Altered Reward Processing Research Articles

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia.

Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood. We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS. In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy. This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

The relation between dopamine D2 receptor blockade and the brain reward system: a longitudinal study of first-episode schizophrenia patients

Psychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients. Twenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride. In line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = -0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035). The results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.

Neural Responsivity to Food Cues in Patients With Unmedicated First-Episode Psychosis

ImportanceSchizophrenia is associated with a reduced life expectancy of 15 to 20 years owing to a high prevalence of cardiometabolic disorders. Obesity, a key risk factor for the development of cardiometabolic alterations, is more prevalent in individuals with schizophrenia. Although obesity is linked to the altered reward processing of food cues, no studies have investigated this link in schizophrenia without the confounds of antipsychotics and illness chronicity.ObjectiveTo investigate neural responsivity to food cues in first-episode psychosis without the confounds of antipsychotic medication or illness chronicity.Design, Setting, and ParticipantsA case-control study was conducted from January 31, 2015, to September 30, 2018, in London, United Kingdom, of 29 patients with first-episode psychosis who were not taking antipsychotic medication and 28 matched controls.Main Outcomes and MeasuresParticipants completed a food cue paradigm while undergoing a functional magnetic resonance imaging scan. Neural activation was indexed using the blood oxygen level–dependent hemodynamic response. The Dietary Instrument for Nutrition Education was used to measure diet, and the International Physical Activity Questionnaire was used to measure exercise.ResultsThere were no significant differences in age, sex, or body mass index between the 29 patients (25 men and 4 women; mean [SD] age, 26.1 [4.8] years) and 28 controls (22 men and 6 women; mean [SD] age, 26.4 [5.5] years). Relative to controls, patients consumed more saturated fat (t46 = –3.046; P = .004) and undertook less high-intensity (U = 304.0; P = .01) and low-intensity (U = 299.5; P = .005) weekly exercise. There were no group differences in neural responses to food vs nonfood cues in whole-brain or region-of-interest analyses of the nucleus accumbens, insula, or hypothalamus. Body mass index was inversely correlated with the mean blood oxygen level–dependent signal in the nucleus accumbens in response to food vs nonfood cues in controls (R = –0.499; P = .01) but not patients (R = 0.082; P = .70).Conclusions and RelevanceRelative to controls, patients with first-episode psychosis who were not taking antipsychotic medication consumed more saturated fat and showed an altered association between body mass index and neural response to food cues in the absence of differences in neural responses to food cues. These findings highlight how maladaptive eating patterns and alterations in the association between body mass index and neural responses to food cues are established early in the course of schizophrenia.

Altered reward processing following an acute social stressor in adolescents.

Altered reward processing is a transdiagnostic factor implicated in a wide range of psychiatric disorders. While prior animal and adult research has shown that stress contributes to reward dysfunction, less is known about how stress impacts reward processing in youth. Towards addressing this gap, the present study probed neural activation associated with reward processing following an acute stressor. Healthy adolescents (n = 40) completed a clinical assessment, and fMRI data were acquired while participants completed a monetary guessing task under a no-stress condition and then under a stress condition. Based on prior literature, analyses focused on a priori defined regions-of-interest, specifically the striatum (win trials) and dorsal anterior cingulate cortex [dACC] and insula (loss trials). Two main findings emerged. First, reward-related neural activation (i.e., striatum) was blunted in the stress relative to the no-stress condition. Second, the stress condition also contributed to blunted neural response following reward in loss-related regions (i.e., dACC, anterior insula); however, there were no changes in loss sensitivity. These results highlight the importance of conceptualizing neural vulnerability within the presence of stress, as this may clarify risk for mental disorders during a critical period of development.

F9EXOME SEQUENCING IN 2 EXTENDED FAMILIES FROM THE ISOLATED ROMA POPULATION REVEALS THE CONTRIBUTION OF RARE RISK VARIANTS FOR AFFECTIVE DISORDER

This chapter focuses on risky decision making and related behaviors among individuals experiencing state positive and negative mood, as well as those diagnosed with a mood or bipolar disorder. The current status of the literature is reviewed, with a close examination of the evidence supporting altered reward processing, state versus trait mood, and the behavioral activation system hypersensitivity hypothesis of bipolar disorder as causes of riskier decision making. Potential contributions of performance on other executive tasks and treatments are also considered.

Hormones, Emotional processing and prepartum Attachment in Pregnant women with Affective Disorders (HEAPAD)

This chapter focuses on risky decision making and related behaviors among individuals experiencing state positive and negative mood, as well as those diagnosed with a mood or bipolar disorder. The current status of the literature is reviewed, with a close examination of the evidence supporting altered reward processing, state versus trait mood, and the behavioral activation system hypersensitivity hypothesis of bipolar disorder as causes of riskier decision making. Potential contributions of performance on other executive tasks and treatments are also considered.

MAMMALIAN GENETICS OF EATING DISORDERS: PRECLINICAL AND CLINICAL GENETIC AND BIOLOGICAL RISK FACTORS

This chapter focuses on risky decision making and related behaviors among individuals experiencing state positive and negative mood, as well as those diagnosed with a mood or bipolar disorder. The current status of the literature is reviewed, with a close examination of the evidence supporting altered reward processing, state versus trait mood, and the behavioral activation system hypersensitivity hypothesis of bipolar disorder as causes of riskier decision making. Potential contributions of performance on other executive tasks and treatments are also considered.

Decrease in Operant Responding Under Obesogenic Diet Exposure is not Related to Deficits in Incentive or Hedonic Processes.

A growing body of evidence suggests that obesity could result from alterations in reward processing. In rodent models, chronic exposure to an obesogenic diet leads to blunted dopamine signaling and related incentive responding. This study aimed to determine which reward-related behavioral dimensions are actually impacted by obesogenic diet exposure. Mice were chronically exposed to an obesogenic diet. Incentive and hedonic processes were tested through operant conditioning and licking microstructures, respectively. In parallel, mesolimbic dopamine transmission was assessed using microdialysis. Prolonged high-fat (HF) diet exposure led to blunted mesolimbic dopamine release, paralleled by a decrease in operant responding in all schedules tested. HF-fed and control animals similarly decreased their operant responding in an effort-based choice task, and HF-fed animals displayed an overall lower calorie intake in this task. Analysis of the licking microstructures during consumption of a freely accessible reward suggested a decrease in basal hunger and a potentiation of gastrointestinal inhibition in HF-fed animals, without changes in hedonic reactivity. These results suggest that the decrease in operant responding under prolonged HF diet exposure is mainly driven by decrease in hunger as well as stronger postingestive negative feedback mechanisms, rather than by a decrease in incentive or hedonic responses.

Delay discounting and affective priming in individuals with negative schizotypy

Previous studies have demonstrated that patients with schizophrenia and individuals with schizotypy experience decreased anticipatory pleasure. However, it is unclear whether this decrease is contributed by altered reward processing at the proximal or distal future. In order to investigate the preference for receiving rewards in the proximal or distal future for individuals with schizophrenia spectrum disorders, individuals with either high or low levels of negative schizotypy performed a delay discounting task under positive, neutral and negative affective priming conditions. Compared with individuals with low levels of negative schizotypy, individuals with high levels of schizotypy exhibited increased delay discounting, preferring to choose immediate but smaller rewards instead of delayed but larger rewards across all three affective priming conditions. Negative affective priming elevated discounting for both groups compared with both the positive and neutral affective conditions. After dividing delayed temporal distance into the proximal and distal future, the results showed that individuals with high levels of negative schizotypy exhibited more preference for immediate but smaller rewards in the distal instead of proximal future compared with controls. Our results suggest that individuals with high levels of negative schizotypy have altered anticipatory reward processing, which is mainly attributed to alterations in representing rewards in the distal future. These findings extend the alterations in representing reward values from schizophrenia patients to schizotypal individuals, and suggest that diminished anticipatory pleasure in schizophrenia spectrum disorders may be due to changes in processing anticipatory rewards in the distal future.

Food vs money? Effects of hunger on mood and behavioral reactivity to reward in anorexia nervosa

BackgroundPrevious studies using neuroimaging and behavioral measures reported altered reward processing in anorexia nervosa (AN). In addition, anhedonia states are frequently reported in AN, potentially due to the physiological stress produced by the permanent starvation. We investigated the effect of fasting and satiety on mood and reaction times to monetary rewards in AN patients and healthy controls. MethodsTwenty-four participants with acute AN (BMI 14.4 (11.9–15.5) Kg/m2) and 17 age and gender matched healthy, normal weight subjects (HW) (BMI 21.8 (18.9–24.9) Kg/m2) performed a reward task (the wheel of fortune) involving uncertain (50/50 probability of winning high and low rewards), safe and risky (30/70 and 10/90 probabilities) categories in fasted (after an 8-h fasting period) and fed (after intake of a standardized meal) states. Data analysis was done with linear mixed models. ResultsAN reacted slower than HW when maximum uncertainty (50/50) was involved. Positive mood in response to winning was higher when fasting especially for HW, while negative mood in response to not winning was higher in the fed state for both groups. Still, HW were more reactive than AN to not winning a highly predictable monetary reward (10/90 safe). ConclusionThe data on the reaction times indicate an impaired motor response to uncertainty in AN. Mood reactivity to winning a monetary reward does not seem to be impaired in AN, however, our results suggest that negative mood in response to not winning is less adaptive in AN. Implications to clinical psychotherapy are discussed.

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats

Objectives: Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Methods: Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. Results: We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria. Discussion: Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours.

Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities

The mu opioid receptor (MOR) plays a critical role in modulating social behavior in humans and animals. Accordingly, MOR null mice display severe alterations in their social repertoire as well as multiple other behavioral deficits, recapitulating core and secondary symptoms of autism spectrum disorder (ASD). Such behavioral profile suggests that MOR dysfunction, and beyond this, altered reward processes may contribute to ASD etiopathology. Interestingly, the only treatments that proved efficacy in relieving core symptoms of ASD, early behavioral intervention programs, rely principally on positive reinforcement to ameliorate behavior. The neurobiological underpinnings of their beneficial effects, however, remain poorly understood. Here we back-translated applied behavior analysis (ABA)-based behavioral interventions to mice lacking the MOR (Oprm1−/−), as a model of autism with blunted reward processing. By associating a positive reinforcement, palatable food reward, to daily encounter with a wild-type congener, we were able to rescue durably social interaction and preference in Oprm1−/− mice. Along with behavioral improvements, the expression of marker genes of neuronal activity and plasticity as well as genes of the oxytocin/vasopressin system were remarkably normalized in the reward/social circuitry. Our study provides further evidence for a critical involvement of reward processes in driving social behavior and opens new perspectives regarding therapeutic intervention in ASD.

Genetic association analyses and meta-analysis of Dynorphin-Kappa Opioid system potential functional variants with heroin dependence

Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (χ2 = 10.824, p = 0.001, OR = 1.419, 95% CI = 1.151–1.748). In addition, the results revealed the patients with the HH genotype showed greater number of withdrawal instances (F(2538) = 7.987, p = 0.0004) compared to the patients with the LL genotype. The Meta-analysis showed the pooled effect of the H allele at this locus is a risk factor for HD in Chinese Han. Gene-gene interaction analysis indicated strong interactions between PDYN rs3830064, 68-bp VNTR and OPRK1 rs16918842, rs3802279. These findings support the important role of PDYN polymorphism in HD, and may guide future studies to identify genetic risk factors for HD.

Effects of neuromodulation on cognitive performance in individuals exhibiting addictive behaviour: a systematic review protocol

BackgroundIndividuals with substance use and addictive disorders often display greater risk-taking behaviour, higher impulsivity, and altered reward processing compared to individuals without these disorders. While it is not known whether cognitive biases precede or result from addictive behaviour, they likely influence addiction-related decision-making, and may facilitate pathological behaviour. There is evidence that cognitive functions—including those shown to be altered in substance use and addictive disorders—can be influenced by neuromodulation techniques (specifically, transcranial direct current stimulation and transcranial magnetic stimulation). Much of this work has been conducted in healthy populations, however, making it unclear whether these methods can be used effectively to modulate cognitive functioning in individuals with substance use and addictive disorders. The purpose of the current review is to shed light on the potential effectiveness and feasibility of neuromodulation as a means to improve cognitive deficits in substance use disorders.MethodsThe review will identify and evaluate studies that have examined the effects of transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) on cognitive task performance in individuals with chronic substance use or dependence. Relevant studies will be identified through searches in PubMed, PsycINFO, Scopus, and Embase, and narrative review will be used to explore evidence that these techniques can be used successfully to modulate cognitive performance in populations exhibiting addictive behaviour. Assessing individual cognitive domains in turn (e.g. risk-taking, impulsivity, attention), we will critically evaluate the validity and reliability of relevant studies and draw conclusions about the strength of evidence for effective use of neuromodulation in that domain. This protocol is not yet registered with PROSPERO.DiscussionTo determine whether neuromodulation holds promise as an effective treatment for neurocognitive deficits in substance use and addictive disorders, it is essential to look carefully at previous studies using this approach in addiction samples. This review will provide an objective and informative description of what is currently known about the efficacy of these techniques, shed light on the feasibility and potential challenges of using neuromodulation in individuals who exhibit addictive behaviour, and identify the most valuable next steps for future research.

The relationship between responsiveness to social and monetary rewards and ADHD symptoms.

Alterations in reward processing are frequently reported in attention deficit hyperactivity disorder (ADHD). One important factor affecting reward processing is the quality of reward as social and monetary rewards are processed by different neural networks. However, the effect of reward type on reward processing in ADHD has not been extensively studied. Hence, in the current study, an exploratory research was conducted to investigate the effect of reward type (i.e., social or monetary) on different phases of reward processing. We recorded event-related potentials (ERPs) during a spatial attention paradigm in which cues heralded availability and type of the upcoming reward and feedbacks informed about the reward earned. Thirty-nine (19 males) healthy individuals (age range: 19-27 years) participated in the study. ADHD symptoms were assessed by using ADHD self-report scale (ASRS). Our results revealed a consistent negative correlation between the hyperactivity subscale of ASRS and almost all social-feedback related ERPs (P2, P3, and FRN). ERP amplitudes after social feedbacks were less positive for P2 and P3 and more negative for FRN for individuals with greater hyperactivity levels. Our findings suggest that hyporesponsiveness to social feedbacks may be associated with hyperactivity. However, the results have to be confirmed with clinical populations.

Not worth the wait: cocaine alters reward processing in the nucleus accumbens.

Not worth the wait: cocaine alters reward processing in the nucleus accumbens.

Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal Self-Injury.

Adolescence is a critical developmental period marked by an increase in risk behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related brain activation and relatively limited recruitment of prefrontal regions contribute to the initiation of risky behaviors in adolescence. However, neural reward processing has not been examined among adolescents who are at risk for future engagement for NSSI specifically, but who have yet to actually engage in this behavior. In the current fMRI study (N=71), we hypothesized that altered reward processing would be associated with adolescents' thoughts of NSSI. Results showed that NSSI youth exhibited heightened activation in the bilateral putamen in response to a monetary reward. This pattern of findings suggests that heightened neural sensitivity to reward is associated with thoughts of NSSI in early adolescence. Implications for prevention are discussed.

Effect of traumatic brain injury on nicotine-induced modulation of dopamine release in the striatum and nucleus accumbens shell.

BackgroundTraumatic brain injury is associated with substantial alterations in reward processing, but underlying mechanisms are controversial.ObjectiveA better understanding of alterations in dopamine (DA) release patterns from the dorsal striatum and nucleus accumbens shell (NAc) may provide insights into posttraumatic reward pathology.Materials and MethodsThe patterns of DA release with or without exposure to nicotine in brain slices with striatum and NAc, isolated from Sprague-Dawley rats with 6 psi fluid percussion (FPI) or sham injury were analysis by using fast-scan cyclic voltammetry. Tonic and phasic DA releases were assessed using single pulse and 10 pulses at 25 Hz, respectively. DA release relative to stimulation intensity, frequency, number of pulses, and paired-pulse facilitation was evaluated to determine release probability and response to bursting.ResultsThere was a profound suppression in tonic DA release after nicotine desensitization after FPI, and the input/output curve for the DA release based on stimulation intensity was shifted to the right. FPI was associated with a significant decrease in frequency-dependent DA release augmentation, DA release induced by high frequency stimulation trains, and DA release in response to paired-pulse facilitation. The effect of nicotine desensitization was similar in FPI and sham-injured animals, although significantly smaller after FPI. Nicotine desensitization–induced differences between phasic and tonic release concentrations that contrasted with the reward-related signals then became less prominent in NAc after FPI.ConclusionsTBI blunts DA release from mesolimbic reward centers, and more intense stimuli are required to produce context-dependent DA release sufficient to have a physiological effect.ImplicationsThe nicotine desensitization-related suppression in tonic DA release was profound with right-ward shift of the input/output curve for DA release after FPI. FPI was associated with a significant decrease in frequency-dependent DA release augmentation, DA release induced by high frequency stimulation trains, and DA release in response to paired-pulse facilitation. Nicotine desensitization–induced differences between phasic and tonic release concentrations that contrasted with the reward-related signals then became less prominent in NAc after FPI. TBI thus blunts DA release from mesolimbic reward centers, and more intense stimuli are required to produce context-dependent DA release sufficient to have a physiological effect.

Altered monetary loss processing and reinforcement-based learning in individuals with obesity

Individuals with obesity are often characterized by alterations in reward processing. This may affect how new information is used to update stimulus values during reinforcement-based learning. Here, we investigated obesity-related changes in non-food reinforcement processing, their impact on learning performance as well as the neural underpinnings of reinforcement-based learning in obesity. Nineteen individuals with obesity (BMI > = 30 kg/m2, 10 female) and 23 lean control participants (BMI 18.5–24.9 kg/m2, 11 female) performed a probabilistic learning task during functional magnetic resonance imaging (fMRI), in which they learned to choose between advantageous and disadvantageous choice options in separate monetary gain, loss, and neutral conditions. During learning individuals with obesity made a significantly lower number of correct choices and accumulated a significantly lower overall monetary outcome than lean control participants. FMRI analyses revealed aberrant medial prefrontal cortex responses to monetary losses in individuals with obesity. There were no significant group differences in the regional representation of prediction errors. However, we found evidence for increased functional connectivity between the ventral striatum and insula in individuals with obesity. The present results suggest that obesity is associated with aberrant value representations for monetary losses, alterations in functional connectivity during the processing of learning outcomes, as well as a decresased reinforcement-based learning performance. This may affect how new information is incorporated to adjust dysfunctional behavior and could be a factor contributing to the maintenance of dysfunctional eating behavior in obesity.

Differential Associations of Distinct Forms of Childhood Adversity With Neurobehavioral Measures of Reward Processing: A Developmental Pathway to Depression.

Childhood adversity is associated with altered reward processing, but little is known about whether this varies across distinct types of adversity. In a sample of 94 children (6-19years), we investigated whether experiences of material deprivation, emotional deprivation, and trauma have differential associations with reward-related behavior and white matter microstructure in tracts involved in reward processing. Material deprivation (food insecurity), but not emotional deprivation or trauma, was associated with poor reward performance. Adversity-related influences on the integrity of white matter microstructure in frontostriatal tracts varied across childhood adversity types, and reductions in frontostriatal white matter integrity mediated the association of food insecurity with depressive symptoms. These findings document distinct behavioral and neurodevelopmental consequences of specific forms of adversity that have implications for psychopathology risk.