Acoustic Startle Stimuli Research Articles

Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats

Huntington's disease (HD) is a progressive neurodegenerative disorder with a spectrum of cognitive, behavioral, and motor abnormalities. The mitochondrial toxin 3-nitropropionic acid (3-NP) effectively induces specific behavioral changes, primarily manifested as prepulse inhibition (PPI) deficit of acoustic startle stimuli, and selective striatal lesions in rats and primates mimicking those in HD. The implications of nitric oxide in a variety of neurodegenerative diseases attract attention to study the possible role of flavonoids in interaction with nitric oxide pathways involved in HD. The present study investigates the potential effect of hesperidin, a flavanone group member, on 3-NP-induced behavioral, neurochemical, histopathological and cellular changes. Systemic administration of 3-NP to rats for 5 days (20mg/kg) caused reduction of locomotor activity by days 2 and 5, 55% deficit of PPI response, elevation of cortical, striatal and hippocampal malondialdehyde (MDA) levels by 63%, 41% and 56%, reduction of respective catalase activity by 50%. Immunohistochemical staining of cortices, striata and hippocampi showed patches of iNOS positive cells. Electron microscopic ultrastructural examination showed marked mitochondrial swelling, perivascular edema and shrunken nerve cells. Pretreatment with hesperidin (100mg/kg) ahead of 3-NP prevented any changes of locomotor activity or PPI response, slightly increased cortical, striatal and hippocampal MDA levels by 10% and reduced respective catalase activity by 22%, 20% and 5%. Only few iNOS positive cells were detected in sections from rats pretreated with hesperidin which also reduced cellular abnormalities induced by 3-NP. This study suggests a potential neuroprotective role of hesperidin against 3-NP-induced Huntington's disease-like manifestations. Such neuroprotection can be referred to its antioxidant and anti-inflammatory activities.

Meditation and the startle response: A case study.

The effects of two kinds of meditation (open presence and focused) on the facial and physiological aspects of the defensive response to an aversive startle stimulus were studied in a Buddhist monk with approximately 40 years of meditation experience. The participant was exposed to a 115-db, 100-ms acoustic startle stimulus under the 2 meditation conditions, a distraction condition (to control for cognitive and attentional load) and an unanticipated condition (startle presented without warning or instruction). A completely counterbalanced 24-trial, single-subject design was used, with each condition repeated 6 times. Most aspects of the participant's responses in the unanticipated condition did not differ from those of a comparison group of 12 age-matched male controls. Both kinds of meditation produced physiological and facial responses to the startle that were smaller than in the distraction condition. Within meditation conditions, open presence meditation produced smaller physiological and facial responses than focused meditation. These results from a single highly expert meditator indicate that these 2 kinds of meditation can differentially alter the magnitude of a primitive defensive response.

Relationship of prepulse inhibition to temperament and character in healthy Japanese subjects

Prepulse inhibition (PPI) of acoustic startle reflex (ASR) and personality, such as temperament and character, are considered candidate endophenotypes of schizophrenia. Gene polymorphism studies have provided evidence that both PPI and self-transcendence (ST) are polygenetic traits that involve several neurotransmitters, including the serotonin and dopamine signaling pathways. However, the relationship between PPI and temperament/character has not been properly addressed to date. Here, we investigated the link between PPI and temperament/character in 169 healthy Japanese subjects. A human startle response monitoring system was used to deliver acoustic startle stimuli and to record and score the electromyographic activity of the orbicularis oculi muscle. PPI was evaluated at signal-to-noise ratios (SnRs: intensity difference between background noise and prepulse) of +12, +16, and +20 dB. The lead interval (from prepulse onset to pulse onset) was 120 ms, and Temperament and Character Inventory was used in both groups. Significant correlations at SnR of +16 and +20 dB to ST were identified. Our results suggest that impaired sensorimotor gating, evaluated as lower PPI of ASR, of healthy subjects is correlated with self transcendence, the character which is closely related with schizophrenia and schizotypy.

In the face of fear: Anxiety sensitizes defensive responses to fearful faces

Fearful faces readily activate the amygdala. Yet, whether fearful faces evoke fear is unclear. Startle studies show no potentiation of startle by fearful faces, suggesting that such stimuli do not activate defense mechanisms. However, the response to biologically relevant stimuli may be sensitized by anxiety. The present study tested the hypothesis that startle would not be potentiated by fearful faces in a safe context, but that startle would be larger during fearful faces compared to neutral faces in a threat-of-shock context. Subjects viewed fearful and neutral faces in alternating periods of safety and threat of shock. Acoustic startle stimuli were presented in the presence and absence of the faces. Startle was transiently potentiated by fearful faces compared to neutral faces in the threat periods. This suggests that although fearful faces do not prompt behavioral mobilization in an innocuous context, they can do so in an anxiogenic one.

Three methodologies for measuring the acoustic startle response in early infancy

The present study investigated whether three methodologies currently used in animal as well as human adult startle research could be adapted for measuring the startle response in 5-month-old infants. The three methods performed: an automated and computerized recording of the infants' whole-body motor reactions (Automated Infant Motor Movement Startle Seat, AIMMSS); a coding of the infants' facial muscular contractions involved in the startle response (FACS, Baby FACS); an analysis of the infants' eyeblink intensity in response to the startle probes (Eye-Blink Strength scale). The results showed that these methods accurately registered the latency and intensity parameters of the reactions to acoustic startle stimuli. A correlational analysis showed, also, that the three methods registered the same motor reaction measuring the infant acoustic startle response in a consistent way.

Cold pressor stress affects cardiac attenuation of startle

Stress may affect cardio-afferent neural traffic. We investigated whether acute autonomic stress has an impact on cardiac modulation of startle (CMS), a ‘background’ methodology for assessing baro-afferent signal transmission. Therefore, 38 healthy volunteers received acoustic startle stimuli (105dB) at 6 different latencies relative to the R-wave (R +0, 100, 200, 300, 400, and 500ms; randomized order), both before and immediately after either a cold pressor (n=19) or a control intervention (n=19). Blood pressure was enhanced significantly in the cold pressor group right after the intervention (+13.7/5.7mmHg), reflecting sustained autonomic activation after the stress procedure. Before stress, startle responses were lowest for latencies of R +200 and +300ms, corroborating previous findings. After the cold pressor test, startle responsiveness was lowest for earlier latencies (R +0, +100 and +200ms). Stress facilitation of pre-ejection baro-afferent traffic originating from atrial mechano-sensitive receptors may be associated with this time shift effect. We conclude that the cardiac modulation of startle is sensitive to altered temporal baro-afferent feedback characteristics induced by stress and autonomic activation.

Is Acoustic Startle a Viable Exposure Protocol for Posttraumatic Stress Disorder? A Clinical Case Study

Exaggerated startle is a common symptom (based on Diagnostic and Statistical Manual of Mental Disorders [fourth edition] Criterion D) for many patients with posttraumatic stress disorder (PTSD). Findings from previous studies suggest that exaggerated startle may be due to trauma exposure or pretrauma vulnerability factors for PTSD development. The present clinical case study reports on a patient with PTSD characterized by a very prominent startle response and preference against standard trauma-related exposure strategies. On the basis of recent findings that interoceptive exposure exercises (e.g. shaking head side to side, hyperventilation) elicit trauma-related memories (Wald & Taylor, 2008), the authors sought to determine whether repeated application of an acoustic startle stimulus would serve to diminish the prominent startle response and facilitate exposure and overall symptom reduction by eliciting trauma-related memories. The protocol was successful in eliciting vivid and distressing trauma-related memories. Over the course of seven exposure trials, the patient demonstrated a decrease in distress elicited during the protocol, improved mood, and reduced general anxiety and trauma-related distress. He also reported significantly decreased startle response to loud noises encountered during activities of daily living. Although preliminary, these finding suggest that the acoustic startle protocol may be a viable (interoceptive) exposure strategy for individuals with PTSD, particularly those with exaggerated startle responses and those who are not amenable to standard trauma-related exposure strategies.

Somatic and neuroendocrine responses to standard and biologically salient acoustic startle stimuli in monkeys

The startle response, a simple defensive response to a sudden stimulus signaling proximal threat, has been well studied in rodents and humans, but has been rarely examined in monkeys. The first goal of the present studies was to develop a minimally immobilizing startle measurement paradigm and validate its usefulness by testing two core features of the startle response (habituation and graded responsivity) in squirrel monkey subjects. Two different types of startle stimuli were used: standard broad-band noise bursts, and species-specific alarm vocalizations ("yaps") which are elicited in response to threat in both wild and captive animals. The second goal of the present studies was to test whether yaps produce enhanced startle responsivity due to their increased biological salience compared to simple, non-biologically relevant noise bursts. The third goal of the present studies was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis response to startle stimuli, as little is known about the stress-activating role of startle stimuli in any species. These experiments determined that the whole-body startle response in relatively unrestrained squirrel monkeys habituates across repeated stimulus presentations and is proportional to stimulus intensity. In addition, differential habituation was observed across biologically salient vs. standard acoustic startle stimuli. Responses to "yaps" were larger initially but attenuated more rapidly over trials. Responses to "yaps" were also larger in the early subepochs of the response window but then achieved a lower level than responses to noise bursts in the later subepochs. Finally, adrenocorticotropic hormone and cortisol concentrations were significantly elevated above baseline after startle stimuli presentation, though monkeys did not exhibit differential HPA axis responses to the two types of startle stimuli. The development of monkey startle methodology may further enhance the utility of this paradigm in translational studies of human stress-related psychiatric disorders.

Longitudinal analysis of the behavioural phenotype in R6/1 (C57BL/6J) Huntington's disease transgenic mice

Huntington's disease is caused by a single mutation on the HTT gene which produces an expansion in the number of glutamine repeats present in the huntingtin protein. This mutation results in an array of motor, cognitive and behavioural problems mediated by a progressive loss of striatal neurons and brain atrophy. The identification of behavioural phenotypes in mouse models of the disease provides a baseline of efficacy for therapeutic interventions. The R6/1 mouse line carries ∼115 CAG repeats and has an aggressive form of the disease. The aim of the present study was to undertake longitudinal behavioural characterisation of this mouse line in order to quantify the time course and severity of disease progression. In the present study, when compared to wildtype littermates, male R6/1 heterozygous mice demonstrated a progressive weight loss from 3 months of age. The R6/1 carriers also demonstrated a relatively stable motor coordination deficit on the rotarod, and progressive impairments on each aspect of the balance beam test: latency to orientate and traverse the beam; number of fore- and hind-limb footslips. The R6/1 carriers were less reactive to acoustic startle stimuli and displayed less inhibition to prepulse warning stimuli than their wildtype littermates. In the Morris water maze, the R6/1 carriers demonstrated a deficit on latency to find the platform and path length measures, which was apparent by 3 months of age but not further progressive. They also demonstrated fewer entries into the target zone during probe trials. The data from the present study demonstrate that the R6/1 mouse has a profound behavioural phenotype that includes motor and cognitive deficits, but that not all of these deficits were robustly progressive in nature.

Emotion regulation deficits in frontotemporal lobar degeneration and Alzheimer's disease.

We examined instructed and spontaneous emotion regulation in patients with frontotemporal lobar degeneration (FTLD, N = 32), which presents with profound emotional and personality changes; patients with Alzheimer's disease (AD, N = 17), which presents with profound memory impairment; and neurologically normal controls (N = 25). Participants were exposed to an aversive acoustic startle stimulus (115 dB) under 3 different conditions: (a) unwarned without instructions to down-regulate, (b) warned without instructions to down-regulate, and (c) warned with instructions to down-regulate. In the last 2 conditions, the warning took the form of a 20-s countdown. In all conditions, visible aspects of the startle response were assessed by measuring overall somatic activity and coding emotional facial expressions. FTLD patients, AD patients, and control participants showed similar patterns of down-regulation in somatic activity across the 3 startle trials. However, differences between the 3 groups emerged in the amount of emotional facial behavior expressed in the startle trials. There were no group differences in response in the unwarned condition, indicating that the startle response was intact in the patients. In the warned with instructions condition, both FTLD and AD patients were moderately impaired in down-regulatory ability compared with controls. In the warned without instructions condition, AD patients and normal controls spontaneously down-regulated their emotional responses, but FTLD patients did not. These findings illuminate specific problems that these patients have in the emotional realm.

Motor preparation is modulated by the resolution of the response timing information

In the present experiment, the temporal predictability of response time was systematically manipulated to examine its effect on the time course of motor pre-programming and release of the intended movement by an acoustic startle stimulus. Participants performed a ballistic right wrist extension task in four different temporal conditions: 1) a variable foreperiod simple RT task, 2) a fixed foreperiod simple RT task, 3) a low resolution countdown anticipation–timing task, and 4) a high resolution anticipation–timing task. For each task, a startling acoustic stimulus (124 dB) was presented at several intervals prior to the “go” signal (“go” − 150 ms, − 500 ms, and − 1500 ms). Results from the startle trials showed that the time course of movement pre-programming was affected by the temporal uncertainty of the imperative “go” cue. These findings demonstrate that the resolution of the timing information regarding the response cue has a marked effect on the timing of movement preparation such that under conditions of low temporal resolution, participants plan the movement well in advance in accordance with the anticipated probability of onset of the cue, whereas movement preparation is delayed until less than 500 ms prior to response time when continuous temporal information is provided.

Extraordinarily Quick Visual Startle Reflexes of Skipper Butterflies (Lepidoptera: Hesperiidae) are Among the Fastest Recorded in the Animal Kingdom

The abilities of animals in movement and coor dination frequently surpass our own abilities and fascinate us. New record speeds found among ani mals, when recorded by the scientific literature, tend to be widely publicized. Such is the case of the trap-jaw ant, Odontomachus bauri Emery, whose mandibles close in 0.13 s at a rate of 35.5 meters per second (ms'1) during a predatory strike, the fastest movement recorded among all animals (Patek et al. 2006). The fastest tactile reflex time belongs to the star-nosed mole, Condylura cristata L., which uses 22 nasal appendages to navigate through soil and can react in just 120 ms, when one of these appendages comes in contact with food (Catania & Remple 2004). Here, I would like to report the startle reflex time in skipper butter flies, which is among the fastest recorded for the animal kingdom and which is at least twice as fast as startle eye-blink reflex of humans. Startle reflexes have evolved as fast defensive (usually escape) responses in animals, engaging subcortical reflex mechanism that bypasses cere bral processing and voluntary movement. Be cause circuits involved are shorter, the latencies of the startle reactions are much shorter than those of voluntary reactions. In terms of elec tromyographic responses recorded in vitro, acous tic startle reflexes tend to be very short. In rats, for example, electromyographic responses can be as fast as 5-10 ms, and in humans as fast as 14 ms (Yeomans & Frankland 1995). The actual behavioral responses recorded in vivo tend to be longer. For example, in the African butterfly fish, Pantodon buchholzi Peters, the fastest response time to an acoustic startle stim ulus recorded on an electromyogram is 5 ms. The fish's fins initiate a motion 10 ms later, hence with the possible reflex time (ballistic jump) ca. 15 ms (Starosciak 2008). The eye-blink reflex of humans elicited by an air puff is 30-50 ms (e.g., Halmagyi & Gresty 1983). Compared to that, voluntary reaction time to a visual 'go' signal in humans is around 150 ms (Brown et al. 1991), and it takes an average of 700 ms for a human driver to move the foot from the accelerator to the brake peddle after seeing a red light (Green 2000). Just like butterfly fish, skipper butterflies rely on ballistic movements to evade preda tors, but they propel themselves through the air, not the water. They are, in fact, named for their quick, darting flight habits. They differ in several morphological characters from other butterflies (e.g., Ackery et al. 1999), most notably in having stockier bodies with stronger wing muscles. While photographing butterflies with a digital camera for several years, I have become convinced that skippers possess an extraordinary reflex time when startled by a photographic flash. Their star tle reflex is faster than I have observed in any other butterfly. Even though other butterflies and other insects are frequently startled by a photographic flash and flee after their picture is taken, their motor re sponse is normally slower than the shutter speed of the camera. Thus, even if they are startled by the flash, they appear still in photographs. Skippers, however, react so quickly to the flash, that their re action is frequently captured by the camera. In the specific camera settings I used in the photographs in Fig. 1, the shutter was open for 1/ 60 sec =17 ms. The flash, synchronized with the shutter, occurred during this time. During this ex posure time, skippers startled by the flash fre quently jumped into the air, and their image was captured in flight near the substrate. They tended to return to their original position imme diately, so that they appeared still to the human eye, and their movement was captured only by the camera. In pairs of photographs (Fig. 1: A1-A2, B1-B2, and C1-C2), one individual was recorded in the act of jumping above the same plant when star tled repeatedly. These shots were captured by fir ing the camera with intervals of ca. 20 s. It was noted by previous studies that habituation (de cline and disappearance of response during repet itive stimuli) occur with other types of startle re flexes (Yeomans & Frankland 1995). I observed the same with the jumping skippers: if they did not escape after the first shot, their jumping re sponse ceased after 2-3 repeated firings of the flash (Fig. 1: C3, D2). These photographs illustrate the unique quickness of skipper reflexes among all the other insects that I have photographed. They document what might be one of the fastest reflex times (<17 ms) so far recorded for the animal kingdom.

The effects of smoking on selective attention as measured by startle reflex, skin conductance, and heart rate responses to auditory startle stimuli

The present study examined the effects of cigarette smoking on attentional processing by measuring nondeprived smokers' (n=39), minimally deprived smokers' (n=36), and nonsmokers' (n=34) startle eyeblink reflex, heart rate, and skin conductance responses (SCR) to acoustic startle stimuli (105 dB) during directed attention tasks. Whereas smokers demonstrated smaller startle responses than nonsmokers during a directed attention visual task, no difference in startle response magnitude emerged between the two smoking groups, nor did we observe an effect of smoking on SCR or heart rate response to the startle stimuli. Our findings suggest that smokers differ from nonsmokers in their selective attention abilities and that smoking does not enhance minimally deprived smokers' selective attention.

Cardiac modulation of startle: Effects on eye blink and higher cognitive processing

Cardiac cycle time has been shown to affect pre-attentive brainstem startle processes, such as the magnitude of acoustically evoked reflexive startle eye blinks. These effects were attributed to baro-afferent feedback mechanisms. However, it remains unclear whether cardiac cycle time plays a role in higher startle-related cognitive processes, as well. Twenty-five volunteers responded first by ’fast as possible’ button pushes (reaction time, RT), and second, rated perceived intensity of 60 acoustic startle stimuli (85, 95, or 105 dB; 50 ms duration; binaural; instantaneous rise time), which were presented either 230 or 530 ms after the R-wave, and eye blink responses were measured by EMG. RT was divided into evaluation and motor response time according to previous research. Increasing stimulus intensity enhanced startle eye blink, intensity ratings, and RT components. Eye blinks and intensity judgments were lower when startle was elicited at a latency of R + 230 ms, but RT components were differentially affected: the evaluative component was attenuated, and the motor component was accelerated when stimuli were presented 230 ms after the R-wave. We conclude that the cardiac cycle affects the attentive processing of acoustic startle stimuli.

Prepulse inhibition of the startle response with chronic schizophrenia: A replication study

Prepulse inhibition (PPI) deficit, the acoustic startle reflex (ASR) and habituation (HAB) impairment are considered to be endophenotypes for schizophrenia. The recent two studies have reported that a PPI deficit was detected in Japanese schizophrenic patients. We replicated that study using larger samples (115 schizophrenic patients and 111 normal controls) than the original study and a method same as original study. A startle response monitoring system was used to deliver acoustic startle stimuli, and to record and score the electromyographic activity of the orbicularis oculi muscle. We evaluated the startle measures of mean magnitude of ASR, HAB, and PPI at prepulse sound pressure intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90). ASR was significantly different between schizophrenic patients and controls. HAB and all PPI session data from schizophrenic patients were significantly lower than in controls. In addition, we detected significant differences for ASR, HAB and each PPI (82, 86 and 90 dB) between schizophrenic patients and controls with the use of multiple regression analysis. The gender and smoking state were not correlated with ASR, HAB or any PPI in multiple regression analysis. In conclusion, we were able to replicate the finding of HAB impairment and PPI deficit in chronic Japanese schizophrenic patients.

Reflexive eye blink is affected by baseline cortisol levels but not by oral cortisol

Event Abstract Back to Event Reflexive eye blink is affected by baseline cortisol levels but not by oral cortisol Diana F. De Sá1*, Sonja Roemer1, Frauke Nees2, Carina M. Zech1, Julia Wager1 and Hartmut Schaechinger1 1 University of Trier, Department of Clinical Physiology, Institute of Psychobiology, Germany 2 Central Institute of Mental Health Mannheim, Department of Cognitive and Clinical Neuroscience, Germany Cortisol was described to impact reflexive eye blink responsiveness, but conflicting results have been reported. In order to investigate this possible link, two studies were conducted. In the first one, we investigated the reflexive startle eye blink responses (EMG technology) to six (inter stimulus interval=10 s) brief (50 ms) and intense (105 dB) binaural acoustic white noise startle stimuli in 81 healthy subjects, 60 minutes after receiving a single oral 30 mg cortisol (n=40) dose, or placebo (n=41, control condition). We found that cortisol administration did not affect startle eye blink response magnitude to acoustic noise probes. In a second study, we assessed the EMG eye blink responses to 6 corneal airpuffs (10 psi, 50ms) in a population of 50 healthy subjects, from whom we obtained 6 samples of saliva immediately after awaking (around 6:30am) in 15-30 min. intervals (until 8am), on two different days, prior to the eye blink assessment. Subjects with higher morning cortisol levels presented a weaker reflexive eye blink response when compared with subjects with low morning cortisol. This finding corroborates previous time-of-day studies showing an inverse correlation between cortisol and reflexive eye blink. It is also in agreement with studies of pharmacological blockade of cortisol production that showed increased reflexive eye blink responses. We conclude that excess cortisol in resting humans does not affect startle, but that a negative correlation between the morning cortisol levels and startle response is present in healthy volunteers. Supported by the International Research Training Group "Psychoneuroendocrinology of Stress" funded by the German Research Foundation (GRK 1389/1) and the Netherlands Organisation for Scientific Research (NWO). Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: De Sá DF, Roemer S, Nees F, Zech CM, Wager J and Schaechinger H (2009). Reflexive eye blink is affected by baseline cortisol levels but not by oral cortisol. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.147 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Jun 2009; Published Online: 09 Jun 2009. * Correspondence: Diana F De Sá, University of Trier, Department of Clinical Physiology, Institute of Psychobiology, Trier, Germany, dferreiradesa@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Diana F De Sá Sonja Roemer Frauke Nees Carina M Zech Julia Wager Hartmut Schaechinger Google Diana F De Sá Sonja Roemer Frauke Nees Carina M Zech Julia Wager Hartmut Schaechinger Google Scholar Diana F De Sá Sonja Roemer Frauke Nees Carina M Zech Julia Wager Hartmut Schaechinger PubMed Diana F De Sá Sonja Roemer Frauke Nees Carina M Zech Julia Wager Hartmut Schaechinger Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Endogenous cortisol suppression with metyrapone enhances acoustic startle in healthy subjects

Previous human studies have shown that excess cortisol sufficient to fully occupy central nervous system (CNS) corticosteroid receptors may reduce startle eye blink. The present study tested whether cortisol depletion and the resulting reduction in activity of CNS corticosteroid receptors has the opposite effect. In a single-blind, placebo-controlled, randomized study, eye blink EMG responses to 105 dB acoustic startle stimuli were assessed in 25 healthy subjects who received oral metyrapone (1500 mg) to suppress endogenous cortisol production, while 24 controls received oral placebo. As expected, metyrapone significantly reduced salivary cortisol, indicating effective endogenous cortisol suppression. Startle eye blink responses were significantly increased in the metyrapone group. Short-term habituation of the startle reflex was not different between groups. Our results suggest that startle is enhanced during depletion of cortisol. This effect may be mediated by CNS mechanisms controlling cortisol feedback.

Neuronal functions, feeding behavior, and energy balance inSlc2a3+/−mice

Homozygous deletion of the gene of the neuronal glucose transporter GLUT3 (Slc2a3) in mice results in embryonic lethality, whereas heterozygotes (Slc2a3+/-) are viable. Here, we describe the characterization of heterozygous mice with regard to neuronal function, glucose homeostasis, and, since GLUT3 might be a component of the neuronal glucose-sensing mechanism, food intake and energy balance. Levels of GLUT3 mRNA and protein in brain were reduced by 50% in Slc2a3+/- mice. Electrographic features examined by electroencephalographic recordings give evidence for slightly but significantly enhanced cerebrocortical activity in Slc2a3+/- mice. In addition, Slc2a3+/- mice were slightly more sensitive to an acoustic startle stimulus (elevated startle amplitude and reduced prepulse inhibition). However, systemic behavioral testing revealed no other functional abnormalities, e.g., in coordination, reflexes, motor abilities, anxiety, learning, and memory. Furthermore, no differences in body weight, blood glucose, and insulin levels were detected between wild-type and Slc2a3+/- littermates. Food intake as monitored randomly or after intracerebroventricular administration of 2-deoxyglucose or d-glucose, or food choice for carbohydrates/fat was not affected in Slc2a3+/- mice. Taken together, our data indicate that, in contrast to Slc2a1, a single allele of Slc2a3 is sufficient for maintenance of neuronal energy supply, motor abilities, learning and memory, and feeding behavior.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.

The auditory startle response in parkinsonism may reveal the extent but not type of pathology

We measured the acoustic startle response (ASR) and blink reflex (ABR) in patients with clinically diagnosed Parkinson's disease (PD) and progressive supranuclear palsy (PSP) and determined the specificity of an abnormal result for the diagnosis of PSP. Thirty patients (11 PD, 19 PSP) and 12 age matched controls were studied. The PSP group was separated into clinical subgroups. Fourteen patients with early falls, cognitive dysfunction and eye movement abnormalities were classified as Richardson's disease (RD), 3 with parkinsonism in the absence of early falls, cognitive dysfunction or eye movement abnormalities were classified PSP-parkinsonism (PSP-P) and 2 who presented with gait unsteadiness and freezing without cognitive dysfunction or eye movement abnormalities were classified as pure akinesia with gait freezing (PAGF). Following an acoustic startle stimulus EMG activity was recorded in the orbicularis oculi and sternomastoid muscles. The likelihood ratio of an absent response being clinically diagnosed PSP was determined. The ABR was present in 11/19 (58%) of patients with PSP, and 11/11 with PD and 12/12 controls (H2 p < 0.05). The ASR measured at the sternomastoid was present in only 2/19 (11%) of patients with PSP, but in 5/11 (45%) with PD and 6/12 (50 %) controls (H2 p < 0.05). The ABR was present in only 6/14 (43%) of the RD group, but in 3/3 PSP-P and 2/2 PAGF. Loss of the ABR was 100% specific for PSP, but only 42 % sensitive. Loss of the sternomastoid ASR had a likelihood ratio of 1.9 for the clinical diagnosis of PSP. The ASR and ABR appear unlikely to be useful in differentiating PSP from PD. Abnormalities in these responses are worse in RD where the pathology is known to be more widespread than in PSP-P and PAGF.