Reward, motivation and brain imaging in human healthy participants – A narrative review

The review addresses how human brain mechanisms mediate reward motivation and their relationship with cognition in healthy participants. A PubMed search using “Reward motivation and brain imaging” identified 2,127 records (2000–October 2022); inclusion criteria were English-language, peer-reviewed studies measuring brain imaging in human subjects. Based on these criteria, 2,058 records were excluded and 64 records were included. The review synthesizes evidence on mesolimbic dopamine circuitry and its interactions with decision-making, reward anticipation and coding, motivated cognitive control, PFC integration, motor system engagement, and effects across incentives (food, money, social reward). It further examines associations with learning, memory (formation, encoding, consolidation, recollection, novelty, episodic retrieval), imagery, working memory, attention, summarizes findings from the monetary incentive delay task (MID/DMRT) and meta-analyses, and discusses implications for addiction and neuropsychiatric disorders, pharmacology and genetics of dopamine, and sex differences.

The review consolidates two decades of human brain imaging research on reward motivation. Key themes include: (1) Meso-limbic dopamine circuitry: fMRI-PET studies link activity in SN/VTA, ventral striatum/nucleus accumbens (VS/NAcc) to dopamine release, with correlations in amygdala and hippocampus; dopamine receptor occupancy relates to reinforcement learning and pleasurable behavior. (2) Decision-making: Distinct neural networks for selection (occipital-parietal, ACC, premotor) versus anticipation (VS); OFC engaged during high-risk/reward choices. (3) Reward anticipation: Ventral and dorsal striatum and oculomotor cortex activate during reward-cued tasks; difficult tasks and high rewards recruit striatum and ACC; resting-state connectivity implicates VS, PFC, occipital/temporal cortices; NAcc and insula modulate choice even without explicit decision requirements. (4) Reward coding: VS, anterior insula, ACC, midbrain encode subjective value; lateral OFC shows posterior-anterior specialization (monetary vs erotic); VS encodes value during cues without choice; information expectation engages left lateral VS and differentiates networks from reward processing. (5) Motivated cognitive control: Midbrain and VS respond to rewards; hippocampus to penalties; high rewards engage globus pallidus, thalamus, subgenual cingulate; penalties engage caudate, insula, ventral PFC. Cognitive effort cost-benefit engages striatum; PET evidence shows NAcc dopamine release during rewarded task switching predicting reaction time benefits. (6) PFC integration: Medial/lateral PFC hierarchically organize motivation and selection, transmitting motivational incentives for top-down control; avPFC-NAcc-VTA interactions facilitate long-term goal pursuit by inhibiting immediate reward, linked to trait impulsivity; adolescent reward sensitivity involves insula, VS, OFC differences; personality modulates mesolimbic responses in adolescents and adults; OFC encodes magnitude/valence, with lateral OFC encoding loss; dIPFC drives VTA during reward availability; vmPFC lesions alter reward incentivization; frontoparietal task coding is enhanced by reward. (7) Motor system: Prospective rewards/losses improve performance; anterior caudate and pre-SMA involved in inhibition/action; loss aversion predicts behavioral and motor cortical sensitivity to incentives; thalamus and insula modulate NAcc during incentive processing. (8) Incentives (food, money, social): Hunger/satiety modulate reward/control networks; secondary rewards (money) increase anticipatory lateral OFC activity and consummatory medial OFC activity; social vs object rewards recruit distinct networks (precuneus/medial OFC vs VS/dorsal striatum); cognitive reward control activates SMA, dIPFC, ventrolateral PFC. (9) Learning: Extrinsic motivation correlates with ACC, amygdala, putamen activation; intrinsic motivation shows negative correlations in these regions; learning motivation engages putamen; performance-based monetary reward can undermine intrinsic motivation (reduced anterior striatum/PFC), while action-outcome contingencies evoke intrinsic motivation (VS/midbrain). Verbal rewards engage anterior striatum/midbrain; withdrawal increases lateral PFC activity; intrinsic reward in naturalistic tasks recruits dlPFC, SPL, insula, putamen; reward cues activate frontoparietal network but may not increase context discrimination. (10) Memory: Limbic striatum D2 binding relates to episodic memory; curiosity and monetary reward enhance memory via VS and attention networks; reward cues before encoding activate NAcc, VTA, hippocampus, improving declarative memory; reward motivation organizes cortical networks for hippocampal detection of expectancy violations; reward vs punishment surprises engage hippocampus vs parahippocampal cortex; recollection under reward engages hippocampus and striatum; novelty and reward interact within mesolimbic system, modulating long-term memory via MTL and OFC; episodic memory retrieval involves SN/VTA, MTL, dmPFC, dlPFC with reward-related connectivity; memory-reward connectivity reflects individual differences (ACC, OFC, VS). (11) Working memory and attention: Reward-sensitive individuals show improved working memory with right lateral PFC engagement even on unrewarded trials; dorsal ACC encodes integrated incentive value predicting performance; reward enhances proactive recruitment of task-positive networks improving sustained attention. (12) MID/DMRT meta-analyses: Anticipation engages VS/dorsal striatum, thalamus, amygdala, midbrain, insula, premotor/SMA, occipital/cuneus; delivery engages VS, amygdala, medial frontal/OFC/PCC; broader analyses show NAcc and cortical regions for valence and anticipation/outcome; VS sensitive to anticipation/consumption and magnitude; valuation networks include dorsal/posterior striatum, dmPFC, anterior insula, thalamus; loss anticipation engages ventrolateral PFC; differences across studies reflect analysis methods and task phases. (13) Clinical implications: Altered reward processing implicated in addiction, externalizing disorders, depression, ADHD; psychostimulants and natural rewards increase striatal dopamine; IGD shows reward circuitry activation and reduced control/connectivity; cue-reactivity in gambling and CSBD engages dopamine reward areas; ADHD shows VS hyporesponsiveness during anticipation; depression shows anhedonia and impaired striatal responses. (14) Reconsolidation and treatment: Memory reconsolidation approaches targeting reward-related memories are proposed for addiction, combining pharmacology and cognitive interventions (cue exposure, reconsolidation, episodic future thinking). (15) Pharmacology/genetics: DAT, DRD4, DRD2 variants modulate striatal responses; COMT Val/Met influences PFC activation; DA’s role is non-linear and modulated by synthesis/release, reuptake, receptors, metabolism, and other neurotransmitters; GWAS recommended to capture polygenic influences; DA medications may differentially affect anticipation vs consummation. (16) Sex differences: PET evidence of lateralized DA release to unpredictable reward (bilateral in women, right-lateralized in men); adolescent males show more risky decisions and greater NAcc activation than females, independent of sex hormones.

Narrative review with targeted database search. A PubMed search using the terms “Reward motivation and brain imaging” identified publications from 2000 to October 2022. Inclusion criteria: English-language articles, peer-reviewed journals, studies measuring brain imaging (e.g., fMRI, PET, fNIRS) in human subjects. Screening yielded 2,127 records; 2,058 were excluded based on criteria, resulting in 64 included records. The review organizes findings across neural circuits, cognitive domains, tasks (e.g., MID/DMRT), meta-analyses, clinical implications, pharmacology/genetics, and sex differences.

• The meso-limbic dopamine circuitry (SN/VTA, VS/NAcc) underpins reward-motivated behavior; fMRI-PET studies show correlations between striatal activity and dopamine release, extending to amygdala/hippocampus. - Decision-making and reward anticipation recruit distinct networks: selection engages occipital-parietal, ACC, premotor, and OFC; anticipation engages VS and striatum; OFC encodes magnitude/valence. - PFC integrates motivation and cognitive control: medial/lateral PFC organize hierarchical control; dIPFC drives VTA to initiate motivated behavior; avPFC-NAcc-VTA interactions facilitate long-term goal pursuit and impulse control. - Motor system: Pre-SMA, anterior caudate, and right inferior frontal cortex support action control/inhibition; motor cortical excitability reflects subjective reward value; thalamus and insula modulate NAcc during incentives. - Reward coding: VS, anterior insula, ACC, midbrain encode subjective value; lateral OFC shows specialization for monetary vs erotic rewards; information expectation dissociates from reward receipt networks. - Learning and motivation: Extrinsic motivation correlates with ACC/amygdala/putamen activation; intrinsic motivation can be undermined by monetary rewards (reduced anterior striatum/PFC) but enhanced by action–outcome contingencies (VS/midbrain). - Memory: Reward enhances encoding and consolidation via NAcc, VTA, hippocampus; curiosity and attention networks boost memory formation; novelty and reward interact in MTL/OFC; recollection under reward involves hippocampus and striatum; limbic striatum D2 binding relates to episodic memory performance. - Working memory and attention: Reward sensitivity improves working memory with right lateral PFC engagement; dorsal ACC encodes integrated incentive value predicting performance; motivated blocks proactively recruit task-positive networks enhancing sustained attention. - MID/DMRT meta-analyses: Anticipation activates VS/dorsal striatum, thalamus, amygdala, midbrain, insula, premotor/SMA, occipital/cuneus; reward delivery activates VS, amygdala, medial frontal/OFC/PCC; loss anticipation engages ventrolateral PFC; variability arises from task phase and analysis methods. - Clinical relevance: Altered reward processing characterizes addiction, externalizing disorders, depression, and ADHD (e.g., VS hyporesponsiveness during anticipation in ADHD; anhedonia in depression). - Pharmacology/genetics: DAT, DRD4, DRD2, COMT variants modulate striatal/PFC responses; DA’s influence is complex and interacts with multiple neurotransmitter systems; GWAS needed to capture polygenic architecture. - Sex and development: Adolescents show heightened reward sensitivity (insula, VS) and different responses to omitted reward (OFC); males may make riskier decisions and exhibit right-lateralized ventral striatal DA release.

The synthesis addresses the central question of how human brain circuits mediate reward motivation and interact with cognitive functions. Convergent evidence implicates the mesolimbic dopamine system (VS/NAcc, SN/VTA) and distributed cortical networks (medial/lateral PFC, OFC, ACC, insula, thalamus) in anticipating, valuing, and executing reward-driven behavior. Distinct phases of reward (anticipation vs receipt) and task demands (decision selection vs anticipation) recruit overlapping yet dissociable circuits. These mechanisms extend to cognitive domains—learning and memory formation (hippocampal engagement via reward cues), working memory (prefrontal modulation), and attention (proactive task-positive network recruitment). The MID/DMRT literature and meta-analyses provide robust task-based mappings of reward processing, though findings vary with analysis strategies and phases examined. Clinically, the reviewed patterns elucidate phenotypes of addiction, externalizing disorders, depression, and ADHD, informing targets for interventions (e.g., enhancing motivation, leveraging memory reconsolidation). Genetic and pharmacological studies highlight the nuanced, non-linear role of dopamine and related neurotransmitters, and the need for polygenic approaches. Developmental and sex differences suggest that reward sensitivity and lateralization contribute to variability in risk-taking and motivational salience.

Reward motivation in healthy humans is mediated by dopamine-centric striatal circuits interacting with PFC, insula, thalamus, and motor networks, shaping anticipation and consummation of reward and influencing decision-making, attention, and memory (including working memory and episodic processes). This narrative review consolidates task-based and meta-analytic evidence, providing a framework that also informs pathological states such as addiction, depression, and ADHD. Gaps remain regarding the genetic underpinnings and sex differences in reward motivation; future research should employ comprehensive imaging-genetics (e.g., GWAS), longitudinal designs across development, and standardized analytic pipelines to clarify circuit-specific contributions and translational targets.

• The review is narrative and not a systematic meta-analysis, potentially introducing selection bias. - Inclusion was limited to English-language, peer-reviewed human brain imaging studies from 2000–2022, which may exclude relevant data. - Across the literature, findings vary by task phase (anticipation vs receipt), paradigm differences, and analytic methods, limiting direct comparability. - There is a paucity of research on genetic mechanisms and sex differences in reward motivation, as explicitly noted by the author. - Adolescent-specific mechanisms and developmental trajectories require further study to resolve inconsistencies in risk-taking and reward sensitivity.