Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression

BackgroundHealthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.MethodIn a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD−). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.ResultsNegative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD− individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD− group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD− group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.ConclusionsOur study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.

Download Full-text

The Role of Social Reward and Corticostriatal Connectivity in Substance Use

10.31234/osf.io/su7vg ◽

2020 ◽

Author(s):

Daniel Sazhin ◽

Angelique Frazier ◽

Caleb River Haynes ◽

Camille Johnston ◽

Iris Ka-Yi Chat ◽

...

Keyword(s):

Substance Use ◽

Social Context ◽

Orbitofrontal Cortex ◽

Strategic Behavior ◽

Reward Processing ◽

Reward Sensitivity ◽

Social Reward ◽

Neural Responses ◽

Social Stimuli ◽

Neuroimaging Study

This report describes an ongoing R03 grant that explores the links between trait reward sensitivity, substance use, and neural responses to social and nonsocial reward. Although previous research has shown that trait reward sensitivity and neural responses to reward are linked to substance use, whether this relationship is impacted by how people process social stimuli remains unclear. We are investigating these questions via a neuroimaging study with college-aged participants, using individual difference measures that examine the relation between substance use, social context, and trait reward sensitivity with tasks that measure reward anticipation, strategic behavior, social reward consumption, and the influence of social context on reward processing. We predict that substance use will be tied to distinct patterns of striatal dysfunction. Specifically, reward hyposensitive individuals will exhibit blunted striatal responses to social and non-social reward and enhanced connectivity with the orbitofrontal cortex; in contrast, reward hypersensitive individuals will exhibit enhanced striatal responses to social and non-social reward and blunted connectivity with the orbitofrontal cortex. We also will examine the relation between self-reported reward sensitivity, substance use, and striatal responses to social reward and social context. We predict that individuals reporting the highest levels of substance use will show exaggerated striatal responses to social reward and social context, independent of self-reported reward sensitivity. Examining corticostriatal responses to reward processing will help characterize the relation between reward sensitivity, social context and substance use while providing a foundation for understanding risk factors and isolating neurocognitive mechanisms that may be targeted to increase the efficacy of interventions.

Download Full-text

Neural responses to negative outcomes predict success in community-based substance use treatment

Addiction ◽

10.1111/add.13734 ◽

2017 ◽

Vol 112 (5) ◽

pp. 884-896 ◽

Cited By ~ 6

Author(s):

Sarah E. Forster ◽

Peter R. Finn ◽

Joshua W. Brown

Keyword(s):

Substance Use ◽

Substance Use Treatment ◽

Negative Outcomes ◽

Neural Responses ◽

Community Based

Download Full-text

Motivational system modulates brain responses during exploratory decision-making

Scientific Reports ◽

10.1038/s41598-021-95311-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chia-Wei Li ◽

Carol Yeh-Yun Lin ◽

Ting-Ting Chang ◽

Nai-Shing Yen ◽

Danchi Tan

Keyword(s):

Decision Making ◽

High Performance ◽

Behavioral Activation ◽

Motivational Orientation ◽

Performance Group ◽

Reward Seeking ◽

Brain Responses ◽

Low Performance ◽

Risk Choice ◽

The Brain

AbstractManagers face risk in explorative decision-making and those who are better at such decisions can achieve future viability. To understand what makes a manager effective at explorative decision-making requires an analysis of the manager’s motivational characteristics. The behavioral activation/inhibition system (BAS/BIS), fitting the motivational orientation of “approach” or “avoidance,” can affect individual decision-making. However, very little is known about the neural correlates of BAS/BIS orientation and their interrelationship with the mental activity during explorative decision-making. We conducted an fMRI study on 111 potential managers to investigate how the brain responses of explorative decision-making interact with BAS/BIS. Participants were separated into high- and low-performance groups based on the median exploration-score. The low-performance group showed significantly higher BAS than that of the high-performance group, and its BAS had significant negative association with neural networks related to reward-seeking during explorative decision-making. Moreover, the BIS of the low-performance group was negatively correlated with the activation of cerebral regions responding to risk-choice during explorative decision-making. Our finding showed that BAS/BIS was associated with the brain activation during explorative decision-making only in the low-performance group. This study contributed to the understanding of the micro-foundations of strategically relevant decision-making and has an implication for management development.

Download Full-text

Dissociable oscillatory networks support gain and loss processing in human orbitofrontal cortex

10.1101/2021.02.25.432874 ◽

2021 ◽

Author(s):

Ignacio Saez ◽

Jack Lin ◽

Edward Chang ◽

Josef Parvizi ◽

Robert T. Knight ◽

...

Keyword(s):

Neural Activity ◽

Orbitofrontal Cortex ◽

Low Frequency ◽

Brain Regions ◽

Reward Processing ◽

Neural Oscillations ◽

Beta Band ◽

Neuronal Ensembles ◽

Gain And Loss

AbstractHuman neuroimaging and animal studies have linked neural activity in orbitofrontal cortex (OFC) to valuation of positive and negative outcomes. Additional evidence shows that neural oscillations, representing the coordinated activity of neuronal ensembles, support information processing in both animal and human prefrontal regions. However, the role of OFC neural oscillations in reward-processing in humans remains unknown, partly due to the difficulty of recording oscillatory neural activity from deep brain regions. Here, we examined the role of OFC neural oscillations (<30Hz) in reward processing by combining intracranial OFC recordings with a gambling task in which patients made economic decisions under uncertainty. Our results show that power in different oscillatory bands are associated with distinct components of reward evaluation. Specifically, we observed a double dissociation, with a selective theta band oscillation increase in response to monetary gains and a beta band increase in response to losses. These effects were interleaved across OFC in overlapping networks and were accompanied by increases in oscillatory coherence between OFC electrode sites in theta and beta band during gain and loss processing, respectively. These results provide evidence that gain and loss processing in human OFC are supported by distinct low-frequency oscillations in networks, and provide evidence that participating neuronal ensembles are organized functionally through oscillatory coherence, rather than local anatomical segregation.

Download Full-text

Effects of compassion training on brain responses to suffering others

10.1101/616029 ◽

2019 ◽

Cited By ~ 2

Author(s):

Yoni K. Ashar ◽

Jessica R. Andrews-Hanna ◽

Joan Halifax ◽

Sona Dimidjian ◽

Tor D. Wager

Keyword(s):

Orbitofrontal Cortex ◽

Smartphone Application ◽

Post Intervention ◽

Placebo Condition ◽

Demand Characteristics ◽

Compassion Meditation ◽

Brain Responses ◽

Author Note ◽

Additional Support ◽

Research Assistants

AbstractWhat are the active ingredients and brain mechanisms of compassion training? To address these questions, we conducted a three-armed randomized trial (N = 57) of compassion meditation (CM). We compared a four-week CM program delivered by smartphone application to i) a placebo condition, in which participants inhaled sham oxytocin, which they were told would enhance compassion, and ii) a familiarity control condition, designed to control for increased familiarity with suffering others. Functional MRI was collected while participants listened to narratives describing suffering others at pre- and post-intervention. CM increased brain responses to suffering others in the medial orbitofrontal cortex (mOFC) relative to both the placebo and familiarity control conditions, and in the nucleus accumbens relative to the familiarity control condition. Results support the specific efficacy of CM beyond effects of expectancy, demand characteristics, and increased familiarity with suffering others, and implicate affective and motivational pathways as brain mechanisms of CM.Author NoteFunded by the John Templeton Foundation’s Positive Neuroscience project (PIs Wager and Dimidjian), with additional support from NIH R01 R01DA035484 (PI Wager). Gratitude to research assistants Jenifer Mutari, Robin Kay, Scott Meyers, Nicholas Peterson, and Brandin Williams for help with data collection.

Download Full-text

Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia

Translational Psychiatry ◽

10.1038/s41398-021-01668-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sara Costi ◽

Laurel S. Morris ◽

Abigail Collins ◽

Nicolas F. Fernandez ◽

Manishkumar Patel ◽

...

Keyword(s):

Mononuclear Cells ◽

Immune Cell ◽

Ex Vivo ◽

Flanker Task ◽

Reward Processing ◽

Neural Responses ◽

Depressed Patients ◽

Reward Anticipation ◽

Peripheral Leukocytes ◽

Immune Score

AbstractIncreased levels of peripheral cytokines have been previously associated with depression in preclinical and clinical research. Although the precise nature of peripheral immune dysfunction in depression remains unclear, evidence from animal studies points towards a dysregulated response of peripheral leukocytes as a risk factor for stress susceptibility. This study examined dynamic release of inflammatory blood factors from peripheral blood mononuclear cells (PBMC) in depressed patients and associations with neural and behavioral measures of reward processing. Thirty unmedicated patients meeting criteria for unipolar depressive disorder and 21 healthy control volunteers were enrolled. PBMCs were isolated from whole blood and stimulated ex vivo with lipopolysaccharide (LPS). Olink multiplex assay was used to analyze a large panel of inflammatory proteins. Participants completed functional magnetic resonance imaging with an incentive flanker task to probe neural responses to reward anticipation, as well as clinical measures of anhedonia and pleasure including the Temporal Experience of Pleasure Scale (TEPS) and the Snaith-Hamilton Pleasure Scale (SHAPS). LPS stimulation revealed larger increases in immune factors in depressed compared to healthy subjects using an aggregate immune score (t49 = 2.83, p = 0.007). Higher peripheral immune score was associated with reduced neural responses to reward anticipation within the ventral striatum (VS) (r = −0.39, p = 0.01), and with reduced anticipation of pleasure as measured with the TEPS anticipatory sub-score (r = −0.318, p = 0.023). Our study provides new evidence suggesting that dynamic hyper-reactivity of peripheral leukocytes in depressed patients is associated with blunted activation of the brain reward system and lower subjective anticipation of pleasure.

Download Full-text

Orbitofrontal cortex output pathways: cingulate cortex, basal ganglia, and dopamine

The Orbitofrontal Cortex ◽

10.1093/oso/9780198845997.003.0005 ◽

2019 ◽

pp. 145-164

Author(s):

Edmund T. Rolls

Keyword(s):

Orbitofrontal Cortex ◽

Instrumental Learning ◽

Cingulate Cortex ◽

Reward Processing ◽

Dopamine Neurons ◽

Anterior Cingulate ◽

Stimulus Response ◽

Related Information ◽

Outcome Information ◽

Reward Information

The medial orbitofrontal cortex projects reward-related information to the pregenual cingulate cortex, and the lateral orbitofrontal cortex projects punishment and non-reward information to the supracallosal anterior cingulate cortex. These projections provide the reward outcome information needed for action-outcome goal value dependent instrumental learning by the cingulate cortex. The orbitofrontal cortex also projects reward-related information to the striatum for stimulus-response habit learning. Via the striatal route, and further in part via the habenula, the orbitofrontal cortex provides information about rewards and non-rewards that reached the brainstem dopamine neurons, some of which respond to positive reward prediction error, and the serotonin (5HT) neurons. The orbitofrontal cortex is therefore perhaps the key brain region involved in reward processing in the brain. The orbitofrontal cortex also has projections that can influence autonomic function, in part via the insula.

Download Full-text

Increased anticipatory but decreased consummatory brain responses to food in sisters of anorexia nervosa patients

BJPsych Open ◽

10.1192/bjpo.bp.115.002550 ◽

2016 ◽

Vol 2 (4) ◽

pp. 255-261 ◽

Cited By ~ 3

Author(s):

Stefanie Horndasch ◽

Sophie O'Keefe ◽

Anneka Lamond ◽

Katie Brown ◽

Ciara McCabe

Keyword(s):

Anorexia Nervosa ◽

Family History ◽

Neural Response ◽

Anterior Cingulate ◽

Neural Responses ◽

Food Cues ◽

Dorsal Anterior Cingulate Cortex ◽

Brain Responses ◽

History Of ◽

Increased Activity

BackgroundWe have previously shown increased anticipatory and consummatory neural responses to rewarding and aversive food stimuli in women recovered from anorexia nervosa (AN).AimsTo determine whether these differences are trait markers for AN, we examined the neural response in those with a familial history but no personal history of AN.MethodThirty-six volunteers were recruited: 15 who had a sister with anorexia nervosa (family history) and 21 control participants. Using fMRI we examined the neural response during an anticipatory phase (food cues, rewarding and aversive), an effort phase and a consummatory phase (rewarding and aversive tastes).ResultsFamily history (FH) volunteers showed increased activity in the caudate during the anticipation of both reward and aversive food and in the thalamus and amygdala during anticipation of aversive only. FH had decreased activity in the dorsal anterior cingulate cortex, the pallidum and the superior frontal gyrus during taste consumption.ConclusionsIncreased neural anticipatory but decreased consummatory responses to food might be a biomarker for AN. Interventions that could normalise these differences may help to prevent disorder onset.

Download Full-text

The Effects of Kisspeptin on Brain Response to Food Images and Psychometric Parameters of Appetite in Healthy Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa746 ◽

2020 ◽

Author(s):

Lisa Yang ◽

Lysia Demetriou ◽

Matthew B Wall ◽

Edouard G Mills ◽

Victoria C Wing ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Brain Activity ◽

Brain Regions ◽

Metabolic Effects ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Brain Response ◽

Healthy Men ◽

Brain Responses ◽

Double Blinded

Abstract Context The hormone kisspeptin has crucial and well-characterized roles in reproduction. Emerging data from animal models also suggest that kisspeptin has important metabolic effects including modulation of food intake. However, to date there have been no studies exploring the effects of kisspeptin on brain responses to food stimuli in humans. Objective This work aims to investigate the effects of kisspeptin administration on brain responses to visual food stimuli and psychometric parameters of appetite, in healthy men. Design A double-blinded, randomized, placebo-controlled, crossover study was conducted. Participants Participants included 27 healthy, right-handed, eugonadal men (mean ± SEM: age 26.5 ± 1.1 years; body mass index 23.9 ± 0.4 kg/m2). Intervention Participants received an intravenous infusion of 1 nmol/kg/h of kisspeptin or rate-matched vehicle over 75 minutes. Main Outcome Measures Measurements included change in brain activity on functional magnetic resonance imaging in response to visual food stimuli and change in psychometric parameters of appetite, during kisspeptin administration compared to vehicle. Results Kisspeptin administration at a bioactive dose did not affect brain responses to visual food stimuli or psychometric parameters of appetite compared to vehicle. Conclusions This is the first study in humans investigating the effects of kisspeptin on brain regions regulating appetite and demonstrates that peripheral administration of kisspeptin does not alter brain responses to visual food stimuli or psychometric parameters of appetite in healthy men. These data provide key translational insights to further our understanding of the interaction between reproduction and metabolism.

Download Full-text