Slow-Wave Sleep Disruption in Adolescence: Brain Responses to Monetary Reward and Loss

Among adolescents, there is an association between sleep deprivation and reward seeking, but more work is needed to better understand this association. The goal of this study was to investigate slow-wave sleep disruption (SWD) and activity in the nucleus accumbens (NAcc) during a task measuring reward processing. Participants were 28 healthy adolescents aged 15–17 years (50% female; 57.1% White) who underwent functional magnetic resonance imaging while performing a monetary incentive delay task to measure reward anticipation and feedback after a baseline (BL) night and a SWD night. There was greater activation of the NAcc during feedback of large loss and less activation of the NAcc during anticipation of large loss after the SWD night relative to the BL night. These results support an association between SWD and reward processing among adolescents. Knowing more about SWD and reward responsivity may provide enhanced treatment and support to adolescents exhibiting sleep problems and risky reward-related behaviors.National Institute on Alcohol Abuse and Alcoholism (R21 AA022339)https://deepblue.lib.umich.edu/bitstream/2027.42/143845/1/Harris__Julia__Revised - Julia Harris.pdfDescription of Harris__Julia__Revised - Julia Harris.pdf : Julia Harris Senior Thesi

Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits

Adolescents, Adults and Rewards: Comparing Motivational Neurocircuitry Recruitment Using fMRI

Background: Adolescent risk-taking, including behaviors resulting in injury or death, has been attributed in part to maturational differences in mesolimbic incentive-motivational neurocircuitry, including ostensible oversensitivity of the nucleus accumbens (NAcc) to rewards. Methodology/Principal Findings: To test whether adolescents showed increased NAcc activation by cues for rewards, or by delivery of rewards, we scanned 24 adolescents (age 12–17) and 24 adults age (22–42) with functional magnetic resonance imaging while they performed a monetary incentive delay (MID) task. The MID task was configured to temporally disentangle potential reward or potential loss anticipation-related brain signal from reward or loss notification-related signal. Subjects saw cues signaling opportunities to win or avoid losing $0,$.50, or $5 for responding quickly to a subsequent target. Subjects then viewed feedback of their trial success after a variable interval from cue presentation of between 6 to17 s. Adolescents showed reduced NAcc recruitment by reward-predictive cues compared to adult controls in a linear contrast with non-incentive cues, and in a volume-of-interest analysis of signal change in the NAcc. In contrast, adolescents showed little difference in striatal and frontocortical responsiveness to reward deliveries compared to adults. Conclusions/Significance: In light of divergent developmental difference findings between neuroimaging incentive paradigms (as well as at different stages within the same task), these data suggest that maturational differences i

Differences in Spontaneously Avoiding or Approaching Mice Reflect Differences in CB1-Mediated Signaling of Dorsal Striatal Transmission

Approach or avoidance behaviors are accompanied by perceptual vigilance for, affective reactivity to and behavioral predisposition towards rewarding or punitive stimuli, respectively. We detected three subpopulations of C57BL/6J mice that responded with avoiding, balancing or approaching behaviors not induced by any experimental manipulation but spontaneously displayed in an approach/avoidance conflict task. Although the detailed neuronal mechanisms underlying the balancing between approach and avoidance are not fully clarified, there is growing evidence that endocannabinoid system (ECS) plays a critical role in the control of these balancing actions. The sensitivity of dorsal striatal synapses to the activation of cannabinoid CB1 receptors was investigated in the subpopulations of spontaneously avoiding, balancing or approaching mice. Avoiding animals displayed decreased control of CB1 receptors on GABAergic striatal transmission and in parallel increase of behavioral inhibition. Conversely, approaching animals exhibited increased control of CB1 receptors and in parallel increase of explorative behavior. Balancing animals reacted with balanced responses between approach and avoidance patterns. Treating avoiding animals with URB597 (fatty acid amide hydrolase inhibitor) or approaching animals with AM251 (CB1 receptor inverse agonist) reverted their respective behavioral and electrophysiological patterns. Therefore, enhanced or reduced CB1-mediated control on dorsal striatal transmission represents the synaptic hallmark of the approach or avoidance behavior, respectively. Thus, the opposite spontaneous responses to conflicting stimuli are modulated by a different involvement of endocannabinoid signaling of dorsal striatal neurons in the range of temperamental traits related to individual differences

Frustration Tolerance and Personality Traits in Patients With Substance Use Disorders

Previous research has suggested the prevalence of certain personality traits, some of which are related to a disorganized attachment, in substance abuse disorders. Further, frustration tolerance (FT) has been proposed as an important factor in addiction, both at the inception—following the “self-medication” hypothesis—and regarding treatment compliance. In turn, an inadequate response to frustrating events has been also associated with a disrupted attachment. Our goal is to explore the mediational role of FT in the relationship between personality traits and two different treatments for substance addiction: therapeutic community (TC) and ambulatory treatment (AT). Eighty-four subjects with substance abuse disorder were recruited in total (22 female), including 46 volunteers (13 female) in TC and 38 (9 female) in AT. They were assessed with Rosenzweig’s test for FT and the Millon Clinical Multiaxial Inventory-III (MCMI-III) test to evaluate personality factors. By comparing with a control sample (335 volunteers, 268 female), we found that FT was lower in patients. Between therapeutic groups, FT was significantly lower in TC. Depressive, antisocial, sadistic, negativistic, schizotypal, borderline, paranoid, anxiety, dysthymia, alcohol use, drug use, posttraumatic stress disorder (PTSD), thought disorder, and delusional disorder traits were suggestive of pathology in the clinical samples and were significantly different between control, AT, and TC groups. Further, anxiety and PTSD traits were higher in TC than in AT. A mediational analysis revealed that the effect of anxiety and PTSD scales on therapeutic group was partially mediated by FT. In conclusion, FT and its interplay with personality traits commonly related to disorganized attachment (anxiety and PTSD) might be important factors to consider within therapeutic programs for persons with substance addiction.We also acknowledge the collaboration of the users and personnel of Fundación Proyecto Hombre Navarra and Asociación Proyecto Hombre Granada for making possible this research. This project was funded by Fundación Caja de Ahorros de Navarra (grant number 70721) and the Spanish Ministerio de Sanidad, Servicios Sociales e Igualdad (2016/057)

Neurobiological correlates of self-control and reward processing in alcohol dependence

Alcohol dependence has been characterized by decreased self-control and altered reward processing. Both are independent but potentially interrelated factors, and have been associated with neurobiological changes related to addiction. To date, research on the neurobiological correlates of self-control and reward processing in alcohol dependence has yielded mixed results. Therefore, the aim of the present dissertation was to contribute to a further understanding of their neurobiological basis. On the one hand, we investigated structural changes in brain areas related to impulsivity and sensation seeking (behavioral tendency towards potentially risky experiences) as potential indicators of self-control in alcohol-dependent patients with high and low life-time alcohol consumption. On the other hand, we focused on the functional activation of brain areas associ-ated with reward anticipation in alcohol-dependent patients and healthy individuals at high genetic risk in order to disentangle potential cause and consequence of reward processing in the context of alcohol dependence. In the course of this: (I) Brain volumetric differences and correlates of self-control (oper-ationalized as impulsivity and sensation-seeking) were investigated using voxel-based morphometry. (II) Neuronal gain anticipation was investigated using the "Monetary Incentive Delay" task. (I) Structural alterations in diverse regions of the frontal cortex were identified in patients with alcohol dependence. In a subgroup characterized by comparatively low life-time consumption, a positive as-sociation between the volume of the grey matter in right middle frontal gyrus and sensation seeking was found. No other structural correlates of self-control were found. (II) At the neural level, anticipation of money gain did not differ between (rather long-term) abstinent subjects with alcohol-dependence, healthy controls and subjects with high genetic risk for alcohol dependence. However, anticipation of monetary loss was associated with a reduced functional response in the anterior insula in alcohol-dependent pa-tients compared to healthy individuals. Altogether, our results replicate findings of decreased prefrontal grey matter in AD, however, not correlated with self-report measures of self-control. Further, our findings might even attribute a protective effect regarding brain volume in the right middle frontal gyrus to sensation seeking. Finally, the lack of group differences in neural reward processing does not support common reward-processing theories of predisposition or disrupted function in prolonged abstinence.Alkoholabhängigkeit wird mit verminderter Selbstkontrolle und veränderter Belohnungsverarbeitung assoziiert. Beide sind unabhängige Faktoren, stehen jedoch in wechselseitiger Beziehung zueinander und werden mit neurobiologischen Veränderungen im Zusammenhang mit Suchterkrankungen definiert. Bislang zeigten sich in Bezug auf neurobiologische Korrelate von Selbstkontrolle und Belohnungsverarbeitung bei Alkoholabhängigkeit gemischte Ergebnisse. Ziel dieser Dissertation war es daher, zum weiteren Verständnis dieser neurobiologischen Grundlagen beizutragen. Einerseits untersuchten wir strukturelle Veränderungen in Hirnarealen, die mit Impulsivität und Sensation Seeking (Verhaltenstendenz zu vielfältigen, teils riskanten Erfahrungen) und damit Indikatoren für möglicherweise verminderte Selbstkontrolle bei alkoholabhängigen Patienten mit hohem und niedrigem Lebenszeitalkoholkonsum zusammenhängen. Andererseits untersuchten wir funktionelle Aktivierung von Hirnarealen, die mit Belohnungsantizipation bei alkoholabhängigen Patienten und gesunden Personen mit genetischem Risiko in Verbindung stehen, um mögliche Ursachen und Folgen der Belohnungsverarbeitung im Zusammenhang mit der Alkoholabhängigkeit zu entflechten. Dabei wurden: (I) Hirnvolumetrische Unterschiede und Korrelate der Selbstkontrolle (operationalisiert durch Impulsivität und Sensation Seeking) mittels Voxel-basierter Morphometrie untersucht. (II) Die neuronale Verstärkungsantizipation wurde mit Hilfe der "Monetary Incentive Delay"-Aufgabe untersucht. (I) Strukturelle Unterschiede in Subregionen des frontalen Kortex wurden bei Patienten mit Alkoholabhängigkeit festgestellt. In einer Untergruppe, ausgezeichnet durch vergleichsweise geringen Lebenszeitkonsum, wurde ein positiver Zusammenhang zwischen dem Volumen der grauen Substanz im rechten mittleren frontalen Gyrus und Sensation Seeking festgestellt. Andere strukturelle Korrelate der Selbstkontrolle wurden nicht gefunden. (II) Auf neuronaler Ebene unterschied sich die Antizipation von Geldgewinnen nicht zwischen (eher Langzeit-) abstinenten Patienten mit Alkoholabhängigkeit, gesunden Kontrollpersonen und Probanden mit hohem genetischem Risiko für Alkoholabhängigkeit. Allerdings war die Erwartung von Geldverlust bei alkoholabhängigen Patienten im Vergleich zu gesunden Personen mit verminderter funktionellen Reaktion in der vorderen Insula assoziiert. Zusammenfassend unterstützen unsere Ergebnisse Befunde über eine verringerte graue Substanz im präfrontalen Bereich bei Alkoholabhängigkeit, die jedoch nicht mit Selbsteinschätzungen zur Selbstkontrolle korreliert. Außerdem könnten unsere Ergebnisse Sensation Seeking in Bezug auf graue Substanz im mittleren frontalen Gyrus sogar eine schützende Wirkung zuweisen. Schließlich stützt das Fehlen von Gruppenunterschieden in neuronaler Belohnungsverarbeitung nicht die gängigen Theorien zur Belohnungsverarbeitung, die von Veranlagung oder gestörter Funktion bei längerer Abstinenz ausgehen

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

Processing of primary and secondary rewards: A quantitative meta-analysis and review of human functional neuroimaging studies

One fundamental question concerning brain reward mechanisms is to determine how reward-related activity is influenced by the nature of rewards. Here, we review the neuroimaging literature and explicitly assess to what extent the representations of primary and secondary rewards overlap in the human brain. To achieve this goal, we performed an activation likelihood estimation (ALE) meta-analysis of 87 studies (1452 subjects) comparing the brain responses to monetary, erotic and food reward outcomes. Those three rewards robustly engaged a common brain network including the ventromedial prefrontal cortex, ventral striatum, amygdala, anterior insula and mediodorsal thalamus, although with some variations in the intensity and location of peak activity. Money-specific responses were further observed in the most anterior portion of the orbitofrontal cortex, supporting the idea that abstract secondary rewards are represented in evolutionary more recent brain regions. In contrast, food and erotic (i.e. primary) rewards were more strongly represented in the anterior insula, while erotic stimuli elicited particularly robust responses in the amygdala. Together, these results indicate that the computation of experienced reward value does not only recruit a core "reward system" but also reward type-dependent brain structures

The human cerebellum in reward anticipation and outcome processing: An activation likelihood estimation meta-analysis

The cerebellum generates internal prediction models and actively compares anticipated and actual outcomes in order to reach a desired end state. In this process, reward can serve as a reinforcer that shapes internal prediction models, enabling context-appropriate behavior. While the involvement of the cerebellum in reward processing has been established in animals, there is no detailed account of which cerebellar regions are involved in reward anticipation and outcome processing in humans. To this end, an activation likelihood estimation meta-analysis of functional neuroimaging studies was performed to investigate cerebellar functional activity patterns associated with reward anticipation and outcome processing in healthy adults. Results showed that reward anticipation (k = 31) was associated with regional activity in the bilateral anterior lobe, bilateral lobule VI, left Crus I and the posterior vermis, while reward outcome (k = 16) was associated with regional activity in the declive and left lobule VI. These findings demonstrate distinct involvement of the cerebellum in reward anticipation and outcome processing as part of a predictive coding routine

FROM PARSING TO ALIGNING REWARD: MULTIMETHOD MEASUREMENT OF REWARD CONSTRUCTS IN SUBSTANCE USE DISORDERS

Substance Use Disorders are characterized by increased reward sensitivity to drugs and a decreased reward sensitivity to substance-free reward. Research has utilized neurobiological and self-report measures to capture reward pathology, yet it is unclear whether these measures are aligned in SUDs. This study tested the relationship between self-report and neural indices of substance-free reward anticipation and response in SUDs. N=31 treatment-seeking adults with SUDs underwent functional neuroimaging during a money-incentivized reward task. Neural indices of reward anticipation and response were collected via BOLD signal and self-report indices of reward anticipation and response were collected via research assistant administration and Qualtrics. Self-reported reward anticipation had a small positive effect (f2 = .10) on neural reward anticipation, and self-reported reward response had a negative effect (f2 = -.18) on neural reward response. Further research is needed on the relationship between multi-method measurement of reward sensitivity to inform clinical utility of these measures.Master of Art