A differential impact of action-effect temporal contiguity on different measures of response inhibition in the Go\No-Go and Stop-signal paradigms.

Response inhibition refers to suppressing a prepotent motor response and is often studied and discussed as an act of cognitive control. Much less attention was given to the potential contribution of motor control processes to response inhibition. Accumulated empirical findings show that a perceptual effect temporally contiguous with a response improves motor control performance. In the current study, we followed this work by manipulating action-effect temporal contiguity to enhance motor performance and investigated its impact on response selection and inhibition. In two experiments, we integrated a Go/No-Go (GNGT; Experiment 1) and a Stop-signal (SST; Experiment 2) task with the Effect-Motivation task, previously used to capture the facilitating impact of action-effect temporal contiguity on response times (RTs). Replicating previous findings, RTs were shorter following temporally contiguous compared to Lagged action-effect in Go trials in both the GNGT (Experiment 1) and SST (Experiment 2). Notably, an Immediate action-effect improved response inhibition in the GNGT (Experiment 1) but did not modulate Stop-signal reaction time (SSRT) in the SST (Experiment 2). Unexpectedly, the error rate on Go trials was higher in the Immediate effect condition in Experiment 2. We interpret the findings to suggest that an action's (Immediate) perceptual effect may promote response inhibition performance by enhancing selective association between the Go stimuli and the Go response and not by improving cognitive control ability. The findings also imply that an Immediate action-effect may hamper action control (e.g., by increasing general readiness to respond), at least when action control does not benefit from automatic stimulus-response association.

Return of fear following extinction in youth: An event-related potential study.

The ability to learn to differentiate safety from danger matures gradually, particularly when such learning occurs over an extended time period. And yet, most research on fear learning examines the early phases of such learning and mainly in adults. The current study examined fear conditioning and extinction, as well as one form of extended learning, return of fear (ROF). Thirty-three typically developing children (age range: 7-14 years) completed fear conditioning and extinction; self-reports and psychophysiological indices were measured at this point. Two weeks later, children completed a ROF test (n = 23), and event-related potentials (ERPs) were recorded. Results indicated successful fear acquisition and extinction. Moreover, participants reported greater fear of the conditioned stimulus (CS+) than the safety stimulus (CS-) in the ROF test 2 weeks later. In electrophysiology data, ROF manifested as a larger late positive potential (LPP) response to the CS+ than the CS-. Finally, these differences in LPP responses were positively correlated with poorer extinction, as indicated by the GSR responses 2 weeks earlier. This is the first ERP study to demonstrate ROF in children. The LPP measure may index an interplay between inhibitory and excitatory brain-related processes underlying the long-term effects of fear learning.

Network Neuromodulation of Opioid and GABAergic Receptors Following a Combination of "Juvenile" and "Adult Stress" in Rats.

Early life stress is suggested to alter behavioral responses during stressful challenges in adulthood and to exacerbate pathological symptoms that reminisce posttraumatic stress disorder (PTSD). These effects are often associated with changes in γ-Aminobutyric acid type A (GABAA) and κ opioid receptor expression and neuromodulation of the limbic system. Anxiety-like and stress coping behaviors were assessed in rats exposed to stress in adulthood on the background of previous exposure to stress in juvenility. Two weeks following behavioral assessment in adulthood, GABAAR α1 and α2 subunits and κ opioid receptor expression levels were measured in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, and periaqueductal gray (PAG). To illustrate changes at the network level, an integrated expression profile was constructed. We found that exposure to juvenile stress affected rats' behavior during adult stress. The combination of juvenile and adult stress significantly affected rats' long term anxious-like behavior. Probabilities predicting model integrating the expression of GABAA α1-α2 and κ opioid receptors in different brain regions yielded highly successful classification rates. This study emphasizes the ability of exposure to stress in juvenility to exacerbate the impact of coping with stress in adulthood. Moreover, the use of integrated receptor expression network profiling was found to effectively characterize the discussed affective styles and their behavioral manifestations.

Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats.

The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and warrant further examination. Hence, the present study investigated the functional relationship between the PAG and amygdala in two different settings, fear conditioning and naturalistic foraging, in rats. In fear conditioning, electrical stimulation of the dorsal PAG (dPAG) produced unconditional responses (URs) composed of brief activity bursts followed by freezing and 22-kHz ultrasonic vocalization. In contrast, stimulation of ventral PAG and the basolateral amygdalar complex (BLA) evoked freezing and/or ultrasonic vocalization. Whereas dPAG stimulation served as an effective unconditional stimulus for fear conditioning to tone and context conditional stimuli, neither ventral PAG nor BLA stimulation supported fear conditioning. The conditioning effect of dPAG, however, was abolished by inactivation of the BLA. In a foraging task, dPAG and BLA stimulation evoked only fleeing toward the nest. Amygdalar lesion/inactivation blocked the UR of dPAG stimulation, but dPAG lesions did not block the UR of BLA stimulation. Furthermore, in vivo recordings demonstrated that electrical priming of the dPAG can modulate plasticity of subiculum-BLA synapses, providing additional evidence that the amygdala is downstream of the dPAG. These results suggest that the dPAG conveys unconditional stimulus information to the BLA, which directs both innate and learned fear responses, and that brain stimulation-evoked behaviors are modulated by context.

Theory of Food: Unravelling the Lifelong Impact of Childhood Dietary Habits on Adult Food Preferences across Different Diet Groups.

The study investigates the behavioral manifestations of the "Theory of Food" (ToF), a novel theoretical framework centered on the early development of food perceptions. The ToF posits that childhood experiences with food shape cognitive networks influencing adult dietary choices. Stemming from the "Theory of Mind," the ToF hypothesizes that individuals construct an associative world of food images and representations mirroring the socio-cognitive world shaped by proper theory of mind development. The study, involving 249 healthy adults, employs the Cognitive Food Preference Questionnaire (CFPQ) and the Adult Food Preference Profile (AFPP) to explore the correlation between childhood and adult food preferences across diet groups (omnivores, vegetarians, and vegans). Results reveal robust correlations in omnivores, varied patterns in vegetarians, and mixed outcomes in vegans. Notably, omnivores show correlations in grains, fast food, dairy products, vegetables, meat, soft drinks, and snack consumption. Vegetarians exhibit correlations in grains, fast food, dairy products, vegetables, snacks, and, surprisingly, meat consumption. Vegans display correlations in grains, fast food, vegetables, and snacks. The study suggests that childhood dietary habits tend to influence adult food choices, offering insights for future research in the field of theory of food (ToF).

Orthorexia and Orthorexia Nervosa: A Comprehensive Examination of Prevalence, Risk Factors, Diagnosis, and Treatment.

Orthorexia nervosa is an emerging and controversial eating disorder characterized by an obsessive preoccupation with healthy eating and an extreme fixation on food purity. Despite growing public interest in orthorexia, its classification as a distinct eating disorder remains a subject of ongoing debate in the mental health community. This paper comprehensively reviews the current literature on orthorexia nervosa, exploring the prevalence rates, risk factors, diagnosis, and treatment options. The paper offers an overview of orthorexia and its historical context and explores the challenges and considerations in diagnosing orthorexia and orthorexia nervosa. Specifically, the distinction between "orthorexia" and "orthorexia nervosa" is a debated issue in eating disorder research due to a lack of clear diagnostic criteria, making it challenging to accurately differentiate between an obsession with healthy eating and a more severe form with potential distress and impairment. Given the absence of formal diagnostic criteria, developing valid and reliable assessment tools is crucial to accurately identify and treat individuals experiencing these disorders. The paper's final section covers the existing treatment approaches for orthorexia nervosa. Overall, the paper highlights the complex and multifaceted nature of orthorexia nervosa. This review contributes to the ongoing discourse surrounding orthorexia and provides valuable insights for clinicians, researchers, and stakeholders in the mental health and eating disorders fields.

Fear conditioning and extinction in anxious and non-anxious youth: A meta-analysis.

Fear conditioning and extinction have been implicated in the etiology and maintenance of anxiety disorders. Most fear conditioning studies have been conducted with adult samples and the few published developmental studies in clinically anxious youth have yielded inconsistent results. The aim of the current review was to use meta-analysis to examine possible differences in fear conditioning and extinction in clinically anxious and non-anxious youth. Seven fear conditioning studies were included in the analysis, with a total of 160 clinically anxious and 166 non-anxious youth. All the studies included in the meta-analysis used a differential conditioning paradigm with at least one or more of the primary dependent variables: self-reported fear, skin conductance response (SCR) and fear potentiated startle (FPS). Similar differential fear acquisition and extinction patterns were observed in anxious and non-anxious individuals. However, anxious youth exhibited stronger fear responses to individual stimuli compared to their non-anxious counterparts. Results in clinically anxious youth resemble those reported in previous studies with clinically anxious adults. Importantly, due to the small number of fear learning studies conducted among youth, these results should be interpreted with caution. Further research is needed so as to better understand fear acquisition and extinction processes in developmental populations. In addition, future studies should focus on other fear-related learning processes such as differences in return of fear, retrieval of fear memory and more subtle differences in fear generalization.

Quantitative ecotoxicological impacts of sewage treatment plant effluents on plankton productivity and assimilative capacity of rivers.

Sewage treatment plants are sources of inorganic and organic matter as well as contaminants for the receiving watercourses. We analyzed the ecological consequences of such effluents by following a holistic and synecological ecotoxicological approach based on quantifying extracellular enzyme activities (EEA), primary production and bacterial cell, and biomass production rates. Samples were obtained at three locations at the Rivers Holtemme and Elbe, Germany and Lower Jordan River, Israel and West Bank, as well as from their adjacent sewage treatment plants. Blending river samples with sewage treatment plant effluents mainly resulted in a stimulation of EEAs, which was diminished in blends with 0.2-µm filtered sewage treatment plant effluents. Stimulation for primary production and bacterial cell and biomass production of River Holtemme and Elbe samples was observed, and inhibition of these rates for Lower Jordan River samples probably linked to generally high turbidity. The quantified bacterial biomass versus cell production rates showed almost unbalanced (≫ 1) growth. Very high biomass to cell production ratios were found for sewage and sewage-containing samples, which provides a semi-quantitative indicator function for high quantities of microbial easy utilizable dissolved organic matter as nutrition source. The presented approach enables the simultaneous quantification of inhibitory and stimulating toxic responses as well as supplying ecosystem-based data for policy decision-making, and for direct incorporation in models to derive management and remediation strategies.

Developmental effects of stimulus gender and the social context in which it appears on threat detection.

This study used a hands-free eye-tracking visual search (VS) task to examine possible developmental differences in target detection. Thirty-two young adults and 27 youth were asked to detect a fearful face (male or female) among a crowd of either neutral or happy faces. Fearful male faces were detected faster than fearful female faces, but only by young adults and only when displayed among neutral faces. Additionally, young adults had shorter scanpath lengths prior to the target detection. Finally, a strong negative correlation emerged between age and detection speed for a male target in a neutral crowd. Using this age-matched VS task, the study found age differences in the way individuals detect a threat in a social-related contextual environment, pointing to subtle differences in the emotion-attention interplay during the course of development. Statement of contribution What is already known on this subject? Visual search of threat detection is critical for survival, specifically regarding expressive faces. Visual search efficiency is affected by both stimulus-driven and higher goal-directed processes. Stimuli and contextual features affect threat speed detection. What does this study add? A novel task was designed to examine age-related differences in visual search. Specific stimuli gender and contextual features yielded age-related differences in threat detection. The study further demonstrates the subtle developmental differences in attention-emotion interaction.

Periaqueductal Grey differential modulation of Nucleus Accumbens and Basolateral Amygdala plasticity under controllable and uncontrollable stress.

Resilience has been conceptualized in part as a dynamic process that includes the ability to adapt to stressful conditions. As such it encompasses the extent to which neural plasticity may be promoted. The current study examined metaplasticity by referring to the "plasticity of synaptic plasticity" in a neural circuit composed of the basolateral amygdala (BLA) and the nucleus accumbens (NAcc), using behavioural stress controllability with or without preceding stimulation of the dorsal periaqueductal gray (i.e. dPAG priming). A tendency for increased plasticity in the controllable versus the uncontrollable group was found in both the BLA and NAcc. dPAG priming suppressed NAcc LTP in all groups, but it suppressed BLA LTP only in the uncontrollable group, demonstrating dissociation between either controllable and uncontrollable groups or the NAcc and BLA. Thus, metaplasticity in the dPAG-BLA-NAcc circuit regulated differentially by controllable or uncontrollable stress may underlie stress coping, and thus contribute to stress-related psychopathologies.

GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.

Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum-BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum-BLA-LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.

Receptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells.

Neuronal transmission is regulated by the local circuitry which is composed of principal neurons targeted at different subcellular compartments by a variety of interneurons. However, mechanisms that contribute to the subcellular localisation and maintenance of GABAergic interneuron terminals are poorly understood. Stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin and its interaction with the guanine nucleotide exchange factor collybistin. Lentiviral knockdown experiments in adult rats indicated that the receptor tyrosine kinase EphA7 is required for the stabilisation of basket cell terminals on proximal dendritic and somatic compartments of granular cells of the dentate gyrus. EphA7 deficiency and concomitant destabilisation of GABAergic synapses correlated with impaired long-term potentiation and reduced hippocampal learning. Reduced GABAergic innervation may be explained by an impact of EphA7 on gephyrin clustering. Overexpression or ephrin stimulation of EphA7 induced gephyrin clustering dependent on the mechanistic target of rapamycin (mTOR) which is an interaction partner of gephyrin. Gephyrin interactions with mTOR become released after mTOR activation while enhanced interaction with the guanine nucleotide exchange factor collybistin was observed in parallel. In conclusion, EphA7 regulates gephyrin clustering and the maintenance of inhibitory synaptic connectivity via mTOR signalling.

Dorsal periaqueductal gray simultaneously modulates ventral subiculum induced-plasticity in the basolateral amygdala and the nucleus accumbens.

The ventral subiculum of the hippocampus projects both to the basolateral amygdala (BLA), which is typically, associated with a response to aversive stimuli, as well as to the nucleus accumbens (NAcc), which is typically associated with a response to appetitive stimuli. Traditionally, studies of the responses to emotional events focus on either negative or positive affect-related processes, however, emotional experiences often affect both. The ability of high-level processing brain regions (e.g., medial prefrontal cortex) to modulate the balance between negative and positive affect-related regions was examined extensively. In contrast, the ability of low-level processing areas (e.g., periaqueductal gray-PAG) to do so, has not been sufficiently studied. To address whether midbrain structures have the ability to modulate limbic regions, we first examined the ventral subiculum stimulation's (vSub) ability to induce plasticity in the BLA and NAcc simultaneously in rats. Further, dorsal PAG (dPAG) priming ability to differentially modulate vSub stimulation induced plasticity in the BLA and the NAcc was subsequently examined. vSub stimulation resulted in plasticity in both the BLA and the NAcc simultaneously. Moreover, depending on stimulus intensity, differential dPAG priming effects on LTP in these two regions were observed. The results demonstrate that negative and positive affect-related processes may be simultaneously modulated. Furthermore, under some conditions lower-level processing areas, such as the dPAG, may differentially modulate plasticity in these regions and thus affect the long-term emotional outcome of the experience.