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Scientific Reports Dec 2023Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This...
Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, prepulse inhibition of acoustic startle response, and startle habituation. This approach provides a scalable, universal resource for quantitative assays of central nervous system function.
Topics: Humans; Reflex, Startle; Smartphone; Acoustic Stimulation; Prepulse Inhibition; Habituation, Psychophysiologic
PubMed: 38129487
DOI: 10.1038/s41598-023-49568-2 -
Behavioural Brain Research Aug 2023The aryl hydrocarbon receptor (AhR), a classic "environmental sensor", has been found to play an important role in cognitive and emotional function. Recent studies...
The aryl hydrocarbon receptor (AhR), a classic "environmental sensor", has been found to play an important role in cognitive and emotional function. Recent studies showed AhR deletion led to an attenuated fear memory, providing a potential target against fear memory, whether it is the consequence of attenuated sense of fear or memory ability deficit or both is unclear. Here this study aims to work this out. The freezing time in contextual fear conditioning (CFC) reduced significantly in AhR knockout mice, indicating an attenuated fear memory. Hot plate test and acoustic startle reflex showed that AhR knockout did not change the pain threshold and hearing, excluded the possibility of sensory impairments. Results from NORT, MWM and SBT showed that deletion of AhR had little effects on other types of memory. But the anxiety-like behaviors reduced both in naïve or suffered (tested after CFC) AhR knockout mice, showing that AhR-deficient mice have a reduced basal and stressful emotional response. The basal low-frequency to high-frequency (LF/HF) ratio of the AhR knockout mice was significantly lower than that of the control group, indicating lower sympathetic excitability in the basal state, suggesting a low level of basal stress in the knockout mice. Before and after CFC, the LF/HF ratio of AhR-KO mice tended to be significantly lower than that of WT mice, and their heart rate was significantly lower; and the AhR-KO mice also has a decreased serum corticosterone level after CFC, suggesting a reduced stress response in AhR knockout mice. Altogether, the basal stress level and stress response were significant reduced in AhR knockout mice, which might contribute to the attenuated fear memory with little impairment on other types of memory, suggesting AhR as a "psychologic sensor" additional to "environmental sensor".
Topics: Animals; Mice; Anxiety; Fear; Memory Disorders; Mice, Inbred C57BL; Mice, Knockout; Receptors, Aryl Hydrocarbon
PubMed: 37217138
DOI: 10.1016/j.bbr.2023.114505 -
Psychophysiology Jul 2023Physical stress has been found to enhance arousability by visual sexual stimuli on a short-term basis, as reflected in higher phasic pupil dilation responses, probably...
Physical stress has been found to enhance arousability by visual sexual stimuli on a short-term basis, as reflected in higher phasic pupil dilation responses, probably mediated by sympathetic nervous system (SNS)-related processes. However, previous research has not addressed the specificity of this effect in terms of emotional valence, that is, whether it reflects an instance of general excitation transfer or a more specific mechanism. Thus, to further investigate changes in sexual processing after acute stress exposure, 40 male participants underwent either a predominantly sympathetic stressor (3 min sustained handgrip) or similar control procedure. After stress induction, pictures varying in valence as well as sexual versus non-sexual arousal were presented (for 5000 ms each). Using principal component analysis, pupillary responses during picture viewing were dissociated into fast and slow components (early vs. late response phases). In addition, startle eyeblink responses were elicited by bursts of white noise (50 ms, 105 dB) in half of the trials and recorded at the orbicularis oculi via electromyography. Skin conductance and heart rate were co-registered, as well. While affective startle modulation and skin conductance responses to emotional stimuli were unaffected by previous stress exposure, both evoked heart-rate deceleration (but not acceleration) and pupil responses were specifically enhanced with sexually arousing stimuli in stressed participants, and this effect was mediated by blood pressure reactivity as an index of preceding SNS activation. Taken together, our findings provide strong evidence for enhancement of sexual processing by acute stress exposure in men and suggest differential involvement of parasympathetic versus sympathetic mechanisms.
Topics: Humans; Male; Pupil; Physical Exertion; Hand Strength; Arousal; Sexual Behavior; Emotions; Reflex, Startle
PubMed: 36708087
DOI: 10.1111/psyp.14254 -
Attention, Perception & Psychophysics Apr 2024The perceived intensity of an intense stimulus as well as the startle reflex it elicits can both be reduced when preceded by a weak stimulus (prepulse). Both phenomena...
The perceived intensity of an intense stimulus as well as the startle reflex it elicits can both be reduced when preceded by a weak stimulus (prepulse). Both phenomena are used to characterise the processes of sensory gating in clinical and non-clinical populations. The latter phenomenon, startle prepulse inhibition (PPI), is conceptualised as a measure of pre-attentive sensorimotor gating due to its observation at short latencies. In contrast, the former, prepulse inhibition of perceived stimulus intensity (PPIPSI), is believed to involve higher-order cognitive processes (e.g., attention), which require longer latencies. Although conceptually distinct, PPIPSI is often studied using parameters that elicit maximal PPI, likely limiting what we can learn about sensory gating's influence on conscious perception. Here, we tested an array of stimulus onset asynchronies (SOAs; 0-602 ms) and prepulse intensities (0-3× perceptual threshold) to determine the time course and sensitivity to the intensity of electrotactile PPIPSI. Participants were required to compare an 'unpleasant but not painful' electric pulse to their left wrist that was presented alone with the same stimulus preceded by an electric prepulse, and report which pulse stimulus felt more intense. Using a 2× perceptual threshold prepulse, PPIPSI emerged as significant at SOAs from 162 to 602 ms. We conclude that evidence of electrotactile PPIPSI at SOAs of 162 ms or longer is consistent with gating of perception requiring higher-level processes, not measured by startle PPI. The possible role of attentional processes, stimuli intensity, modality-specific differences, and methods of investigating PPIPSI further are discussed.
Topics: Humans; Reflex, Startle; Male; Female; Adult; Young Adult; Prepulse Inhibition; Sensory Gating; Attention; Sensory Thresholds; Electric Stimulation; Touch Perception; Reaction Time
PubMed: 36385671
DOI: 10.3758/s13414-022-02597-x -
Psychophysiology May 2024Prepulse inhibition (PPI) of the startle reflex serves as a pre-cognitive marker of sensorimotor gating, and its deficit may predict cognitive impairments. Startle...
Prepulse inhibition (PPI) of the startle reflex serves as a pre-cognitive marker of sensorimotor gating, and its deficit may predict cognitive impairments. Startle reflex is modulated by many factors. Among them, stress has been a topic of interest, but its effects on both pre-cognitive and cognitive variables continue to yield divergent results. This study aims to analyze the effect of acute stress on PPI of the startle reflex and cognitive function (working memory, attention, inhibition, and verbal fluency). Participants were exposed to the MAST stress induction protocol or a stress-neutral task: stress group (n = 54) or control group (n = 54). Following stress induction, participants' startle responses were recorded, and cognition was assessed. The results revealed that participants in the stress group exhibited greater startle magnitude, lower PPI, and lower scores in working memory tests compared with the control group. Additionally, a correlation was found between working memory and PPI across all the participants, independent of stress group. These findings support the notion that after stress, both greater startle magnitude and diminished PPI could play an adaptive role by allowing for increased processing of stimuli potentially dangerous and stress-related. Similarly, our results lend support to the hypothesis that lower PPI may be predictive of cognitive impairment. Considering the impact of stress on both pre-cognitive (PPI) and cognitive (working memory) variables, we discuss the possibility that the effect of stress on PPI occurs through motivational priming and emphasize the relevance of considering stress in both basic and translational science.
PubMed: 38691020
DOI: 10.1111/psyp.14599 -
Frontiers in Behavioral Neuroscience 2023Noise-induced tinnitus is generally associated with hearing impairment caused by traumatic acoustic overexposure. Previous studies in laboratory animals and human...
Noise-induced tinnitus is generally associated with hearing impairment caused by traumatic acoustic overexposure. Previous studies in laboratory animals and human subjects, however, have observed differences in tinnitus susceptibility, even among individuals with similar hearing loss. The mechanisms underlying increased sensitivity or, conversely, resistance to tinnitus are still incompletely understood. Here, we used behavioral tests and ABR audiometry to compare the sound-evoked responses of mice that differed in the presence of noise-induced tinnitus. The aim was to find a specific pre-exposure neurophysiological marker that would predict the development of tinnitus after acoustic trauma. Noise-exposed mice were screened for tinnitus-like behavior with the GPIAS paradigm and subsequently divided into tinnitus (+T) and non-tinnitus (-T) groups. Both groups showed hearing loss after exposure, manifested by elevated audiometric thresholds along with reduced amplitudes and prolonged latencies of ABR waves. Prior to exposure, except for a slightly increased slope of growth function for ABR amplitudes in +T mice, the two groups did not show significant audiometric differences. Behavioral measures, such as the magnitude of the acoustic startle response and its inhibition by gap pre-pulse, were also similar before exposure in both groups. However, +T mice showed significantly increased suppression of the acoustic startle response in the presence of background noise of moderate intensity. Thus, increased modulation of startle by background sounds may represent a behavioral correlate of susceptibility to noise-induced tinnitus, and its measurement may form the basis of a simple non-invasive method for predicting tinnitus development in laboratory rodents.
PubMed: 38144362
DOI: 10.3389/fnbeh.2023.1321277 -
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 -
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 -
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 -
Biological Psychiatry. Cognitive... Jul 2023Treatments for anxiety and related disorders target exaggerated escape/avoidance as a core feature, but current methods fail to improve escape/avoidance habits for many...
BACKGROUND
Treatments for anxiety and related disorders target exaggerated escape/avoidance as a core feature, but current methods fail to improve escape/avoidance habits for many treatment-seeking individuals. To support developing tools that increase treatment efficacy by targeting mechanisms more directly, the current work examined potential distinctions in the neurophysiologies of escape and avoidance and tested how clinical anxiety affects these neurophysiologies.
METHODS
Twenty-five treatment-seeking individuals with varied principal diagnoses (e.g., generalized anxiety disorder, posttraumatic stress disorder) and 20 non-treatment-seeking control subjects participated. In the study task, approximately 5.25-second cues predicted aversive images that could be avoided (blocked by a button press before image onset), escaped (ended by a button press after image onset), or not controlled. To examine neural processing and defensive response modulation, anticipatory event-related potentials were derived, and startle reflexes were probed throughout each cue.
RESULTS
Multidimensional profiles were observed such that 1) anticipatory event-related potential enhancement was only reliable during avoidance preparation, and event-related potentials potentially reflected perceived/instrumental control; and 2) startle reflexes were inhibited during avoidance preparation, relatively enhanced during escape preparation, and further enhanced during uncontrollable anticipation, thus potentially reflecting fear-related activation. Treatment-seeking status, then, did not affect cortical processing, but it did moderate context-dependent fear (if individuals with severe depression were excluded) such that treatment-seeking individuals without depression showed exaggerated startle during escape, but not avoidance, preparation.
CONCLUSIONS
Data suggest a specific effect of anxiety on fear system activation during preparation to escape aversion. This effect warrants further investigation as a precision target for interventions that directly modulate the specific underlying neural circuitry.
Topics: Humans; Anxiety; Anxiety Disorders; Fear; Stress Disorders, Post-Traumatic; Adaptation, Psychological
PubMed: 35952971
DOI: 10.1016/j.bpsc.2022.07.010