Early attentional deficits in an attention-to-prepulse paradigm in ADHD adults.

Adults with attention-deficit/hyperactivity disorder (ADHD) were examined for early and late attentional processes as a function of controlled attention. The test paradigm was the attentional modulation of prepulse inhibition (PPI; early controlled attentional processing) and prepulse facilitation (PPF; late controlled attentional processing). In 49 patients and 49 controls, the authors measured acoustic startle responses to 96-dB startle pulses preceded 120, 240 (for PPI), 2,000, and 4,500 (for PPF) ms by a 68-dB prepulse noise. Geometric figures signaled that prepulses were to be ignored or attended to (automatic vs. controlled attention). ADHD patients exhibited deficits in prepulse modulation, but these reflected an interaction of controlled attention and time of information processing. Normal PPI and PPF occurred under all conditions except for controlled attentional modulation of PPI. Attention deficits in ADHD patients may reflect not general derangements in information processing or ability to attend but, rather, selective disturbances of controlled attention during early information processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus quality affects expression of the acoustic startle response and prepulse inhibition in mice.

The relationship between stimulus intensity and startle response magnitude (SIRM) can assess the startle reflex and prepulse inhibition (PPI) with advantages over more commonly used methods. The current study used the SIRM relationships in mice to determine differences between white noise and pure tone (5 kHz) stimuli. Similarly to rats, the SIRM relationship showed a sigmoid pattern. The SIRM-derived reflex capacity (RMAX) and response efficacy (slope) of the white noise and pure tone stimuli in the absence of prepulses were equivalent. However, the pure tone startle response threshold (DMIN) was increased whereas the stimulus potency (1/ES??) was decreased when compared to white noise. Prepulses of both stimulus types inhibited RMAX and increased DMIN, but the white noise prepulses were more effective. Both stimulus intensity gating and motor capacity gating processes are shown to occur, dependent on prepulse intensity and stimulus onset asynchrony. Prepulse intensities greater than 10 dB below the startle threshold appear to produce PPI via stimulus intensity gating, whereas a motor capacity gating component appears at prepulse intensities near to the startle threshold. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation and inhibition of the acoustic startle reflex in the rat after a momentary increase in background noise level

Small increments in background noise were shown to increase the amplitude of a subsequently elicited acoustic startle reflex (ASR) in rats by as much as 100% under optimal conditions. Increment lead time (5-160 ms) and level (1.5-15 dB), initial noise level (30-70 dB), startle level (95-125 dB), number of test days (1-5), and drug condition (diazepam or saline ip) were varied in 6 experiments. Prepulse facilitation (PPF), measured by difference scores, was greatest for intermediate increments (3 dB) and lead times (20-40 ms) and was replaced by prepulse inhibition (PPI) for higher values, especially in the later test days. Diazepam reduced baseline ASR and diminished PPI, but it did not affect PPF. These data argue against hypotheses that attribute PPF of this sort to either temporal integration within the ASR pathways or to the elicitation of a nonspecific arousal reaction by the prepulse.     

Effects of the first prepulse on the blink response to a startling noise.

Startle is inhibited when a startling stimulus follows 30–300 ms after a weak prepulse. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is deficient in several neuropsychiatric disorders. Previous reports argue both for and against a learned component to the inhibitory effects of prepulses, but this issue has yet to be fully investigated using stimuli that most commonly detect PPI deficits in clinical populations. If the inhibitory impact of a prepulse is learned, PPI should not be evident when the prepulse is the first stimulus experienced by the subject. Eyeblink electromyography in normal adults was recorded after either a 118 dB(A) 40-ms noise pulse alone (PA) or the same pulse preceded 120 ms by an 86 dB(A) 5-ms noise prepulse (pp + P). In 25 subjects (Order 1), Trial 1 was a PA, and Trial 2 was a pp + P; 23 subjects experienced the opposite order (Order 2). In 34 subjects, Trials 1 and 2 were both PA (control order). Background was 70 dB(A). Startle magnitude increased from Trial 1 to 2 if no prepulse was presented (control order). Compared with the control order, startle inhibition by prepulses was evident in both Orders 1 and 2, and was more robust in Order 2 (first trial = pp + P). Startle magnitude was significantly lower on pp + P than on PA trials in Order 2 but not Order 1 (F     

Amygdala central nucleus lesions attenuate acoustic startle stimulus-evoked heart rate changes in rats.

Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment. the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R. N. Leaton, see record 1995-12737-001) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic mechanisms in startle and prepulse inhibition: Effects of the false cholinergic precursor N-aminodeanol.

Examined the effects of cholinergic deficiency on prepulse inhibition (PPI) of the acoustic startle. Rats treated with a choline-free diet that contained the false cholinergic precursor N-aminodeanol showed great deficit in PPI. This deficit does not appear to be secondary to an increase of stereotyped behaviors. Startle threshold was also greatly reduced, as these rats startled to the 70-dB prepulse, and the baseline startle amplitude was increased by 60% over the control rats. Arecoline (4 mg/kg) partially reversed the deficit in PPI. This improvement persisted beyond the period of drug treatment. On the other hand, scopolamine (1 mg/kg) reduced PPI in the control rats. Results suggest that cholinergic systems play a major role in both the elicitation and prepulse inhibition of startle. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Habituation of prepulse inhibition of the startle reflex using an auditory prepulse close to background noise.

This study examined whether prepulse inhibition habituates with repeated presentation of the prepulse alone. Prepulse inhibition was determined by measuring the decrement in the startle response when the acoustic startle-eliciting stimulus was preceded by an auditory prepulse. Rats received repetitive exposures of the same auditory prepulse alone (experimental condition) and of a visual prepulse alone (control condition). To reduce habituation of startle itself and the possible dishabituating influence the startle stimulus might have on habituation of prepulse inhibition, startle stimulus presentations were infrequently interspersed among a much larger number of prepulse-alone presentations. Stimulus-specific habituation of prepulse inhibition occurred using an auditory prepulse 2.5 dB, but not 13 dB, above background noise. Implications are discussed for the role of prepulse inhibition in sensory gating. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of a distinct arousal state immediately after spontaneous awakening from sleep

In contrast to the many neural studies into the mechanisms of sleep onset and maintenance, few studies have focused specifically on awakening from sleep. However, the abrupt electrographic changes and large brief cardio-respiratory activation at awakening suggest that a distinct, transiently aroused, awake state may exist compared to later wakefulness. To test this hypothesis we utilized the acoustic startle reflex, a standard un-conditioned reflex elicited by a sudden loud noise. This reflex is modulated under specific conditions, one being a diminution of startle when a quieter pre-stimulus is presented immediately before the loud stimulus. This pre-pulse inhibition (PPI) is used as a measure of sensorimotor gating, with smaller PPI indicating less filtering of sensory inputs and increased responsiveness to external stimuli. Eight rats with electrodes for recording sleep-wake state were studied. An accelerometer measured startle responses. The startle reflex was elicited by 115 dB, 40 ms tones. PPI was produced by 74 dB, 20 ms tones preceding the 115 dB tone by 100 ms. Responses within 100 ms were measured. Stimuli were applied either 3-10 s after spontaneous awakenings, or in established wakefulness (> 30 s). Responses to the startle stimuli alone were similar in the different awake states (P = 0.821). However, PPI was smaller at awakening from non-REM sleep compared to established wakefulness (45.4 +/- 7.5% vs. 74.3 +/- 6.1%, P = 0.0002). PPI after awakening from REM sleep (52.8 +/- 17.9%) was not significantly different than established wakefulness (P = 0.297). Reduced PPI of the startle reflex at awakening from non-REM sleep supports the hypothesis that wakefulness immediately after spontaneous sleep episodes is neurophysiologically distinct from later wakefulness and associated with reduced gating of motor responses to sensory inputs. Spontaneous activation of this distinct, transiently aroused, state upon awakening may serve a protective function, preparing an animal to respond immediately to potentially threatening stimuli.     

Prestimulus effects on startle magnitude: Sensory or motor?

Startle may be inhibited when the startling event is preceded by a stimulus; this is called prepulse inhibition (PPI) when the prestimulus is weak and nonstartling (s) and paired pulse inhibition when the prestimulus elicits startle (S1). The authors examined the relationship of these measures across species and tested whether paired pulse inhibition-like PPI-is independent of the startling effects of the prestimulus. PPI (s-S1 configuration) and paired pulse inhibition (S1-S2 configuration) were elicited in 1 test, using similar stimulus parameters in rats and humans. The amount of PPI and paired pulse inhibition was significantly correlated within subjects in both rats and humans. Paired pulse inhibition was not diminished when the startling effects of S1 were eliminated by a weak prepulse (s-S1-S2 configuration), nor was it enhanced when these prepulse effects were eliminated by the dopamine agonist apomorphine (in rats). Despite apparent differences in the inhibitory processes mediating PPI and paired pulse inhibition, both are independent of the motoric response to the prestimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exposure to inescapable stress persistently facilitates associative and nonassociative learning in rats.

The present study examined the proactive effects of inescapable stress on aversive Pavlovian conditioning. Stressed rats were restrained and exposed to 90 1-mA tailshocks. Twenty-four hours later, all rats were exposed to 10 conditioned stimuli (CS; 350 ms of white noise at 85 dB). Rats then received either paired training in which the CS coterminated with a 100-ms, 0.7-mA periorbital shock or the same stimuli presented in an explicitly unpaired fashion. After the unpaired exposures, these rats were also exposed to paired training. Previously stressed rats exhibited persistent sensitization to the white-noise stimulus. Stressed rats exposed to unpaired stimuli, and no longer exhibiting a sensitized response, acquired the eyeblink conditioned response at a facilitated rate when these stimuli were presented in a paired fashion. These results also demonstrate that the effect of stress on classical conditioning is long-lasting, in excess of 48 hr. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal specificity of fear conditioning: Effects of different conditioned stimulus--unconditioned stimulus intervals on the fear-potentiated startle effect.

Separate groups of rats were given 30 pairings of a light (conditioned stimulus, CS) and a 500-ms shock (unconditioned stimulus, US) at CS–US intervals of 0, 25, 50, 100, 200, 800, 3,200, 12,800, or 51,200 ms. Other groups had lights and shocks inconsistently paired. The startle reflex was elicited 2–4 days later with a noise burst alone or 25–51,200 ms after light onset. After CS–US pairings over a range of intervals (25–51,200 ms), startle was potentiated in testing, as rapidly as 50 ms after light onset. Magnitude of potentiation and resistance to extinction were generally greater with longer CS–US intervals. In several groups, potentiation was maximal at a test interval that matched the CS–US interval used in training. This temporal specificity sharpened with increasing numbers of training trials but even occurred with a single training trial in which a 51,200-ms CS–US interval was used. Data indicate that even during simple fear conditioning (FC), animals rapidly learn a temporal CS–US relationship. This has implications for understanding the neural mechanisms of FC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immediate-startle stimulus presentation fails to condition freezing responses to contextual cues.

Placed 28 male Wistar rats in a novel and distinctive environment. 18 of these received an intense startle-eliciting white noise stimulus. Animals that experienced a 60-sec delay between placement and the startle stimulus demonstrated significant freezing in the context, both poststartle (Session 1) and on a later startle-free test (Session 2). Animals that received immediate startle, however, did not differ on either occasion from animals that did not experience the startle stimulus. The amplitude of the startle response was not affected by this manipulation, which indicates a dissociation between freezing and startle responses with immediate- vs delay-startle presentation. The findings are consistent with M. S. Fanselow's (1986) conditioned stimulus (CS)-based associative explanation of the immediate-shock freezing deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in prepulse inhibition (PPI) between Wistar and Sprague-Dawley rats clarified by a new method of PPI standardization.

Rat strain differences in the acoustic startle response (ASR) and prepulse inhibition (PPI) of that response are of increasing interest, especially as the genetics of PPI may provide an approach to studying the genetics of certain mental illnesses. However, strain differences in PPI are confounded by differences in ASR. To clarify this issue, the authors investigated the ASR and PPI across a range of startling stimulus intensities (70 dB-120 dB) in Wistar and Sprague-Dawley rats (N=96). Sprague-Dawleys showed more PPI of ASR capacity (response limit) than Wistars. In contrast, Wistars exhibited greater PPI than Sprague-Dawleys, as measured by an increase in response threshold. This dissociation suggests that PPI is more complex than that assessed by single startling stimulus intensity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Seroquel restores sensorimotor gating in phencyclidine-treated rats

Phencylidine (PCP) is a psychotomimetic noncompetitive glutamate antagonist that has been used in studies of the neural substrates of psychosis. Both schizophrenic patients and PCP-treated rats exhibit reduced amounts of prepulse inhibition (PPI) of the startle reflex, which is the normal inhibition of startle that occurs when the starting noise is preceded 30 to 500 msec by a weak prepulse. The present study assessed the effects of seroquel (ICI 204,636), a mixed D2/5-hydroxytryptamine2 antagonist with a preclinical profile suggestive of potential antipsychotic efficacy, on the PCP-induced disruption of PPI. Clozapine, risperidone and haloperidol were also studied as comparison compounds. PCP (1.25 mg/kg) significantly reduced PPI, with prepulses that were 1 to 12 dB above background. Seroquel and clozapine significantly restored PPI in PCP-treated rats, whereas haloperidol and risperidone did not. Similar findings were obtained in studies using separate animals, a slightly lower dose of PCP (1.0 mg/kg) and a high dose of each of these antipsychotics. Separate studies verified that risperidone and haloperidol restored PPI in apomorphine-treated rats. In the present studies, seroquel exhibited a profile consistent with those exhibited by other "atypical" antipsychotics.     

Sensitivity of the mouse to changes in azimuthal sound location: Angular separation, spectral composition, and sound level.

Auditory spatial acuity was measured in mice using prepulse inhibition (PPI) of the acoustic startle reflex as the indicator response for stimulus detection. The prepulse was a “speaker swap” (SSwap), shifting a noise between two speakers located along the azimuth. Their angular separation, and the spectral composition and sound level of the noise were varied, as was the interstimulus interval (ISI) between SSwap and acoustic startle reflex elicitation. In Experiment 1 a 180° SSwap of wide band noise (WBN) was compared with WBN Onset and Offset. SSwap and WBN Onset had near equal effects, but less than Offset. In Experiment 2 WBN SSwap was measured with speaker separations of 15, 22.5, 45, and 90°. Asymptotic level and the growth rate of PPI increased with increased separation from 15 to 90°, but even the 15° SSwap provided significant PPI for the mean performance of the group. SSwap in Experiment 3 used octave band noise (2–4, 4–8, 8–16, or 16–32 kHz) and separations of 7.5 to 180°. SSwap was most effective for the highest frequencies, with no significant PPI for SSwap below 8–16 kHz, or for separations of 7.5°. In Experiment 4 SSwap had WBN sound levels from 40 to 78 dB SPL, and separations of 22.5, 45, 90, and 180°: PPI increased with level, this effect varying with ISI and angular separation. These experiments extend the prior findings on sound localization in mice, and the dependence of PPI on ISI adds a reaction time-like dimension to this behavioral analysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Partial disruption of fear conditioning in rats with unilateral amygdala damage: correspondence with unilateral temporal lobectomy in humans

Conditioned fear in rats was assessed for the effects of pretraining amygdala lesions (unilateral vs. bilateral) across unconditioned stimulus (US) modalities (white noise vs. shock). In contrast to sham controls, unilateral amygdala lesions significantly reduced conditioned freezing responses, whereas bilateral amygdala lesions resulted in a nearly complete lack of freezing to both the conditioned stimulus (CS) and the context. The lesion effects were more pronounced for CS conditioning but were consistent across US modalities. It was concluded that white noise can serve as an effective US and that unilateral amygdala lesions attenuate but do not eliminate conditioned fear in rats. The results support our interpretation of a recent fear conditioning study in humans (K. S. LaBar, J. E. LeDoux, D. D. Spencer, & E. A. Phelps, 1995).     

Conditioned-reflex facilitation in young and older adults

Young (18-30 years) and elderly (63-88 years) human subjects received 70 trials of single-cue classical eyeblink conditioning (paired group), or 70 explicitly unpaired presentations of the tone conditioned stimulus (CS) and airpuff unconditioned stimulus (unpaired group). Before and after conditioning, reflex-eliciting white noise and corneal airpuff stimuli were presented alone or paired with the CS to investigate the effects of conditioning on eyeblink reflex amplitude. The results showed increased conditioned responses in the paired group compared to the unpaired group for the young but not the elderly subjects. There was, however, evidence of conditioned facilitation of noise-elicited reflexes in both young and elderly subjects. These data indicate that conditioned facilitation of the startle reflex may be a sensitive indicator of classical conditioning processes in human subjects.     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats.

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explicitly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat

In normal subjects, if an acoustic startle stimulus is immediately preceded by a small brief change in background noise intensity, the magnitude of the subsequent startle response is decreased. This prepulse inhibition (PPI) of an acoustic startle response has been shown to be associated with sensorimotor gating. PPI is disrupted in schizophrenic patients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 mumol/kg IP) (equivalent to 0.03, 0.1, and 0.3 mg/kg base) and the nicotinic cholinergic receptor (nAChR) channel blocker, mecamylamine (5.0 and 50 mumol/kg IP) (equivalent to 1.0 and 10.0 mg/kg) on PPI of the acoustic startle response in the rat. Nicotine increased the PPI at the lowest prepulse signal levels but not at the stronger levels. Mecamylamine was without effect at 5.0 mumol/kg, but the 50 mumol/kg dose decreased the inhibition at both weak and strong prepulse (PP) levels. Mecamylamine (5.0 mumol/kg) pretreatment did not block the (-)-nicotine-induced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mumol/kg IP) (equivalent to 0.071, 0.23, 0.71, and 2.3 mg/kg) was without effect. These results are consistent with a mecamylamine-insensitive effect of nicotine to improve gating in normal rats. The nAChR subtype involved in producing nicotine's increase of PPI needs further investigation.     

Modification of the acoustic startle response in hearing-impaired C57BL/6J mice: Prepulse augmentation and prolongation of prepulse inhibition.

Modification of acoustic startle amplitude by a 10-ms tone prepulse (S1) was evaluated as a function of the interstimulus interval (ISI) between the onset of S1 and the onset of the startle-evoking stimulus (S2). Subjects were normal-hearing 1-month-old C57BL/6J (C57) mice and CBA/CaJ mice and 5-month-old C57 mice with high-frequency hearing loss. With a 2-ms ISI, 5-month-old C57 mice (but not the normal-hearing mice) exhibited pronounced prepulse augmentation (PPA) of startle: Amplitudes were much larger when S1 was present. Prepulse inhibition (PPI) occurred with ISls of 10–100 ms in all subject groups. With long ISls of 200 and 500 ms, however, PPI was strong only in 5-month-old C57 mice and only with S1 frequencies of 8, 12, and 16 kHz. Physiological studies of neural plasticity have shown that frequencies of 8–16 kHz become "over-represented" (more neurons responding) in the central auditory system of C57 mice, suggesting a link with prolonged PPI observed here. (PsycINFO Database Record (c) 2010 APA, all rights reserved)