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PubMed1995

Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease.

The corpus striatum serves a critical function in inhibiting involuntary, intrusive movements. Striatal degeneration in Huntington's disease results in a loss of motor inhibition, manifested by abnormal involuntary choreiform movements. Sensorimotor inhibition, or "gating", can be measured in humans using the startle reflex: the startle reflex is normally inhibited when the startling stimulus is preceded 30-500 ms earlier by a weak prepulse. In the present study, prepulse inhibition (PPI) was measured in patients with Huntington's disease to quantify and characterise sensorimotor gating. Compared with age matched controls, patients with Huntington's disease exhibit less PPI. Startle gating deficits are evident in patients with Huntington's disease when startle is elicited by either acoustic or tactile stimuli. Even with stimuli that elicit maximal PPI in normal subjects, patients with Huntington's disease exhibit little or no PPI, and their pattern of startle gating does not show the normal modulatory effects usually elicited by changing the prepulse interval or intensity. Startle amplitude and habituation and latency facilitation are largely intact in these patients, although reflex latency is significantly slowed. In patients with Huntington's disease, startle reflex slowing correlates with cognitive impairment measured by the dementia rating scale, and with the performance disruptive effects of interference measured by the Stroop test. These findings document a profound disruption of sensorimotor gating in patients with Huntington's disease and are consistent with preclinical findings that identify the striatum and striatopallidal GABAergic efferent circuitry as critical substrates for sensorimotor gating of the startle reflex.

Acoustic Stimulation↗

PubMed1990

Facilitation and inhibition of the human startle blink reflexes by stimulus anticipation.

The cutaneous eyeblink has 2 electromyographic components, 1 unilateral and early (R1) and 1 bilateral and late (R2), which are served by different neural pathways. These 2 reactions were measured when the eliciting stimulus was expected or relatively surprising. Forewarning was varied in 3 ways: Subjects received notice that the stimulus was about to occur on some trials (Experiment 1); delivered the stimulus to themselves on some trials (Experiments 2 & 3); or experienced a series of trials in which a tone was paired with the eliciting stimulus, followed by tone-alone trials interspersed with test trials (Experiment 4). In each case, forewarning enhanced R1 amplitudes while depressing R2 but reduced the latency of both components. This mixed pattern of effects reveals that the preparatory state provoked by forewarning focuses excitatory and inhibitory processes simultaneously on different reflex pathways: inhibition central and excitation peripheral.

Adult↗

PubMed1999

The electrically elicited startle blink reflex in patients with schizophrenia: A threshold study of different reflex components.

The electrically elicited blink reflex consists of three components (R1, R2, R3). In humans the excitability of these components is influenced by attentional states. In particular, distraction from the stimulus leads to facilitation of the bilateral R2 and R3. The present study was performed in order to investigate the excitability of the different components of the electrically evoked blink reflex in 13 patients with schizophrenia and 13 normal controls under standard conditions. Therefore, the thresholds of the distinct components were determined without any inhibitory or facilitatory procedure. There was no significant difference in R1 and R2 thresholds between patients and controls. In contrast, the R3 threshold was significantly reduced in schizophrenic patients (R3 threshold = 17.5 mA in normal subjects, 10.5 mA in patients, p = 0. 0001). In recent studies the R3 magnitude was found to be highly susceptible to changes in the attentional state of normal subjects. The lower threshold of R3 in patients with schizophrenia might therefore be a neurophysiological marker of attentional dysfunctions in schizophrenia.

Adult↗

PubMed1998

Effects of caffeine and caffeine-associated stimuli on the human startle eyeblink reflex.

An experiment was performed (n = 19) that investigated the effect of caffeine and expectancy of caffeine on the eyeblink component of the startle reflex. Nineteen habitual caffeine users received caffeinated coffee, caffeinated juice, decaffeinated coffee, or decaffeinated juice in four sessions spaced 1 week apart. Twenty-five to 30 min after ingestion of the liquid, 30 acoustic startle stimuli were presented. The results showed that caffeine increased startle eyeblink amplitude. Startle reflex onset latency was significantly longer in the decaffeinated coffee condition than in the other three conditions. This may have been due to the activation of a compensatory slowing of the reflex by the anticipation of caffeine, a slowing that was then overridden by caffeine speeding the response.

Acoustic Stimulation↗

PubMed1982

[Facilitation effect of lead stimulation on the startle, eyeblink reflex: an analysis of changes in heart rate and some somatic responses (author's transl)].

Some skeletal startle reflexes are facilitated or inhibited when a weak neutral stimulus (S1) precedes a startle-eliciting stimulus (S2). These effects are called the "lead-stimulation effects", and the present research is concerned with the facilitation effect of them in the long-ISI condition. The present findings were as follows: the facilitation of the startle eyeblink reflex could not be explained by any changes in HR, spontaneous eyeblinks, and chin EMG activity; and the HR changes were independent of the changes in spontaneous eyeblinks and chin EMG activity. These findings were evaluated from the standpoints of Graham's rebound hypothesis, the Laceys cardiac afferent feedback hypothesis, and the notion of Obrist and his associates against Lacey.

Acoustic Stimulation↗

PubMed2003

Acoustic startle evokes bilaterally synchronous oscillatory EMG activity in the healthy human.

Despite animal evidence that the reticulospinal system is of major importance to movement, this motor pathway has remained relatively inaccessible to experimentation in the human. Consequently, little is known about its function in health and disease. Here, we use the acoustic startle response to demonstrate that one type of reticulospinal activity in the human is associated with a characteristic pattern of bilateral synchronization between motor units. Surface electromyography (EMG) was recorded from upper limb muscles in 15 healthy subjects during the reflex startle to unexpected acoustic stimulation, voluntary movements mimicking the startle and during sustained voluntary tonic contraction. Frequency analysis demonstrated autospectral peaks at approximately 14 Hz in deltoid and biceps muscles only during the startle reflex. Similarly, coherence spectra of the EMG recorded between homologous proximal upper limb muscles demonstrated a peak centered approximately 12-16 Hz during reflex startles. Coherence in the 10- to 20-Hz band was significantly greater in the startle reflex than during voluntary sham startles or voluntary tonic contraction for deltoid, but not first dorsal interosseous, muscles. The coherence at 10-20 Hz between EMGs from homologous muscles represents a potential surrogate measure of reticulospinal activity that may be useful in determining the contribution of the reticulospinal system to different types of movement in health and disease.

Acoustic Stimulation↗

PubMed2003

Hippocampal modulation of sensorimotor processes.

While the hippocampus makes unique contributions to memory, it has also long been associated with sensorimotor processes, i.e. innate processes involving control of motor responses to sensory stimuli. Moreover, hippocampal dysfunction has been implicated in neuropsychiatric diseases, such as schizophrenia and anxiety disorders, primarily characterized by non-mnemonic deficits in the processing of and responding to sensory information. This review is concerned with the hippocampal modulation of three sensorimotor processes in rats-locomotor activity, prepulse inhibition (PPI) of the startle reflex, and the startle reflex itself-whose alterations are related to human psychosis or anxiety disorders. Its main purpose is to present and discuss the picture emerging from studies examining the effects of pharmacological manipulations of the dorsal and ventral hippocampus by local drug microinfusions. While a role of the hippocampus in regulating locomotor activity, PPI, and startle reactivity has also been suggested based on the effects of hippocampal lesions, the microinfusion studies have revealed additional important details of this role and suggest modifications of notions based on lesion studies. In summary, the microinfusion studies corroborate that hippocampal mechanisms can directly influence locomotor activity, PPI, and startle reactivity, and that aberrant hippocampal function may contribute to neuropsychiatric diseases, in particular psychosis. The relation between different sensorimotor processes and hippocampal neurotransmission, the role of ventral and dorsal hippocampus, and the extrahippocampal mechanisms mediating the hippocampal modulation of different sensorimotor processes can partly be dissociated. Thus, the hippocampal modulation of these sensorimotor processes appears to reflect multiple operations, rather than one unitary operation.

Animals↗

PubMed1991

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats.

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05-10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (-) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 micrograms) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methyl-para-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, to an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.

Acoustic Stimulation↗

PubMed2000

The time course of emotional and attentional modulation of the startle eyeblink reflex during imagery.

Two studies were conducted to examine the time course of attentional and emotional processing using the startle eyeblink reflex. Forty-eight participants listened to a series of 1500-ms tones that occurred every 6 s. The tones signaled participants to generate emotional images that were positive or negative in valence and high or low in arousal. Auditory startle probes occurred 120 ms, 1400 ms, or 4000 ms after tone onset. Startle inhibition was seen 120 ms after tone onset and startle facilitation was found at 1400 ms, compared to startles elicited 4000 ms after tone onset. Startle inhibition was greater at 120 ms when the tone signaled imagery, indicating an attentional effect. A second experiment found that this effect was not caused by the comparative rarity of the tones signaling imagery. Startle magnitude was also smaller at 1400 ms when the tone signaled imagery compared to no-imagery tones. The type of imagery did not modulate the startle response 120 ms after tone onset, but negative valence imagery enhanced startle magnitude at 1400 ms and 4000 ms after tone onset, and high arousal also enhanced startle magnitude at 4000 ms. Thus, attention and emotion followed different time courses in affecting the startle reflex response during imagery.

Acoustic Stimulation↗

PubMed1996

The varying time courses of attentional and affective modulation of the startle eyeblink reflex.

In previous research on modulation of the startle eyeblink reflex, emotional effects have been demonstrated only at late probe positions, whereas attentional effects have been found at both early and late positions but only when the prepulses were affectively neutral. In Experiment 1, participants viewed emotionally valenced pictures and were instructed to attend to the duration of half of the slides. Affective modulation of the startle eyeblink occurred at long lead intervals, but attentional modulation also occurred late. In Experiment 2, participants viewed the same slides used in Experiment 1 but were instructed to attend to the duration of only the positive or the negative slides. Affective modulation occurred at both early and late probe positions, whereas attentional effects occurred only following slide offset. Early (250 ms) affective modification of startle eyeblink has not been previously reported. These results suggest that the time courses of emotional and attentional modulation of startle are variable and can occur at both early and late startle probe positions, depending on task requirements.

Adult↗

PubMed1995

Modulation of spinal reflexes: arousal, pleasure, action.

The human startle reflex is reliably modulated by the affective valence of foreground pictures, with larger reflexes elicited when viewing unpleasant relative to pleasant scenes. If this modulation is due to priming of the defensive startle reflex by an aversive foreground, a different pattern should occur for a reflex that is not inherently defensive in nature. In the current study, affective modulation was investigated using the spinal tendinous (T) reflex, which is well documented as sensitive to differences in arousal and is involved in actions that are both appetitively defensively motivated. As such, T reflexes elicited during unpleasant pictures were not expected to be augmented relative to those elicited in the context of pleasant pictures. Results showed that T reflexes were facilitated during processing of arousing stimuli-either pleasant or unpleasant relative to low-arousal neutral materials. These effects of emotional stimuli on T-reflex amplitude are consistent with hypothesis that motivational priming underlies affective reflex modulation.

Adult↗

PubMed1994

Quinolinic acid lesions of the ventral striatum reduce sensorimotor gating of acoustic startle in rats.

The startle reflex is inhibited when the startling stimulus is preceded 30-500 ms by a weak noise or 'prepulse'. While the primary startle circuit is organized at or below the pons, the amount of 'prepulse inhibition' (PPI) is modulated by forebrain activity and is reduced in certain neuropsychiatric disorders. The reduction of PPI in these disorders is thought to reflect disturbances in sensorimotor inhibition which underlie an inability to 'gate' irrelevant sensory, motor or cognitive information. PPI is altered by pharmacologic manipulations of the ventral striatum, which is thought to modulate PPI via sequential efferent projections through the ventral pallidum and pontine reticular formation. In the present study, we assessed the effects of cellular lesions of the ventral striatum (VS) on PPI. Quinolinic acid lesions of the VS significantly reduced PPI and increased startle amplitude; however, changes in PPI and startle amplitude were not significantly correlated within rats. Infusion of the GABA agonist muscimol into ventral striatal terminal fields in the ventral pallidum significantly restored PPI in VS-lesioned rats, but did not reverse lesion effects on startle amplitude. It was verified that muscimol infusions were made into an area which receives direct VS innervation, using ventral pallidal injections of the retrograde tracer Nuclear yellow in VS sham-lesioned rats. Cells in the ventral striatum appear to modulate sensorimotor gating of the startle reflex via a GABAergic innervation of the ventral pallidum.

Acoustic Stimulation↗

PubMed2006

Prepulse inhibition of the startle blink reflex is modulated during a memory task requiring prepulses to be encoded for later report.

Prepulse inhibition (PPI) of the startle blink reflex in humans can be modulated by selective attention to the prepulse. The present experiment used a memory task to determine whether the encoding of information for later report can modulate PPI. Participants were briefly presented with a display of one or three letters followed by a pattern mask and asked to make a delayed report of the letter(s) shown. Memory recall was better in the 1-letter condition than in the 3-letter condition. Prepulse inhibition was greater in the 3-letter condition than in the 1-letter condition at lead intervals of 120 and 240 ms following the onset of the letter display. Blink modulation did not differ between the letter conditions at lead intervals of 120, 240, 360, or 2600 ms following the mask, ruling out other explanations (e.g., rehearsal) for the earlier difference in PPI. The results suggest that the short-term consolidation of memory, and possibly any cognitive process that requires access to a theoretical limited capacity central processing mechanism modulates PPI.

Adolescent↗

PubMed1995

Acoustic startle and anticipatory anxiety in humans: effects of monaural right and left ear stimulation.

The startle reflex elicited by binaural acoustic startle stimuli is potentiated by the threat of electric shock. The present study explored the lateralization of this fear-potentiated startle reflex effect using acoustic startle stimuli delivered binaurally or monaurally to the left or right ear and recorded from the left and right orbicularis oculi muscles. Consistent with previous results, the acoustic startle to binaural stimulation was potentiated during the anticipation of shock. This effect was also present for monaural stimulation but was greater when startle stimuli were delivered to the right than to the left ear. The results are discussed in terms of hemispheric lateralization during shock anticipation.

Acoustic Stimulation↗

PubMed2001

The specificity of infant emotional expression for emotion perception.

Attachment theory emphasizes the role of negative emotional expression in infancy for establishing proximity to and care of the caregiver. According to Lang's biphasic model of emotions protective reflexes (e.g. startle response) are primed if a defensive motivational set is activated. The aim of the study was to examine whether the perception of an infant emotional expression can prime such defensive behavior. The sample consisted of 48 university students. Startle reflex, corrugator and zygomatic EMG activity and subjective ratings of valence and arousal were assessed as a response to presentation of pictures of different emotional valence. Affective startle modulation was obtained when probes were presented during pictures of the International Affective Pictures System replicating previous findings. By contrast, negative infant emotion pictures did not prompt an augmentation of the startle response, although both the subjective ratings and the mimic EMG activity indicated a clear differentiation between negative and positive infant pictures. This pattern of findings was found only in a between-subject design, but not when the two picture sets were presented in the same session, indicating an interference of contrasting content of pictures.

Adult↗

PubMed2004

Plasminogen regulates pro-opiomelanocortin processing.

BACKGROUND: Plasminogen-deficient mice exhibit behavioral differences in response to stress, including a markedly reduced acoustic startle reflex response compared with wild-type (WT) littermates. The acoustic startle reflex activates the hypothalamic-pituitary axis and is modulated by these hormones. OBJECTIVES: The purpose of this study was to investigate whether plasminogen plays a role in the processing of hormones in the hypothalamic-pituitary axis. METHODS: In this study the concentration of plasma, pituitary, and brain hypothalamic-pituitary axis hormones and precursor processing was examined in WT and plasminogen deficient (Plg-/-) mice before and after acoustic startle reflex testing. RESULTS: Plasma adrenocorticotropic hormone (ACTH), beta-endorphin and alpha-melanocyte stimulating hormone were elevated after acoustic startle reflex testing in both WT and (Plg-/-) mice. However, in the Plg-/- mice, beta-endorphin values were 43, 35, and 45% lower in the plasma, pituitary, and whole brain, respectively, compared with the WT mice. Plasmin readily degraded precursor peptides, the 23-kDa precursor, beta-lipotropin, and ACTH, when presented as purified proteins or as the secretory products of mouse pituitary cells (AtT-20). The precursor peptide, 23 kDa, for beta-endorphin and alpha-melanocyte stimulating hormone was reduced in the pituitaries from the Plg-/- mice, and the mRNA for Plg was found in pituitaries from WT mice. Infusion of beta-endorphin and alpha-melanocyte stimulating hormone into the brain of Plg-/- mice increased acoustic startle reflex. CONCLUSIONS: The results of this study show that plasmin is involved in the processing of hormones derived from the pro-opiomelanocortin precursor in the intermediate pituitary. A deficiency of plasminogen reduces processing of beta-endorphin and alpha-melanocyte stimulating hormone, and interferes with normal brain function.

Adrenocorticotropic Hormone↗

PubMed2003

Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia.

BACKGROUND: Prepulse inhibition (PPI) is the normal suppression of the startle reflex when an intense startling stimulus is preceded by a barely detectable prepulse. Habituation of the acoustic startle reflex is decrement in response when the same stimulus is presented repeatedly. These factors have been proposed as neurophysiologic measures of sensorimotor gating or filtering and discussed as trait-linked markers for information-processing deficits in schizophrenia-spectrum disorders. The aim of this study was to examine whether first-episode schizophrenia patients also exhibit deficits in PPI and habituation. METHODS: Never-medicated male schizophrenic and schizophreniform patients in their first psychotic episode (n=24) were compared with age-matched healthy men (n=21) in an acoustic startle paradigm assessing PPI (30-, 60-, 120-, 240-, and 2000-msec interstimulus intervals) and habituation. RESULTS: Compared with control subjects, first-episode patients exhibited significant deficits in both PPI in the 60-msec prepulse condition and startle habituation. Patients also exhibited less facilitation in the 2000-msec prepulse condition. CONCLUSIONS: In combination with other studies, these findings indicate that PPI and habituation may be sensitive intermediate phenotypic markers for information-processing deficits in schizophrenic patients.

Acoustic Stimulation↗

PubMed1998

Are different parts of the extended amygdala involved in fear versus anxiety?

Although there is a close correspondence between fear and anxiety, and the study of fear in animals has been extremely valuable for understanding brain systems that are important for anxiety, it is equally clear that a richer animal model of human anxiety disorders would include measures of both stimulus-specific fear and something less stimulus specific, more akin to anxiety. Studies in patients with posttraumatic stress syndrome indicate these individuals seem to show normal fear reactions but abnormal anxiety measured with the acoustic startle reflex. Studies in rats, also using the startle reflex, indicate that highly processed explicit cue information (lights, tones, touch) activates the central nucleus of the amygdala, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear. Somewhat less explicit information, such as that produced by exposure to a threating environment for several minutes or by intraventricular administration of the peptide corticotropin-releasing hormone may activate a brain area closely related to the amygdala, called the bed nucleus of the stria terminalis, which in turn activates hypothalamic and brain stem target areas involved in specific signs of fear or anxiety. Because the nature of this information may be less specific than that produced by an explicit cue, and of much longer duration, activation of the bed nucleus of the stria terminalis may be more akin to anxiety than to fear.

Amygdala↗