State-dependent Effects Research Articles

Measuring the State Dependence Effect in Hospital Payment Adjustment.

Since FY 2013, as a part of the Affordable Care Act (ACA) program, the Hospital Value-Based Purchasing (HVBP) program has adjusted Medicare's payments to hospitals based on the total performance score of the hospital. First, the program reduces a portion of the hospital's Medicare payments in a specific fiscal year, and then, by the end of the same fiscal year, the amount of the payment reductions will be awarded to the hospitals based on the total performance score; thus, the hospitals that do not receive the reward will lose the portion of money reduced by Medicare. In this research, we apply the theory of state dependence and use the dynamic random effect probit model to estimate this effect. The results show that the hospital payment adjustment dynamics have a very significant state dependence effect (0.341); this means that hospitals that received a reward in the previous year are 34.1% more likely to receive a reward this year than the ones that received a penalty in the previous year. Meanwhile, we also find that the state dependence effect varies significantly across hospitals with different ownership (proprietary/government owned/voluntary nonprofit), and the results show that voluntary nonprofit hospitals exhibit the largest effect of state dependence (0.370), while government-owned hospitals exhibit the lowest effect of state dependence (0.293), and proprietary hospitals are in the middle. Among the factors that influence the likelihood that a hospital receives a reward, we find that teaching hospitals with a large number of beds (>400) are less likely be rewarded; in terms of ownership, we find that voluntary nonprofit hospitals are more likely be rewarded; in terms of demographic factors, hospitals where the average household income are higher within the region are more likely be rewarded.

Public debt and state-dependent effects of fiscal policy in the euro area

We investigate public debt related state dependencies of fiscal policy shocks for fifteen euro area economies during the period from 2000:Q1 to 2019:Q4. Our estimated impulse response functions suggest that the impact of fiscal policy shocks varies depending on the level of public debt characterizing an economy. Macroeconomic variables, notably output and consumption, go up in response to a positive government spending shock in the high-debt cross-sectional state, and these responses are distinctly different from those in the low-debt state. Using an extended model that considers both cross-sectional and time-serial high- and low-debt states we find that, for euro area economies, cross-sectional debt variation is more important than time-serial debt variation in driving differences in the responses of macroeconomic variables to government spending shocks.

Altered functional and directed connectivity in propofol-induced loss of consciousness: A source-space resting-state EEG study

ObjectiveGeneral anesthesia might disrupt neuronal network communications measured by functional connectivity (FC; undirected connectivity) and directional information flow (directed connectivity). We sought to characterize the state-dependent effects of propofol on cortico-cortical undirected and directed FC. MethodsWe collected 256-channel high-density EEGs from 14 patients undergoing surgery while awake (AWA) or in propofol-induced moderate sedation (SED) or loss of consciousness (LOC) states. Using source-space EEG, we estimated neuronal oscillatory activity for 68 cortical regions of interest. FC was analyzed using the weighted phase lag index. Directed connectivity was computed using directed phase transfer entropy (dPTE) as a measure of information flow in the bilateral prefrontal, frontal, parietal, and occipital areas. ResultsFC strength evidently reduced during LOC compared with those during the AWA and SED states. The dPTE analysis showed significant propofol-induced changes in directed connectivity. In the alpha band, the prefrontal-to-frontal information flow was significantly stronger in the AWA than in the SED (p = 0.033) and LOC states (p = 0.033). The parietal-to-frontal dPTE was significantly weaker during LOC than during the AWA (p = 0.033) and SED states (p = 0.007). Finally, a loss of occipital-to-frontal connectivity occurred during LOC but not the AWA state (p = 0.001). In the beta band, the dominant occipital-to-frontal direction of information flow in the AWA state was gradually converted to a frontal-to-occipital direction during LOC. ConclusionsPropofol-induced unconsciousness is marked by a decrease in FC and posterior-to-anterior (feedforward) directed connectivity, which may be useful as a measure to discriminate different conscious states caused by propofol administration. SignificanceThe study demonstrates that propofol produces state-dependent effects on cortico-cortical undirected and directed FC, supporting the idea that propofol induces loss of consciousness may through disrupting network interactions and cortical coordination.

State-dependent tDCS modulation of the somatomotor network: A MEG study

ObjectiveTranscranial direct current stimulation (tDCS) is a non-invasive technique widely used to investigate brain excitability and activity. However, the variability in both brain and behavioral responses to tDCS limits its application for clinical purposes.This study aims to shed light on state-dependency, a phenomenon that contributes to the variability of tDCS. MethodsTo this aim, we investigated changes in spectral activity and functional connectivity in somatomotor regions after Real and Sham tDCS using generalized additive mixed models (GAMMs), which allowed us to investigate how modulation depends on the initial state of the brain. ResultsResults showed that changes in spectral activity, but not connectivity, in the somatomotor regions depend on the initial state of the brain, confirming state-dependent effects. Specifically, we found a non-linear interaction between stimulation conditions (Real vs Sham) and initial state: a reduction of alpha and beta power was observed only in participants that had higher alpha and beta power before Real tDCS. ConclusionsThis study highlights the importance of considering state-dependency to tDCS and shows how it can be taken into account with appropriate statistical models. SignificanceOur findings bear insight into tDCS mechanisms, potentially leading to discriminate between tDCS responders and non-responders.

State dependence of arousal from torpor in brown long-eared bats (Plecotus auritus)

To cope with periods of low food availability and unsuitable environmental conditions (e.g., short photoperiod or challenging weather), many heterothermic mammals can readily go into torpor to save energy. However, torpor also entails several potential costs, and quantitative energetics can, therefore, be influenced by the individual state, such as available energy reserves. We studied the thermal energetics of brown long-eared bats (Plecotus auritus) in the northern part of its distributional range, including torpor entry, thermoregulatory ability during torpor and how they responded metabolically to an increasing ambient temperature (Ta) during arousal from torpor. Torpor entry occurred later in bats with higher body mass (Mb). During torpor, only 10 out of 21 bats increased oxygen consumption (V̇O2) to a greater extent above the mean torpor metabolic rates (TMR) when exposed to low Ta. The slope of the torpid thermoregulatory curve was shallower than that of resting metabolic rate (RMR) during normothermic conditions, indicating a higher thermal insulation during torpor. During exposure to an increasing Ta, all bats increased metabolic rate exponentially, but the bats with higher Mb aroused at a lower Ta than those with lower Mb. In bats with low Mb, arousal was postponed to an Ta above the lower critical temperature of the thermoneutral zone. Our results demonstrate that physiological traits, which are often considered fixed, can be more flexible than previously assumed and vary with individual state. Thus, future studies of thermal physiology should to a greater extent take individual state-dependent effects into account.

Nonlinear unemployment effects of the inflation tax

Long-run inflation has nonlinear and state-dependent effects on unemployment, output, and welfare. We show this using a standard monetary search model with two shocks – productivity and monetary – and frictions in both labor and goods markets. Inflation lowers the surplus from a worker–firm match, in turn making it more sensitive to both productivity shocks and further increases in inflation. We calibrate the model to match key aspects of the US labor market and monetary data. The calibrated model is consistent with a number of empirical correlations, which we document using panel data from the OECD: (1) there is a positive long-run relationship between anticipated inflation and unemployment; (2) there is also a positive correlation between anticipated inflation and unemployment volatility; (3) the long-run inflation-unemployment relationship is stronger when unemployment is higher. The key mechanism through which the model generates these results is the negative effect of inflation on measured output per worker, which is likewise consistent with cross-country data. Finally, we show that the welfare cost of inflation is nonlinear in the level of inflation and is amplified by the presence of aggregate uncertainty.

Business cycle asymmetries and the labor market

This paper shows that a search and matching model with idiosyncratic training cost shocks can explain the asymmetric movement of the job-finding rate over the business cycle and the decline of matching efficiency in recessions. Large negative aggregate shocks move the hiring cutoff into a part of the training cost distribution with higher density. The position of the hiring cutoff in the distribution is disciplined by the empirical elasticity of the job-finding rate with respect to market tightness. Our model explains a large fraction of the matching efficiency decline during the Great Recession and generates state-dependent effects of policy interventions.

Hunger state and not personality determines task participation in a spider society

Task specialization is a hallmark of social success as it can minimize among-individual conflict in task participation, and thereby optimize colony productivity. Task specialization is therefore predicted to manifest as a consequence of social evolution. While age or caste in some species explains task participation, a recent hypothesis states that personality type determines differential task participation and thereby facilitates specialization. The social spider Stegodyphus sarasinorum exhibits no castes or conspicuous dominance hierarchies or age polyethism yet shows consistent among-individual differences in prey capture. We tested whether one personality trait (boldness) determines task specialization by exploring the determinants causing consistent participation in prey attack. By integrating a personality type and individual hunger, we tested two mutually exclusive hypotheses. (1) Among-individual differences in personality determine consistent differences in participation in prey capture, leading to specialization. (2) Individuals are flexible, and individual hunger state determines the propensity to capture prey. We found that hunger state was the only significant determinant of attacking prey. By reversing individual hunger state, we were able to dramatically increase or decrease individual attack propensities. Spiders exhibited consistent among-individual differences in boldness, yet this personality type did not predict foraging participation. Therefore, we found no evidence for behavioural specialization in prey capture. Our study emphasizes the importance of internal state as a mechanism underlying variable task participation, suggesting caution in attributing behavioural specialization to personality without appropriate integration of state-dependent effects.

An efficient and scalable data analysis solution for automated electrophysiology platforms.

Ion channels are drug targets for neurologic, cardiac, and immunologic diseases. Many disease-associated mutations and drugs modulate voltage-gated ion channel activation and inactivation, suggesting that characterizing state-dependent effects of test compounds at an early stage of drug development can be of great benefit. Historically, the effects of compounds on ion channel biophysical properties and voltage-dependent activation/inactivation could only be assessed by using low-throughput, manual patch clamp recording techniques. In recent years, automated patch clamp (APC) platforms have drastically increased in throughput. In contrast to their broad utilization in compound screening, APC platforms have rarely been used for mechanism of action studies, in large part due to the lack of sophisticated, scalable analysis methods for processing the large amount of data generated by APC platforms. In the current study, we developed a highly efficient and scalable software workflow to overcome this challenge. This method, to our knowledge the first of its kind, enables automated curve fitting and complex analysis of compound effects. Using voltage-gated sodium channels as an example, we were able to immediately assess the effects of test compounds on a spectrum of biophysical properties, including peak current, voltage-dependent steady state activation/inactivation, and time constants of activation and fast inactivation. Overall, this automated data analysis method provides a novel solution for in-depth analysis of large-scale APC data, and thus will significantly impact ion channel research and drug discovery.

Motivational state-dependent renewal and reinstatement: Discriminative and motivational functions of food deprivation and satiation states

Interoceptive stimuli (e.g., those associated with drugs and other motivational/emotional states) can acquire discriminative control over behavior when they are reliably correlated with particular Pavlovian or operant contingencies. This has been called state-dependent learning. Recent studies have shown that extinction learning can be specific to the interoceptive context in which it occurs, and interoceptive conditions can also contribute to the state-dependent renewal of operant behavior following extinction. Many of the events that induce interoceptive conditions that may contribute to renewal following extinction in this way concurrently function as motivating operations (MOs) that alter the value of reinforcers for operant behavior, and these functions may also contribute to the recovery of extinguished behavior. Three experiments were conducted to study interactions between the discriminative functions of interoceptive contexts associated with food deprivation and satiation MOs and their motivational functions in the renewal and reinstatement of extinguished operant behavior. We found evidence of the motivational state-dependent effects of extinction, as well as state-dependent renewal and reinstatement of operant behavior under food deprivation conditions. However, state-dependent renewal and reinstatement were not observed under food satiation conditions, even when these served as acquisition or non-extinction contexts. The results suggest that interoceptive states associated with food deprivation/satiation MOs can serve as discriminative parts of context that contribute to the recovery of extinguished operant behavior, but that relatively little renewal/reinstatement may be expected in the absence of the relevant motivational conditions.

State-dependent effects of neural stimulation on brain function and cognition.

Invasive and non-invasive brain stimulation methods are widely used in neuroscience to establish causal relationships between distinct brain regions and the sensory, cognitive and motor functions they subserve. When combined with concurrent brain imaging, such stimulation methods can reveal patterns of neuronal activity responsible for regulating simple and complex behaviours at the level of local circuits and across widespread networks. Understanding how fluctuations in physiological states and task demands might influence the effects of brain stimulation on neural activity and behaviour is at the heart of how we use these tools to understand cognition. Here we review the concept of such 'state-dependent' changes in brain activity in response to neural stimulation, and consider examples from research on altered states of consciousness (for example, sleep and anaesthesia) and from task-based manipulations of selective attention and working memory. We relate relevant findings from non-invasive methods used in humans to those obtained from direct electrical and optogenetic stimulation of neuronal ensembles in animal models. Given the widespread use of brain stimulation as a research tool in the laboratory and as a means of augmenting or restoring brain function, consideration of the influence of changing physiological and cognitive states is crucial for increasing the reliability of these interventions.

The Mesencephalic Locomotor Region: Beyond Locomotor Control.

The mesencephalic locomotor region (MLR) was discovered several decades ago in the cat. It was functionally defined based on the ability of low threshold electrical stimuli within a region comprising the cuneiform and pedunculopontine nucleus to evoke locomotion. Since then, similar regions have been found in diverse vertebrate species, including the lamprey, skate, rodent, pig, monkey, and human. The MLR, while often viewed under the lens of locomotion, is involved in diverse processes involving the autonomic nervous system, respiratory system, and the state-dependent activation of motor systems. This review will discuss the pedunculopontine nucleus and cuneiform nucleus that comprises the MLR and examine their respective connectomes from both an anatomical and functional angle. From a functional perspective, the MLR primes the cardiovascular and respiratory systems before the locomotor activity occurs. Inputs from a variety of higher structures, and direct outputs to the monoaminergic nuclei, allow the MLR to be able to respond appropriately to state-dependent locomotion. These state-dependent effects are roughly divided into escape and exploratory behavior, and the MLR also can reinforce the selection of these locomotor behaviors through projections to adjacent structures such as the periaqueductal gray or to limbic and cortical regions. Findings from the rat, mouse, pig, and cat will be discussed to highlight similarities and differences among diverse species.

Estrous cycle contributes to state-dependent contextual fear in female rats

The increased susceptibility of women to stress and trauma-related disorders compared to men suggests a role for ovarian hormones in modulating fear and anxiety. In both humans and rodents, estrogen and progesterone have been shown to influence fear learning during acquisition, expression, and extinction. Recently, we showed that allopregnanolone (ALLO), a progesterone (PROG) metabolite and GABAA receptor potentiator, confers state-dependent contextual fear when infused into the bed nucleus of the stria terminalis of male rats. In order to determine whether estrous cycle-related fluctuations in circulating PROG confer state-dependent contextual fear in female rats, animals received Pavlovian fear conditioning during an estrous cycle phase when PROG was either low (late diestrus) or high (late proestrus). After conditioning, animals were tested for contextual fear in either the same or different estrous cycle phase. Subjects conditioned in diestrus and tested in proestrus showed lower levels of contextual fear compared to subjects conditioned and tested in the same estrous cycle phase (either diestrus or proestrus), suggesting a state-dependent effect of estrous cycle phase on fear learning. This state dependence was asymmetric, however, as animals trained in proestrus and tested in diestrus exhibited high levels of contextual fear. In ovariectomized (OVX) females treated acutely with either PROG or vehicle, state dependence was not observed. These results suggest that the hormonal state in diestrus may play a role in conferring state dependence to conditioned fear in naturally cycling female rats but not in an OVX model.

Bottlenecks, Modularity, and the Neural Control of Behavior.

In almost all animals, the transfer of information from the brain to the motor circuitry is facilitated by a relatively small number of neurons, leading to a constraint on the amount of information that can be transmitted. Our knowledge of how animals encode information through this pathway, and the consequences of this encoding, however, is limited. In this study, we use a simple feed-forward neural network to investigate the consequences of having such a bottleneck and identify aspects of the network architecture that enable robust information transfer. We are able to explain some recently observed properties of descending neurons—that they exhibit a modular pattern of connectivity and that their excitation leads to consistent alterations in behavior that are often dependent upon the desired behavioral state of the animal. Our model predicts that in the presence of an information bottleneck, such a modular structure is needed to increase the efficiency of the network and to make it more robust to perturbations. However, it does so at the cost of an increase in state-dependent effects. Despite its simplicity, our model is able to provide intuition for the trade-offs faced by the nervous system in the presence of an information processing constraint and makes predictions for future experiments.

State-Dependent Effects of Monetary Policy: The Refinancing Channel

This paper studies how the impact of monetary policy depends on the distribution of savings from refinancing mortgages. We show that the efficacy of monetary policy is state dependent, varying in a systematic way with the pool of potential savings from refinancing. We construct a quantitative dynamic life-cycle model that accounts for our findings and use it to study how the response of consumption to a change in mortgage rates depends on the distribution of savings from refinancing. These effects are strongly state dependent. We also use the model to study the impact of a long period of low interest rates on the potency of monetary policy. We find that this potency is substantially reduced both during the period and for a substantial amount of time after interest rates renormalize. (JEL D15, E21, E43, E52, G21, G51, R31)

Enhanced antidepressant-like effects of a delta opioid receptor agonist, SNC80, in rats under inflammatory pain

Depression is a debilitating mental disorder that affects a large population worldwide. Depression and pain comorbidity is well recognized in both clinical and preclinical settings. Research studies suggest delta opioid receptor (DOR) may be involved in modulating pain as well as depression. DOR agonists produce antidepressant-like effects in animal models and their antihyperalgesic effects are enhanced in rats under inflammatory pain. However, it is unclear whether the antidepressant-like effects of DOR agonists may change in the models of pain. In this study, the antidepressant-like effects of a DOR agonist, SNC80, and a tricyclic antidepressant, amitriptyline, were compared following intracerebroventricular (i.c.v.) administration in rats under normal or inflammatory pain state elicited by injection of complete Freund's adjuvant. The forced swim test was used to determine the antidepressant-like effects. Results showed that i.c.v. SNC80 and amitriptyline dose-dependently produced antidepressant-like effects in rats under normal state. The potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. This study provides functional evidence of the state-dependent effects of DOR agonists and suggests that DOR agonists may be more effective as potential antidepressants for patients experiencing both depression and pain.

Prospective examination of pre-trauma anhedonia as a risk factor for post-traumatic stress symptoms

ABSTRACT Background Anhedonia, the reduction of pleasure and reward-seeking behaviour, is a transdiagnostic symptom with well-described neural circuit mediators. Although typically observed during disease state, extant hypotheses suggest that anhedonia may also be an early risk factor for development of psychopathology. Understanding the contribution of anhedonia to the trauma-response trajectory may bolster inferences about biological mechanisms contributing to pre-trauma risk versus trauma-related symptom expression, knowledge of which could aid in targeted interventions. Objective Using a prospective, longitudinal design in a population at risk for trauma disorders, we tested the hypothesis that anhedonia may be a pre-trauma risk factor for post-traumatic stress disorder (PTSD) symptoms. Methods Adult male participants from the Marine Resilience Study (N = 2,593) were assessed across three time-points (pre-deployment, 3-month and 6-month post-deployment). An anhedonia factor was extracted from self-report instruments pre-trauma and tested for its relationship with development of PTSD re-experiencing symptoms after deployment. Results Higher pre-deployment anhedonia predicted increased PTSD intrusive re-experiencing symptoms at 3- and 6-months post-deployment when controlling for pre-trauma PTSD and depression symptoms. Depression symptoms were not significant predictors of subsequent PTSD intrusive re-experiencing symptoms. Anhedonia at 3 mo also robustly predicted maintenance of PTSD intrusive re-experiencing symptoms at the 6 mo time point. Conclusions Pre-deployment anhedonia may be a pre-trauma risk factor for PTSD, not simply a state-dependent effect of trauma exposure and PTSD symptom expression. Anhedonia may contribute to persistence and/or chronicity of re-experiencing symptoms after the emergence of PTSD symptoms.

Mechanisms of Memory Updating: State Dependency vs. Reconsolidation.

Reactivating a memory trace has been argued to put it in a fragile state where it must undergo a stabilization process known as reconsolidation. During this process, memories are thought to be susceptible to interference and can be updated with new information. In the spatial context paradigm, memory updating has been shown to occur when new information is presented in the same spatial context as old information, an effect attributed to a reconsolidation process. However, the integration concept holds that memory change can only occur when reactivation and test states are the same, similar to a state-dependent effect. Thus, in human episodic memory, memory updating should only be found when state is the same across the study, reactivation, and test sessions. We investigated whether memory updating can be attributed to state dependency in two experiments using mood as a state. We found evidence of memory updating only when mood was the same across all sessions of the experiments, lending support to the integration concept and posing a challenge to a reconsolidation explanation.

State-Dependent Effects of Tax Changes in Germany and the United Kingdom

We study state-dependent effects of narratively identified tax shocks in Germany and the UK over the period 1974Q1–2018Q4 using local projections. In addition, we distinguish between aggregated and disaggregated tax types (direct and indirect taxes) as well as look for possible asymmetries between tax hikes and tax cuts. We find a number of differences across the business cycle, and between sample countries, tax types, and direction of tax changes. For instance, aggregated tax cuts initially have a larger effect during times of nonrecession in Germany, whereas we find no state-dependent effects for the UK. When disaggregating tax types, German indirect tax cuts only appear expansionary during downturns, whereas the effect is positive throughout the business cycle in the UK. Furthermore, we find different reactions when considering tax cuts and hikes individually: tax hikes can be expansionary in Germany (UK) when implemented during non-recessionary (recessionary) periods whereas they are contractionary during recessions (non-recessions). When considering tax cuts, German GDP rises only when cuts are enacted in times of non-recession, whereas in the UK, the reactions is positive in either case and mostly symmetric. All these findings are robust to various changes in the econometric setup.

Nonlinear effects of instantaneous and delayed state dependence in a delayed feedback loop

<p style='text-indent:20px;'>We study a scalar, first-order delay differential equation (DDE) with instantaneous and state-dependent delayed feedback, which itself may be delayed. The state dependence introduces nonlinearity into an otherwise linear system. We investigate the ensuing nonlinear dynamics with the case of instantaneous state dependence as our starting point. We present the bifurcation diagram in the parameter plane of the two feedback strengths showing how periodic orbits bifurcate from a curve of Hopf bifurcations and disappear along a curve where both period and amplitude grow beyond bound as the orbits become saw-tooth shaped. We then 'switch on' the delay within the state-dependent feedback term, reflected by a parameter <inline-formula><tex-math id="M1">\begin{document}$ b>0 $\end{document}</tex-math></inline-formula>. Our main conclusion is that the new parameter <inline-formula><tex-math id="M2">\begin{document}$ b $\end{document}</tex-math></inline-formula> has an immediate effect: as soon as <inline-formula><tex-math id="M3">\begin{document}$ b>0 $\end{document}</tex-math></inline-formula> the bifurcation diagram for <inline-formula><tex-math id="M4">\begin{document}$ b = 0 $\end{document}</tex-math></inline-formula> changes qualitatively and, specifically, the nature of the limiting saw-tooth shaped periodic orbits changes. Moreover, we show — numerically and through center manifold analysis — that a degeneracy at <inline-formula><tex-math id="M5">\begin{document}$ b = 1/3 $\end{document}</tex-math></inline-formula> of an equilibrium with a double real eigenvalue zero leads to a further qualitative change and acts as an organizing center for the bifurcation diagram. Our results demonstrate that state dependence in delayed feedback terms may give rise to new dynamics and, moreover, that the observed dynamics may change significantly when the state-dependent feedback depends on past states of the system. This is expected to have implications for models arising in different application contexts, such as models of human balancing and conceptual climate models of delayed action oscillator type.</p>