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Biological Psychiatry Jan 2024
Topics: Humans; Anxiety; Fear; Anxiety Disorders; Reflex, Startle
PubMed: 38030310
DOI: 10.1016/j.biopsych.2023.10.009 -
Gait & Posture Feb 2024Gait analysis using foot-mounted IMUs is a promising method to acquire gait parameters outside of laboratory settings and in everyday clinical practice. However, the...
BACKGROUND
Gait analysis using foot-mounted IMUs is a promising method to acquire gait parameters outside of laboratory settings and in everyday clinical practice. However, the need for precise sensor attachment or calibration, the requirement of environments with a homogeneous magnetic field, and the limited applicability to pathological gait patterns still pose challenges. Furthermore, in previously published work, the measurement accuracy of such systems is often only validated for specific points in time or in a single plane.
RESEARCH QUESTION
This study investigates the measurement accuracy of a gait analysis method based on foot-mounted IMUs in the acquisition of the foot motion, i.e., position and angle trajectories of the foot in the sagittal, frontal, and transversal plane over the entire gait cycle.
RESULTS
A comparison of the proposed method with an optical motion capture system showed an average RMSE of 0.67° for pitch, 0.63° for roll and 1.17° for yaw. For position trajectories, an average RMSE of 0.51 cm for vertical lift and 0.34 cm for lateral shift was found. The measurement error of the IMU-based method is found to be much smaller than the deviations caused by the shoes.
SIGNIFICANCE
The proposed method is found to be sufficiently accurate for clinical practice. It does not require precise mounting, special calibration movements, or magnetometer data, and shows no difference in measurement accuracy between normal and pathological gait. Therefore, it provides an easy-to-use alternative to optical motion capture and facilitates gait analysis independent of laboratory settings.
Topics: Humans; Foot; Gait; Gait Analysis; Motion; Shoes; Biomechanical Phenomena; Somatoform Disorders; Reflex, Startle
PubMed: 37988888
DOI: 10.1016/j.gaitpost.2023.11.002 -
Behavioural Brain Research Feb 2024The Roman high- (RHA) and low-avoidance (RLA) rats were bidirectionally selected and bred for, respectively, their rapid vs. extremely poor acquisition in the two-way...
The Roman high- (RHA) and low-avoidance (RLA) rats were bidirectionally selected and bred for, respectively, their rapid vs. extremely poor acquisition in the two-way active avoidance task. Consistent between-strain neurobehavioural differences have been found in anxiety- and stress-linked traits, as well as in schizophrenia-related phenotypes. RLAs display enhanced anxious- and stress-related phenotypes, whereas RHA rats show impulsivity, hyperactivity and attention/cognition-related impairments. Many of these typical behavioural phenotypes have been reported to be positively modulated by environmental treatments such as neonatal handling (NH). However, most studies on the Roman rat strains have been carried out in males. Thus, the present study for the first time focused on the joint evaluation of differences in novel object exploration (NOE), social interaction (SI), prepulse inhibition of the startle response (PPI), and cognitive performance and flexibility in various spatial tasks (using the Morris water maze, MWM) in females of both Roman rat strains. We also aimed at evaluating the long-lasting effects of NH treatment on the RHA vs. RLA profiles in these tests/tasks. Results show that anxiety-related behavior, as measured by the NOE test and self-grooming in the SI test, was increased in RLA rats, and dramatically reduced by NH. In the SI test RLA rats displayed diminished social interaction, which was rescued by NH. RHA females exhibited a deficit of PPI, which was not affected by NH. Spatial tasks in the MWM showed impairments of working memory, reference learning/memory and spatial reversal learning (i.e., cognitive flexibility) in RHA females. Spatial reference learning and cognitive flexibility (i.e., reversal task) showed some improvement in rats (mainly in RHAs) that had received NH during the first three weeks of life. With the exception of the SI test, the pattern of differences between female RHA vs. RLA profiles was overall consistent with what has previously been found in males of both strains, and NH treatment was able to enduringly improve some emotion-related and (spatial) cognitive outcomes in both strains.
Topics: Female; Male; Rats; Animals; Schizophrenia; Prepulse Inhibition; Reflex, Startle; Cognition; Attention; Avoidance Learning
PubMed: 37977340
DOI: 10.1016/j.bbr.2023.114762 -
Myogenic artifacts masquerade as neuroplasticity in the auditory frequency-following response (FFR).BioRxiv : the Preprint Server For... Apr 2024The frequency-following response (FFR) is an evoked potential that provides a "neural fingerprint" of complex sound encoding in the brain. FFRs have been widely used to...
The frequency-following response (FFR) is an evoked potential that provides a "neural fingerprint" of complex sound encoding in the brain. FFRs have been widely used to characterize speech and music processing, experience-dependent neuroplasticity (e.g., learning, musicianship), and biomarkers for hearing and language-based disorders that distort receptive communication abilities. It is widely assumed FFRs stem from a mixture of phase-locked neurogenic activity from brainstem and cortical structures along the hearing neuraxis. Here, we challenge this prevailing view by demonstrating upwards of ~50% of the FFR can originate from a non-neural source: contamination from the postauricular muscle (PAM) vestigial startle reflex. We first establish PAM artifact is present in all ears, varies with electrode proximity to the muscle, and can be experimentally manipulated by directing listeners' eye gaze toward the ear of sound stimulation. We then show this muscular noise easily confounds auditory FFRs, spuriously amplifying responses by 3-4x fold with tandem PAM contraction and even explaining putative FFR enhancements observed in highly skilled musicians. Our findings expose a new and unrecognized myogenic source to the FFR that drives its large inter-subject variability and cast doubt on whether changes in the response typically attributed to neuroplasticity/pathology are solely of brain origin.
PubMed: 37961324
DOI: 10.1101/2023.10.27.564446 -
Psychophysiology Mar 2024Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue...
Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue (CS-) in trauma-exposed individuals during fear acquisition. However, the relationships of UCR with defensive responses during extinction training, posttraumatic stress disorder (PTSD) symptom severity, and fearful traits in trauma-exposed individuals are not known. In a sample of 100 trauma-exposed adults with a continuum of PTSD severity, we recorded startle responses and skin conductance responses (SCR) during fear acquisition and extinction training using a 140 psi, 250-ms air blast to the larynx as the unconditioned stimulus. We explored dimensional associations of two different measures of UCR (unconditioned startle and unconditioned SCR) with conditioned defensive responding to CS+ and CS-, conditioned fear (CS+ minus CS-), PTSD symptom severity, and a measure of fearful traits (composite of fear survey schedule, anxiety sensitivity index, and Connor-Davidson resilience scale). Unconditioned startle was positively associated with startle potentiation to the threat cue and the safety cue across both learning phases (CS+ Acquisition, CS- Acquisition, CS+ Extinction Training, CS- Extinction Training) and with fearful traits. Unconditioned SCR was positively associated with SCR to the CS+ and CS- and SCR difference score during Acquisition. Neither type of UCR was associated with PTSD symptom severity. Our findings suggest that UCR, particularly unconditioned startle to a naturally aversive stimulus, may inform research on biomarkers and treatment targets for symptoms of pervasive and persistent fear in trauma-exposed individuals.
Topics: Adult; Humans; Stress Disorders, Post-Traumatic; Self Report; Fear; Learning; Reflex, Startle; Extinction, Psychological; Psychological Tests; Resilience, Psychological
PubMed: 37919832
DOI: 10.1111/psyp.14473 -
Yakugaku Zasshi : Journal of the... 2023p-Hydroxyamphetamine (p-OHA) is an active metabolite of amphetamine (AMPH) and methamphetamine (METH), and can be detected in the brain for a relatively long period...
p-Hydroxyamphetamine (p-OHA) is an active metabolite of amphetamine (AMPH) and methamphetamine (METH), and can be detected in the brain for a relatively long period after high-dose administration of AMPH in rodents. p-OHA may be involved in the abnormal behavior observed during the withdrawal period after a chronic administration of AMPH or METH. Therefore, the author investigated the effect of an intracerebroventricular (i.c.v.) administration of p-OHA on the changes of locomotor activity and prepulse inhibition (PPI) in the acoustic startle response in rodents. The i.c.v. administration of p-OHA significantly increased locomotor activity in mice. This effect was prevented by a pretreatment with a dopamine (DA) uptake inhibitor. Furthermore, local infusion of p-OHA into the nucleus accumbens (NAc) significantly increased locomotor activity in rats. Together these results suggest that dopaminergic systems in the rodent NAc may play important roles in p-OHA-induced locomotor activity. Next, the author tested the effects of the i.c.v. administration of p-OHA on PPI in mice. p-OHA induced PPI disruptions that were significantly improved by the pretreatment with a typical or an atypical antipsychotic, D or D receptor antagonists, respectively. p-OHA-induced PPI disruptions were also improved by a serotonin (5-HT) receptor antagonist, a 5-HT synthesis inhibitor or a 5-HT neurotoxin. These results suggest that p-OHA-induced PPI disruptions were mediated by DA and 5-HT release and subsequent stimulation of D, D and 5-HT receptors. Our recent series of reports indicate that the study of p-OHA may provide new insights into drug abuse as well as psychiatric disorders such as schizophrenia.
Topics: Humans; Rats; Mice; Animals; Dopamine; p-Hydroxyamphetamine; Serotonin; Rodentia; Reflex, Startle; Amphetamine; Methamphetamine; Synaptic Transmission; Dose-Response Relationship, Drug
PubMed: 37914334
DOI: 10.1248/yakushi.23-00120 -
Pediatric and Developmental Pathology :... 2024Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal...
Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal encephalopathy. This report describes a case of fatal neonatal encephalopathy associated with biallelic stop-gain mutation in (NM_001258392.3:c.1159C>T/p.Arg387*). Neurologic disorder encompasses pre- and post-natal features including polyhydramnios, intrauterine growth restriction, respiratory insufficiency, lethargy, excessive startle reflex, generalized hypertonia, and epileptic seizures. Brain macroscopic examination demonstrates frontal severe periventricular cystic leukoencephalopathy, along with mild ex-vacuo tri-ventricular dilatation. The most striking immunohistopathologic features are striato-thalamic neurodegeneration and deep white matter loss associated with strong reactive astrogliosis. This report supports that CLPB deficiency should be considered among the neurometabolic disorders associated with severe prenatal-onset neurologic impairment that may result from cystic leukoencephalopathy.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Brain; Codon, Nonsense; Endopeptidase Clp; Epilepsy; Infant, Newborn, Diseases; Leukoencephalopathies
PubMed: 37903135
DOI: 10.1177/10935266231204785 -
Laryngoscope Investigative... Oct 2023Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes,...
OBJECTIVE
Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus-induced rats.
METHODS
To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na-Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single-unit recordings were performed on a separate group that was treated as in group 4. Gap-prepulse inhibition of the acoustic startle (GPIAS) and pre-pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days.
RESULTS
Western blot analysis showed that the expression of γ-Aminobutyric acid Aα1 subunit (GABA Aα1), N-methyl-d-aspartate receptor subtype 2B (NR2B or NMDAR2B), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR1 (GluR1), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na-Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus.
CONCLUSION
NPPC can play an effective role in the treatment of tinnitus in salicylate-induced rats, and MGB is one of the brain areas involved in these processes.
LEVEL OF EVIDENCE
NA.
PubMed: 37899856
DOI: 10.1002/lio2.1156 -
Developmental Neuroscience Oct 2023The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies...
The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress. The use of variable frequency ultrasound in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of prenatal stress induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.
PubMed: 37857257
DOI: 10.1159/000534687 -
Translational Psychiatry Oct 2023Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic...
Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic startle response and prepulse inhibition (PPI) of startle are widely used translational measures for assessing sensory processing and sensorimotor gating, respectively. The Cntnap2 knockout (KO) rat has proven to be a valid model for ASD, displaying core symptoms, including sensory processing perturbations. Here, we used a novel method to assess startle and PPI in Cntnap2 KO rats that allows for the identification of separate scaling components: startle scaling, which is a change in startle amplitude to a given sound, and sound scaling, which reflects a change in sound processing. Cntnap2 KO rats show increased startle due to both an increased overall response (startle scaling) and a left shift of the sound/response curve (sound scaling). In the presence of a prepulse, wildtype rats show a reduction of startle due to both startle scaling and sound scaling, whereas Cntnap2 KO rats show normal startle scaling, but disrupted sound scaling, resulting in the reported PPI deficit. These results validate that startle and sound scaling by a prepulse are indeed two independent processes, with only the latter being impaired in Cntnap2 KO rats. As startle scaling is likely related to motor output and sound scaling to sound processing, this novel approach reveals additional information on the possible cause of PPI disruptions in preclinical models.
Topics: Animals; Rats; Acoustic Stimulation; Autism Spectrum Disorder; Prepulse Inhibition; Reflex, Startle; Sensory Gating
PubMed: 37852987
DOI: 10.1038/s41398-023-02629-6