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Behaviour Research and Therapy Jul 2024Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions,... (Randomized Controlled Trial)
Randomized Controlled Trial
Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions, further research is needed regarding the effects of glucose on fear extinction. In two experimental studies with healthy participants (Study 1: N = 68, 39 females; Study 2: N = 89, 67 females), we investigated the effects of glucose on fear extinction learning and its consolidation. Participants completed a differential fear conditioning paradigm consisting of acquisition, extinction, and return of fear tests: reinstatement, and extinction recall. US-expectancy ratings, skin conductance response (SCR), and fear potentiated startle (FPS) were collected. Participants were pseudorandomized and double-blinded to one of two groups: They received either a drink containing glucose or saccharine 20 min before (Study 1) or immediately after extinction (Study 2). The glucose group showed a significantly stronger decrease in differential FPS during extinction (Study 1) and extinction recall (Study 2). Additionally, the glucose group showed a significantly lower contextual anxiety at test of reinstatement (Study 2). Our findings provide first evidence that glucose supports the process of fear extinction, and in particular the consolidation of fear extinction memory, and thus has potential as a beneficial adjuvant to extinction-based treatments. Registered through the German Clinical Trials Registry (https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html; Study 1: DRKS00010550; Study 2: DRKS00018933).
Topics: Humans; Extinction, Psychological; Fear; Female; Male; Glucose; Adult; Young Adult; Double-Blind Method; Conditioning, Classical; Galvanic Skin Response; Reflex, Startle; Adolescent; Mental Recall
PubMed: 38728832
DOI: 10.1016/j.brat.2024.104553 -
Behaviour Research and Therapy Jul 2024Although observational fear learning has been implicated in the development of phobic-related fears, studies investigating observational learning of fear of bodily...
Although observational fear learning has been implicated in the development of phobic-related fears, studies investigating observational learning of fear of bodily symptoms remain scarce. Therefore, the aim of the present study was to investigate whether fear in response to bodily symptoms can be acquired simply by observing a fearful reaction to provocation of aversive bodily symptoms in others. Forty healthy participants underwent an observational fear conditioning paradigm consisting of two phases. In the first phase, participants observed a demonstrator reacting to an aversive bodily symptom provocation (unconditioned stimulus or US, i.e., labored breathing) paired with one conditioned stimulus (CS+) but not with the other one (CS-, both CSs were geometric symbols presented on a screen the demonstrator was watching). In the second phase, participants were directly presented with the same conditioned stimuli, but in the absence of the US. Our results revealed enhanced conditioned fear responses in the beginning of the second phase to the CS + as compared to CS-, as indexed by greater skin conductance and subjective fear responses, as well as greater potentiation of startle eyeblink responses to the CS + as compared to the ITI. Taken together, these findings implicate that fear of bodily symptoms can be learned through observation of others, that is, without first-hand experience of bodily threat.
Topics: Humans; Fear; Female; Male; Conditioning, Classical; Reflex, Startle; Young Adult; Galvanic Skin Response; Adult; Adolescent; Blinking
PubMed: 38718630
DOI: 10.1016/j.brat.2024.104555 -
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 -
Epileptic Disorders : International... May 2024Herein, we present the case of a 21-year-old man with a history of generalized tonic seizures since the age of 4 years. These seizures occurred either spontaneously or...
Herein, we present the case of a 21-year-old man with a history of generalized tonic seizures since the age of 4 years. These seizures occurred either spontaneously or could be provoked by auditory stimuli such as the sounds of a vacuum cleaner or an electric shaver. Despite trials with 10 different anti-seizure medications, his seizures remained refractory. Interictal electroencephalography (EEG) revealed generalized epileptiform activity, whereas ictal EEG showed a generalized attenuation pattern. Magnetic resonance imaging revealed extensive chronic infarctions, predominantly in the bilateral cerebral watershed areas. At the age of 17, the patient underwent a one-stage complete callosotomy, which only achieved remission of auditory-provoked seizures. Based on this experience and published reports, we propose that the posterior corpus callosum, particularly the isthmus and anterior splenium, may be involved in seizures caused by unexpected sound stimuli.
PubMed: 38713433
DOI: 10.1002/epd2.20238 -
Schizophrenia Research Jul 202422q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS...
BACKGROUND
22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk.
METHODS
Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers.
RESULTS
Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed.
CONCLUSIONS
Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.
Topics: Humans; Male; Female; Reflex, Startle; Adult; Adolescent; Young Adult; DiGeorge Syndrome; Prepulse Inhibition; Blinking; Reaction Time; Electromyography; Acoustic Stimulation
PubMed: 38703519
DOI: 10.1016/j.schres.2024.04.022 -
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 -
Autonomic Neuroscience : Basic &... Jun 2024Unilateral nociceptive stimulation is associated with subtle signs of pupil asymmetry that may reflect lateralized activity in the locus coeruleus. To explore drivers of...
Unilateral nociceptive stimulation is associated with subtle signs of pupil asymmetry that may reflect lateralized activity in the locus coeruleus. To explore drivers of this pupil asymmetry, electrical stimuli, delivered alone or 200 ms before or after an acoustic startle stimulus, were administered to one ankle under four experimental conditions: with or without a 1.6 s anticipatory period, or while the forearm ipsilateral or contralateral to the electrical stimulus was heated tonically to induce moderate pain (15 healthy participants in each condition). Pupil diameter was measured at the start of each trial, at stimulus delivery, and each second for 5 s after stimulus delivery. At the start of the first trial, the pupil ipsilateral to the side on which electric shocks were later delivered was larger than the contralateral pupil. Both pupils dilated robustly during the anticipatory period and dilated further during single- and dual-stimulus trials. However, pupil asymmetry persisted throughout the experiment. Tonically-applied forearm heat-pain modulated the pupillary response to phasic electrical stimuli, with a slight trend for dilatation to be greater contralateral to the forearm being heated. Together, these findings suggest that focusing anxiously on the expected site of noxious stimulation was associated with dilatation of the ipsilateral pupil whereas phasic nociceptive stimuli and psychological arousal triggered bilateral pupillary dilatation. It was concluded that preparatory cognitive activity rather than phasic afferent nociceptive input is associated with pupillary signs of lateralized activity in the locus coeruleus.
Topics: Humans; Male; Pupil; Female; Young Adult; Adult; Electric Stimulation; Nociception; Reflex, Startle; Anticipation, Psychological; Functional Laterality; Pain; Hot Temperature
PubMed: 38677128
DOI: 10.1016/j.autneu.2024.103179 -
Brain Research Aug 2024Prepulse inhibition (PPI) of the auditory startle response, a key measure of sensorimotor gating, diminishes with age and is impaired in various neurological conditions....
Prepulse inhibition (PPI) of the auditory startle response, a key measure of sensorimotor gating, diminishes with age and is impaired in various neurological conditions. While PPI deficits are often associated with cognitive impairments, their reversal is routinely used in experimental systems for antipsychotic drug screening. Yet, the cellular and circuit-level mechanisms of PPI remain unclear, even under non-pathological conditions. We recently showed that brainstem neurons located in the caudal pontine reticular nucleus (PnC) expressing the glycine transporter type 2 (GlyT2) receive inputs from the central nucleus of the amygdala (CeA) and contribute to PPI but via an uncharted pathway. Here, using tract-tracing, immunohistochemistry and in vitro optogenetic manipulations coupled to field electrophysiological recordings, we reveal the neuroanatomical distribution of GlyT2 PnC neurons and PnC-projecting CeA glutamatergic neurons and we provide mechanistic insights on how these glutamatergic inputs suppress auditory neurotransmission in PnC sections. Additionally, in vivo experiments using GlyT2-Cre mice confirm that optogenetic activation of GlyT2 PnC neurons enhances PPI and is sufficient to induce PPI in young mice, emphasizing their role. However, in older mice, PPI decline is not further influenced by inhibiting GlyT2 neurons. This study highlights the importance of GlyT2 PnC neurons in PPI and underscores their diminished activity in age-related PPI decline.
Topics: Animals; Prepulse Inhibition; Neurons; Reflex, Startle; Mice; Brain Stem; Glycine Plasma Membrane Transport Proteins; Male; Glycine; Optogenetics; Mice, Transgenic; Mice, Inbred C57BL; Synaptic Transmission; Central Amygdaloid Nucleus
PubMed: 38615924
DOI: 10.1016/j.brainres.2024.148938 -
Journal of Integrative Neuroscience Mar 2024Rats with a loss-of-function mutation in the contactin-associated protein-like 2 () gene have been validated as an animal model of autism spectrum disorder (ASD)....
BACKGROUND
Rats with a loss-of-function mutation in the contactin-associated protein-like 2 () gene have been validated as an animal model of autism spectrum disorder (ASD). Similar to many autistic individuals, knock-out rats () are hyperreactive to sound as measured through the acoustic startle response. The brainstem region that mediates the acoustic startle response is the caudal pontine reticular nucleus (PnC), specifically giant neurons in the PnC. We previously reported a sex-dependent genotypic effect in the sound-evoked neuronal activity recorded from the PnC, whereby female rats had a dramatic increase in sound-evoked responses compared with wildtype counterparts, but male rats showed only a modest increase in PnC activity that cannot fully explain the largely increased startle in male rats. The present study therefore investigates activation and histological properties of PnC giant neurons in rats and wildtype littermates.
METHODS
The acoustic startle response was elicited by presenting rats with 95 dB startle pulses before rats were euthanized. PnC brain sections were stained and analyzed for the total number of PnC giant neurons and the percentage of giant neurons that expressed phosphorylated cAMP response element binding protein (pCREB) in response to startle stimuli. Additionally, electrophysiology was conducted to assess the resting state activity and intrinsic properties of PnC giant neurons.
RESULTS
Wildtype and rats had similar total numbers of PnC giant neurons and similar levels of baseline pCREB expression, as well as similar numbers of giant neurons that were firing at rest. Increased startle magnitudes in rats were associated with increased percentages of pCREB-expressing PnC giant neurons in response to startle stimuli. Male rats had increased pCREB-expressing PnC giant neurons compared with female rats, and the recruited giant neurons in males were also larger in soma size.
CONCLUSIONS
Recruitment and size of PnC giant neurons are important factors for regulating the magnitude of the acoustic startle response in rats, particularly in males. These findings allow for a better understanding of increased reactivity to sound in rats and in -associated disorders such as ASD.
Topics: Animals; Female; Male; Rats; Acoustic Stimulation; Autism Spectrum Disorder; Neurons; Reflex, Startle; Reticular Formation; Disease Models, Animal
PubMed: 38538232
DOI: 10.31083/j.jin2303063 -
Sleep and Biological Rhythms Apr 2024Sleep deprivation (SD) impairs pre-stimulus inhibition, but the effect of quetiapine (QET) remains largely unknown.
BACKGROUND
Sleep deprivation (SD) impairs pre-stimulus inhibition, but the effect of quetiapine (QET) remains largely unknown.
OBJECTIVE
This study aimed to investigate the behavioral and cognitive effects of QET in both naïve and sleep-deprived rats.
MATERIALS AND METHODS
Seven groups ( = 49) of male Wistar Albino rats were used in this study. SD was performed using the modified multiple platform technique in a water tank for 72 h. Our study consists of two experiments investigating the effect of QET on pre-pulse inhibition (PPI) of the acoustic startle reflex. The first experiment tested the effect of short- and long-term administration of QET on PPI response in non-sleeping (NSD) rats. The second experiment used 72 h REM sleep deprivation as a model for SD-induced impairment of the PPI response. Here, we tested the effect of QET on the % PPI of SD rats by short- and long-term intraperitoneal injection at the last 90 min of sleep SD and immediately subsequently tested for PPI.
RESULTS
72 h SD impaired PPI, reduced startle amplitude, and attenuated the PPI% at + 4 dB, + 8 dB, and + 16 dB prepulse intensities. 10 mg/kg short and long-term QET administration completely improved sensorimotor gating deficit, increased startle amplitude, and restored the impaired PPI% at + 4 dB, + 8 dB, and + 16 dB after 72 h SD in rats.
CONCLUSION
Our results showed short- and long-term administration of QET improved sensorimotor gating deficit in 72 h SD. Further research is required for the etiology of insomnia and the dose-related behavioral effects of QET.
PubMed: 38524169
DOI: 10.1007/s41105-023-00504-x