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PLoS Biology Jun 2024Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized...
Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram. However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated. Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC supporting cells. As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds. We now show that IHC synapse density does not influence the magnitude of the acoustic startle reflex or its prepulse inhibition. In contrast, gap-prepulse inhibition, a behavioral test for auditory temporal processing, is reduced or enhanced according to Ntf3 expression levels. These results indicate that IHC synaptopathy causes temporal processing deficits predicted in HHL. Furthermore, the improvement in temporal acuity achieved by increasing Ntf3 expression and synapse density suggests a therapeutic strategy for improving hearing in noise for individuals with synaptopathy of various etiologies.
Topics: Animals; Hair Cells, Auditory, Inner; Synapses; Neurotrophin 3; Mice; Auditory Threshold; Evoked Potentials, Auditory; Reflex, Startle; Auditory Perception; Spiral Ganglion; Female; Male; Hearing Loss, Hidden
PubMed: 38935589
DOI: 10.1371/journal.pbio.3002665 -
Frontiers in Psychology 2024Bilateral stimulation is a core element of Eye Movement Desensitization and Reprocessing Therapy, a psychotherapeutic intervention for the treatment of Posttraumatic...
Apples and oranges: PTSD patients and healthy individuals are not comparable in their subjective and physiological responding to emotion induction and bilateral stimulation.
OBJECTIVES
Bilateral stimulation is a core element of Eye Movement Desensitization and Reprocessing Therapy, a psychotherapeutic intervention for the treatment of Posttraumatic Stress Disorder (PTSD). Promising previous findings showed measurable physiological effects of bilateral stimulation in healthy individuals, but studies that replicated these findings in PTSD patients are sparse.
METHODS
23 patients with PTSD and 30 healthy controls were confronted with affective standard scripts (pleasant, neutral, unpleasant) while bilateral tactile stimulation was applied. Monolateral and no stimulation served as control conditions. Noise-induced startle reflex response (valence measure) and galvanic skin response (arousal measure) were used for physiological responses and the valence and arousal scale of the Self-Assessment-Manikin for subjective responses.
RESULTS
Both groups showed a subjective distress reduction for unpleasant scripts and a subjective attention increase for positive scripts under bilateral stimulation. In healthy individuals, this was also for physiological measures, and a general startle-reducing effect of bilateral stimulation in the absence of affective stimuli was found. In PTSD patients, however, the effects were restricted on the subjective level, and no concomitant physiological effects were observed.
CONCLUSIONS AND SIGNIFICANCE
The findings indicate, that generalizing the effects of BLS in healthy individuals to PTSD patients may be problematic. The herein-reported group differences can be explained by PTSD-specific peculiarities in emotion processing and cognitive processing style.
PubMed: 38933577
DOI: 10.3389/fpsyg.2024.1406180 -
The Journal of Head Trauma... Jun 2024We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but...
OBJECTIVES
We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but no current symptoms. We hypothesized that individuals with recent concussion would have a suppressed startle response compared to healthy controls.
METHODS
We conducted a cross-sectional study on 49 adolescent athletes with a recent concussion (n = 20; age: 14.6 ± 1.6 years; 60% female), a concussion history > 1 year prior (n = 16; age: 14.8 ± 2.0 years; 44% female), and healthy controls (n = 13; age: 13.3 ± 2.8 years; 54% female). We measured the eyeblink of the general startle reflex via electromyography activity of the orbicularis oculi muscle using electrodes placed under the right eye. Measurement sessions included twelve 103 decibel acoustic startle probes ~50 milliseconds in duration delivered ~15-25 seconds apart. The primary dependent variable was mean startle magnitude (µV), and group was the primary independent variable. We used a one-way analysis of variance followed by a Tukey post hoc test to compare mean startle magnitude between groups.
RESULTS
Mean startle magnitude significantly differed (F = 5.49, P = .007) among the groups. Mean startle magnitude was significantly suppressed for the concussion (P = .01) and concussion history groups (P = .02) compared to healthy controls. There was no significant difference between the recent concussion and concussion history groups (P = 1.00).
CONCLUSION
Our results provide novel evidence for startle suppression in adolescent athletes following concussion. The concussion history group had an attenuated startle response beyond resolution of their recovery, suggesting there may be lingering physiological dysfunction.
PubMed: 38916433
DOI: 10.1097/HTR.0000000000000979 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024The article describes the main diagnostic criteria and principles of posttraumatic stress disorder (PTSD) diagnostic with the consideration of risk factors and specific... (Review)
Review
The article describes the main diagnostic criteria and principles of posttraumatic stress disorder (PTSD) diagnostic with the consideration of risk factors and specific clinical features. The main biomarkers search trends and existing limitations are considered. The role of the psychophysiological arousal symptoms claster is highlighted in the clinical picture of PTSD as well as in connection with the main cluster of re-experiencing symptoms activation and slowing of sanogenesis process. The necessity of PTSD detection in somatic medicine is thoroughly described. The article presents therapeutic algorithms of the latest international and Russian PTSD treatment clinical guidelines based on the individual combination of psychotherapy and psychopharmacotherapy treatment choice. Additionally the accumulated during the last decades national clinical experience of the anxiety disorders treatment, including the symptoms of psychophysiological arousal is highlighted that determined the list of the recommended drugs indicating the evidence level, in the PTSD treatment standards and guidelines. The treatment choices possibilities with the consideration of different PTSD symptoms cluster expression and comorbid states and individual case distress level specific are presented. Main evidence based psychotherapeutic methods are described.
Topics: Stress Disorders, Post-Traumatic; Humans; Practice Guidelines as Topic; Psychotherapy; Arousal; Russia
PubMed: 38884431
DOI: 10.17116/jnevro202412405158 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Jun 2024To unveil the pathological changes associated with demyelination in schizophrenia (SZ) and its consequential impact on interstitial fluid (ISF) drainage, and to...
OBJECTIVE
To unveil the pathological changes associated with demyelination in schizophrenia (SZ) and its consequential impact on interstitial fluid (ISF) drainage, and to investigate the therapeutic efficacy of ursolic acid (UA) in treating demyelination and the ensuing abnormalities in ISF drainage in SZ.
METHODS
Female C57BL/6J mice, aged 6-8 weeks and weighing (20±2) g, were randomly divided into three groups: control, SZ model, and UA treatment. The control group received intraperitoneal injection (ip) of physiological saline and intragastric administration (ig) of 1% carboxymethylcellulose sodium (CMC-Na). The SZ model group was subjected to ip injection of 2 mg/kg dizocilpine maleate (MK-801) and ig administration of 1% CMC-Na. The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801. The treatment group received UA pretreatment via ig administration for one week, followed by a two-week drug intervention for all the three groups. Behavioral assessments, including the open field test and prepulse inhibition experiment, were conducted post-modeling. Subsequently, changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions. Immunofluorescence analysis was employed to examine alterations in aquaporin 4 (AQP4) polarity distribution in the brain and changes in protein expression. Myelin reflex imaging using Laser Scanning Confocal Microscopy (LSCM) was utilized to study modifications in myelin within the mouse brain. Quantitative data underwent one-way ANOVA, followed by TukeyHSD for post hoc pairwise comparisons between the groups.
RESULTS
The open field test revealed a significantly longer total distance [(7 949.39±1 140.55) cm . (2 831.01±1 212.72) cm, < 0.001] and increased central area duration [(88.43±22.06) s . (56.85±18.58) s, =0.011] for the SZ model group compared with the controls. The UA treatment group exhibited signifi-cantly reduced total distance [(2 415.80±646.95) cm . (7 949.39±1 140.55) cm, < 0.001] and increased central area duration [(54.78±11.66) s . (88.43±22.06) s, =0.007] compared with the model group. Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the startle reflex in the model group relative to the controls ( < 0.001 for both), with the treatment group displaying significant improvement ( < 0.001 for both). Myelin sheath analysis indicated significant demyelination in the model group, while UA treatment reversed this effect. Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thalamus in the model group relative to the controls [(13.93±3.35) mm . (2.79±0.94) mm, < 0.001 for diffusion area; (2.48±0.38) mm . (0.05±0.12) mm, < 0.001 for reflux area], with significant impairment of drainage in brain regions. The treatment group demonstrated significantly reduced tracer diffusion and reflux areas [(7.93±2.48) mm . (13.93±3.35) mm, < 0.001 for diffusion area; (0.50±0.30) mm . (2.48±0.38) mm, < 0.001 for reflux area]. Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls [(3 663.88±733.77) μm . (13 354.92±4 054.05) μm, < 0.001]. The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression [(11 104.68±3 200.04) μm . (3 663.88±733.77) μm, < 0.001].
CONCLUSION
UA intervention ameliorates behavioral performance in SZ mice, Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function. The underlying mechanism may involve the improvement of demyelination and ISF drainage dysregulation in SZ mice.
Topics: Animals; Mice; Triterpenes; Schizophrenia; Mice, Inbred C57BL; Female; Disease Models, Animal; Demyelinating Diseases; Extracellular Fluid; Ursolic Acid; Dizocilpine Maleate; Aquaporin 4
PubMed: 38864135
DOI: 10.19723/j.issn.1671-167X.2024.03.016 -
International Journal of Developmental... Jun 2024Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly...
Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly required. Melatonin administration following brain insults has been considered a promising therapeutic strategy due to its antioxidant and anti-inflammatory effects. Not surprisingly, it has been extensively studied for preventing disturbances following brain injury. This study evaluated the effects of melatonin on developmental disturbances, memory disruption, and hippocampal cell loss induced by neonatal anoxia in rats. Neonatal Wistar rats were subjected to anoxia and subsequently treated with melatonin. Later, maturation of physical characteristics, ontogeny of reflexes, learning and memory in the Morris water maze (MWM), and estimates of the number of hippocampal neurons, were evaluated. Melatonin treatment attenuated (1) female anoxia-induced delay in superior incisor eruption, (2) female anoxia-induced vibrissae placement reflexes, and (3) male and female anoxia-induced hippocampal neuronal loss. Melatonin also promoted an increase (5) in swimming speeds in the MWM. In addition, PCA analysis showed positive associations between the acoustic startle, auditory canal open, and free fall righting parameters and negative associations between the male vehicle anoxia group and the male melatonin anoxia group. Therefore, melatonin treatment attenuates both anoxia-induced developmental deficits and hippocampal neuronal loss.
PubMed: 38858858
DOI: 10.1002/jdn.10351 -
Frontiers in Neuroscience 2024Prepulse inhibition (PPI) is a well-established phenomenon wherein a weak sensory stimulus attenuates the startle reflex triggered by a subsequent strong stimulus....
Prepulse inhibition (PPI) is a well-established phenomenon wherein a weak sensory stimulus attenuates the startle reflex triggered by a subsequent strong stimulus. Within the circuit, variations in target responses observed for PPI paradigms represent prepulse-induced excitability changes. However, little is known about the mechanism of PPI. Here, we focused on short-latency PPI of the trigeminal blink reflex R1 signal with an oligosynaptic reflex arc through the principal sensory trigeminal nucleus and the facial nucleus. As the facial nucleus is facilitatory to any input, R1 PPI is the phenomenon in the former nucleus. Considering that GABAergic modulation may be involved in PPI, this study investigated whether the PPI mechanism includes GABA-A equivalent inhibition, which peaks at approximately 30 ms in humans. In 12 healthy volunteers, the reflex was elicited by electrical stimulation of the supraorbital nerve, and recorded at the ipsilateral lower eyelid by accelerometer. Stimulus intensity was 1.5 times the R1 threshold for test stimulus and 0.9 times for the prepulse. The prepulse-test interval (PTI) was 5-150 ms. Results showed significant inhibition at 40-and 80-150-ms PTIs but not at 20-, 30-, 50-, 60-, and 70-ms PTIs, yielding two distinct inhibitions of different time scales. This corresponds well to the early and late components of inhibitory post synaptic potentials by GABA-A and GABA-B receptor activation. Thus, the data support the contribution of inhibitory post synaptic potentials elicited by the prepulse to the observed PPI. As inhibitory function-related diseases may impair the different inhibition components to varying degrees, methods deconvoluting each inhibitory component contribution are of clinical importance.
PubMed: 38841093
DOI: 10.3389/fnins.2024.1357368 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Jun 2024To explore the clinical and genetic characteristics of three children with Hyperekplexia.
OBJECTIVE
To explore the clinical and genetic characteristics of three children with Hyperekplexia.
METHODS
Three children who were diagnosed with Hyperekplexia at the Third Affiliated Hospital of Zhengzhou University between June 2018 and March 2020 were selected as the study subjects. Clinical data of the three children were collected. All children were subjected to whole exome sequencing. Pathogenicity of candidate variants were verified by Sanger sequencing and bioinformatic analysis.
RESULTS
The three children were all males, and had presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimulation, or had frequent traumatic falls following exaggerated startle. All children had shown positive nose-tapping reflex, though EEG and cranial MRI exams were all negative. Whole exome sequencing revealed that two children had harbored homozygous variants of the GLRB gene, of which the c.1017_c.1018insAG (p.G340Rfs*14) was unreported previously. The third child had harbored compound heterozygous variants of the GLRA1 gene, among which the c.1262T>A (p.IIe421Asn) variant showed an unreported autosomal recessive inheritance. All children had responded well to clonazepam treatment.
CONCLUSION
Patients with Hyperekplexia have typical clinical manifestations. Early clinical identification and genetic analysis can facilitate their diagnosis.
Topics: Humans; Male; Receptors, Glycine; Child; Hyperekplexia; Exome Sequencing; Mutation; Child, Preschool; Receptors, GABA-A; Genetic Testing; Homozygote
PubMed: 38818557
DOI: 10.3760/cma.j.cn511374-20211125-00938 -
Social Cognitive and Affective... Jun 2024Elevated arousal in anxiety is thought to affect attention control. To test this, we designed a visual short-term memory (VSTM) task to examine distractor suppression...
Elevated arousal in anxiety is thought to affect attention control. To test this, we designed a visual short-term memory (VSTM) task to examine distractor suppression during periods of threat and no-threat. We hypothesized that threat would impair performance when subjects had to filter out large numbers of distractors. The VSTM task required subjects to attend to one array of squares while ignoring a separate array. The number of target and distractor squares varied systematically, with high (four squares) and low (two squares) target and distractor conditions. This study comprised two separate experiments. Experiment 1 used startle responses and white noise as to directly measure threat-induced anxiety. Experiment 2 used BOLD to measure brain responses. For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. For Experiment 2, we found that accuracy was affected by threat, such that the distractor load negatively impacted accuracy only in the threat condition. We also found threat-related differences in parietal cortex activity. Overall, these findings suggest that threat affects distractor susceptibility, impairing filtering of distracting information. This effect is possibly mediated by hyperarousal of parietal cortex during threat.
Topics: Humans; Male; Female; Young Adult; Magnetic Resonance Imaging; Memory, Short-Term; Attention; Reflex, Startle; Adult; Visual Perception; Brain; Photic Stimulation; Fear; Adolescent; Brain Mapping; Oxygen; Anxiety; Reaction Time
PubMed: 38809714
DOI: 10.1093/scan/nsae036 -
The Journal of the Acoustical Society... May 2024Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise....
Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.
Topics: Animals; Female; Male; Mice; Acoustic Stimulation; Auditory Pathways; Auditory Perception; Auditory Threshold; Behavior, Animal; Cochlea; Evoked Potentials, Auditory, Brain Stem; Hearing; Mice, Inbred C57BL; Mice, Knockout; Noise; Olivary Nucleus; Perceptual Masking; Phenotype; Receptors, Nicotinic; Reflex, Startle
PubMed: 38738939
DOI: 10.1121/10.0025985