Affective reactivity of language and the startle response in schizophrenia.
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Acoustic Stimulation↗
Biomedical subjects
C Grillon
Publications and source records attributed to C Grillon.
Effects of ethanol on the processing of low probability stimuli: an ERP study.
The effect of a moderate dose of ethanol on the processing of low probability task-relevant and task-irrelevant stimuli was investigated using event-related potentials (ERPs). Sixteen subjects received alcoholic and placebo beverages on alternate days. ERPs were recorded from 15 locations on the scalp. The subjects were asked to press a button upon detection of rare target stimuli embedded among frequent standard and rare "novel" stimuli. Ethanol 1) reduced the amplitude of P3 to novel stimuli, but not P3 to target stimuli, 2) did not affect the mismatch negativity, and 3) delayed P3 latency and reaction time independently. These results suggest that 1) the processing of rare task-irrelevant stimuli is more vulnerable to the effects of ethanol than is the processing of task-relevant stimuli, and 2) ethanol impacts stimulus evaluation time and response production stages of information processing.
Acoustic Stimulation↗
Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder.
Preclinical and clinical studies have suggested that the acoustic startle reflex (ASR) is a useful model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist, yohimbine, increases the amplitude of the ASR in laboratory animals and in healthy human controls. Because of the growing body of data that support the hypothesis that severe stress results in substantial alterations in noradrenergic neuronal reactivity, the present investigation evaluated the effects of yohimbine on the ASR of 18 patients with PTSD and 11 healthy combat controls. Subjects received IV yohimbine (0.4 mg/kg) or saline placebo on 2 separate days in a randomized double blind placebo control design. A trial of two tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise and instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25-60 s, for a 40-ms duration. Startle testing was performed 80 min post-infusion and lasted 15-20 min. Yohimbine significantly increased the amplitude, magnitude and probability of the ASR in combat veterans with PTSD, but did not do so in combat controls. Overall startle was significantly larger in the PTSD subjects; however, this did not account for the differential effect of yohimbine, since yohimbine had no significant effect in the control group. This study demonstrates an excitatory effect of yohimbine on the amplitude, magnitude and probability of the ASR in PTSD patients that is not seen in combat controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
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↗
Startle gating deficits occur across prepulse intensities in schizophrenic patients.
The effects of prepulse stimuli of different intensities in inhibiting the startle reflex was assessed in 14 age-matched and gender-matched schizophrenic patients and 14 normal controls. The subjects were presented with startling stimuli consisting of bursts of white noise (106 dBA) with or without prepulse stimuli. Four intensities of prepulse stimuli were utilized: 75, 80, 85, and 90 dBA. Throughout the testing, the background noise was maintained at 70 dBA. The prepulse stimuli more effectively inhibited the startle reflex in the control group compared to the schizophrenic patients who showed deficient prepulse inhibition (gating) of the startle reflex. These results suggest that schizophrenics have impaired central inhibitory mechanisms over a fairly broad range of background noise to prepulse ratios. Further studies are needed to clarify exactly which ratios are optimal in eliciting prepulse inhibition (PPI) and in differentiating between schizophrenic and control groups.
Adult↗
Gating and habituation of the startle reflex in schizophrenic patients.
Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. Through human and animal model research, these fundamental cognitive deficits have well-described neurobiologic bases and offer insights into the neuroanatomic and neurotransmitter abnormalities that characterize patients with schizophrenic spectrum disorders. In this context, the startle response is particularly interesting, because it is a cross-species response to strong stimuli that is plastic or alterable using experimental and neurobiologic manipulations. Thirty-nine medicated schizophrenic patients and 37 normal control subjects were studied in a new electromyography based startle response paradigm in which both prepulse inhibition (an operational measure of sensorimotor gating) and habituation (the normal decrease in response magnitude to repeated stimuli over time) can be separated and assessed in one test session. The results indicate that schizophrenic patients have extensive deficits in both intramodal and cross-modal sensorimotor gating and a trend to show acoustic startle habituation deficits. The deficit in prepulse inhibition of startle amplitude exhibited by schizophrenic patients was evident when an acoustic prepulse stimulus preceded either an acoustic or a tactile startle stimulus. No deficit was observed in the prepulse-induced facilitation of startle latencies, indicating that the failure of gating was not due to a failure of stimulus detection. These findings suggest centrally mediated deficits in sensorimotor gating in schizophrenic patients.
Acoustic Stimulation↗
Changes in the expression of lectins in human T lymphocyte membrane upon mitogenic stimulation.
Surface lectins, specific for given sugar structures, are expressed on human T cells, as shown by flow cytofluorometry using F-neoglycoproteins bearing either beta- and alpha-D-galactosyl, beta-D-galactosyl 6-phosphate, or alpha-L-rhamnosyl groups, but not by F-neoglycoproteins bearing other sugar groups (such as alpha-D-mannosyl groups). After stimulation with Phaseolus vulgaris mitogen, the number of cells that bind beta-D-galactosyl 6-phosphate groups (6-P-beta-D-Galp lec+ cells) increased fourfold during the first five days; these cells are helper (CD4+) T cells. Conversely, cells that bind alpha-L-Rha groups belong to the T suppressor (CD8+) family and their number moderately increased. Upon stimulation by concanavalin A, the number of cells expressing the lectin recognizing alpha-L-Rha groups increased during the first two days and then decreased within the next two days. These results are discussed with regard to the implication of lymphocyte membrane lectins in the suppressor mechanism and in the homing process.
Animals↗
N400 and semantic categorization in schizophrenia.
The N400 component of event-related potentials (ERPs) was investigated in medicated schizophrenic patients and normal controls in a semantic categorization task. The subjects' task was to indicate whether pairs of words were semantically related or unrelated. The ERPs to the unrelated second words of the pairs contained a negative component, N400, which was reduced and delayed in the patients. However, inspection of individual subjects' data indicated that N400 was abnormal only in a subgroup of schizophrenics. Abnormalities in the amplitude of N400 suggest impairments in semantic expectancies, whereas abnormalities in the latency of N400 suggest a delay in information processing.
Adult↗
Soluble human lymphocyte sugar binding proteins with immunosuppressive activity.
Suppression of the immune response, which involves suppressor factors released from specialized T cells, is inhibited by alpha-L-rhamnose. In this paper, we show the presence of rhamnose-specific receptors on a human CD8+ T cell-rich population and describe a novel method to isolate cells which express a given sugar-binding protein on their surface. We describe the isolation of alpha-L-rhamnose-specific molecules (rhamnose-binding fractions: RBF) from a water-soluble extract from lymphocytes, their purification by affinity chromatography on immobilized neoglycoproteins containing rhamnose residues. RBF kept their ability to bind rhamnose, as shown by the binding of fluorescein-labeled RBF to rhamnosylated BSA-substituted beads. RBF efficiently suppresses DNA synthesis of mitogen-stimulated human lymphocytes as well as B cell immunoglobulin production. Therefore, these rhamnose-binding molecules appear to be antigen-independent suppressor factors.
Carrier Proteins↗
Human keratinocyte membrane lectins: characterization and modulation of their expression by cytokines.
In an attempt to identify cell surface molecules involved in recognition phenomena between cells such as keratinocytes and melanocytes and putatively target biological responses modifiers to keratinocytes, we undertook the detection of cell surface sugar specific receptors: membrane lectins. Keratinocyte membrane lectins were found to bind synthetic glycoproteins (neoglycoproteins) carrying either alpha-L-fucosyl or alpha-L-rhamnosyl residues. Fluorescence microscopy observations indicate that cultured keratinocytes are able to bind these two neoglycoproteins while frozen sections of human skin labelled with neoglycoprotein-coated covaspheres show that the selectivity of the binding to keratinocytes is restricted to alpha-L-rhamnosyl-BSA. Keratinocytes were adapted to grow on collagen; harvesting conditions allowing the analysis of keratinocytes by flow cytometry are described. This technique allows the quantification of the binding at 4 degrees C, and the estimation of the endocytosis of F-, neoglycoproteins: F-, alpha-L-Rha-BSA and F-, alpha-L-Fuc-BSA were efficiently internalized. Thereafter, alpha-L-rhamnose-substituted liposomes containing 5-(6)carboxyfluorescein were prepared in order to follow the delivery of the fluorescent dye into cells. This was measured both by flow cytometry and by spectrofluorimetry. The expression of surface lectins was checked upon action of cytokines (IL1 alpha, IL1 beta, IL2 and TNF) which are known as biological response modifiers of keratinocytes.
Binding Sites↗
Fear-potentiated startle in humans: effects of anticipatory anxiety on the acoustic blink reflex.
The effects of fear/anticipatory anxiety on the acoustic startle reflex were investigated in humans using a paradigm involving anticipation of electric shocks. The eyeblink component of the startle reflex, elicited by an abrupt auditory stimulus, was measured in 9 normal volunteers during either the anticipation of electric shocks (anticipatory anxiety) or periods in which no shocks were anticipated (safe period). The eyeblink was consistently higher in amplitude, and shorter in latency, during periods when the subjects anticipated shocks, compared to the safe periods. This effect could not be attributed solely to a reduction in habituation and was statistically significant before the subjects actually received any shock (a single 30 mA stimulation on the median nerve). These results indicate that anticipatory anxiety can be measured objectively in humans using the fear-potentiated startle reflex in a paradigm not actually requiring any shock. Because a great deal is known about the neuroanatomical and pharmacological mechanisms of fear-potentiated startle in laboratory animals, this test procedure may be especially useful in humans to investigate the neurobiological substrates of anxiety disorders and their pharmacological treatments.
Acoustic Stimulation↗
Formation of acetyl-Ser-Asp-Lys-Pro, a new regulator of the hematopoietic system, through enzymatic processing of thymosin beta 4.
The demonstration that AcSDKP, a new regulator of the hematopoietic system, is formed in the bone marrow by a one-step enzymatic maturation processing of thymosin beta 4 (T beta 4) is presented. AcSDKP and T beta 4 were both detected in bone marrow cells (BMC). Incubation of [3H]T beta 4 with either intact or lysed BMC led to the formation of [3H]AcSDKP, whereas the labeled tetrapeptide was not degraded under these conditions. Model enzymatic degradation of T beta 4 carried out with bacterial enzymes suggests that a mammalian endoproteinase Asp-N might be involved in the formation of AcSDKP through the specific cleavage of the Pro4-Asp5 peptidic bond of T beta 4. In contrast, alpha-prolyl-endopeptidase was ineffective in carrying out a similar processing.
Amino Acid Sequence↗
Involvement of thymosin beta 4 and endoproteinase Asp-N in the biosynthesis of the tetrapeptide AcSerAspLysPro a regulator of the hematopoietic system.
It is shown that AcSDKP a new regulator of the hematopoietic system can be generated from thymosin beta 4 by a one-step enzymatic cleavage in vitro and in vivo. AcSDKP and T beta 4 were both detected in bone marrow cells (BMC). Incubation of [3H]T beta 4 with either intact or lysed BMC led to the formation of [3H]AcSDKP whereas the labelled tetrapeptide was not degraded under these conditions. Model enzymatic degradation of T beta 4 carried out with bacterial enzymes suggests that a mammalian endoproteinase Asp-N might be involved in the formation of AcSDKP through the specific cleavage of the 4Pro-5 Asp peptide bond of T beta 4.
Amino Acid Sequence↗
Brainstem auditory-evoked potentials to different rates and intensities of stimulation in schizophrenics.
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Acoustic Stimulation↗
Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence.
The inability of schizophrenics to filter irrelevant information has often been implicated in the psychopathology of schizophrenia. Despite numerous attempts at characterizing the behavior of schizophrenics in the presence of distractors, evidence of increased distractibility has been equivocal due to the difficulty of assessing simultaneously the behavioral and neurophysiological effects of distracting stimuli. We report the results of an experiment in which event-related potential and performance measures were used to assess distractibility during reaction time tasks under different distracting conditions. The results supported the view of an increased distractibility in schizophrenic patients. Event-related potential data suggested that in schizophrenic patients, a reduced amount of processing resources is allocated to process external stimuli and attention is abnormally apportioned to task-irrelevant vs task-relevant stimuli.
Adolescent↗
Effects of rare non-target stimuli on brain electrophysiological activity and performance.
In order to assess the effects of non-target stimuli on task performance and electrophysiological activity, 16 subjects performed reaction time (RT) experiments under 3 conditions. In all conditions, subjects had to press a button upon detection of rare (15%) target stimuli (1600 Hz) presented among frequent (85%) non-target stimuli. The 3 conditions differed based on their non-target stimuli. In one condition, the non-targets consisted of 'standard' stimuli (900 Hz). In the two other conditions, rare and deviant non-target stimuli were randomly added to the standard stimuli. These deviant non-target stimuli consisted of either constant (700-Hz tones) or novel (buzzes, filtered noises and other unusual sounds) stimuli. Both the rare target and non-target stimuli elicited P300, responses. Behavioral (RT) and electrophysiological (event-related potential) data showed that stimuli that followed standard stimuli were processed differently compared to stimuli that followed deviant non-target stimuli. In the conditions containing deviant non-target stimuli, the P3b to the target stimuli was smaller and later, and the mean RT longer than in the condition with no deviant stimuli. These behavioral and electrophysiological changes induced by the deviant non-target stimuli were discussed with reference to two factors, distraction and increased level of task difficulty. It was suggested that each of these factors were differentially sensitive to the novelty of the rare deviant stimuli.
Acoustic Stimulation↗
Cell surface lectins of human granulocytes: their expression is modulated by mononuclear cells and granulocyte/macrophage colony-stimulating factor.
This paper presents the characterization of a sugar-specific receptor on the surface of human circulating polymorphonuclear cells. With the help of fluorescent neoglycoproteins and flow cytometry, a receptor was identified as being specific for alpha-L-rhamnosyl residues. The number of receptors was 55,000/cell and their affinity reached 2 x 10(8) l mol-1. This number changed as a function of the biological state of the cells. Indeed, receptor expression was modulated by the presence of other cells. T cells and B cells increased the number of receptors on the granulocyte surface. Expression of the alpha-L-rhamnose-specific lectin was dependent on lymphocyte derived soluble factor(s), which induce(s) growth and differentiation of polymorphonuclear phagocytes. Granulocyte/macrophage colony-stimulating factor (GM-CSF) specifically produced a significant increase in the number of receptors for alpha-L-rhamnose (2-10-fold/cell). This modulation was independent of protein kinase C activators such as phorbol ester, which produced no effect on alpha-L-rhamnose receptor expression. These findings demonstrate that GM-CSF may stimulate post differentiation functions and properties of mature granulocytes.
Antibodies, Monoclonal↗
Brainstem and middle latency auditory evoked potentials in autism and developmental language disorder.
Brainstem auditory evoked potentials (BAEP) and middle latency responses (MLR) were studied in 8 nonretarded subjects with infantile autism (mean age = 23.3, SD = 2.8), 8 subjects with receptive developmental language disorder (mean age = 16.3, SD = 1.4), and normal control subjects matched to each group for age, gender, and Performance IQ. Click stimuli were delivered monaurally to the left and the right ear and binaurally for both the BAEPs (70-dB HL, 7/sec) and the MLRs (60-dB HL, 13/sec). Amplitudes and latencies (Waves I to VI), interwave latencies (III-V, I-V, and I-III), and Wave I/V amplitude ratio of the BAEPs were determined for each group. For the MLR study, Wave Na, Pa, and Nb latencies, and Wave Na-Pa and Pa-Nb amplitudes were calculated. There were no consistent differences in the BAEP and MLR characteristics of the control and the experimental groups. These results suggest that the abnormal cognitive processes indexed by the cognitive and attention-related event-related potential components in infantile autism and receptive developmental language disorder are not due to abnormal sensory processing in the brainstem and in areas central to the brainstem whose activity generates the BAEPs and MLRs.
Adolescent↗