Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

Salamone, John D.; Yohn, Samantha E.; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

doi:10.1093/brain/aww050

Cited by 352Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesSchizophrenia research and treatment

Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

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Salamone, John D., Yohn, Samantha E., López-Cruz, Laura, San Miguel, Noemí, Correa, Mercè·2016·Brain

DOI 10.1093/brain/aww050PMC PMC5839596

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Abstract

Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort-based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson's disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology.

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Neurophysiological data show that the amygdala plays an important role in valuing effort.
“Recent evidence points to the amygdala as playing a crucial role in effort-based decision making in rodents, with neurophysiological data showing that the amygdala plays an important role in valuing effort [40, 41].”
From Neurocomputational mechanisms underlying subjective valuation of effort costs (2017) · cites this paper as [40]
The amygdala plays a crucial role in effort-based decision making in rodents.
“Recent evidence points to the amygdala as playing a crucial role in effort-based decision making in rodents, with neurophysiological data showing that the amygdala plays an important role in valuing effort [40, 41].”
From Neurocomputational mechanisms underlying subjective valuation of effort costs (2017) · cites this paper as [40]

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Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms
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Effects of d-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens.
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The pharmacology of effort-related choice behavior: Dopamine, depression, and individual differences
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Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder
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The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure
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The relation between depression, anhedonia and olfactory hedonic estimates—A pilot study in major depression
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Cannabinoid CB1 antagonists and dopamine antagonists produce different effects on a task involving response allocation and effort-related choice in food-seeking behavior
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The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs
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THREE PREDICTIONS OF THE ECONOMIC CONCEPT OF UNIT PRICE IN A CHOICE CONTEXT
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Orexin‐1 receptor signaling increases motivation for cocaine‐associated cues
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Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task
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Motivational states influence effort-based decision making in rats: The role of dopamine in the nucleus accumbens
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Effort Cost Computation in Schizophrenia: A Commentary on the Recent Literature
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Nucleus Accumbens Dopamine and the Forebrain Circuitry Involved in Behavioral Activation and Effort-Related Decision Making: Implications for Understanding Anergia and Psychomotor Slowing in Depression
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Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats
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Sweet liking in patients with Parkinson’s disease.
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Forebrain circuitry involved in effort-related choice: Injections of the GABAA agonist muscimol into ventral pallidum alter response allocation in food-seeking behavior
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Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats
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Effects of bupropion on simulated demand for cigarettes and the subjective effects of smoking
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Toward a rational and mechanistic account of mental effort
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“There is not scope to fully review this literature here, but there is now an overwhelming wealth of behavioural evidence which highlights the crucial role of the ACC-VS loop in motivating the exertion of effort towards a goal, sustaining this effort and in learning whether a behaviour is worthwhile (Salamone et al., 2…”
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Motivation and cognitive control in depression
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Brain mechanisms underlying apathy
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Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms
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Reward Processing, Neuroeconomics, and Psychopathology
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Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson’s disease
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Dopamine, effort-based choice, and behavioral economics: basic and translational research.
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The fatigue conundrum
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The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine
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Inflammation and decreased functional connectivity in a widely-distributed network in depression: Centralized effects in the ventral medial prefrontal cortex
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Vagus nerve stimulation boosts the drive to work for rewards
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The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation
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Advantages and Limitations of Animal Schizophrenia Models
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Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization
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Effort but not Reward Sensitivity is Altered by Acute Sickness Induced by Experimental Endotoxemia in Humans
Draper, A., Koch, R. M., van der Meer, J. W., Apps, M. A. J., Pickkers, P., Masud Husain, B., & van der Schaaf, M. E. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.231 · Cited by 91 · see citing works
Dopamine and the motivation of cognitive control
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Process-based framework for precise neuromodulation
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The Urge to Decide and Act: Implications for Brain Function and Dysfunction
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The Roles of Phasic and Tonic Dopamine in Tic Learning and Expression
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Blockade of uptake for dopamine, but not norepinephrine or 5-HT, increases selection of high effort instrumental activity: Implications for treatment of effort-related motivational symptoms in psychopathology
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Human complex exploration strategies are enriched by noradrenaline-modulated heuristics
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From movement to motivation: a proposed framework to understand the antidepressant effect of exercise
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Apathy in Parkinson’s Disease: Clinical Patterns and Neurobiological Basis
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The Neurobiology of Pathological Fatigue: New Models, New Questions
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Dual contributions of noradrenaline to behavioural flexibility and motivation
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Neural Circuitry of Salience and Reward Processing in Psychosis
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Intoxication and substance use disorder to Areca catechu nut containing betel quid: A review of epidemiological evidence, pharmacological basis and social factors influencing quitting strategies
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New Developments on the Adenosine Mechanisms of the Central Effects of Caffeine and Their Implications for Neuropsychiatric Disorders
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“However, the A2AR–D2R heteromer is also localized in the ventral striatum, involved in more motivational aspects of behavior.(3,38)”
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PPARα modulation of mesolimbic dopamine transmission rescues depression-related behaviors
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Authors: Salamone, J. D., Yohn, S. E., López-Cruz, L., San Miguel, N., & Correa, M.
Affiliations: University of Connecticut (US)
Universitat Jaume I (ES)
ORCID: Salamone, John D.
Yohn, Samantha E.
Correa, Mercè
Venue: Brain
Publisher: Oxford University Press (OUP)
Published: 2016-04-26
Volume: 139
Issue: 5
Pages: 1325-1347
ISSN: 0006-8950 (ISSN-L)
1460-2156
DOI: 10.1093/brain/aww050
PMC: PMC5839596
OpenAlex: W2342940951
Cited by: 350
References: 299
Citations by year: 2026: 33 · 2025: 29 · 2024: 19 · 2023: 31 · 2022: 36 · 2021: 39 · 2020: 39 · 2019: 37 · 2018: 39 · 2017: 37 · 2016: 11
FWCI: 4.53
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Brain (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Open Research Online - ORO (The Open University) (acceptedVersion)
HighWire Press Open Archive (submittedVersion)
Repositori UJI (Universitat Jaume I) (submittedVersion, public-domain)
Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, other-oa)
Funders: National Institute of Mental Health (R03MH094966)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: motivation, behavioral activation, dopamine, anergia, fatigue, psychomotor retardation, depression, schizophrenia, Parkinson's disease, effort-based decision making, motivational dysfunction
MeSH terms: Animals, Decision Making, Major Depressive Disorder, Dopamine, Physical Exertion, Humans, Motivation, Neural Pathways, Parkinson Disease, Schizophrenia

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Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

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