Early Extinction Research Articles

Neural Processing Dysfunctions During Fear Learning but Not Reward-Related Processing Characterize Depressed Individuals With High Levels of Repetitive Negative Thinking

BackgroundRepetitive negative thinking (RNT) is a symptom dimension of depression that is associated with a poorer prognosis in terms of higher recurrence, treatment resistance, residual symptoms, and disability. This investigation examined whether RNT is associated with aberrant reward processing and fear learning. MethodsVery high RNT (VH-RNT) (n = 60) and high RNT (H-RNT) (n = 60) propensity-matched individuals with depression (age, sex, race/ethnicity, income/employment, body mass index, depressive and anxiety symptom severity) participated in this study along with matched healthy comparison volunteers (n = 30). This propensity-matched sample was selected from the larger Tulsa 1000 study. Participants performed two functional magnetic resonance imaging tasks: the monetary incentive delay task probing reward processing and the fear conditioning task probing aversive learning and extinction. ResultsBoth VH-RNT and H-RNT groups showed lower neural activity than healthy comparison subjects in reward circuitry, including the inferior frontal gyrus (VH-RNT: β = −1.24, H-RNT: β = −1.28) and the cerebellum (VH-RNT: β = −0.93, H-RNT: β = −1.14). However, individuals with VH-RNT exhibited lower activation than those with H-RNT in central autonomic network components during fear conditioning (β = −0.84) and continued conditioned responses during early extinction in the postcentral cortex (β = 0.71). ConclusionsVH-RNT showed aberrant processing in fear conditioning during both learning and extinction phases compared with H-RNT. These findings demonstrate that dysfunctions of negative valence associated with RNT may be domain specific, which should be taken into account for identifying potential specific targets of intervention.

Early Indigenous Extinctions and Modern Deforestation in the Amazon

Early Indigenous Extinctions and Modern Deforestation in the Amazon

Response to Comment on "An early Miocene extinction in pelagic sharks".

Naylor et al. argue that the existence of multiple denticle types within a single species precludes the use of this metric as a measure of the decline of multiple shark species. We show that species-level shark diversity would have to decrease by >90% to account for the observed >70% denticle extinction, implying that the early Miocene shark extinction was larger than previously recognized.

Response to Comment on "An early Miocene extinction in pelagic sharks".

Feichtinger et al. assert that the reduction in denticle abundance and diversity we found are incorrect, claiming that we failed to consider changes in sedimentation rate. However, we used standard methods that explicitly account for changes in sedimentation rate and density. We maintain that our initial dataset and conclusions are robust and provide evidence for a major early Miocene extinction in pelagic sharks.

Comment on "An early Miocene extinction in pelagic sharks".

Sibert and Rubin (Reports, 4 June 2021, p. 1105) report an early Miocene extinction in pelagic sharks based on the loss of shark denticle diversity in two widely separated deep-sea sediment cores. We assert that the pattern observed is not a consequence of extinction but results from shifting species ranges induced by global current reorganization.

Comment on "An early Miocene extinction in pelagic sharks".

Sibert and Rubin (Reports, 4 June 2021, p. 1105) claim to have identified a previously unidentified, major extinction event of open-ocean sharks in the early Miocene. We argue that their interpretations are based on an experimental design that does not account for a considerable rise in the sedimentation rate coinciding with the proposed event, nor for intraspecific variation in denticle morphology.

Genomic signature of sexual reproduction in the bdelloid rotifer Macrotrachella quadricornifera.

Bdelloid rotifers, common freshwater invertebrates of ancient origin and worldwide distribution have long been thought to be entirely asexual, being the principal exception to the view that in eukaryotes the loss of sex leads to early extinction. That bdelloids are facultatively sexual is shown by a study of allele sharing within a group of closely related bdelloids of the species Macrotrachella quadricornifera, supporting the view that sexual reproduction is essential for long-term success in all eukaryotes.

Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources.

Transposons are genomic elements that can relocate within a host genome using a ‘cut’- or ‘copy-and-paste’ mechanism. They make up a significant part of many genomes, serve as a driving force for genome evolution, and are linked with Mendelian diseases and cancers. Interactions between two specific retrotransposon types, autonomous (e.g., LINE1/L1) and nonautonomous (e.g., Alu), may lead to fluctuations in the number of these transposons in the genome over multiple cell generations. We developed and examined a simple model of retrotransposon dynamics under conditions where transposon replication machinery competed for cellular resources: namely, free ribosomes and available energy (i.e., ATP molecules). Such competition is likely to occur in stress conditions that a malfunctioning cell may experience as a result of a malignant transformation. The modeling revealed that the number of actively replicating LINE1 and Alu elements in a cell decreases with the increasing competition for resources; however, stochastic effects interfere with this simple trend. We stochastically simulated the transposon dynamics in a cell population and showed that the population splits into pools with drastically different transposon behaviors. The early extinction of active Alu elements resulted in a larger number of LINE1 copies occurring in the first pool, as there was no competition between the two types of transposons in this pool. In the other pool, the competition process remained and the number of L1 copies was kept small. As the level of available resources reached a critical value, both types of dynamics demonstrated an increase in noise levels, and both the period and the amplitude of predator–prey oscillations rose in one of the cell pools. We hypothesized that the presented dynamical effects associated with the impact of the competition for cellular resources inflicted on the dynamics of retrotransposable elements could be used as a characteristic feature to assess a cell state, or to control the transposon activity.

An early Miocene extinction in pelagic sharks.

Shark populations have been decimated in recent decades because of overfishing and other anthropogenic stressors; however, the long-term impacts of such changes in marine predator abundance and diversity are poorly constrained. We present evidence for a previously unknown major extinction event in sharks that occurred in the early Miocene, ~19 million years ago. During this interval, sharks virtually disappeared from open-ocean sediments, declining in abundance by >90% and morphological diversity by >70%, an event from which they never recovered. This abrupt extinction occurred independently from any known global climate event and ~2 million to 5 million years before diversifications in the highly migratory, large-bodied predators that dominate pelagic ecosystems today, indicating that the early Miocene was a period of rapid, transformative change for open-ocean ecosystems.

Propranolol rescued secondary trauma induced by immediate extinction

<p id="p00005">One hallmark of posttraumatic stress disorder (PTSD) involves impairments in the ability to extinguish conditioned fear memory. Accumulating evidence suggests that extinction training that occurs shortly after fear conditioning is less effective than delayed extinction training in yielding long-term extinction memory, a phenomenon that is referred to as immediate extinction deficit (IED). However, unknown is whether the IED is just an aberration or continues to affect re-extinction. <p id="p00010">This study revealed that the early extinction intervention after severe trauma may not only fail to inhibit the fear response but also act as a secondary trauma which can continually damage the ability to extinguish fear memory. Propranolol may be a good candidate to repair such damage. Our findings improve our understanding of the pathogenesis of PTSD and outcomes of an early intervention and may be helpful for selecting appropriate and effective interventions after trauma exposure and avoid secondary trauma that is caused by the intervention itself. <p id="p00015">In Experiment 1, 32 Sprague-Dawley rats were randomly divided into four groups (Immediate-Extinction, Immediate-No Extinction, Delayed-Extinction, Delayed-No Extinction) and underwent a standard fear conditioning procedure in which they received five tone-footshock trials in chamber A. After either 1 h (immediate) or 24 h (delayed), half of the animals underwent 30 extinction trials (1^st extinction session) in chamber B where the tone was presented alone. The other half remained in chamber B without any tone or footshock (these animals served as a no-extinction control group). Twenty-four hours later, these rats underwent the 2^nd extinction session (re- extinction) in chamber B. Twenty-four hours after the 2^nd extinction session, the rats were once again returned to chamber B and tested for their fear response to four continuous tones. The fear response was assessed by freezing behavior, and the effect of the 1^st extinction session was assessed by the average freezing response across the first four trials of the 2^nd extinction session. Compared with rats in the delayed extinction group, recently conditioned rats exhibited significantly higher levels of fear in the 2^nd extinction session, although an equivalent decline in freezing was observed in both groups across the 1^st extinction session, suggesting that immediate extinction failed to maintain fear suppression the next day. Furthermore, after undergoing two extinction training sessions, rats in the immediate extinction group exhibited no significant reduction of freezing compared with the non-extinguished control during the retention test, suggesting that the deficit reappeared during re-extinction. <p id="p00020">The aim of Experiment 2 was to investigate whether the deficit that was induced by immediate extinction could be rescued by the β-adrenergic receptor antagonist propranolol. In Experiment 2, 20 Sprague-Dawley rats underwent the same procedures as the immediate extinction groups in Experiment 1, with the exception that they received saline or propranolol (10 mg/kg, i.p.) within minutes after fear conditioning. We found that one injection of propranolol immediately after fear acquisition rescued the deficit of re-extinction but not immediate extinction.

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.

Poor fear extinction learning and recall are linked to the development of fear-based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear-related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat-related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma-related psychopathology by facilitating extinction learning. However, how this FAAH variant affects fear extinction neural circuitry remains unknown. In the present study, we used a novel, immersive-reality fear extinction paradigm paired with functional neuroimaging to assess FAAH C385A effects on fear-related neural circuitry and conditioned fear responding (US expectancy ratings, subjective units of distress, and skin conductance responding) in healthy adults from an urban area (Detroit, MI; N=59; C/C=35, A-carrier=24). We found lesser amygdala activation in A-allele carriers, compared to C/C homozygotes, during early extinction recall. Likewise, we found lesser dorsal anterior cingulate cortex and greater hippocampus activation in early extinction learning in A-carriers compared to C/C homozygotes. We found no effects of FAAH C385A on vmPFC activation or behavioral fear indices. These data support and extend previous findings that FAAH genetic variation, associated with increased eCB signaling and subsequent enhanced fear extinction, may predict individual differences in successful fear learning.

Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms in male mice.

Dopaminergic signaling plays an important role in associative learning, including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive one of the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct novel mechanisms by which mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1 receptors. Early extinction training augments both GABA co-release onto dorsomedial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior.

Water Stress is a Key Factor Influencing the Parameter Sensitivity of the WOFOST Model in Different Agro-Meteorological Conditions

Sensitivity analysis is helpful for improving the efficiency and accuracy of the calibration of crop growth models. However, parameter sensitivity is still not well understood when combined with different meteorological and production conditions, especially adverse conditions such as water stress. This study simulated the production of winter wheat in four ecological areas in Henan Province, China. The Extend Fourier Amplitude Sensitivity Test algorithm (EFAST) was used for analyzing the sensitivity of 43 crop parameters of the WOrld FOod STudies (WOFOST) model to yield, aboveground biomass, and leaf area index (LAI) with or without water-limited conditions. The results demonstrated that yield and biomass were the objective outputs, and the main limiting factors for the model results were assimilation and dry matter conversion efficiency. Under water-limited conditions, the parameter sensitivity of related extinction coefficient, early wheat leaf area, and root growth increased with increased water stress. With the process variable LAI as the target output, the parameter sensitivity varied at different growth stages, whereas the parameter sensitivity was almost the same under different agro-meteorological conditions. Under water-limited conditions, the parameter sensitivity of wheat early extinction coefficient, maximum root depth, and death rate of the leaves also increased with increased water stress. Therefore, water stress is a key factor affecting parameter sensitivity under different agro-meteorological conditions.

Effects of repeated anodal transcranial direct current stimulation on auditory fear extinction in C57BL/6J mice

BackgroundTrauma-based psychotherapy is a first line treatment for post-traumatic stress disorder (PTSD) but not all patients achieve long-term remission. Transcranial direct current stimulation (tDCS) received considerable attention as a neuromodulation method that may improve trauma-based psychotherapy. ObjectiveWe explored the effects of repeated anodal tDCS over the prefrontal cortex (PFC) on fear extinction in mice as a preclinical model for trauma-based psychotherapy. MethodsWe performed auditory fear conditioning with moderate or high shock intensity on C57BL6/J mice. Next, mice received anodal tDCS (0.2 mA, 20 min) or sham stimulation over the PFC twice daily for five consecutive days. Extinction training was performed by repeatedly exposing mice to the auditory cue the day after the last stimulation session. Early and late retention of extinction were evaluated one day and three weeks after extinction training respectively. ResultsWe observed no significant effect of tDCS on the acquisition or retention of fear extinction in mice subjected to fear conditioning with moderate intensity. However, when the intensity of fear conditioning was high, tDCS significantly lowered freezing during the acquisition of extinction, regardless of the extinction protocol. Moreover, when tDCS was combined with a strong extinction protocol, we also observed a significant improvement of early extinction recall. Finally, we found that tDCS reduced generalized fear induced by contextual cues when the intensity of conditioning is high and extinction training limited. ConclusionsOur data provide a rationale to further explore anodal tDCS over the PFC as potential support for trauma-based psychotherapy for PTSD.

Siliceous microfossils as a potential age marker for the early Hirnantian Mass Extinction horizon in South China

Abundant cone-shaped siliceous microfossils have been recovered from Upper Ordovician black shales of the Wufeng Formation in South China. They occur in the Hirnantian Metabolograptus extraordinarius Biozone. An investigation of their internal structure conducted using focused ion beam-scanning electron microscope (FIB-SEM) and transmitted light microscope shows that the specimens are possibly composed of three parts: cephalis, thorax and foot. Robust, longitudinal costae are developed, sometimes branching at the thorax. The geological distribution of these microfossils in South China indicates that they occurred in a restricted epicontinental sea on the Upper Yangtze Platform, which was connected to the open ocean in the north. It seems likely that these microfossils have a limited temporal range relative to the Late Ordovician Mass Extinction (LOME) in the early Hirnantian. In the absence of coeval graptolites or other index fossils, their occurrence therefore provides an age marker for the LOME, and has utility for future shale gas exploration in the Wufeng Formation. Xuejin Wu [xjwu@nigpas.ac.cn], State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, 210008, PR China; University of Science and Technology of China, Hefei, 230026, PR China; *Hui Luo* [huiluo@nigpas.ac.cn], State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, 210008, PR China; *Yuandong Zhang [ydzhang@nigpas.ac.cn], State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, 210008, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Chao Li [chaoli@nigpas.ac.cn], State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, 210008, China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.

Catastrophic climate change, population ethics and intergenerational equity

Climate change threatens irreversible and dangerous impacts, possibly leading to extinction. The most relevant trade-off then may not be between present and future consumption but between present consumption and the mere existence of future generations. To investigate this trade-off, we build an integrated assessment model that explicitly accounts for the risk of extinction of future generations. Using the class of number-dampened utilitarian social welfare functions, we compare different climate policies that change the probability of catastrophic outcomes yielding an early extinction. We analyse the role of inequality aversion and population ethics. Low inequality aversion and a preference for large populations favour the most ambitious climate policy, although there are cases where the effect of inequality aversion on the preferred policy is reversed. This is due to the fact that a higher inequality aversion both decreases the welfare loss of reducing consumption of the current generation and also decreases the welfare gain of reducing the future risk of extinction.

Sarmatian biostratigraphy of a marginal sea in northern Croatia based on calcareous nannofossils

Calcareous nannofossils of the Serravallian/Tortonian transition, known as the Sarmatian in the Paratethys were obtained from northern Croatia, Central Paratethys. The nannofossil biostratigraphy of the studied area included early Sarmatian biohorizons; the reliability of these and previous biohorizons was tested, and the known biostratigraphic and magnetostratigraphic datums of the Paratethys were compared with those from the adjacent Mediterranean and beyond. Six out of sixteen bioevents were selected to define five subzones (PNN6d-PNN8b) and crossover for the Badenian/Sarmatian boundary. Variations in the index fossil datums between the Paratethys and Tethys provide a broad perspective on local versus regional and global impacts on the nannofloras. The Paratethys/Tethys gateways (PTGs), and their progressive geodynamical closure, exerted a fundamental control on the salinity, circulation patterns and climate of the area. The global regression at the end of the Badenian, and the tectonic events associated with the Badenian/Sarmatian transition, also restricted the PTGs, initiating acmes of Calcidiscus pataecus and Reticulofenestra pseudoumbilicus, causing a small, early Sarmatian extinction event that occurred in coastal environments, which are the most affected by short-term environmental fluctuations. Stronger connections through the PTGs during the early/mid-Sarmatian transition induced a transgression that brought deep-dwelling Discoaster species into the area. The final closure of the PTG with the Mediterranean, which had been placed at the Badenian/Sarmatian boundary, actually occurred in the late Sarmatian as a result of tectonic movements that caused shallowing and a drastic reduction in nannofossil biodiversity. The PTG with the Indian Ocean existed until the early Tortonian, which allowed an early, but brief, occurrence of small, warm-water ceratoliths.

Measuring fear: Association among different measures of fear learning.

Background and objectivesFear conditioning paradigms use various measures to assess learned fear, including autonomic arousal responses like skin conductance, and self-reports of both associative (US-expectancies) and evaluative (affective ratings) learning. The present study uses a dimensional approach to examine associations among fear indices directly. MethodsSeventy-three participants completed a differential fear conditioning experiment, during which a neutral stimulus (CS+) was paired with an electric shock (US), while another stimulus (CS-) was never paired with the shock (partially instructed fear acquisition). Ten minutes later, both stimuli were presented without any shocks (fear extinction). Skin conductance responses and US-expectancy ratings were recorded during each phase, while self-reported negative affect was assessed for each CS at the end of extinction. ResultsResults showed a positive association among US-expectancy ratings and skin conductance responses during acquisition and early extinction. US-expectancy ratings during overall extinction were positively associated with post-extinction negative affect. LimitationsThe lack of affective ratings post-acquisition may have obscured associations between associative and evaluative learning indices. ConclusionsResults provide evidence for the expected correspondence among different indices of associative fear learning. Findings emphasize the need for incorporating both associative and evaluative learning measures in fear conditioning paradigms.

Two pulses of extinction of larger benthic foraminifera during the Pliensbachian-Toarcian and early Toarcian environmental crises

The early Toarcian (Early Jurassic, ~183 Ma) was characterized by a pronounced oceanic anoxic event (OAE), global warming, major changes in hydrological cycling and a second order mass extinction. Most studies of early Toarcian geobiology have focused on the Northern Hemisphere, and only a few studies have been carried out on strata from the southwestern Tethys Ocean and Southern Hemisphere. This limits our understanding of the geographic extent of the early Toarcian mass extinction (ETME). To address this issue, in this study we have analyzed foraminiferal assemblages from the East Selong and Nianduo sections of South Tibet, China. Our results show that 14 species disappeared during the ETME, accounting for 21.9% (14/64) of overall taxonomic richness. Of these, nine of the victims were larger benthic foraminifera (LBF), accounting for 75% (9/12) of LBF species. We also find that close to the Pliensbachian-Toarcian boundary, six species of foraminifera disappear, and five of these victims were LBF (5/17). Our work thus demonstrates two extinction pulses of LBF in South Tibet, i.e. at the Pliensbachian-Toarcian boundary, and coeval the early Toarcian OAE. The results suggest LBF were more vulnerable to environmental stress than smaller foraminifera, which is consistent with other mass extinctions such as the Permian-Triassic extinction. Our findings confirm that the Southern Hemisphere, like the Northern Hemisphere, was severely affected by environmental changes across the late Pliensbachian to early Toarcian interval, and that extinctions were synchronous with the Northern Hemisphere.

A Rat Model of Cocaine-Alcohol Polysubstance Use Reveals Altered Cocaine Seeking and Glutamate Levels in the Nucleus Accumbens.

Preclinical models of cocaine use disorder are widely utilized to identify neuroadaptations underlying cocaine seeking and to screen medications to reduce seeking. However, while the majority of cocaine users engage in poly-substance use (PSU), a minority of preclinical studies employ PSU models. We previously reported that when rats consume alcohol after daily intravenous cocaine self-administration, nucleus accumbens (NA) core basal glutamate levels are reduced below those of rats that consumed only cocaine, and do not increase during cue + cocaine-primed reinstatement of cocaine-seeking. Here we used the same model of sequential cocaine and alcohol self-administration to test the hypothesis that a similar pattern of glutamate changes would be observed in the NA core prior to and during a cocaine-primed reinstatement test. Rats underwent intravenous cocaine self-administration followed by access to unsweetened alcohol in the home cage for 12 days. Rats underwent a minimum of 12 daily extinction sessions prior to a cocaine-primed reinstatement test conducted during microdialysis procedures. Contrary to our previous work using the same model, here we found that access to alcohol increased cocaine intake and increased responding during early extinction training. We found that as in our previous work, cocaine + alcohol-consuming rats displayed basal glutamate levels below those of rats that self-administered only cocaine. During the cocaine-primed reinstatement test, rats that consumed only cocaine displayed increased glutamate efflux in the NA core while those that consumed cocaine + alcohol did not. These results indicate that preclinical models of PSU should be utilized to develop experimental therapeutics for the reduction of cocaine seeking.