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Medicina (Kaunas, Lithuania) Sep 2023: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations....
: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. : After the exposure, the animals' hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. : We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. : In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus.
Topics: Animals; Tinnitus; Reflex, Startle; Deafness; Anxiety; Anxiety Disorders
PubMed: 37763802
DOI: 10.3390/medicina59091683 -
European Journal of Applied Physiology Mar 2024For whole-body sway patterns, a compound motor response following an external stimulus may comprise reflexes, postural adjustments (anticipatory or compensatory), and...
For whole-body sway patterns, a compound motor response following an external stimulus may comprise reflexes, postural adjustments (anticipatory or compensatory), and voluntary muscular activity. Responses to equilibrium destabilization may depend on both motor set and a subject`s expectation of the disturbing stimulus. To disentangle these influences on lower limb responses, we studied a model in which subjects (n = 14) were suspended in the air, without foot support, and performed a fast unilateral wrist extension (WE) in response to a passive knee flexion (KF) delivered by a robot. To characterize the responses, electromyographic activity of rectus femoris and reactive leg torque was obtained bilaterally in a series of trials, with or without the requirement of WE (motor set), and/or beforehand information about the upcoming velocity of KF (subject`s expectation). Some fast-velocity trials resulted in StartReact responses, which were used to subclassify leg responses. When subjects were uninformed about the upcoming KF, large rectus femoris responses concurred with a postural reaction in conditions without motor task, and with both postural reaction and postural adjustment when WE was required. WE in response to a low-volume acoustic signal elicited no postural adjustments. When subjects were informed about KF velocity and had to perform WE, large rectus femoris responses corresponded to anticipatory postural adjustment rather than postural reaction. In conclusion, when subjects are suspended in the air and have to respond with WE, the prepared motor set includes anticipatory postural adjustments if KF velocity is known, and additional postural reactions if KF velocity is unknown.
Topics: Humans; Posture; Electromyography; Wrist; Reflex; Lower Extremity; Postural Balance; Movement; Muscle, Skeletal
PubMed: 37755580
DOI: 10.1007/s00421-023-05323-z -
Scientific Reports Sep 2023
PubMed: 37739990
DOI: 10.1038/s41598-023-42343-3 -
Scientific Reports Aug 2023Two studies examined the amplitude of the startle response as a function of the Dark Tetrad of personality (narcissism, Machiavellianism, psychopathy, and sadism). We...
Two studies examined the amplitude of the startle response as a function of the Dark Tetrad of personality (narcissism, Machiavellianism, psychopathy, and sadism). We measured electromyographic activity of the orbicularis oculi muscle evoked by a startle stimulus while participants viewed images on a computer screen. Both studies revealed a negative correlation between general startle reactivity (averaged across positive, negative, and neutral images) and sadistic tendencies. In Study 2, all four dark traits were negative correlates of general startle reactivity. Study 2 also examined the personality correlates of aversive startle potentiation (ASP; indexed by greater reactivity while viewing negatively-valenced images than positive or neutral images). ASP correlated negatively with a variety of personality measures of psychopathy and sadism, their facets, and related personality tendencies (callousness, risk-taking, and restricted affect). These findings suggest that ordinary people with high levels of callousness and antagonism display physiological evidence of non-reactivity (i.e., blunted acoustic startle in general), whereas psychopathy and sadism are preferentially associated with reduced ASP.
Topics: Humans; Reflex, Startle; Sadism; Antisocial Personality Disorder; Personality Disorders; Personality
PubMed: 37648765
DOI: 10.1038/s41598-023-41043-2 -
Nutrients Aug 2023Recent studies involving transplantation of feces from schizophrenia (SCZ) patients and their healthy controls into germ-free mice have demonstrated that the gut...
Recent studies involving transplantation of feces from schizophrenia (SCZ) patients and their healthy controls into germ-free mice have demonstrated that the gut microbiome plays a critical role in mediating SCZ-linked physiology and behavior. To date, only one animal model (a metabotropic glutamate receptor 5 knockout) of SCZ has been reported to recapitulate SCZ-linked gut dysbiosis. Since human 22q11.2 microdeletion syndrome is associated with increased risk of SCZ, we investigated whether the 22q11.2 microdeletion ("Q22") mouse model of SCZ exhibits both SCZ-linked behaviors and intestinal dysbiosis. We demonstrated that Q22 mice display increased acoustic startle response and ileal (but not colonic) dysbiosis, which may be due to the role of the ileum as an intestinal region with high immune and neuroimmune activity. We additionally identified a negative correlation between the abundance of a species in the ilea of Q22 mice and their acoustic startle response, providing early evidence of a gut-brain relationship in these mice. Given the translational relevance of this mouse model, our work suggests that Q22 mice could have considerable utility in preclinical research probing the relationship between gut dysbiosis and the gut-brain axis in the pathogenesis of SCZ.
Topics: Chromosomes, Human, Pair 22; Disease Models, Animal; Chromosome Deletion; Schizophrenia; Dysbiosis; Gastrointestinal Microbiome; Ileum; Reflex, Startle; Acoustics; Humans; Animals; Mice; Mice, Inbred C57BL
PubMed: 37630824
DOI: 10.3390/nu15163631 -
Bioengineering (Basel, Switzerland) Aug 2023Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic...
Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague-Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1β levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1-4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.
PubMed: 37627826
DOI: 10.3390/bioengineering10080941 -
Scientific Reports Aug 2023Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity... (Randomized Controlled Trial)
Randomized Controlled Trial
Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.
Topics: Male; Humans; Reflex, Startle; Cross-Over Studies; Ketamine; Brain; Emotions
PubMed: 37587171
DOI: 10.1038/s41598-023-40099-4 -
Psychopharmacology Sep 2023Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have...
RATIONALE
Rodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination.
OBJECTIVES
We explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR).
METHODS
We selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats.
RESULTS
SD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs.
CONCLUSIONS
SD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.
Topics: Rats; Male; Female; Animals; Dopamine; Rats, Sprague-Dawley; Prepulse Inhibition; Apomorphine; Dopamine Agonists; Acetylcholine; Pharmaceutical Preparations; Glutamic Acid; Dizocilpine Maleate; Reflex, Startle; Acoustic Stimulation; Scopolamine Derivatives
PubMed: 37580441
DOI: 10.1007/s00213-023-06444-1 -
BMC Psychology Aug 2023Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple...
BACKGROUND
Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple pathologies. A phenomenon disrupted in several disorders is prepulse inhibition (PPI) of the startle response, in which startle to an intense sensory stimulus, or pulse, is reduced if a weak stimulus, or prepulse, is previously presented.
OBJECTIVE AND METHODS
The present systematic review analyzed the role of PPI deficit as a possible transdiagnostic process for four main groups of neuropsychiatric disorders: (1) trauma-, stress-, and anxiety-related disorders (2) mood-related disorders, (3) neurocognitive disorders, and (4) other disorders such as obsessive-compulsive, tic-related, and substance use disorders. We used Web of Science, PubMed and PsycInfo databases to search for experimental case-control articles that were analyzed both qualitatively and based on their potential risk of bias. A total of 64 studies were included in this systematic review. Protocol was submitted prospectively to PROSPERO 04/30/2022 (CRD42022322031).
RESULTS AND CONCLUSION
The results showed a general PPI deficit in the diagnostic groups mentioned, with associated deficits in the dopaminergic neurotransmission system, several areas implied such as the medial prefrontal cortex or the amygdala, and related variables such as cognitive deficits and anxiety symptoms. It can be concluded that the PPI deficit appears across most of the neuropsychiatric disorders examined, and it could be considered as a relevant measure in translational research for the early detection of such disorders.
Topics: Humans; Prepulse Inhibition; Reflex, Startle; Cognition Disorders; Mood Disorders; Anxiety Disorders; Acoustic Stimulation
PubMed: 37550772
DOI: 10.1186/s40359-023-01253-9 -
International Journal of Molecular... Jul 2023Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms...
Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms underlying hyperacusis in FXS are still largely unknown and effective therapies are lacking. Big conductance calcium-activated potassium (BKCa) channels were proposed as a therapeutic target to treat several behavioral disturbances in FXS preclinical models, but their role in mediating their auditory alterations was not specifically addressed. Furthermore, studies on the acoustic phenotypes of FXS animal models mostly focused on central rather than peripheral auditory pathways. Here, we provided an extensive characterization of the peripheral auditory phenotype of the -knockout (KO) mouse model of FXS at adulthood. We also assessed whether the acute administration of Chlorzoxazone, a BKCa agonist, could rescue the auditory abnormalities of adult mutant mice. -KO mice both at 3 and 6 months showed a hyperacusis-like startle phenotype with paradoxically reduced auditory brainstem responses associated with a loss of ribbon synapses in the inner hair cells (IHCs) compared to their wild-type (WT) littermates. BKCa expression was markedly reduced in the IHCs of KOs compared to WT mice, but only at 6 months, when Chlorzoxazone rescued mutant auditory dysfunction. Our findings highlight the age-dependent and progressive contribution of peripheral mechanisms and BKCa channels to adult hyperacusis in FXS, suggesting a novel therapeutic target to treat auditory dysfunction in NDDs.
Topics: Animals; Mice; Auditory Pathways; Chlorzoxazone; Disease Models, Animal; Fragile X Mental Retardation Protein; Fragile X Syndrome; Hyperacusis; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Mice, Knockout
PubMed: 37511622
DOI: 10.3390/ijms241411863