioning to detect the prepulse
but not to gate out or attenuate the startle stimulus.
Braff et al. (1992) used an 85 dB(A) 20 ms noise burst prepulse against a
70 dB(A) background noise, a 116 dB(A) 40 ms white noise startle burst, and
lead intervals at 30, 60, and 120 ms, and found that schizophrenia patients
exhibited deficient PPI (significantly less PPI compared to controls) at each lead
interval. Both groups, however, showed the greatest amount of PPI to a 120 ms
lead interval. Furthermore, the results showed that both groups exhibited similar
peak latencies, again indicating that the schizophrenia patients’ deficits were not
due to an inability to detect the prepulse, indicating again that the patients’
transient detectors are functioning to detect the prepulse but are unable to gate
out or attenuate the startle stimulus. In a similar study Cadenhead, Geyer, &
Braff (1993) also used an 85 dB(A) 20 ms white noise prepulse against a 70
dB(A) background noise, a 116 dB(A) 40 ms white noise startle burst, and lead
intervals of 30, 60, and 120 ms and found that those diagnosed with schizotypal
personality disorder exhibited reduced PPI compared to controls; all subjects
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12
again showed the most PPI to a 120 ms lead interval. These findings suggest
that persons with schizophrenia spectrum disorders have automatic preattentive
mechanism deficits, since no attentional manipulation paradigm was used, and
possibly have a general sensory gating deficit which could lead to sensory
overload, cognitive fragmentations, thought disorder, and other symptoms (Braff
et al., 1992).
Dawson, Schell, and colleagues, on the other hand, have shown that
recent-onset schizophrenia patients (Dawson, Hazlett, Filion, Nuechterlein, &
Schell, 1993) and at-risk groups (Schell, Dawson, Hazlett, & Filion, 1995) are
deficient in attentional modulation of startle, but not in “basic” prepulse inhibition
as seen in the Braff studies. In the Dawson et al. (1993) study, 70 dB(A) 5 s or 7
s 800 Hz and 1200 Hz continuous prepulses with rise/fall times of 25 ms, a 50
ms 100 dB(A) white noise burst, and lead intervals of 60, 120, 240, and 2000 ms
were used. Using an active attention task, they found that controls showed a
significant difference at the 120 ms lead interval in the amount of PPI between
to-be-attended and to-be-ignored prepulses, whereas recent-onset
schizophrenia patients did not show this difference. However, schizophrenia
patients did not exhibit deficient passive PPI. In the Dawson, Schell, and
colleague studies, passive PPI is the amount of inhibition seen to the to-be-
ignored prepulse; in the Braff studies, uninstructed passive attention paradigms
were used (subjects were not instructed to attend selectively to any of the
stimuli); thus all PPI seen is assumed to be passive PPI.
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13
Similarly, Schell et al. (1995) showed that psychosis-prone subjects
(those scoring high on perceptual aberration-magical ideation) as assessed
using the Chapman scales for Anhedonia and Perceptual Aberration exhibited
similar patterns to schizophrenia patients of deficient attentional modulation
using the same prepulse parameters and lead intervals, but had normal passive
PPI. Dawson and colleagues have hypothesized that PPI at a lead interval of 60
ms reflects an automatic inhibitory mechanism, since controlled, attentional
processes such as instructions have had no effect at that lead interval, whereas
PPI at a lead interval of 120 ms is subject to controlled processes, thus allowing
startle to be inhibited to a greater degree during attended stimuli (see Filion et
al., 1998).
To reiterate, in the Braff et al. studies, controls have greater passive
prepulse inhibition than schizophrenia patients; in the Dawson et al. studies,
schizophrenia patients and controls did not differ in the amount of passive PPI.
Rather, patients did not show significant differences between the to-be-attended
and to-be-ignored prepulses at 120 ms, whereas the controls did. The findings
from the studies of Dawson, Schell and colleagues suggest that recent-onset
schizophrenia patients and at-risk groups have deficits in controlled attentional
mechanisms, but their preattentional/automatic mechanisms are relatively intact.
On the other hand, Braff and colleagues hypothesize that chronic schizophrenia
patients have automatic attentional deficits.
Dawson et al. (1993) acknowledge that the differences seen between the
two laboratories might be due to the patient populations (chronic, long-term
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14
medicated patients versus recent-onset, short-term less-medicated patients)
or to the use of the active attention task. The discrepancies might also be due to
the nature of the prepulse used in the different laboratories and thus to different
filters being activated by the different prepulses used in the respective labs. All
but one of the studies in the Braff lab that have shown deficient passive PPI in
schizophrenia patients and schizotypals used discrete white noise prepulses
against a continuous background noise. This suggests that patients with
schizophrenia are not able to process transient changes in the environment as
well as normal controls, possibly because of sensory overload due to the
constant background noise and to a sensory gating deficit.
The finding of normal “basic” PPI in patients using continuous prepulses
but not discrete prepulses may theoretically be due to a “ transient shift” (that is,
patients’ optimal window for detecting transient changes in the environment may
be greater than the optimum of 20-50 ms in normal controls). With a continuous
prepulse the sustained portion of the prepulse allows the patients more time to
detect the prepulse (by transient detectors). The finding of deficient attentional
modulation of PPI on the other hand may be due to a deficit in the sustained
detectors or controlled attentional mechanisms; this deficit may be due to a
malfunction in the low-pass filter/generalized OR, a mechanism which is known
to be dysfunctional in schizophrenia (Bernstein et al., 1982; Dawson and
Nuechterlein, 1984; Ohman, 1981). Sustained deficiency could be due to the fact
that sustained detectors are involved in the process of identifying and
discriminating prepulses, a task which schizophrenia patients are less able to
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15
accomplish at short lead intervals, resulting in equal amounts of PPI to to-be-
attended and to to-be-ignored prepulses. The use of these different forms of
prepulses and paradigms is thus a possible critical factor in the magnitude of
inhibition of startle during a prepulse, and possibly in understanding differences
between schizophrenia patients and controls.
The first experiment reported here attempted to replicate past findings
that the transient aspect of prepulses results in greater prepulse inhibition. Three
forms of prepulses were used (discrete tone, continuous tone, and discrete white
noise) along with only one startle stimulus (white noise). It was expected that
both discrete prepulses would result in greater prepulse inhibition than the
continuous prepulse. It is also further expected that SCORs will be greater to
continuous prepulses than to discrete prepulses, as predicted by Graham (1992).
Experiment 1
Method
Subjects
Forty two undergraduate students at the University of Southern California
were recruited from undergraduate psychology classes and received course
credit for participation. There were 6 males and 36 females.
Design
This study used a 2 X 3 completely within subject design. The first
variable was lead interval (60 ms and 120 ms). The second variable was
prepulse type (discrete white noise, continuous tone, and discrete tone).
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16
Experimental Stimuli
The startle stimulus consisted of a 40 ms 104 dB(A) white noise burst with
a near instantaneous rise/fall time, generated by a Grason-Stadler 901B noise
generator. The discrete white noise prepulse consisted of a 20 ms 75 dB(A)
white noise burst with a near instantaneous rise/fall time, generated by a
Grason-Stadler 901B noise generator. The continuous tone prepulse was a 1000
Hz 75 dB(A) tone with a duration of 1000 ms and a rise/fall time of 25 ms and the
discrete tone prepulse was a 1000 Hz 75 dB(A) tone with a duration of 20 ms
and a near instantaneous rise/fall time, both generated by a sound card
(SoundBlaster 16). All of the auditory stimuli were presented binaurally through
headphones (Telephonies TDH-49P). The onsets, durations and intervals
between stimuli were controlled by a custom built 386 computer with a Metrabyte
DAS-16 A/D board using a custom written program written in Microsoft C Version
1.5 (Troyer, 1997).
Recording and Scoring of Dependent Variables
The primary dependent variables were startle eyeblink magnitude and
skin conductance orienting responses. Startle eyeblink was measured as
electromyographic (EMG) activity from two miniature Ag-AgCI electrodes (4 mm
in diameter) placed over the orbicularis oculi muscle of the left eye, one centered
below the pupil and the other approximately 10 mm lateral to the first. The EMG
signal was fed to a Grass 7P3 wide band integrator/preamplifier and a 7DA
driver amplifier. Eyeblinks were recorded at full wave rectification with and
without integration at a time constant of 20 ms. The EMG signal was digitized at
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17
a rate of 2000 Hz for 200 ms preceding and 300 ms following the presentation
of each startle-eliciting loud noise. Skin conductance orienting responses were
collected from the volar surface of the distal phalanges of the first and second
fingers of the left hand using two Ag-AgCI electrodes (10 mm in diameter) filled
with a .05 Molar NaCI Unibase paste. A constant 0.5 V was applied across the
electrodes and the skin conductance signal was amplified by a Grass 7P1
preamplifier and a 7DAE driver amplifier. The SCORs were collected and stored
on the computer and were also recorded on paper. SCORs to unprobed
prepulses, which were hand scored, were increases in skin conductance
beginning between 1.0 and 4.0 seconds following prepulse onset and having a
minimum response amplitude of 0.05 pS.
The startle eyeblink amplitude (raw EMG activity) was scored off line with
a custom written C program (Oray & Wynn, 1998) and then converted to pV
units. Percentage change units were then computed as the measure of prepulse
inhibition: [(probe - baseline startle) / baseline startle X 100%]. Percentage
change units are preferred over difference scores (probe - ITI alone) because
difference scores in absolute pV units are correlated with baseline startle blink
amplitude whereas percentage change units are not, removing the dependence
on baseline startle (Jennings et al., 1996).
Procedure
Upon arrival to the laboratory, subjects were asked to read and sign a
consent form and to fill out a general health questionnaire. A brief introduction
was then presented on audiotape followed by the attachment of electrodes for
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18
the recording of skin conductance and startle eyeblink. After attachment of
electrodes a brief set of instructions, simply requesting the subject to remain
awake and alert and to keep still, were presented on audiotape.
The testing session began with the presentation of three startle-alone
probes. Following this, probed prepulses were presented in a mixed, pseudo
random order. There were a total of 36 prepulses, 12 of each prepulse type. Of
each prepulse type only 8 were probed. Of these 8 probed prepulses, 4 were
probed at 60 ms and 4 were probed at 120 ms. There were also 24 startle-alone
trials interspersed between prepulse trials. The average intertrial interval was 15
s, with a range of 12-18 s. The entire testing session lasted approximately 20
minutes.
Results
Skin Conductance Orienting Responses
There were a total of 42 subjects in Experiment 1. However, due to
equipment malfunction or orienting responses that were contaminated by
movement or noise, the number of usable subjects was reduced in the analysis
of orienting. Therefore, a total of 37 subjects had usable SCORs to the discrete
white noise, 36 had usable SCORs to the discrete tone, and 35 had usable
SCORs to the continuous tone. Analyses therefore used the data from the 35
subjects where all orienting responses were recorded. For all subsequent
analyses Greenhouse-Geisser epsilon correction factors were used for repeated
measures ANOVAs with more than one degree of freedom and Rom’s procedure
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19
(Rom, 1990) was used for all groups of post-hoc t-tests to control for
experiment-wise Type I error.
A one way (prepulse: discrete white noise, discrete tone, continuous tone)
within subject repeated measures ANOVA was performed on skin conductance
orienting response (SCOR) magnitudes. There was no main effect of prepulse.
Mean magnitudes for each prepulse are presented in Figure 3. Post-hoc t-tests
revealed no significant difference between any of the magnitudes. However, the
difference in orienting to a discrete tone compared to a continuous tone
approached significance, t (34) = 2.00, g < .06, with the continuous tone eliciting
larger ORs.
0.14
□ Discrete White Noise
■ Discrete Tone
■ Continuous Tone
Prepulse Type
Figure 3: SCOR Results for Experiment 1
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20
Startle Modification
Of the 42 subjects in Experiment 1, four had to be discarded due to
equipment malfunction in recording EMG activity and four had to be discarded
from the startle modification analysis due to excessive nonresponsiveness to the
startling stimuli. Nonresponsivity was defined as having an average blink
magnitude on the startle-alone trials of less than 1 pV.
A 2 (lead interval: 60 ms, 120 ms) X 3 (prepulse: discrete white noise,
discrete tone, continuous tone) within subject repeated measures ANOVA was
performed on percent change EMG scores. Means are presented graphically in
Figure 4. There was a main effect of prepulse, F (2, 66) = 12.26, p < .001, e =
0.9760, with greater inhibition produced by the discrete white noise at both lead
intervals, and a main effect of lead interval, F (1, 33) = 8.66, p < .01, with greater
inhibition seen with a lead interval of 120 ms with all prepulses. There was no
lead interval by prepulse interaction. Post-hoc t-tests revealed the following
significant differences: at a lead interval of 60 ms, only the discrete white noise
and discrete tone differed significantly (t (33) = 3.17, p < .01); at a lead interval of
120 ms, the discrete white noise differed significantly from the discrete tone (t
(33) = 4.72, p < .001) and from the continuous tone (t (33) = 5.86, p < .001).
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21
Discrete Continuous Discrete
White Noise Tone Tone
-5 0
Figure 4: PPI Results for Experiment 1
Discussion
It was expected that a discrete prepulse, regardless of the nature of its
sound, would produce greater PPI than a continuous prepulse. Based on
previous findings that the transient nature of the prepulse is responsible for PPI,
two discrete prepulses were used in Experiment 1 and were expected to produce
similar results. However, it was found that the discrete white noise produced
significantly more PPI than either the discrete tone or the continuous tone.
Moreover, contrary to the initial hypothesis, the amount of PPI produced by the
discrete tone did not significantly differ from that produced by the continuous
tone. Also, orienting to the continuous prepulse was not significantly different
from the two discrete prepulses (although the differences did approach
significance), contrary to the initial hypothesis. There are in theory at least two
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22
possible reasons for the finding of greater PPI seen only to the discrete white
noise prepulse. The first is that there might be more attention directed to the
discrete white noise because it is similar in nature to the startle-eliciting white
noise. Second, there might also be a refractory effect of the white noise prepulse
affecting the results, if that prepulse itself has a tendency to elicit startle.
As mentioned in the introduction, Dawson, Schell and colleagues have
demonstrated that directing attention to a prepulse results in increased PPI.
Acocella and Blumenthal (1990) also examined the effects of directed attention
on the startle reflex. Three prepulses were used, all 20 ms in duration, 60 dB
intensity, and with near instantaneous rise/fall times. The prepulses were either
1000 Hz, 2000 Hz, or broadband (20 Hz-20 kHz) noise. The startle stimulus was
a 50 ms, 90 dB broadband noise burst with an instantaneous rise/fall time.
Subjects were instructed in one block to attend to specific prepulses (only one of
the three) and press a button when they heard their prepulse and to completely
ignore all prepulses in another block. Briefly, attentional effects on response
probability (the probability of responding to the startle stimulus) were found, with
probability decreasing when the subjects attended to the prepulse. It was also
found that the noise prepulse was slightly (but not significantly) more effective in
inhibiting startle than the tone prepulses. Acocella and Blumenthal suggested
that this might be due to the similarity in bandwidth between the noise prepulse
and the startle.
These findings of similarity between the bandwidth of the prepulse and
the startle producing greater PPI are similar to the findings of Experiment 1.
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23
Acocella and Blumenthal’s (1990) procedures, however, do not entirely match
those of Experiment 1 in two ways. First, they used a lead interval of 200 ms
whereas a 120 ms lead interval was used in Experiment 1. It has been shown in
several experiments that PPI is maximal at a 120 ms lead interval, at least using
acoustic stimuli (see Blumenthal, in press). Second, they used weaker prepulses
and startles than used in Experiment 1 (60 dB vs. 75 dB prepulses and 90 dB vs.
104 dB startle bursts). It has also been shown that more intense prepulses
produce more PPI (Blumenthal, in press; Graham & Murray, 1977) and that
increasing the intensity of the startle burst also produces more PPI (Blumenthal,
1996; Hoffman & Ison, 1992).
The results of Experiment 1 may also be due to a refractory effect of the
prepulse. During piloting, it seemed that the discrete white noise prepulse
sometimes elicited a startle by itself. However, there is evidence that PPI is not
affected by a prepulse-elicited response. Hammond, McAdam, and Ison (1972)
found that rats exhibited startle inhibition (measured by a stabilimeter) even if
EMG activity was seen in forelimb flexor and extensor muscles while the
prepulse was presented. Graham and Murray (1977) also found that even
though there was significant responsiveness to the prepulses, this still did not
account for the blink inhibition seen in the presence of those prepulses, meaning
that there was no refractory effect of the prepulse on PPI.
The purpose of the second experiment was to replicate the findings of
Experiment 1 and to determine whether discrete and continuous prepulses are
processed differently in a passive attention task. Furthermore, it expanded on
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24
and examined in greater detail the finding that greater PPI occurs when the
prepulse and startle have the same sound quality. Moreover, EMG activity
elicited by unprobed prepulses was recorded to determine whether or not there
was a refractory effect elicited by the prepulse. This was accomplished by using
four forms of prepulses (discrete tone, continuous tone, discrete white noise, and
continuous white noise) and two forms of startle stimuli (tone bursts and white
noise bursts). It was hypothesized that the inhibition seen to a startle stimulus of
the same nature as the prepulse (e.g., the prepulse and the startle burst are both
a 1000 Hz tone) will be greater than if the prepulse and the startle were of
dissimilar nature (e.g., the prepulse is a 1000 Hz tone but the startle burst is
white noise). It was also hypothesized that, overall, discrete prepulses would
result in greater PPI than continuous prepulses. It is again hypothesized that the
SCORs will be greater to continuous prepulses than to discrete prepulses, as
predicted by Graham (1992).
Experiment 2
Method
Subjects
Sixty one undergraduate students at the University of Southern California
were recruited from undergraduate psychology classes and received course
credit for participation. There were 10 males and 51 females.
Design
This experiment used a 2 X 2 X 2 mixed design. The first variable was
startle stimulus type (tone startle vs. white noise startle), which was a between-
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25
groups variable. The second variable was prepulse duration (discrete vs.
continuous) and the third variable was sound quality (white noise prepulse vs.
tone prepulse), both varied within subjects, with a constant lead interval of 120
ms in duration.
Procedure
All recording and presentation of experimental stimuli remained the same
as in Experiment 1 with the exception of the following: the tone startle was
generated by a BK Precision 3011B function generator and fed through an
amplifier, the continuous prepulses were only 120 ms in duration, and all
prepulses and startles had a near instantaneous rise/fall time. Upon arrival to the
laboratory, subjects were asked to read and sign a consent form and to fill out a
general health questionnaire. A brief introduction was then presented on
audiotape followed by the attachment of electrodes for the recording of skin
conductance and startle eyeblink. After attachment of electrodes a brief set of
instructions, simply requesting the subject to remain awake and alert and to keep
still, were presented on audiotape.
The testing session began with the presentation of three startle alone
probes. Following this, probed prepulses were presented in a mixed, pseudo
random order. There were a total of 40 prepulses, 10 of each prepulse type. Of
each prepulse type only 6 were probed. EMG activity to each of the four
unprobed prepulses also recorded in this experiment. There were also a total of
24 startle-alone trials interspersed between prepulse trials. The average intertrial
interval was 15 s, with a range of 12-18 s. Subjects were randomly assigned to
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26
either group with the expectation that there would not be less than 20 subjects
per group. The entire testing session lasted approximately 20 minutes.
Results
Skin Conductance Orienting Responses
There were a total of 61 subjects in Experiment 2. However, equipment
malfunction (where there was no available signal mark to determine when
stimulus onset began on the polygraph recording paper) or orienting responses
that were contaminated by movement or noise reduced the number of usable
subjects in the analysis of orienting. A total of 39 subjects had usable, scorable
SCORs, with 20 of these subjects falling in the white noise startle group and 19
in the tone startle group.
A 2 (group: white noise startle vs. tone startle) X 2 (prepulse duration:
discrete vs. continuous) X 2 (prepulse sound quality: white noise vs. tone)
repeated measures ANOVA was performed on SCOR magnitudes. There was
no main effect of group. There was a main effect of prepulse duration (F (1, 37)
= 17.68, p < .001) with the continuous prepulses eliciting greater SCOR
magnitudes than the discrete prepulses. There also was a main effect of
prepulse sound quality (F (1, 37) = 16.78, p < .001) with the white noise
prepulses eliciting greater SCOR magnitudes than the tone prepulses. There
were no interactions. Mean SCOR magnitudes, for each group, are presented
graphically in Figure 5.
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27
0.25
0
□ Discrete White Noise
H Continuous White
Noise
■ Discrete Tone
■ Continuous Tone
White Noise Tone Startle
Startle Group Group
Figure 5: SCOR Results for Experiment 2
EMG Activity to Unprobed Prepulses
Of the 61 subjects in experiment 2, eight had to be discarded from the
startle modification analysis due to excessive nonresponsiveness to the startling
stimuli. Nonresponsivity was defined as having an average blink magnitude to
the startle-alone trials of less than 1 pV. As a result, a total of 29 subjects
remained in the white noise startle group and a total of 24 subjects in the tone
startle group. A 2 (group: white noise startle vs. tone startle) X 2 (prepulse
duration: discrete vs. continuous) X 2 (prepulse sound quality: white noise
prepulse vs. tone prepulse) repeated measures ANOVA was performed on the
EMG activity elicited by the unprobed prepulses. There was no group main
effect. There was a main effect of prepulse sound quality, F (1, 51) = 14.98, g <
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28
.001, with the white noise prepulses eliciting more EMG activity than the tone
prepulses. There was also a main effect of prepulse duration, F (1, 51) = 4.15, j d
< .05, and a significant sound quality by prepulse duration interaction, F (1, 51) =
10.43, p < .01, with the continuous white noise prepulse eliciting more EMG
activity than any of the other three prepulses. The means of the unprobed
prepulses are presented graphically in Figure 6.
7
6
>
□ White Noise
Startle Group
■ Tone Startle
Group
Discrete Continuous Discrete Continuous
White White Tone Tone
Noise Noise
Figure 6: Raw EMG for Unprobed Prepulses
Startle Modification
A 2 (group: white noise startle vs. tone startle) X 2 (prepulse duration: discrete
vs. continuous) X 2 (prepulse sound quality: white noise vs. tone) repeated
measures ANOVA was performed on the percent change EMG scores. There
was no group main effect. There was a main effect of prepulse sound quality, F
(1, 51) = 9.48, p < .01, a main effect of prepulse duration, F (1, 51) = 9.34, g <
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29
.01, and a significant prepulse sound quality by prepulse duration interaction,
F (1, 51) = 6.62, < .05. These effects seem to be due mainly to the discrete
white noise, which in both groups produced the greatest amount of inhibition.
Means are presented in Figure 7. Post-hoc t-tests were performed only
comparing the discrete white noise in each group against the three other
prepulses. All of these t-tests were significant (all ts > 2.35, p < .05), with the
discrete white noise prepulse producing significantly more inhibition than any of
the other three prepulses.
Discrete Continuous Discrete Continuous
White Noise White Noise Tone Tone
-10
-20
c o
Ǥ -30
^ -40 —
-50
-60
□ White Noise Startle
Group
■ Tone Startle Group
Figure 7: PPI Results for Experiment 2
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30
General Discussion
It was hypothesized for Experiment 2 that PPI would be greater if the
prepulse and the startle were of similar sound quality than if they were of
different sound quality. This hypothesis was based on the findings of Acocella
and Blumenthal (1990) and on the findings of Experiment 1. However, the
hypothesis was not confirmed by Experiment 2, since the discrete white noise
prepulse once again produced the greatest amount of PPI, regardless whether
the startle burst was a white noise or a pure tone. It was also again hypothesized
that there would be a dissociation between orienting and PPI, as suggested by
Graham (1992), and this hypothesis held up in Experiment 2, with the continuous
prepulses producing greater SCORs than discrete prepulses.
The principal finding of the two experiments was that a discrete white
noise prepulse produced significantly more prepulse inhibition than either a
discrete tone, a continuous tone or a continuous white noise. The original
argument that discrete prepulses produce greater prepulse inhibition due to their
inherent “ transient advantage” may have to be reexamined in light of the present
findings. Additional orienting data also corroborate Graham’s (1992) distinction
between the dissociation of the TDR and the OR.
It was expected that a discrete white noise would be more effective than a
continuous white noise, but the failure of the discrete tone to produce more PPI
than a continuous tone is not in keeping with a “ transient advantage”
interpretation. The reliably greater effectiveness of the discrete white noise
compared with the discrete tone also requires explanation. It was thought that
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31
this advantage of the discrete white noise may have been due to its similarity
to the startle noise, based on the results of Acocella and Blumenthal (1990).
However, the results of Experiment 2 clearly show that this is not the case.
Regardless of whether the subject received white noise startle stimuli or tone
startle stimuli, the discrete white noise consistently produced significantly more
prepulse inhibition than either the discrete tone, continuous tone or continuous
white noise.
Additional data collected in both experiments would not seem to point to
any clear advantage of the discrete white noise in producing greater prepulse
inhibition. In both experiments, there was either a marginal finding or significant
finding that the continuous prepulses (either white noise or tone) produced a
greater amount of orienting. Since orienting reflects greater attention devoted to
a stimulus and since there is strong evidence that by directing attention to some
aspect of a prepulse increases the amount of prepulse inhibition (for a review,
see Filion, Dawson, & Schell, 1998), it would seem that the prepulses that
produced the greatest amount of orienting in these two experiments would have
also produced the greatest amount of prepulse inhibition. However, this was not
shown, possibly since this was a passive attention paradigm. What was shown
was a dissociation between orienting and prepulse inhibition which is consistent
with Graham’s (1992) distinction between the OR (low-pass filter) and the TDR
(high-pass filter). It was shown that the OR was sensitive to the sustained portion
of a prepulse (continuous prepulses) resulting in larger SCORs than the discrete
prepulses, and that the TDR was sensitive to the transient portions of a prepulse
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32
(discrete prepulses) resulting in greater PPI than continuous prepulses, as
predicted by Graham.
In Experiment 1, during piloting and setting up the experiment, there
seemed to be some tendency for the discrete white noise to elicit a blink itself.
Therefore, it was decided that EMG activity to the unprobed prepulses would be
measured in Experiment 2 as it may have been possible that the discrete white
noise prepulse was creating a muscle refractory period that could increase the
inhibition produced by that prepulse. However, the continuous white noise
elicited more EMG activity than any of the other three prepulses, although the
white noise sound quality overall elicited more EMG activity than the tone sound
quality. If a muscle refractory period is elicited by a prepulse and if that refractory
period is able to increase the inhibition produced by that prepulse, the
continuous white noise would have been more effective than other prepulses.
So the question remains, Why it is that the discrete white noise produced
the greatest amount of prepulse inhibition when it does not elicit greater orienting
nor does it elicit greater EMG activity? It is clear from numerous studies that the
transient portion of a prepuise is responsible for prepulse inhibition. However,
this leads to the expectation that the discrete white noise and the discrete tone
would have produced nearly equal amounts of prepulse inhibition, and that both
would have been more effective than their continuous counterparts. It is
plausible that the discrete white noise produced more PPI than the continuous
white noise because of the “ transient advantage” of discrete prepulses but does
not explain why the discrete tone was not as effective.
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33
Perhaps the reason why the discrete white noise produced more PPI
than the discrete tone is because it covered a broader range of frequencies,
which activated more of the cochlear nucleus. Studies in rats have shown that
when the ventral cochlear nucleus (VCN) receives a stimulus, such as a
prepulse, this activates the pedunculopontine nucleus (PPN), which then sends
inhibitory signals to the nucleus reticularis pontis caudalis (NRPC), the nucleus
linked to the motor neurons which control eyeblink, producing PPI (see Dawson,
Schell, Swerdlow, & Filion, 1997). It may be that the white noise activates the
entire inhibitory circuit, particularly transient neurons, to a greater extent than a
tone.
Alternatively, some sound frequencies may be more effective in eliciting
PPI than others, the white noise prepulse may contain more of these
frequencies. However, Hoffman and Searle (1968) performed a similar
experiment in rats that tested for a frequency advantage of prepulses on
prepulse inhibition. Discrete prepulses that were 10 ms long of either 700 or
5120 Hz were presented 100 ms prior to 700 or 5120 Hz tone bursts that were
20 ms long, all with a 70 dB SPL broad band random noise background. The rats
received all possible combinations of startle and prepulse, and there were no
significant differences among any of the prepulse inhibition effects seen.
Therefore, there was no frequency advantage and there was also no
prepulse/startle sound quality interaction, consistent with Experiment 2. Hoffman
and Searle state that, at least in rats, “ the combination of prepulse frequency and
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34
primary stimulus frequency [the startle burst] is irrelevant in determining
whether or not inhibition occurs." (p. 276).
Perhaps the most compelling evidence that would suggest why the
discrete white noise was the most effective prepulse comes from basic
psychophysical research. It has been shown that the subjective loudness of a
noise (as measured in phons) increases as the bandwidth of a noise increases,
even though the physical intensity (dB) remains the same (for a review, see
Scharf & Houtsma, 1986). For example, a white noise is subjectively louder than
a 1000 Hz tone at the same physical intensity due to loudness summation of the
white noise. It has previously been shown, as stated in the introduction, that as
the loudness of a prepulse increases (as measured in sound pressure level),
more PPI is produced. It would therefore reasonably follow that as the subjective
loudness of a prepulse increases more PPI would be produced as well. The
combination of a “ transient advantage” and the subjective loudness of the
discrete white noise may possibly be the reason why the discrete white noise
produced the greatest amount of PPI.
What does this mean for schizophrenia? In the studies that have shown
impairments in basic, automatic PPI in schizophrenia discrete prepulses were
used with a constant background noise (white noise). Perhaps the schizophrenia
patients are distracted by the background noise. This background noise would
almost certainly be distracting to the patients and could affect their ability to
detect and/or gate out subsequent stimuli. Furthermore, the constant
background noise may be distracting to the patients, thus impairing the ability to
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35
detect and/or gate out new transient changes in the environment This would
seem to point to an automatic failure of PPI in schizophrenia. But, the Braff and
colleague studies have shown that the patients are able to detect the prepulse.
The Dawson, Schell, and colleagues studies, on the other hand, show sufficient
PPI but no attentional modulation of PPI. This would point to a controlled failure
of PPI in schizophrenia. The main difference between the Dawson et al.
paradigms (continuous prepulse paradigms) and the Braff et al. paradigms
(discrete prepulse paradigms) is that a background noise is not employed and an
attentional manipulation paradigm is used instead of a passive attention
paradigm. Therefore, maybe the patients are distracted by a background noise in
the Braff et al. studies and there is nothing to distract the subjects in the Dawson
et al. studies. Alternatively, the patients may be able to process continuous
stimuli better because they have just a bit longer to process it. This would allow
for detection of transient changes in the environment but not the discrimination
necessary to determine if that stimuli needs to be passed on to higher cortical
areas for controlled attentional processing.
Future studies can be conducted to better understand the nature of how
prepulse inhibition functions and under what conditions is that functioning
optimal. One study can be done to determine if there is a frequency advantage
of the prepulse to produce greater PPI. Another study can be implemented to
determine if background noise affects either or both transient and sustained
neurons in a prepulse inhibition paradigm using discrete and continuous
prepulses. Further studies can also investigate whether controlled attentional
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36
manipulation paradigms can affect discrete prepulses as they have affected
continuous prepulses. And perhaps the most important study is to run a prepulse
inhibition paradigm with schizophrenia patients using both discrete and
continuous prepulses that are white noise and or tones in conditions of no
background noise and background noise. This may answer several questions
regarding the differences seen in the Dawson et al. paradigms and the Braff et
al. paradigms.
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References
37
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Ymn, Jonathan Kajzovar
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Is there more to discrete prepulses than meets the eye?
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Psychology
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