Greater general startle reflex is associated with greater anxiety levels: a correlational study on 111 young women

Startle eyeblink reflex is a valid non-invasive tool for studying attention, emotion and psychiatric disorders. In the absence of any experimental manipulation, the general (or baseline) startle reflex shows a high inter-individual variability, which is often considered task-irrelevant and therefore normalized across participants. Unlike the above view, we hypothesized that greater general startle magnitude is related to participants\u2019 higher anxiety level. 111 healthy young women, after completing the State-Trait Anxiety Inventory (STAI), were randomly administered 10 acoustic white noise probes (50 ms, 100 dBA acoustic level) while integrated EMG from left and right orbicularis oculi was recorded. Results showed that participants with greater state anxiety levels exhibited larger startle reflex magnitude from the left eye (r109 = 0.23, p < 0.05). Furthermore, individuals who perceived the acoustic probe as more aversive reported the largest anxiety scores (r109 = 0.28, p < 0.05) and had the largest eyeblinks, especially in the left eye (r109 = 0.34, p < 0.001). Results suggest that general startle may represent a valid tool for studying the neural excitability underlying anxiety and emotional dysfunction in neurological and mental disorders

The effects of 3-nitropropionic acid on the behavior and cortical electrical activity of rats in acute administration

In this study, the acute effects of 3-nitropropionic acid was investigated on open field and startle behavior of rats, and on their cortical electrical activity. Spontaneous locomotor activity, acoustic startle response, and pre-pulse inhibition of acoustic startle were measured in male Wistar rats (10 weeks old, 180-200g body weight) after a single dose of 10 or 20 mg/kg i.p. 3-nitropropionic acid. After the behavioral tests, the rats were anaesthetized, and spontaneous cortical electrical activity was recorded. The vertical, horizontal and local open field performance showed dose-dependent deterioration in the rats treated with 3-nitropropionic acid. The number of “noise-positive” startle responses showed non-significant changes, but the inhibition by pre-pulse was significantly reduced in the high dose animals. High dose also increased the proportion of low-frequencies in the cortical activity. Three-nitropropionic acid, known primarily to act in repeated doses (e.g., in animal models of Huntington’s disease) had also some clear-cut acute effects on behavioral and electrophysiological parameters of the treated rats

Psychophysiological correlates of peritraumatic dissociative responses in survivors of life-threatening cardiac events

The psychophysiological startle response pattern associated with peritraumatic dissociation (DISS) was studied in 103 survivors of a life-threatening cardiac event (mean age 61.0 years, SD 13.95). Mean time period since the cardiac event was 37 (79 IQD) months. All patients underwent a psychodiagnostic evaluation (including the Peritraumatic Dissociative Experiences Questionnaire) and a psychophysiological startle experience which comprised the delivery of 15 acoustic startle trials. Magnitude and habituation to trials were measured by means of electromyogram (EMG) and skin conductance responses (SCR). Thirty-two (31%) subjects were indexed as patients with a clinically significant level of DISS symptoms. High-level DISS was associated with a higher magnitude of SCR (ANOVA for repeated measures p = 0.017) and EMG (p = 0.055) and an impaired habituation (SCR slope p = 0.064; EMG slope p = 0.005) in comparison to subjects with no or low DISS. In a subgroup analysis, high-level DISS patients with severe post-traumatic stress disorder (PTSD; n = 11) in comparison to high-level DISS patients without subsequent PTSD (n = 19) exhibited higher EMG amplitudes during all trials (repeated measures analysis of variance IF = 5.511, p = 0.026). The results demonstrate exaggerated startle responses in SCR and EMG measures - an abnormal defensive response to high-intensity stimuli which indicates a steady state of increased arousal. DISS patients without PTSD exhibited balanced autonomic responses to the startle trials. DISS may, therefore, unfold malignant properties only in combination with persistent physiological hyperarousability. Copyright (C) 2002 S. Karger AG, Basel

The Effects of Startle and Non-Startle Auditory Stimuli on Wrist Flexion Movement in Parkinson's Disease

[Abstract] Startle stimuli lead to shorter reaction times in control subjects and Parkinson's disease (PD) patients. However, non-startle stimuli also enhance movement initiation in PD. We wanted to examine whether a startle-triggered movement would retain similar kinematic and EMG-related characteristics compared to one induced by a non-startle external cue in PD patients. In this study we investigated the electromyography pattern and the reaction time during a wrist flexion movement in response to three different stimuli: a visual imperative stimulus; visual stimulus simultaneous with a non-startle auditory stimulus and with a startle auditory stimulus. Ten PD patients and ten aged matched controls participated in this study. The reaction times were faster for startle and non-startle stimuli in comparison with the visual imperative stimulus, in both patients and control subjects. The startle cue induced a faster reaction than the non-startle cue. The electromyography pattern remained unchanged across the conditions. The results suggest that the startle reaction effect for upper limb movements are unimpaired in PD patients and has different characteristics than the effect of non-startle stimuli.Ministerio de Ciencia e Innovación; DEP2011-2246

Pdxdc1 modulates prepulse inhibition of acoustic startle in the mouse.

Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic prepulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains. We examined several brain regions involved in PPI and schizophrenia: hippocampus, striatum, and brainstem, found a number of transcripts that showed good correlation with PPI level, and confirmed this with real-time quantitative PCR. We then selected one candidate gene for further study, Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1), because it is a putative enzyme that could metabolize catecholamine neurotransmitters, and thus might be a feasible target for new medications. We determined that Pdxdc1 mRNA and protein are both strongly expressed in the hippocampus and levels of Pdxdc1 are inversely correlated with PPI across the six mouse strains. Using shRNA packaged in a lentiviral vector, we suppressed Pdxdc1 protein levels in the hippocampus and increased PPI by 70%. Our results suggest that Pdxdc1 may regulate PPI and could be a good target for further investigation as a potential treatment for schizophrenia

A phenotypic and molecular characterization of the fmr1-tm1Cgr Fragile X mouse

Fragile X Syndrome is the most common form of\ud inherited mental retardation. It is also known for having\ud a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always\ud caused by inactivation of the X-linked FMR1 gene. A\ud single knockout mouse model, fmr1-tm1Cgr, exists. In\ud this report we further characterize the cognitive and\ud behavioral phenotype of the fmr1-tm1Cgr Fragile X\ud mouse through the use of F1 hybrid mice derived from\ud two inbred strains (FVB/NJ and C57BL/6J). Use of F1\ud hybrids allows focus on the effects of the fmr1-tm1Cgr\ud allele with reduced influence from recessive alleles\ud present in the parental inbred strains. We find that the\ud cognitive phenotype of fmr1-tm1Cgr mice, including\ud measures of working memory and learning set formation\ud that are known to be seriously impacted in humans with\ud Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any\ud fmr1-tm1Cgr cognitive deficit is surprisingly mild or\ud absent. There is, however, clear support presented for a\ud robust audiogenic seizure phenotype in all strains tested,\ud as well as increased entries into the center of an open\ud field. Finally, a molecular examination of the fmr1-tm1Cgr\ud mouse shows that, contrary to common belief, it is not a\ud molecular null. Implications of this finding for interpretation of the phenotype are discussed.\u

The effects of memantine on prepulse inhibition.

Reduced prepulse inhibition (PPI) of startle provides evidence of deficient sensorimotor gating in several disorders, including schizophrenia. The role of NMDA neurotransmission in the regulation of PPI is unclear, due to cross-species differences in the effects of NMDA antagonists on PPI. Recent reports suggest that drug effects on PPI differ in subgroups of normal humans that differ in the levels of baseline PPI or specific personality domains; here, we tested the effects of these variables on the sensitivity of PPI to the NMDA antagonist, memantine. PPI was measured in male Sprague-Dawley rats, after treatment with memantine (0, 10 or 20 mg/kg, s.c.). Baseline PPI was then measured in 37 healthy adult men. Next, subjects were tested twice, in a double-blind crossover design, comparing either (1) placebo vs 20 mg of the NMDA antagonist memantine (n=19) or (2) placebo vs 30 mg memantine (n=18). Tests included measures of acoustic startle amplitude, PPI, autonomic indices and subjective self-rating scales. Memantine had dose- and interval-dependent effects on PPI in rats. Compared with vehicle, 10 mg/kg increased short-interval (10-20 ms) PPI, and 20 mg/kg decreased long-interval (120 ms) PPI. In humans, memantine caused dose-dependent effects on psychological and somatic measures: 20 mg was associated with increased ratings of happiness, and 30 mg was associated with increased ratings of dizziness. PPI at the 120 ms prepulse interval was increased by 20 mg, but not 30 mg of memantine. Subgroups most sensitive to the PPI-enhancing effects of memantine were those with low baseline PPI, or with personality scale scores suggestive of high novelty seeking, high sensation seeking, or high disinhibition. NMDA blockade with memantine appears to have dose- and interval-dependent effects on sensorimotor gating in rats and humans, particularly among specific subgroups of normal human subjects. These findings are discussed as they relate to consistencies across other studies in humans, as well as apparent inconsistencies in the NMDA regulation of PPI across species

Aging is associated with positive responding to neutral information but reduced recovery from negative information

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 years). We recorded eye-blink startle magnitudes and corrugator activity during and after the presentation of positive, neutral and negative pictures. The most robust age effect was found in response to neutral stimuli, where increasing age is associated with a decreased corrugator and eyeblink startle response to neutral stimuli. These data suggest that an age-related positivity effect does not essentially alter the response to emotion-laden information, but is reflected in a more positive interpretation of affectively ambiguous information. Furthermore, older women showed reduced corrugator recovery from negative pictures relative to the younger women and men, suggesting that an age-related prioritization of well-being is not necessarily reflected in adaptive regulation of negative affect

Modeling startle eyeblink electromyogram to assess fear learning

Pavlovian fear conditioning is widely used as a laboratory model of associative learning in human and nonhuman species. In this model, an organism is trained to predict an aversive unconditioned stimulus from initially neutral events (conditioned stimuli, CS). In humans, fear memory is typically measured via conditioned autonomic responses or fear-potentiated startle. For the latter, various analysis approaches have been developed, but a systematic comparison of competing methodologies is lacking. Here, we investigate the suitability of a model-based approach to startle eyeblink analysis for assessment of fear memory, and compare this to extant analysis strategies. First, we build a psychophysiological model (PsPM) on a generic startle response. Then, we optimize and validate this PsPM on three independent fear-conditioning data sets. We demonstrate that our model can robustly distinguish aversive (CS+) from nonaversive stimuli (CS-, i.e., has high predictive validity). Importantly, our model-based approach captures fear-potentiated startle during fear retention as well as fear acquisition. Our results establish a PsPM-based approach to assessment of fear-potentiated startle, and qualify previous peak-scoring methods. Our proposed model represents a generic startle response and can potentially be used beyond fear conditioning, for example, to quantify affective startle modulation or prepulse inhibition of the acoustic startle response

Effectiveness of Indonesian Essential Oil Mixture of Lemongrass, Cananga, and Patchouli in Relaxation Through Inhalation: a Clinical Test on Healthy Woman with High Potential for Stress

Relaxation is one of many mechanisms for coping with stress. One of the most widely used methods for relaxation is aromatherapy with the application of essential oils. Known for their therapeutic benefits, essential oils can be extracted from various Indonesian native herbs such as lemongrass (sereh wangi or Cymbopogon winterianus), cananga or ylang-ylang (kenanga or Canarium odoratum), and patchouli (nilam or Pogostemon cabin). This study aims to examine the effectiveness of a mixture of Indonesian essential oil made of lemongrass, cananga, and patchouli extracts. Experiment was conducted by asking a number of subjects to inhale the oil mixture and assessing its effectiveness in terms of psychological relaxation by using Visual Analog Scale or VAS) and of physical relaxation by examining the subjects&rsquo; blood pressure (MAP), pulse frequency, and breathing frequency. The result was then compared with that of lavender oil and with the control group. The study was conducted on 60 healthy women through single-blind clinical trials (before and after) using the &ldquo;intent to treat&rdquo; approach, followed by a startle test. Participants were divided into three groups: (1) 20 participants who were treated with Indonesian essential oil mixture, (2) 20 participants who were treated with lavender oil, and (3) 20 participants who served as the control group. Psychological relaxation measurement showed that Indonesian essential oil mixture produced the same degree of effectiveness as lavender oil and the control groups did, although both treatments tended to produce better results than the control group did. However, physical relaxation measurement showed that Indonesian essential oil mixture produced a higher degree of effectiveness than lavender oil and tended to produce a better result than the control group did, especially in terms of blood pressure based on MAP scores.&nbsp; &nbsp; &nbsp