Testing previously proposed models of the Tonic Immobility Scale in a peritraumatic sample of Israeli civilians: Support for a three-factor model.

OBJECTIVE: Tonic immobility (TI) is a peritraumatic response to extreme threats. It is associated with trauma psychopathology and poor treatment outcomes. Yet, previous psychometric evaluations have yielded inconsistent results regarding the number of latent factors of the Tonic Immobility Scale (TIS). Moreover, the TIS has never been validated in a Hebrew-speaking population. This study had two objectives: (a) to reassess previously proposed models of the TIS to determine whether it is best represented by a one-factor model of TI, a two-factor model of TI and fear, or a three-factor model of TI, fear, and detachment; and (b) to validate the TIS in a Hebrew translation. METHOD: A sample of Israeli adults was culled from an online survey following rocket attacks. Confirmatory factor analysis was applied to test the previously proposed models, and Pearson's correlations were used to test the association between each of the subscales representing the latent factors and psychological distress. RESULTS: The best representation of the data was provided by a three-factor model with latent constructs of TI, fear, and detachment. All three peritraumatic responses had significant correlations with peritraumatic distress. Moreover, the internal consistency of the TIS was good for the three subscales; this supports the reliability of the Hebrew version. CONCLUSION: This study supports using a three-factor model with latent constructs, and the scale appears to be psychometrically sound when translated into Hebrew. Future research should seek to replicate these findings in different trauma populations and should study the unique association of trauma symptomatology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Reality of Tonic Immobility in Victims of Sexual Violence: "I was Paralyzed, I Couldn't Move".

Tonic immobility (TI) is a state of temporary, involuntary motor inhibition that occurs in states of intense fear and has been studied among victims of sexual violence. Studies on TI are scarce and mainly focus on rape victims. The present study is a literature review of research that has examined TI in women victims of sexual violence. A database search was carried out using the Preferred data elements for systematic reviews and meta-analyses (PRISMA) method. In order to be included in the analysis, the manuscripts had to deal exclusively with research involving samples of subjects and the study analyzed TI in victims of sexual violence. In all, 11 manuscripts met the above criteria and were included in the review. Research describes that TI is characterized by two factors: fear and immobility. Quantitative research was conclusive in affirming the presence of a state of paralysis and fear in TI. The immobility factor is the determining factor in explaining the victim's lack of defense or resistance and causes effects such as trembling, physical and mental paralysis, inability to vocalize, and eye closure. In addition, TI has been correlated with long-term negative clinical manifestations as victims are more likely to suffer from post-traumatic stress disorder. These findings contribute to an understanding of TI in victims of sexual violence. Therefore, legal and care practitioners must be able to recognize TI to understand the victim's behavior, differentiate it from consent, and to be able to assist in their recovery.

The relationship between tonic immobility and the development, severity, and course of posttraumatic stress disorder: Systematic and meta-analytic literature review.

BACKGROUND: Tonic immobility (TI) is a reflexive, involuntary response that causes motor inhibition, vocal suppression, and analgesia. TI is elicited by extreme fear and perception of entrapment in a life-threatening situation. Research suggests that TI is a frequent peritraumatic response and may be related to subsequent posttraumatic stress disorder (PTSD). However, findings are mixed and, as of yet, no systematic or meta-analytic review examining associations between TI and PTSD has been published. OBJECTIVE: We systematically and meta-analytically reviewed the literature and investigated whether TI is associated with the development, severity, and course of PTSD. Additionally, we evaluated whether different types of traumatic events are differentially associated with TI, and whether TI severity differs according to sex. METHODS: A systematic literature search was conducted using Embase, PubMed, PsycINFO, and Scopus. Meta-analyses were performed on the included articles. RESULTS: We identified 27 eligible articles. We found a significant association between TI and PTSD symptom severity (r = 0.39, 95% CI: 0.34-0.44; p < .0001). TI was more severe among females (Cohen's d=0.37, 95% CI: 0.25-0.48; p < .0001) and was more often elicited in situations involving interpersonal violence. We found limited longitudinal data to perform a meta-analysis of the association between TI and the development and/or course of PTSD. However, the literature available seems to support the role of TI in both the development and course of PTSD. CONCLUSIONS: Peritraumatic TI is associated with PTSD symptom severity, occurs more often during interpersonal violence, and is more severe among females. More longitudinal research is needed to investigate the role of TI in psychopathology development and course.

Differences among domestic chicken breeds in tonic immobility responses as a measure of fearfulness.

Background: One priority for animal welfare is for animals to experience less fear, especially during human contact. For domestic animals, breeds that are less fearful may provide genetic resources to develop strains with improved welfare due to lower susceptibility to fear. Genetic predispositions inherited in these breeds might reflect the large diversity of chicken breeds. The goal of the present study was to systematically test a diverse group of chicken breeds to search for breeds that experience less fear. Methods: Nineteen chicken breeds from commercial hybrid lines, native layer-type, meat-type and dual-purpose breeds, ornamental breeds as well as bantam breeds were tested in a standardized tonic immobility (TI) test. Chickens were manually restrained on their back, and the time to first head movement and first leg movement, the duration of TI, as well as the number of attempts needed to induce TI were measured. Results: The TI response differed among chicken breeds (p ≤ 0.001) for naïve, mature hens. The median number of attempts required to induce TI ranged from 1 to 2 and did not differ significantly among breeds. Median durations were much more variable, with Lohmann Brown showing shortest durations (6 s, 12 s, 58 s for time to first head movement, first leg movement and total duration of TI, respectively). In contrast, medians reached the maximum of 600 s for all three measures in German Creepers. Repeated tests on the same individuals did not affect attempts needed to induce TI nor TI durations. Breeds clustered into two main groups, with layer-type native breeds and ornamental breeds having longer TI durations, and bantam, dual-purpose and meat-type native breeds having shorter TI durations. Conclusions: Our findings provide evidence for substantial variation of fearfulness among breeds. This variation could be linked to the intended use during the breed's specific history. Knowledge and quantitative measurement of these behavioural responses provide the opportunity to improve welfare through selection and future breeding.

Tonic immobility is associated with posttraumatic stress symptoms in healthcare professionals exposed to COVID-19-related trauma.

The Coronavirus Disease 2019 (COVID-19) pandemic has exposed healthcare workers (HCW) to traumatic situations that might lead to the development of posttraumatic stress disorder (PTSD). An important vulnerability factor for PTSD is the peritraumatic tonic immobility (TI) reaction, an involuntary and reflexive defensive response evoked by an intense and inescapable threat. TI is largely understudied in humans and has not been investigated during trauma related to COVID-19. For HCW, the pandemic context might be experienced as an intense and potentially inescapable threat, i.e., an overwhelming situation. Here, we investigated if TI response occurred during traumatic events related to the pandemic and its association with posttraumatic stress symptoms (PTSS). An online survey of 1001 HCW investigated COVID-19-related traumatic experiences, TI and PTSS. TI was reported for all types of traumatic events, and multivariate regression models revealed that TI was significantly associated with PTSS severity. HCW who reported high TI scores exhibited an increase of 9.08 times the probability of having a probable diagnosis of PTSD. Thus, TI was evoked by pandemic-related traumatic situations and associated with PTSS severity and higher odds of a PTSD diagnosis. Tonic immobility occurrence should be screened, and psychoeducation about its reflexive biological nature should be introduced.

Responses to artificial selection for locomotor activity: A focus on death feigning in red flour beetle.

Whole-organism performance, including locomotor activity, is an important fitness trait in many animals. Locomotor activity is often classified into sprint speed and locomotor endurance and differences in sprint speed and locomotor endurance affect on other traits such as life-history traits. Previous studies found that locomotor endurance, sprint speed and brain dopamine (DA) levels are correlated with artificial selection for death feigning (an anti-predator behaviour that we refer to as 'death-feigning syndrome') in some insect species. Thus, if the syndrome has a genetic basis, death feigning, sprint speed and brain DA levels may be affected by artificial selection for locomotor endurance. We artificially selected for locomotor endurance over 10 generations in the red flour beetle Tribolium castaneum, and established higher (H) and lower activity (L) strains, then compared their death-feigning behaviour, sprint speed and brain DA levels. H-strain beetles exhibited significantly shorter duration of death-feigning, and significantly higher sprint speeds, suggesting variation in death-feigning syndrome. Surprisingly, although brain DA expression affects various animal behaviours, we found no significant differences in the brain DA expressions of H- and L-strain beetles. Thus, our results imply genetic correlations between locomotor endurance, sprint speed and death feigning, but not with brain DA expression, suggesting that differences in the biogenic amine results of our and previous studies may reflect differences in behavioural expression mechanisms.

Environmental, ecological and methodological factors of Tonic Immobility (TI) modulation.

Modulation of Tonic Immobility (TI) concerns environmental and individual factors. TI is modulated by processes of habituation and sensitization. In poikilotherm frog and lizard, TI duration is much shorter at usual environmental temperatures and is potentiated at higher or lower temperatures, as the last resource for survival. During ontogeny, age may differentially affect TI susceptibility to the induction procedures, as in the case of newborn ectothermic and older endothermic rabbits. TI duration displays a daily rhythm, with longer TI in the night. Its resistance to habituation indicates that in the dark TI is the most prominent defense against nocturnal predators. In all studied species, there is synchronization of the prey's defensive responses with the feeding activity of predators. Ecological factors and exposure to different anthropogenic environmental pressures may alter morphology, behavior and TI in wild populations. TI duration has been associated with a genomic region comprising the dystrophin gene on quail chromosome 1.

Neurophysiological mechanisms involved in tonic immobility (TI).

This chapter summarizes the main neurophysiological characteristics of tonic immobility (TI), in many susceptible species of mammals and birds. During TI, cortical EEG shows high voltage slow waves whose amount is affected by events preceding TI induction and is positively correlated with TI duration. The pattern of hippocampal activity helps to predict TI onset and TI termination. Both polysynaptic flexor and monosynaptic heteronymous reflexes are depressed independently from the EEG activity. Brain metabolism, signaled by glycogen mobilization and glucose utilization, indicates a reduced neuronal activity during TI. Learned avoidance responses to shock can be extinguished during TI and recover after TI. Moreover, during TI animals may learn how to avoid the shock by a motor response that may be followed by TI interruption. Decortication, decerebellation and telencephalic sections do not affect TI characteristics, whereas ponto-mesencephalic sections abolish both righting reflexes and TI.

Neuroendocrine correlates of stress and tonic immobility.

Threatening stimuli challenging animal homeostasis are the primary events triggering defensive responses, including TI. The stress-response system (allostasis) is signaled by increased corticosteroid basal levels. In bird animal lines genetically selected for stress-induced corticosterone, there is a covariation between stress physiology and coping styles. Rabbit studies, in which the effects of TI are dissociated from those of induction per se, support the view that TI takes part in the homeostatic stress-response system. An increase of corticosterone is recorded just after the end of the induction procedure but not in the corresponding groups in which induction is followed by TI, suggesting a recovery process during TI. Similarly to corticosterone but in opposite direction, testosterone plasma levels decrease following induction and recover during TI. Recovery mechanisms are also suggested in two bird genotypes selected for long and short TI duration. The positive relation between corticosterone levels and TI duration has been confirmed after exogenous corticosterone administration.

Autonomic correlates of defense responses, including tonic immobility (TI).

Animal models of autonomic correlates of defense behavior range from fish to mammals. There is however no study reporting heart and respiratory rate, blood pressure and body temperature simultaneously recorded in the same animal in association to different forms of immobility in response to threat: freezing, restraint-sustained immobility and tonic immobility (TI). In a prey/ predator context freezing behavior is associated with bradycardia and no change in blood pressure but in other conditions (e.g., extreme stressful stimuli) may be associated with tachycardia and hypertension. Restraint-sustained immobility does not affect blood pressure but may reduce heart rate according to the type of stimulus and mechanical pressure. Blood pressure and heart rate oscillate during TI induction and adjust at basal levels during TI, sometimes gradually decreasing below basal levels. In conclusion, in all these passive defense responses, the immobility is not due to a blood pressure collapse.

Tonic immobility as a survival, adaptive response and as a recovery mechanism.

In this conclusive chapter, we review findings giving support to the hypothesis that TI represents an adaptive, survival response to threatening situations. In models of prey-predator interactions, in vertebrates and invertebrates, there are evidence that immobility per se contributes to survival, as the predator loses interest for a prey in which TI is experimentally induced. TI duration is also reciprocally modulated by the evaluation of the risk factors in the environment, and by the opportunity to reach a safe refuge. This supports the adaptive value of TI and suggests that, during TI, the animal may be transiently aware of the environmental situation. As for the adaptive value of TI, genetic correlations with other behavioral systems contributing to fitness (e.g., mating) are taken into account. Moreover, neurophysiological and endocrine findings in mammals support our hypothesis that TI activates the mechanisms responsible for recovery from disruptive experiences and body lesions.

Synthesis of defense response characteristics.

In previous chapters, the available theories and experimental findings related to animals' defense responses have been reported and discussed in detail. This chapter reports their comprehensive synthesis, considering the main immobility-related responses in defense. Within the same modality (i.e., immobility) different kinds of immobility may in fact correspond to different functions and motivations, as proved by their neurobiological correlates profile.

Neurochemical anatomy of dorsal and tonic immobility responses.

The dorsal immobility response (DIR) and the tonic immobility response (TIR) are cutaneo-motor reflexes typically triggered when a prey is seized. The neurochemical basis of the DIR appears to pass through the basal ganglia via dopaminergic fibers, while the neurochemical basis of the TIR appears to include a circuit comprising the amygdala, the periaqueductal gray (PAG), the dorsal raphe, and the nucleus magnus raphe (NMR) via glutamatergic, serotonergic, cholinergic, GABAergic, and opioid fibers. For the DIR, the basal ganglia also seem to be involved in regard to estradiol, while for the TIR, the HPA axis appears involved at the level of the amygdala and the oral pontine reticular nucleus.

Genomic characterization between strains selected for death-feigning duration for avoiding attack of a beetle.

Predator avoidance is an important behavior that affects the degree of adaptation of organisms. We compared the DNA variation of one of the predator-avoidance behaviors, the recently extensively studied "death-feigning behavior", between the long strain bred for feigning death for a long time and the short strain bred for feigning death for a short time. To clarify how the difference in DNA sequences between the long and short strains corresponds to the physiological characteristics of the death-feigning duration at the transcriptome level, we performed comprehensive and comparative analyses of gene variants in Tribolium castaneum strains using DNA-resequencing. The duration of death feigning involves many gene pathways, including caffeine metabolism, tyrosine metabolism, tryptophan metabolism, metabolism of xenobiotics by cytochrome P450, longevity regulating pathways, and circadian rhythm. Artificial selection based on the duration of death feigning results in the preservation of variants of genes in these pathways in the long strain. This study suggests that many metabolic pathways and related genes may be involved in the decision-making process of anti-predator animal behavior by forming a network in addition to the tyrosine metabolic system, including dopamine, revealed in previous studies.

Should Catatonia Be Conceptualized as a Pathological Response to Trauma?

ABSTRACT: Although catatonia is related to several medical conditions, catatonia as a response to trauma and posttraumatic stress disorder (PTSD) is less clear. The aim of this review is to explore the small emerging body of preliminary evidence that suggests a possible correlation between psychological trauma and catatonia. Initial data suggests a correlation between episodes of intense fear associated with trauma and PTSD and some forms of catatonic responses. Although this relationship is still speculative to be causative, it can have important implications if confirmed. This is especially salient when it is examined alongside existing studies of the response to fear in animals and the phenomenon of tonic immobility, which bears a striking resemblance to catatonia in humans. If prospective studies further support the initial findings, it could change our conceptual understanding of the etiology of a subtype of catatonia substantially while pointing to likely targets of further research to understand the biological mechanisms that underlie the illness.

The use of behavioral tests of fearfulness in chicks to distinguish between the Japanese native chicken breeds, Tosa-Kukin and Yakido.

The aim of this study was to investigate the differences in fearfulness between two Japanese native chicken breeds, Tosa-Kukin (TOK) and Yakido (YKD). In a tonic immobility test, TOK breed chicks showed longer duration and lower induction number compared with YKD. The number of peeps in YKD in an isolation test was lower than that in TOK, whereas there were more bouts of peeping in YKD than in TOK. In a manual restraint test, YKD showed more active responses and initiated peeps and struggling earlier than TOK. The three behavioral tests all indicated that YKD are less fearful than TOK chickens. A latent structures discriminant (OPLS-DA) analysis was used to identify behavioral parameters that contributed to the differences between the breeds. The major parameters were duration and number of inductions in the tonic immobility test and number of struggle in the manual restraint test. These results suggest that three behavioral tests can be used together to evaluate fearfulness of Japanese native breeds of chickens.

Genetic Architecture of Innate Fear Behavior in Chickens.

The genetic architecture of innate fear behavior in chickens is poorly understood. Here, we performed quantitative trait loci (QTL) analysis of innate responses to tonic immobility (TI) and open field (OF) fears in 242 newly hatched chicks of an F2 population between the native Japanese Nagoya breed and the White Leghorn breed using 881 single nucleotide polymorphism markers obtained by restriction site-associated DNA sequencing. At genome-wide 5% significance levels, four QTL for TI traits were revealed on chromosomes 1-3 and 24. Two of these loci had sex-specific effects on the traits. For OF traits, three QTL were revealed on chromosomes 2, 4 and 7. The TI and OF QTL identified showed no overlaps in genomic regions and different modes of inheritance. The three TI QTL and one OF QTL exerted antagonistic effects on the traits. The results demonstrated that context-dependent QTL underlie the variations in innate TI and OF behaviors.

Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease.

Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.

Chemogenetic inhibition of lateral habenula projections to the dorsal raphe nucleus reduces passive coping and perseverative reward seeking in rats.

The lateral habenula (LHb) processes information about aversive experiences that contributes to the symptoms of stress disorders. Previously, we found that chemogenetic inhibition of rat LHb neurons reduced immobility in the forced swim test, but the downstream target of these neurons was not known. Using an intersectional viral vector strategy, we selectively transduced three different output pathways from the LHb by injecting AAV8-DIO-hM4Di into the LHb and CAV2-CRE (a retrograde viral vector) into one of the three target areas as follows: dorsal raphe nucleus (DRN), ventral tegmental area (VTA), or rostromedial tegmentum (RMTg). Using the forced swim test, we found that chemogenetic inhibition of DRN-projecting LHb neurons reduced passive coping (immobility), whereas inhibition of the other pathways did not. Chemogenetic activation of DRN-projecting neurons using hM3Dq in another cohort did not further exacerbate immobility. We next examined the impact of inhibiting DRN-projecting LHb neurons on reward sensitivity, perseverative behavior, and anxiety-like behavior using saccharin preference testing, reward-omission testing, and open-field testing, respectively. There was no effect of inhibiting any of these pathways on reward sensitivity, locomotion, or anxiety-like behavior, but inhibiting DRN-projecting LHb neurons reduced perseverative licking during reward-omission testing, whereas activating these neurons increased perseverative licking. These results support the idea that inhibiting LHb projections to the DRN provides animals with resilience during highly stressful or frustrating conditions but not under low-stress circumstances, and that inhibiting these neurons may promote persistence in active coping strategies.

Assaying Fear Memory Discrimination and Generalization: Methods and Concepts.

Generalization describes the transfer of conditioned responding to stimuli that perceptually differ from the original conditioned stimulus. One arena in which discriminant and generalized responding is of particular relevance is when stimuli signal the potential for harm. Aversive (fear) conditioning is a leading behavioral model for studying associative learning and memory processes related to threatening stimuli. This article describes a step-by-step protocol for studying discrimination and generalization using cued fear conditioning in rodents. Alternate conditioning paradigms, including context generalization, differential generalization, discrimination training, and safety learning, are also described. The protocol contains instructions for constructing a cued fear memory generalization gradient and methods for isolating discrete cued-from-context cued conditioned responses (i.e., "the baseline issue"). The preclinical study of generalization is highly pertinent in the context of fear learning and memory because a lack of fear discrimination (overgeneralization) likely contributes to the etiology of anxiety-related disorders and post-traumatic stress disorder. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Tone cued fear generalization gradient Basic Protocol 2: Quantification of freezing Support Protocol: Alternate conditioning paradigms.