One night of partial sleep deprivation affects habituation of hypothalamus and skin conductance responses

Sleep disturbances are prevalent in clinical anxiety, but it remains unclear whether they are cause and/or consequence of this condition. Fear conditioning constitutes a valid laboratory model for the acquisition of normal and pathological anxiety. To explore the relationship between disturbed sleep and anxiety in more detail, the present study evaluated the effect of partial sleep deprivation (SD) on fear conditioning in healthy individuals. The neural correlates of 1) nonassociative learning and physiological processing and 2) associative learning (differential fear conditioning) were addressed. Measurements entailed simultaneous functional MRI, EEG, skin conductance response (SCR), and pulse recordings. Regarding nonassociative learning, partial SD resulted in a generalized failure to habituate during fear conditioning, as evidenced by reduced habituation of SCR and hypothalamus responses to all stimuli. Furthermore, SCR and hypothalamus activity were correlated, supporting their functional relationship. Regarding associative learning, effects of partial SD on the acquisition of conditioned fear were weaker and did not reach statistical significance. The hypothalamus plays an integral role in the regulation of sleep and autonomic arousal. Thus sleep disturbances may play a causal role in the development of normal and possibly pathological fear by increasing the susceptibility of the sympathetic nervous system to stressful experiences.

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Impairment in acquisition of conditioned fear in schizophrenia: a pooled analysis of four studies

10.1101/2021.05.26.21257857 ◽

2021 ◽

Author(s):

Lauri Tuominen ◽

Liana Romaniuk ◽

Mohammed R Milad ◽

Donald C Goff ◽

Jeremy Hall ◽

...

Keyword(s):

Associative Learning ◽

Fear Conditioning ◽

Conditioned Fear ◽

Pooled Analysis ◽

Control Group ◽

Pavlovian Fear Conditioning ◽

Schizophrenia Group ◽

Skin Conductance Responses ◽

Sufficient Power ◽

Prior Models

Background: Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power. Methods: To address this issue, data were pooled from 4 independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) during fear conditioning to stimuli that were paired (the CS+) and not paired (CS-) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS+ vs CS- SCRs) and responses to CS+ and CS- separately were assessed. Results: Acquisition of differential conditioned fear responses was significantly lower in individuals with schizophreania than in healthy controls (Cohen's d = 0.53). This effect was primarily related to a significantly higher response to the CS- stimulus in the schizophrenia compared to the control group. The magnitude of this response to the CS- in the schizophrenia group was correlated with the severity of delusional ideation. Other symptoms or antipsychotic dose were not associated with fear conditioning measures. Conclusions: Individuals with schizophrenia who endorse delusional beliefs are over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of aberrant learning in psychosis.

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MPP2 Interacts With SK2 Rescue The Excitability of Glutamatergic Neurons in The BLA and Facilitate The Extinction of Conditioned Fear in Mice

10.21203/rs.3.rs-1036689/v1 ◽

2021 ◽

Author(s):

Xiao-Han Peng ◽

Pan-Pan Chen ◽

Yang Zhang ◽

Ke Wu ◽

Ningning Ji ◽

...

Keyword(s):

Fear Conditioning ◽

Basolateral Amygdala ◽

Conditioned Fear ◽

Fear Memory ◽

Fear Extinction ◽

Definitive Evidence ◽

Glutamatergic Neurons ◽

Integral Role ◽

Calcium Activated Potassium Channel ◽

Increased Activity

Abstract Posttraumatic stress disorder (PTSD) and other anxiety disorders stem from dysregulated fear memory in which the basolateral amygdala (BLA) plays an integral role. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergic neurons. However, definitive evidence for the involvement of the SK2 channel in the BLA in fear extinction is lacking. Here, we discovered that fear conditioning decreased the levers of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levers of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane palmitoylated protein 2 (MPP2). Collectively, our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of fear memory. These findings expand our understanding of the neurobiological mechanism of PTSD and provide a new direction for PTSD treatment.

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Impact of the expectation on memory reconsolidation using a post retrieval extinction paradigm

10.1101/2020.10.26.354977 ◽

2020 ◽

Author(s):

Julia Marinos ◽

Andrea Ashbaugh

Keyword(s):

Fear Conditioning ◽

Skin Conductance ◽

Skin Conductance Response ◽

Conditioned Fear ◽

Memory Reconsolidation ◽

Physiological Measures ◽

Learning Group ◽

Return Of Fear ◽

Group A ◽

Fear Potentiated Startle

AbstractObjectiveThe present study examined if the expectation for learning enhances reconsolidation of conditioned fear memories using the post-retrieval extinction paradigm in an undergraduate sample (n = 48).MethodsThe study took place over three consecutive days. The expectation for learning was manipulated through oral instructions prior to memory reactivation. On day one, participants underwent differential fear conditioning to two spider images (CS+ and CS-). On day two, participants were assigned to either a reactivation with expectation for learning group, a reactivation with no expectation for learning group, or a no reactivation group. On day three, return of fear in response to the CS+ spider image was measured following reinstatement (i.e., four shocks). Fear potentiated startle (FPS) and skin conductance response (SCR) were taken as measures of fear.ResultsThe study found evidence that the expectation for learning may enhanced reconsolidation with FPS as a measure of fear as it was only the expectation for learning group in which FPS to the CS+ remained stable following reinstatement, however this effect was small and non-robust. In contrast, no evidence of reconsolidation was observed for SCR, as all participants exhibited a return of fear following reinstatement.ImplicationsThese findings suggest that a verbal manipulation of the expectation for learning may not be salient enough to induce reconsolidation as measured by SCR but may be sufficient as measured by FPS. Additionally, given in the inconsistent findings between SCR and FPS, the study’s results bring into question whether the post-retrieval extinction paradigm is appropriate to investigate reconsolidation using both physiological measures concurrently.

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The role of Anxiety Sensitivity in fear conditioning: a moderation effect

10.31234/osf.io/tu8h7 ◽

2019 ◽

Author(s):

Bianca Gerardo ◽

Raquel Nunes R. M. Guiomar ◽

Mariana Moura-Ramos ◽

Ana Ganho-Ávila

Keyword(s):

Anxiety Disorders ◽

Fear Conditioning ◽

Skin Conductance ◽

Anxiety Sensitivity ◽

Conditioned Fear ◽

Moderation Effect ◽

Skin Conductance Responses ◽

The Relationship ◽

Over Time

Anxiety sensitivity (AS; the degree of fear of experiencing or imagining experiencing anxiety symptoms and its possible consequences) is associated with expression of conditioned fear responses. However, findings regarding the relationship between AS and fear acquisition indexed by skin conductance responses are rather conflicting. Here we aim to clarify this interaction. We classified 144 women that underwent fear conditioning procedures as either high-AS or low-AS. We found that high-AS participants show one of two patterns maintained over time: poor stimuli discrimination or good stimuli discrimination. This suggests that different patterns of fear acquisition potentially support the distinction between anxiety disorders.

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Sleep, health, and society

10.1093/oso/9780198778240.003.0001 ◽

2018 ◽

Author(s):

Francesco P. Cappuccio ◽

Michelle A. Miller ◽

Steven W. Lockley ◽

Shantha M. W. Rajaratnam

Keyword(s):

Sleep Deprivation ◽

Sleep Duration ◽

Sleep Disturbances ◽

Modern Society ◽

Social Conditions ◽

Sleep Health ◽

Health And Wellbeing

Sleep disturbances are common in modern society. Since the beginning of the century, populations have shown a decline in sleep duration, owing to changes in environmental and social conditions. Industry was the first to appreciate the detrimental effects of sleep disturbances on health and wellbeing. It has taken, however, many decades to understand the implications for individuals and populations of sustained sleep deprivation.

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Fear-induced brain activations distinguish anxious and trauma-exposed brains

Translational Psychiatry ◽

10.1038/s41398-020-01193-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhenfu Wen ◽

Marie-France Marin ◽

Jennifer Urbano Blackford ◽

Zhe Sage Chen ◽

Mohammed R. Milad

Keyword(s):

Neural Network ◽

Fear Conditioning ◽

Psychiatric Diagnosis ◽

Data Analytics ◽

Conditioned Fear ◽

Brain Regions ◽

Brain Network ◽

Neuroimaging Data ◽

Task Irrelevant ◽

Translational Models

AbstractTranslational models of fear conditioning and extinction have elucidated a core neural network involved in the learning, consolidation, and expression of conditioned fear and its extinction. Anxious or trauma-exposed brains are characterized by dysregulated neural activations within regions of this fear network. In this study, we examined how the functional MRI activations of 10 brain regions commonly activated during fear conditioning and extinction might distinguish anxious or trauma-exposed brains from controls. To achieve this, activations during four phases of a fear conditioning and extinction paradigm in 304 participants with or without a psychiatric diagnosis were studied. By training convolutional neural networks (CNNs) using task-specific brain activations, we reliably distinguished the anxious and trauma-exposed brains from controls. The performance of models decreased significantly when we trained our CNN using activations from task-irrelevant brain regions or from a brain network that is irrelevant to fear. Our results suggest that neuroimaging data analytics of task-induced brain activations within the fear network might provide novel prospects for development of brain-based psychiatric diagnosis.

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Fear conditioning and stimulus generalization in association with age in children and adolescents

European Child & Adolescent Psychiatry ◽

10.1007/s00787-021-01797-4 ◽

2021 ◽

Author(s):

Julia Reinhard ◽

Anna Slyschak ◽

Miriam A. Schiele ◽

Marta Andreatta ◽

Katharina Kneer ◽

...

Keyword(s):

Children And Adolescents ◽

Fear Conditioning ◽

Repeated Measures ◽

Conditioned Fear ◽

Fear Learning ◽

Stimulus Generalization ◽

Healthy Children ◽

Older Individuals ◽

Age Related ◽

Current Task

AbstractThe aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

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