U-shaped Function Research Articles

Reinforcing effects of phenethylamine analogs found in dietary supplements.

Synthetic phenethylamine (PEA) analogs, such as β-methylphenethylamine (BMPEA) and N,α-diethylphenethylamine (DEPEA), are often found in dietary supplements, despite regulations prohibiting their sale. PEA analogs are structurally related to amphetamine, and we have shown that BMPEA and DEPEA produce cardiovascular stimulation mimicking the effects of amphetamine. However, few studies have examined behavioral effects of BMPEA, DEPEA, and other PEA analogs. Here, we examined the reinforcing effects of α-ethylphenethylamine (AEPEA, 1mg/kg/injection), DEPEA (1mg/kg/injection), and BMPEA (3mg/kg/injection) as compared to amphetamine (0.1mg/kg/injection) using a fixed-ratio 1 self-administration paradigm in male rats. Male rats were trained in self-administration chambers containing 2 nose-poke holes. A nose-poke response in the active hole delivered drug or saline, whereas a nose-poke response in the inactive hole had no programmed consequence. Four groups of rats were initially trained for 10days with the doses noted above. Upon acquisition of drug self-administration, a dose-effect function was determined by training rats on 3 additional doses for 3days each. A separate group of rats was trained with saline. Male rats self-administered each PEA analog and amphetamine, as shown by significant increases in active responses versus inactive responses. Subsequent dose-response testing showed clear differences in potency of the compounds. Amphetamine showed a typical inverted U-shaped dose-effect function, peaking at 0.1mg/kg/injection. AEPEA and DEPEA also showed inverted dose-effect functions, with each peaking at 0.3mg/kg/injection. BMPEA did not show an inverted U-shaped dose-effect function, but active responding slowly increased up to a dose of 6mg/kg/injection. Taken together, our findings indicate that dietary supplements containing PEA analogs may have significant abuse liability when used recreationally.

Minimally counterintuitive stimuli trigger greater curiosity than merely improbable stimuli

Curiosity plays a key role in directing learning throughout the lifespan. Prior work finds that violations of expectations can be powerful triggers of curiosity in both children and adults, but it is unclear which expectation-violating events induce the greatest curiosity and how this might vary over development. Some theories have suggested a U-shaped function such that stimuli of moderate extremity pique the greatest curiosity. However, expectation-violations vary not only in degree, but in kind: for example, some things violate an intuitive theory (e.g., an alligator that can talk) and others are merely unlikely (e.g., an alligator hiding under your bed). Combining research on curiosity with distinctions posited in the cognitive science of religion, we test whether minimally counterintuitive (MCI) stimuli, which involve one violation of an intuitive theory, are especially effective at triggering curiosity. We presented adults (N = 77) and 4- and 5-year-olds (N = 36) in the United States with stimuli that were ordinary, unlikely, MCI, and very counterintuitive (VCI) and asked which one they would like to learn more about. Adults and 5-year-olds chose Unlikely over Ordinary and MCI over Unlikely, but not VCI over MCI, more often than chance. Our results suggest that (i) minimally counterintuitive stimuli trigger greater curiosity than merely unlikely stimuli, (ii) surprisingness has diminishing returns, and (iii) sensitivity to surprisingness increases with age, appearing in our task by age 5.

Revisiting the nexus between financial agglomeration and energy efficiency: A spatial spillover approach

ABSTRACT Financial agglomeration (FA) may play an essential role in enhancing energy efficiency (EE) and, thus, is important from both theoretical and empirical viewpoints. However, few studies have investigated the causal nonlinear relationship between FA and EE. Hence, we first extend the novel ray slacks-based measure with global technology to evaluate the urban EE in China during 2003–2018. Next, we reexamine the nonlinear causality of FA on EE and then explore the underlying impact mechanism. The empirical results show that China’s urban EE is generally relatively low with distinct patterns of regional differences. Moreover, we find that the causal relationship between FA and EE follows an inverted U-shaped function rather than a linear one. FA promotes the improvement of EE only up to a certain threshold point, after which it reverses into an inhibitory effect. A further analysis based on the two-regime spatial Durbin panel model suggests that FA can indeed improve the EE of surrounding cities through positive externalities when the degree of FA in focal cities is not substantially greater than that in surrounding cities. However, when financial resources absorbed in certain focal cities become increasingly higher than that in most surrounding cities, the positive spillover effect would gradually disappear and even reverse into an undesirable siphon, thereby inhibiting the improvement of overall EE. These findings provide new insights for understanding the role of FA in sustainable development.

Profit Effects of Consumers’ Identity Management: A Dynamic Model

We consider a nondurable good monopolist that collects data on its customers in order to profile them and subsequently practice price discrimination on returning customers. The monopolist’s price discrimination scheme is leaky in the sense that an endogenous fraction of consumers choose to incur a privacy cost to conceal their identity when they return in the following periods. We characterize the Markov perfect equilibrium of the game under two alternative customer profiling regimes: full information acquisition (FIA) and purchase history information (PHI). In both cases, we find that, contrary to what could be expected, the monopolist’s aggregate profit is not monotonically increasing in the level of the privacy cost, but a U-shaped function of it, leading to ambiguous profit effects: a reduction in privacy costs increases the fraction of customers who choose to be anonymous (detrimental profit effect), but it also softens the firm’s introductory price, reducing the pace at which prices targeted to new customers fall over time (positive profit effect). When comparing results under FIA and PHI, we find that market expansion is faster, and more customers conceal their identity under FIA than under PHI. Equilibrium profits are also higher in the FIA case. Although equilibrium profits are U-shaped functions of the privacy cost in both profiling regimes, they tend to be globally decreasing with the privacy cost under PHI and globally increasing under FIA. This paper was accepted by Eric Anderson, marketing. Funding: This work was supported by Fundação para a Ciência e a Tecnologia [Grants NORTE-01-0145-FEDER-028540 and POCI-01-0145-FEDER-006890]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.4511 .

The sweet spot between predictability and surprise: musical groove in brain, body, and social interactions.

Groove—defined as the pleasurable urge to move to a rhythm—depends on a fine-tuned interplay between predictability arising from repetitive rhythmic patterns, and surprise arising from rhythmic deviations, for example in the form of syncopation. The perfect balance between predictability and surprise is commonly found in rhythmic patterns with a moderate level of rhythmic complexity and represents the sweet spot of the groove experience. In contrast, rhythms with low or high complexity are usually associated with a weaker experience of groove because they are too boring to be engaging or too complex to be interpreted, respectively. Consequently, the relationship between rhythmic complexity and groove experience can be described by an inverted U-shaped function. We interpret this inverted U shape in light of the theory of predictive processing and provide perspectives on how rhythmic complexity and groove can help us to understand the underlying neural mechanisms linking temporal predictions, movement, and reward. A better understanding of these mechanisms can guide future approaches to improve treatments for patients with motor impairments, such as Parkinson’s disease, and to investigate prosocial aspects of interpersonal interactions that feature music, such as dancing. Finally, we present some open questions and ideas for future research.

Impacts of digital business on global value chain participation in European countries.

As the first empirical study of the nonlinear effects of digital business on global value chains (GVC), we provide insight into the nonlinear effects of digital business on the global value chain (GVC) values. We employ four indicators, including the value of online selling, sales through E-commerce, and customer relationship management (CRM) usage, to capture the prevalence of digital business in the economy. By testing a sample of 25 European countries that have been analyzed using various econometric techniques over the period 2012–2019, our estimation results confirm that GVC values are a U-shaped function of digitalization. That is, an increase in digitalization pervasiveness initially induces more significant risks and uncertainties, hindering European countries from getting involved in or scale-up within the GVC. However, a rise in digitalization pervasiveness goes beyond a specific threshold, which facilitates GVC activities as more opportunities are created. Furthermore, our findings suggest that digital business contributes significantly to reducing the adverse influences of global uncertainty on the GVC values, while the marginal effects of digital business on GVC values become more pronounced in countries with the most advanced institutional structure.

Economic Growth, CO2 Emissions Quota and Optimal Allocation under Uncertainty

This study attempts to link greenhouse gas emissions and economic development, and under the premise of considering economic development, proposes an optimal quota of greenhouse gas emissions. Based on the environmental Kuznets curve hypothesis, the logarithmic value of greenhouse gas emissions is an inverted U-shaped function of the logarithmic value of GDP per capita. The empirical results showed that most countries in the world support the Kuznets curve hypothesis. Moreover, using data collected from Our World in Data, the optimal allocation of a greenhouse gas emissions quota can be found by minimizing the uncertainty risk subject to a prespecified global economic growth rate. For government policymakers, they may apply the framework in this study to determine an optimal allocation of greenhouse gas emissions for each sector that will ensure the intended level of domestic economic growth.

The role of color contrast gain control in global form perception.

A Glass pattern consists of randomly distributed dot pairs, or dipoles, whose orientation is determined by a geometric transform, which defines the global percept perceived by an observer. The perception of Glass patterns involves a local process that associates dot pairs into dipoles and a global process that groups the dipoles into a global structure. In the present study, we used a variant of Glass patterns, which was composed of randomly distributed tripoles instead of dipoles, to estimate the influence of color contrast on perceptual grouping. Each tripole contained an anchor dot and two context dots. Grouping the anchor dot with one of the context dots resulted in a global percept of a clockwise spiral, while grouping with the other dot, a counter-clockwise spiral. All dots in each pattern were modulated in the same color direction but different contrasts. Four colors were involved, namely, red, green, blue, and yellow. The observers were to determine whether the spiral in each trial was clockwise or counter-clockwise. The probability of a context dot being grouped with the anchoring dot increased with its color contrast to a certain level, then decreased when the contrast continued to increase. Such probability decreased as the contrast of the other context dot increased. Our result cannot be explained by existing models in the literature, but with a divisive inhibition model. The equiluminance contrast result observed here is similar to the inverted U-shaped function for luminance contrast result previously reported by us, except that the color contrast model comprises a weaker self-inhibition component.

Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P‐AL‐LAD

Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important tool for clinical research. A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergamide N,N‐diethyl‐1‐propanoyl‐6‐(prop‐2‐en‐1‐yl)‐9,10‐didehydroergoline‐8β‐carboxamide (1P‐AL‐LAD) using various mass spectrometric, gas‐ and liquid chromatographic and spectroscopic methods. In vitro metabolism studies using pooled human liver microsomes (pHLM) confirmed that 1P‐AL‐LAD converted to AL‐LAD as the most abundant metabolite consistent with the hypothesis that 1P‐AL‐LAD may act as a prodrug. Fourteen metabolites were detected in total; metabolic reactions included hydroxylation of the core lysergamide ring structure or the N 6‐allyl group, formation of dihydrodiol metabolites, N‐dealkylation, N 1‐deacylation, dehydrogenation, and combinations thereof. The in vivo behavioral activity of 1P‐AL‐LAD was evaluated using the mouse head twitch response (HTR), a 5‐HT2A‐mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. 1P‐AL‐LAD induced a dose‐dependent increase in HTR counts with an inverted U‐shaped dose–response function, similar to lysergic acid diethylamide (LSD), psilocybin, and other psychedelics. Following intraperitoneal injection, the median effective dose (ED50) for 1P‐AL‐LAD was 491 nmol/kg, making it almost three times less potent than AL‐LAD (174.9 nmol/kg). Previous studies have shown that N 1‐substitution disrupts the ability of lysergamides to activate the 5‐HT2A receptor; based on the in vitro metabolism data, 1P‐AL‐LAD may induce the HTR because it acts as a prodrug and is metabolized to AL‐LAD after administration to mice.

Binary QUATRE Using Time-varying Transfer Functions

<p>QUasi-Affine TRansformation Evolutionary (QUATRE) is an excellent algorithm that generalized differential evolution algorithm to matrix form. There are two approaches of Binary QUATRE (BQUATRE) algorithm that convert the continuous search space to the binary one. The convergence process of meta-heuristic algorithms can be regarded as two stages: exploration and exploitation. Generally speaking, transfer function plays an important role in the binary metaheuristic algorithms. Therefore, four families of transfer functions are converted into the time-varying form to balance the exploration and exploitation. In particular, a new timevarying formula for the V-shaped, U-shaped and Z-shaped transfer functions is designed in this manuscript. Then, two new approaches of BQUATRE algorithm using the timevarying transfer functions are proposed. In addition, a wrapper feature selection algorithm is designed based on the proposed time-varying BQUATRE. In order to verify the performance of the proposed algorithms, the UCI repository is used in the experiment and the results show that the proposed algorithms are superior to the original BQUATRE and the state-of-the-art algorithms.</p> <p> </p>

Development of a Nonhuman Primate Model of Resistance to Punishment of Ethanol Choice

Several of the diagnostic criteria for alcohol use disorder (AUD) reflect the fact that some people continue to drink despite negative consequences. That is, vulnerable individuals are resistant to punishment. A better understanding of the behavioral and neurobiological factors that underlie this characteristic will lead to better preventive and treatment approaches to AUD. The objective of this study was to extend rodent studies by developing and validating a model of resistance to punishment of alcohol drinking in nonhuman primates. To increase translational relevance, the study was conducted in the context of an ethanol‐water choice procedure. Each day two 800‐ml bottles were hung on the monkey’s home cage for three hours, one containing a 4% ethanol solution and the other containing water. The primary dependent variable was ethanol choice (ml of ethanol consumed divided by total ml consumed x 100). When choice was stable (±10% of the 3‐day mean with no upward or downward trend), several manipulations were made. Experiment 1 characterized choice of several concentrations of ethanol (0%‐8%) versus water by substituting other ethanol concentrations for the 4% solution until choice again stabilized. The relationship between the available ethanol concentration and ethanol choice was characterized by an inverted U‐shaped function. In Experiment 2, the alternative (water) was manipulated to further validate the procedure as a model of choice. For monkeys in whom choice of the 4% ethanol solution was relatively low (<30%), the bitter tastant quinine (0.01‐1.0 g/L) was added to the water solution. For monkeys with higher choice of 4% ethanol (>70%), sucrose (1.0‐5.0%) was added to the water solution. These manipulations predictably increased and decreased, respectively, choice of the 4% ethanol solution. Finally, in Experiment 3, consumption of the 4% ethanol solution was punished by adding quinine (0.01‐5.6 g/L) to the ethanol solution. Increasing quinine concentrations decreased ethanol choice and ethanol intake in all monkeys without decreasing the total volume of fluid consumed. Individual differences were observed in the potency of quinine which can be interpreted as individual differences in sensitivity to punishment. These studies established and validated a novel nonhuman primate model of punishment of ethanol choice which can be used to characterize factors that underlie susceptibility versus resistance to punishing effects of adverse consequences of alcohol drinking.

Does quality pay off? “Superstar” wines and the uncertain price premium across quality grades

AbstractWe use data from Wine Spectator on 266,301 bottles from 12 countries sold in the United States to investigate the link between the score awarded by the guide and the price charged. The link between quality and price is positive, in line with the literature. In a deeper inspection, however, hedonic regressions show that the price premium attached to higher quality is significant only for “superstar” wines with more than 90 points (on a 50–100 scale), while prices of wines between 50 and 90 points are not statistically different from each other. Furthermore, an analysis performed through normal heteroskedastic and quantile regression models shows that the dispersion of quality-adjusted prices is described by an asymmetric U-shaped function of the score; that is, products with the lowest and highest quality have the highest residual standard deviation. Pursuing excellence is a risky strategy; the average price is significantly higher only for wines that achieve top scores, and the price premium becomes more volatile.

Association of urinary metabolites of non-persistent pesticides with serum sex hormones among the US females: NHANES 2013–2014

BackgroundEvidence indicated the possibility of non-persistent pesticides disrupting the homeostasis of sex hormones. However, few studies have focused on this relationship in females. We aimed to explore the relationship between non-persistent pesticide exposure and sex hormones among the US females from the National Health and Nutrition Examination Survey 2013–2014. MethodsA total of 790 females, including girls (6–11 years), female adolescents (12–19 years), and adult females (>19 years), were enrolled in this study. Age stratified associations of individual non-persistent pesticide metabolites and their mixtures with sex hormones were analyzed by weighted multiple linear regression and Bayesian kernel machine regression (BKMR) using spot urinary non-persistent pesticide measurement, including 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloropyridinol (TCPY), para-nitrophenol (PNP) and 3-phenoxybenzoic acid (3-PBA), and three serum sex hormones [total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)]. ResultsIn girls, weighted multivariate linear regression indicated that both 2,4-D and PNP were negatively associated with TT, and TCPY was inversely associated with SHBG. In female adolescents, TCPY was negatively associated with TT and E2, and 3-PBA was negatively associated with SHBG; positive associations were detected both in 2,4-D with SHBG, and in PNP with TT. In adult females, a higher concentration of 3-PBA was associated with higher levels of TT. The BKMR model showed that in female adolescents, the concentrations of pesticide metabolite mixtures at or above the 55th percentile were negatively related to the levels of E2 compared with their mixtures at 50th percentile, and an inverse U-shaped exposure-response function between PNP and E2 was found. ConclusionsAssociations between the four non-persistent pesticide metabolites and serum sex hormones were identified in the US females from NHANES 2013–2014 and these associations were age dependent, especially in adolescents. Large-scale cohort studies are needed to confirm these findings and elucidate the potential biological mechanisms.

The Dawn of the Experimental Study of Time Perception: Höring (1864) and Mach (1865)

Abstract This article discusses the contents of two of the earliest publications about the experimental psychology of time, those from Höring (1864) and Mach (1865). Höring’s thesis, conducted under Vierordt’s supervision, involved the discrimination of the relative rates of successive periods of beats of a metronome. In general, timing sensitivity decreased as the beats slowed, thus violating Weber’s Law of constant sensitivity for time. Mach (1865) conducted a range of experiments, using metronomes, pendulums, and different sorts of apparatus of his own design. He, likewise, found violations of Weber’s Law, with the Weber fraction following a U-shaped function of duration, with a minimum (of around 5%) at 500 or 600 ms. Mach also conducted research on the smallest temporal intervals that could be distinguished, following an earlier suggestion by Czermak, and reported that the smallest values were obtained with the auditory sense. Mach’s article also discussed the perception of rhythms, and the possibility that different animal species show different sensitivity to time. Some modern work on Weber’s Law and timing is briefly discussed at the end of the article.

Object Gathering With a Tethered Robot Duo

We devise a cooperative planning framework to generate optimal trajectories for a tethered robot duo, who is tasked to gather scattered objects spread in a large area using a flexible net. Specifically, the proposed planning framework first produces a set of dense waypoints for each robot, serving as the initialization for optimization. Next, we formulate an iterative optimization scheme to generate smooth and collision-free trajectories while ensuring cooperation within the robot duo to efficiently gather objects and properly avoid obstacles. We validate the generated trajectories in simulation and implement them in physical robots using Model Reference Adaptive Controller (MRAC) to handle unknown dynamics of carried payloads. In a series of studies, we find that: (i) a U-shape cost function is effective in planning cooperative robot duo, and (ii) the task efficiency is not always proportional to the tethered net's length. Given an environment configuration, our framework can gauge the optimal net length. To our best knowledge, ours is the first that provides such estimation for tethered robot duo.

Novel binary differential evolution algorithm based on Taper-shaped transfer functions for binary optimization problems

In order to efficiently solve the binary optimization problems by using differential evolution (DE), a class of new transfer functions, Taper-shaped transfer function, is firstly proposed by using power functions. Then, the novel binary differential evolution algorithm based on Taper-shaped transfer functions (T-NBDE) is proposed. T-NBDE transforms a real vector representing the individual encoding into a binary vector by using the Taper-shaped transfer function, which is suitable for solving binary optimization problems. For verifying the practicability of Taper-shaped transfer functions and the excellent performance of T-NBDE, T-NBDE is firstly compared with binary DE based on S-shaped, U-shaped and V-shaped transfer functions, respectively. Subsequently, it is compared with the state-of-the-art algorithms for solving the knapsack problem with a single continuous variable (KPC) and the uncapacitated facility location problem (UFLP). The comparison results show that Taper-shaped transfer functions are competitive than existing transfer functions, and T-NBDE is more effective than existing algorithms for solving KPC problem and UFLP problem.

When Success Is Rare and Competitive: Learning from Others’ Success and My Failure at the Speed of Formula One

Organizations can learn from prior successes and failures to improve organizational performance. Few learning-curve studies have investigated this phenomenon at the individual level. A notable exception found that surgeons learn from their own success and others’ failure. Success in surgery is common and individually independent from other surgeries. We study learning from success and failure in a context where success is rare and competitive: Formula One (F1) racing. Only one driver will win a race, preventing the other competitors from winning. Even severe failures causing drivers to abandon the race are common. We investigate two types of abandonments: car failures and driver failures. Our data set covers F1 from the start of F1 in 1950 through 2017, yielding 21,487 driver-race observations. We find that win probability follows an inverted U-shaped function of racing experience. We also find that drivers learn from their own success, teammates’ success, as well as own car failures. However, drivers do not learn from their own driver failures. A teammate’s win increases the probability of winning the next race by 1.8%. An own car failure increases the probability of winning the next race by 1.9%. We use two characteristics of success, frequency and competitiveness, to define a spectrum of organizational settings. Placement of our F1 findings and the surgery findings on this spectrum reveals when managers can expect benefits from their own versus others’ success and failure. This paper was accepted by Charles Corbett, operations management. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4324 .

L-DOPA administration shifts the stability-flexibility balance towards attentional capture by distractors during a visual search task

RationaleThe cognitive control dilemma describes the necessity to balance two antagonistic modes of attention: stability and flexibility. Stability refers to goal-directed thought, feeling, or action and flexibility refers to the complementary ability to adapt to an ever-changing environment. Their balance is thought to be maintained by neurotransmitters such as dopamine, most likely in a U-shaped rather than linear manner. However, in humans, studies on the stability-flexibility balance using a dopaminergic agent and/or measurement of brain dopamine are scarce.ObjectiveThe study aimed to investigate the causal involvement of dopamine in the stability-flexibility balance and the nature of this relationship in humans.MethodsDistractibility was assessed as the difference in reaction time (RT) between distractor and non-distractor trials in a visual search task. In a randomized, placebo-controlled, double-blind, crossover study, 65 healthy participants performed the task under placebo and a dopamine precursor (L-DOPA). Using 18F-DOPA-PET, dopamine availability in the striatum was examined at baseline to investigate its relationship to the RT distractor effect and to the L-DOPA-induced change of the RT distractor effect.ResultsThere was a pronounced RT distractor effect in the placebo session that increased under L-DOPA. Neither the RT distractor effect in the placebo session nor the magnitude of its L-DOPA-induced increase were related to baseline striatal dopamine.ConclusionsL-DOPA administration shifted the stability-flexibility balance towards attentional capture by distractors, suggesting causal involvement of dopamine. This finding is consistent with current theories of prefrontal cortex dopamine function. Current data can neither confirm nor falsify the inverted U-shaped function hypothesis with regard to cognitive control.

Dopamine supports idea originality: the role of spontaneous eye blink rate on divergent thinking

The neurotransmitter dopamine plays a crucial role in human creative behaviour. Specifically, striatal dopamine seems to be associated with specific dimensions of divergent thinking performance, especially with categorical diversity (flexibility) of ideas. In experimental contexts, spontaneous Eye Blink Rate (sEBR) has been used as a proxy for striatal dopamine, and an inverted U-shape relationship between sEBR and flexibility has been demonstrated, such that a medium sEBR level predicts highest flexibility levels. The present study aimed at carrying out further investigations about the relationship between sEBR and idea generation through divergent thinking, specifically focusing on the relationship between idea originality and dopamine level, since originality is a key element for creativity. We asked 80 participants, whose sEBR at rest was measured, to perform an Alternative Uses Task (AUT) to measure their divergent thinking performance. Results revealed that the relationship between sEBR and originality, as measured through subjective ratings of external raters, followed an inverted U-shape function with medium sEBR being associated with highest originality scores. Moreover, and most importantly, we demonstrated that sEBR predicted originality through the mediation of flexibility. Our results provide further insights on the possible role of dopamine on divergent thinking performance, demonstrating that an adequate dopamine level may facilitate the generation of original ideas through the exploration of diverse conceptual categories (higher flexibility).

Increasing stimulus similarity drives nonmonotonic representational change in hippocampus.

Studies of hippocampal learning have obtained seemingly contradictory results, with manipulations that increase coactivation of memories sometimes leading to differentiation of these memories, but sometimes not. These results could potentially be reconciled using the nonmonotonic plasticity hypothesis, which posits that representational change (memories moving apart or together) is a U-shaped function of the coactivation of these memories during learning. Testing this hypothesis requires manipulating coactivation over a wide enough range to reveal the full U-shape. To accomplish this, we used a novel neural network image synthesis procedure to create pairs of stimuli that varied parametrically in their similarity in high-level visual regions that provide input to the hippocampus. Sequences of these pairs were shown to human participants during high-resolution fMRI. As predicted, learning changed the representations of paired images in the dentate gyrus as a U-shaped function of image similarity, with neural differentiation occurring only for moderately similar images.