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Scientific Reports Sep 2023
PubMed: 37739990
DOI: 10.1038/s41598-023-42343-3 -
Perceptual and Motor Skills Oct 2023The application of a noxious stimulus reduces the perception of other noxious stimuli, which can be assessed by an experimental method called "counterirritation." The...
The application of a noxious stimulus reduces the perception of other noxious stimuli, which can be assessed by an experimental method called "counterirritation." The question arises whether this type of inhibition also affects the processing of other aversive (but not nociceptive) stimuli, such as loud tones. If aversiveness or, in other words, negative emotional valence qualifies a stimulus to be affected by counterirritation, the general emotional context may also play a role in modulating counterirritation effects. We involved 63 participants in this study ( age = 38.8, = 10.5 years; 33 males, 30 females). We tried to counterirritate their perceptual and startle reactions to aversively loud tones (105 db) by immersing the hand into a painful hot water bath (46°C) in two emotional valence conditions (i.e., a neutral and a negative valence block in which we showed either neutral pictures or pictures of burn wounds). We assessed Inhibition by loudness ratings and startle reflex amplitudes. Counterirritation significantly reduced both loudness ratings and startle reflex amplitudes. The emotional context manipulation did not affect this clear inhibitory effect, showing that counterirritation by a noxious stimulus affects aversive sensations not induced by nociceptive stimuli. Thus, the assumption that "pain inhibits pain" should be widened to "pain inhibits the processing of aversive stimuli." This broadened understanding of counterirritation leads to a questioning of the postulate of clear pain specificity in paradigms like "conditioned pain modulation" (CPM) or "diffuse noxious inhibitory controls" (DNIC).
Topics: Male; Female; Humans; Adult; Pain; Emotions; Affect; Perception; Pain Perception
PubMed: 37340659
DOI: 10.1177/00315125231183604 -
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 -
Brain and Behavior May 2024Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to...
INTRODUCTION
Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to stress-induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses.
METHODS
We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re-experiencing of trauma.
RESULTS
Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle).
CONCLUSION
This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.
Topics: Animals; Male; Rats; ADAM17 Protein; Behavior, Animal; Prefrontal Cortex; Rats, Inbred Lew; Reflex, Startle; Stress, Psychological; Female
PubMed: 38715397
DOI: 10.1002/brb3.3482 -
Physiology & Behavior Oct 2023Rats emit ultrasonic vocalizations (USV). During aversive situations, rats emit 22-kHz USV, which are considered "alarm calls" and supposed to reflect a negative...
Rats emit ultrasonic vocalizations (USV). During aversive situations, rats emit 22-kHz USV, which are considered "alarm calls" and supposed to reflect a negative affective state of the sender. During appetitive situations, rats emit 50-kHz USV, which are believed to reflect a positive affective state. Here, we recorded USV emission in adult male rats during the acoustic startle response test. Our results indicate varied USV emission in both the 22- and 50-kHz USV ranges. Enhanced startle responses were observed in rats with a predominant 22-kHz call profile, supporting the notion that 22-kHz USV emission is associated with a negative affective state.
Topics: Rats; Male; Animals; Ultrasonics; Vocalization, Animal; Reflex, Startle; Emotions; Affect
PubMed: 37423456
DOI: 10.1016/j.physbeh.2023.114290 -
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; Mice, Knockout; Evoked Potentials, Auditory, Brain Stem; Noise; Auditory Threshold; Receptors, Nicotinic; Acoustic Stimulation; Reflex, Startle; Perceptual Masking; Behavior, Animal; Mice; Mice, Inbred C57BL; Cochlea; Male; Phenotype; Olivary Nucleus; Auditory Pathways; Female; Auditory Perception; Hearing
PubMed: 38738939
DOI: 10.1121/10.0025985 -
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 -
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 -
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 -
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